PSY1202 Biological Psychology Term 2

Learning and Memory - Neural Plasticity: from behaviour to genes Synapse plasticity in learning and memory

"When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased" - Donald O. Hebb (1949) The Organisation of Behaviour Synaptic plasticity - biological processes at the synapse by which patterns of synaptic activity change (increase or decrease synaptic strength)

Vision - The first steps in image processing

- A 100 megapixel modern camera is a poor technical imitation of the retina which has a much larger sensor area and much more sophisticated processing circuits - Lens to focus image - Aperture to control light entering (Iris) - Pixels to register image (photoreceptors)Filtering media (glass body, macula, pigment) - Filter to protect lens (cornea) - Lenses cover for when not in use (eyelid) - Cleaning mechanisms (tears) - Processing algorithms (retinal interneurons)

Electrophysiological recordings of brain activity EPSP and the resulting Field Potential (FP)

- A temporary deficit of positive charge develops in the area of extracellular space where sodium enters the neuron, the synapse, because of the sodium entering the neuron - A temporary surplus of positive charge develops in the area near the soma, where potassium exits the cell There is a change in field potential Field Potential: potential measured outside the neuron, occurs when you have a difference in electrical charge which can be measured using electrodes - When the scalp is below and the EEG is above it picks up the change in field potential underneath in the group of neurons, then it deducts that from the reference and the difference is plotted, use those changes compared to the reference - This basically indicates the positive and negative electrical value of change in those neurons

Learning and Memory - Neural Plasticity: from behaviour to genes AMPA Receptors in CA1 Pyramidal Neurons

- AMPA receptors are ionotropic receptors (ligand-gated ion channels) - AMPA receptors open if glutamate binds to them, when Na+ flow into the postsynaptic neuron, this depolarises the membrane and causes an EPSP - The synapse is excitatory, because the influx of Na+ depolarizes the membrane (EPSPs)

Synaptic Sequence - Substances can interfere with the release of the transmitter e.g. Acetylcholine

- Acetylcholine is a neurotransmitter that has two types of receptors: nicotinic (excitatory) and muscarinic (inhibitory) - Botulinum toxin (formed by bacteria in improperly canned food) interferes with the release of Acetylcholine at nicotinic synapses, by preventing the vesicles from fusing with the cell membrane - This toxin is used in the cosmetic agent BOTOX, used to treat wrinkles by reducing synaptic effectiveness at the neuromuscular junction in facial muscles

Vision - Dim-light vision (rods) does not use central fovea

- Acuity of vision is highest in fovea and decreases towards the periphery of the retina - Eye movements position the fovea in those positions of the visual field where it is most important to collect high-acuity information - At night high acuity is sacrificed for sensitivity, and it is more advantageous to have no rods in the fovea - The cones are more present in lower densities and only close to the fovea and in the fovea itself they are well represented - The optic disc is where the axons of the ganglion cells leave the eye because the structure is inverted, the axons lay on top of the retina and obviously they have to have somewhere to exit to connect to the brain, so this is our blind spot which is just a hole in the eyeball - The acuity is highest in the fovea because it has the highest density of receptors, when we use night vision the density of our rods is still lower than that of the fovea so we can see quite well when it's not too dark, but still in the fovea during the day we have out sharpest vision - Eye movements position the fovea in the pats of the visual field, so where we look, in order to collect the most important high acuity information - At night when light levels decrease, the lower the light level the blurrier the image becomes, and even if we have many rods the neural process start summing up that information and there is a lot of spatial temporal summation going on in order to increase the contrast edges which comes at the cost of acuity - So typically, in order to enhance sensitivity, you also open the aperture, and the pupil widens, and more light can enter but that also means the images become blurrier and usually then neuronal mechanisms will help to increase sensitivity by pooling together the signals from many rods

Biology of Stress - Adrenaline

- Adrenaline has a wider range of effects including: - Heart beating faster and stronger - Increased blood flow to muscles - Reduced blood flow to digestive functions and skin - Stimulating glycogenolysis by liver (glycogen broken down to glucose which raises blood sugar) - Causes adipose tissue to release fat into the blood - Widens bronchioles (air passageways in lung) - Dilates pupils - Assists the body to escape from or deal with the stressful situation e.g., faster, stronger, sharper etc ... - Accompanied by activation of hypothalamic-pituitary-adrenal (HPA) axis - ACTH stimulates adrenal cortex to release cortisol and other steroids - Engages slower-acting, passive coping mechanisms, useful when fight/flight is ineffective Adaptive redirection of energy: - Direction of oxygen and nutrients to the brain Stimulates lipolysis (breakdown of fats) - Stimulates gluconeogenesis (production of glucose) - Inhibits growth and reproduction - Suppresses immune system - Contains inflammatory responses - Enhances arousal, vigilance and cognition

Human Genetic Variation - Categories of human participants in psychological research (biological or not biological)

- Age, developmental stage, reproductive stage - Health, disability, addiction, physiological state - Sex, gender, sexual orientation - Race, ethnicity - Occupation, work status, leadership - Socio-economic status - Education, family - Political views, religion

The Cognitive Neuroscience of Addiction - Many people use psychoactive substances regularly for a variety of reasons

- Alcohol to relax, sleep, enhancing social experiences, reduce anxiety (anxiolytic = they lower anxiety) or feelings of depression - Coffee to wake up - Nicotine for the experience, stimulant, social reasons - MDMA to improve social experience - Cocaine to be more confident, focus on work, enhance social experience - Heroin to relax, or to feel a belonging or safety Etc

The Cognitive Neuroscience of Addiction - Neuropathology Alcohol

- Alcoholism is strongly linked to the Wernicke-Korsakoff syndrome - Wernicke encephalopathy is the general brain shrinkage shown below - Korsakoff syndrome is the chronic "end stage" of this phenomenon. It is a psychiatric diagnosis characterised by anterograde amnesia (inability to remember new things), which can sometimes be treated with thiamine supplements (Vitamin B12) because the reason the shrinkage occurs is because of a lack of vitamin B12 Top = 63-year-old healthy male Bottom = 63-year-old male alcoholic with Wernicke-Korsakoff syndrome showing enlarged ventricles and cortical sulci indicating loss of brain tissue

The Cognitive Neuroscience of Addiction

- All these drugs do different things and for the most part the result is positive, or people wouldn't do them - There is large variation between people and why they take certain substances, the vast majority of people that do that do not get addicted - Some people get addicted, most people don't, about 6% of alcohol users meet the criteria for alcohol use disorder - Addict's experience intense cravings for the desired substance and severe withdrawal symptoms when it is taken away - Addicts often go to extreme lengths to obtain the drug - This can have a profound effect on their physical and/or mental health - This can have a potentially devastating effect on their families, their work, education and social life - The degrees to which these things happen different greatly between people and the drugs/behaviours in question

Hormones and Behaviour - Social behaviour in meerkats:

- Allonursing - Sentinel duty - Pup feeding - Digging

Vision - Inverted responses in OFF-centre ganglion cells

- Also respond to light/dark ratios but not to uniform illumination - Responses are inverted - If a spot illuminates the centre of the OFF-centre ganglion cell, the spike rate is reduced - If a spot illuminates the ON-surround of the OFF-centre ganglion cell, the spike is increased - If the whole receptive field is illuminated, the ganglion cell is at rest and fires at its spontaneous rate

Synaptic Sequence - Substances can enhance the release of the transmitter e.g. Amphetamine

- Amphetamine is very similar in structure to the neurotransmitter dopamine - Due to its similarity to dopamine, amphetamine can enter the dopamine-releasing neuron either directly through the membrane of by binding to the dopamine transporter (molecule that 'recycles' dopamine back into the cell from the synaptic cleft) - Once inside the cell, amphetamine facilitates the release of dopamine from the vesicles when these fuse with the membrane

Synaptic Sequence - Anxiety and GABA

- Anxiety disorders are in part characterized by deficits in GABA-ergic transmission - Benzodiazepines (Valium) are GABA agonists used to treat anxiety disorders - Although their effect may seem similar to that of alcohol, they bind to different sites on GABA receptors - They also do not bind to the same receptor sites as GABA itself: such an action is one of a non-competitive agonist - A competitive agonist binds with receptor activated but from that moment on GABA itself can no longer bind there, whereas Valium and GABA can act together at the same time at the same receptors as non-competitive agonists

Human Genetic Variation - No agreement for ethnic or racial group labels

- Arbitrary numbers of clusters along geographical, political and cultural factors - Racial and ethnic labels occur in different social systems e.g., Northern Ireland census categories compared to census of India: no race/ethnicity, but schedules castes (16% population) and tubes (8%)

Learning and Memory - Associative learning: the classical conditioning paradigm

- Associative learning on the other hand means that the animal has to learn an association between events or stimuli - However classical conditioning has been observed in a number of invertebrates as well, invertebrates are very good learners and research suggests invertebrates learn very well associatively - E.g., Fruit fly, flatworm, etc ...

The Cognitive Neuroscience of Addiction - Causes of Addiction A learning perspective

- Associative learning theories of addiction construe drug taking as conditioning - In the instrumental conditioning paradigm, the drug is the reinforcer which strengthens the associations between drug-related cues and drug use - Classical conditioning, stimuli are being associated with the drug, this means stimuli in a broad sense in that it can be an environment or people or weather etc ... - Instrumental conditioning paradigm, the drug is the reinforcers which strengthens the association between drug-related cues and drug use

Vision - Ganglion cells respond to ratios of light/dark

- At rest, a ganglion cell fires action potentials (spikes) at a spontaneous rate - Whilst the ON-centre bipolar cell depolarises, the ON-centre ganglion cell responds by increasing its spike rate - Whilst the OFF-centre bipolar cell hyperpolarizes, the OFF-centre ganglion cell responds by decreasing its spike rate - If you shine a spot of light onto the central cone, the bipolar cell will respond with an EPSP because there is no light shone on the surround and so there is no inhibition - This then corresponds to a high rate of action potentials in the ganglion cells, if you place the spot in the surround of these photoreceptors neighbours now start inhibiting the central cone but also the central cone does not receive any light so it's not responding, and we get a strong hyperpolarization and correspondingly the ganglion cell will show a reduced rate of spiking - That means that these bipolar and ganglion cells are sensitive to the location and the size of the spot and this is why it is a spatial filter - Another notable aspect learned is that when the neuron is addressed it doesn't transmit a signal, however there's another possibility that when a neuron is addressed and that typically happens in some of the interneurons, that is can actually spike at a spontaneous rate between the maximum and the minimum - The reason being that then if there is a signal coming like this EPSP and release of neurotransmitters from the bipolar cell, it can increase the spiking rate. And when the bipolar cell is inhibited and not releasing neurotransmitters it can reduce its spontaneous activity - So, it can code in both directions in the same way that a bipolar cell can respond with de- and hyper-polarization, so this is another way neuron can respond with different frequencies of action potentials

Neuroimaging - MRI scanner

- Basically, an extremely strong magnet, usually 1.5-7 tesla - 1.5 tesla = 15,000 gauss - Earth's magnetic field strength = 0.5 gauss - Exeter MRI scanner = 30,000 X earth's magnetic field strength - Not allowed any metal in the scanner, copper shielded rooms

Electrophysiological recordings of brain activity Excitatory Postsynaptic Potential (EPSP) at the dendrite end

- Basically, measuring excitatory postsynaptic potentials which happen at the end of the dendrite which meet up with axons from other cells - The presynaptic neuron is the axon coming from another cell which releases neurotransmitters, and they bond at the gates of the dendrites of one particular cell, and they set in motion the action potential, a signal from this neuron travelling to the next

Sensory Modalities - Stereocilia (stiff hair) help to stretch open the ion channels

- Bending of the stereocilia (input zone) - Opening of non-selective ion channels that allow influx of K+ and Ca2+ ions - Depolarisation of the hair cell opens voltage gated Ca2+ channels in the base of the hair cell (output zone) - Neurotransmitter is released to excite afferent nerves

Human Genetic Variation - From maxi to mini

- Biometry, quantitative genetics measure observable traits (height, colouration, behaviour) - Genetics focussed on differences between chromosomes and the sequences of selected genes Genomics searches at many hundreds of loci for markets in genes and non-coding DNA (like in a massive word puzzle): - Short sequences - Repeated sequences (non-coding DNA) - Single base-pairs - 4 base pairs = T A C G

Hormone Structure and Action - What are hormones?

- Bioregulators of the endocrine system - Secreted by specialised cells directly into the blood - Selectively act on target cells - Synaptic communication when neuron released neurotransmitter which diffuse across the synaptic cleft and affecting the postsynaptic membrane of another neuron - Autocrine communication can be seen where the substance produced by the cell is feeding back into the same cell - Paracrine communication can also be seen where the substance diffuses across the extracellular space to affect nearby cells - Focus on endocrine cells which produce a hormone directly into bloodstream that travels around the body and affects target cells often in organs that are far away from the original production site - There is also a specialised type of cell called neurosecretory cells or neuroendocrine cells that are somewhat between an endocrine cell and a classical neuron, rather than releasing neurotransmitter to affect another neuron instead they are releasing hormones that travel in the bloodstream

Hormones and Behaviour - Endocrine and nervous systems compared

- Both are communication and control systems - Both take inputs and effect outputs - Both can be influenced by prior exposure (habituation/immunity) - Endocrine systems refer to chemical substances as messenger whereas nervous system refers to action potentials - In the endocrine system the message is conveyed in blood whereas in the nervous system it is transmitted along nerve fibre - In the endocrine system hormones have a diffuse effect across the body, whereas the nervous systems produce a targeted effect in a specific cell or organ In the endocrine system hormonal signals are more analogue (graded) signals whereas in the nervous system they are digital (all or nothing) signals - In the endocrine system the 'slow' response (secs or minutes) whereas the nervous system response is fast (ms) - In the endocrine system the response persists over time whereas in the nervous system the responses are generally short-lived - In the endocrine system there is no voluntary control whereas in the nervous system there is some voluntary control

Motor Control - Sagittal view of the brain

- Brain stem going down into spinal cord - Can see various regions dedicated to motor control such as the primary motor cortex, the premotor cortex, supplementary motor area, there are also many areas which perform dual roles for example in motor function and cognition - For example, there are large parts of the frontal lobe which are involved in motor control however are not dedicated to motor control

Synapses and Networks - The neuron doctrine:

- Brains are composed of separate neurons and other cells - Cells are independent - Neurons are polarised cells - Information is transmitted from cell to cell across tiny gaps

Synaptic Sequence - Some chemicals interfere with the signals going through the axon

- By blocking sodium channels in the axon's membrane (e.g., tetrodotoxin, or TTX - toxin is found in certain species of fish) - TTX can produce paralysis of the diaphragm and death due to respiratory failure (over 10,000 times deadlier than cyanide)

Learning and Memory - Standard LTM Consolidation Model

- Connections between the hippocampus and various cortical modules are critical for encoding and consolidation but not later retrieval and reconsolidation - Hippocampus is then inhibited by the prefrontal cortex. It has a time-limited role - Strengthened cortico-cortical connection integrate new memories with pre-existing ones

Motor Control - Subcortical motor structures: Cerebellum

- Contains more neurons than rest of CNS combine - Control's balance and eye/body coordination (but also does lots more) - Lesions result in balance/ait problems, ataxia (fine coordination) as well as attentional, planning and language problems

Human Genetic Variation - Genotyping: genome-wide association studies (GWAS)

- Current methods of genotyping decipher the whole genome and studies that sequence the genome and extract the snips/single nucleotide polymorphisms are called genome-wide association studies - There are two types of these studies: e.g. - Where the associations with disease are investigating the genome of people in control group and in a case group and will be compared where studies investigate the distribution of traits and a certain sample will be drawn from the population where the genome is fully sequenced - Tam et al (2019), Benefits and limitations of genome-wide association studies, Nature Reviews Genetics, 20(8), 467-484

Vision - Visual functions in blind humans and primates

- Damage to the VI causes cortical blindness, the loss of conscious vision - Patients are able to perform visually guided behaviours, like grasping or pointing to the location of objects or avoiding obstacles, correctly at a level above chance. This is known as blindsight - Cortical blindness doesn't mean the individual has lost all of their visual sense; they retain some - These studies suggest that there are cortical connections that bypass the VI such as between the thalamus, (something 5) or area MT that connects to the parietal cortex and guides our movement so that if that area of the visual pathway spread there is a possibility to detect stimuli without actually seeing it, the visual systems can still perform some functions - If other areas are lesioned, the most severe being the optic nerve which can produce full blindness, but may possibly spare endocrine functions that help controlling sleep wake cycles by sparing those parts of the optic nerve projecting to the superior colliculus - There are other remaining responses such as reflective pupil responses, again id those projections are spared, and they can be implicit reactions as emotional reactions again through pathways that bypass the V1

Human Genetic Variation - Misuse of Darwin's theory of evolution: breeding 'perfect' humans in a 'perfect' society

- Darwin's theory of evolution explains the diversity of species on Earth and how species with different adaptations appear and disappear - Misplaced morality and Social Darwinism: evolution is not the "survival of the fittest" (Victorian economist and philosopher Herbert Spencer, 1884) - Misconception of selective (human-riven, artificial) breeding as evolution - Natural selection is/does not: - Goal-orientated - Optimise traits and results in progress - Remove variation or prevent individuals from reproducing

Synapses and Networks - Signal transmission involves mostly chemical synapses Signal transmission within a spiking neuron

- Depolarisation (graded potential before reaching threshold) when the neuron is excited (received signal) - Action potentials (spikes) are generated in the integration zone if depolarisation reaches threshold, signal transmission inside neuron - Signal transmission to next neuron starts when action potentials reach the output zone and neurotransmitter is released (chemical synapse) - Signal transmission is accomplished if a graded potential in the input zone of the postsynaptic neuron is elicited

Vision - Atypical eye movements in dyslexia

- Difficulties in reading words, sentences and text - Longer durations of fixations and shorter saccades, more fixations during reading - Shorter visual attention span impact on eye movement patterns - There are many disorders which eye movements can be atypical or not normal - Has been discovered in dyslexia that the way that dyslexics read is often disrupt which is largely to do with shorter visual attention spans that influence the eye movements Prado et al (2007) where they compared normal and dyslexic readers, in the first test they were given a text to read whereas in the visual search task they had a text, a word, puzzles, so they have to detect a word in a lot of letters, they could balance the visual input by the number and types of letters, but the tasks were different, in visual search you can see that the dyslexic reader are no different from normal readers This is summarised in the number of rightward fixations, fixations where the eyes move to the right which is one way of quantifying eye movements, and this shows that during visual search both show the same rate of these rightward fixations, but then in the normal reader during reading because of the training and the way these words are recognised these fixations are occurring less frequently whereas dyslexic readers perform the same high number of rightward fixations in the reading task as well as the visual search task So, in addition having previously observed that dyslexic readers have a longer duration of fixations, short circuits and more fixations during reading, these data suggest that the reasons not so much they can't control eye movement effectively and it's not impaired cognition of letters, but is actually the control of the visual attention span that produces this difference

Genes and Behaviour - To what extent is behaviour transmitted by genes? Challenges of behavioural genetics research (Sokolowski, 2001)

- Difficulty in defining and quantifying behaviour - Environmental influences on behaviour - Within- and between- individual variation in behaviour - Involvement of many genes - Different genes function in different tissues at different times during the development of an organism

Human Genetic Variation - Paucity of Studies in Africa

- Earliest Modern humans in Africa 200,000 years ago: longest time to accumulate largest genetic diversity "Signature and a story book of human origins" (Tang & Barsh 2017) - Overdue to focus and understand human diversity of Africa - Recent studies have found new gene variants and that the distribution of skin colour in Africa shows a lot of deviations from this correlation with latitude - Close to equator we have people who are relatively light skinned, compared to those further away who are darker skinned

Electrophysiological recordings of brain activity Micro-electrode Recordings

- Electrical activity can be measured from brain tissue using very thin electrodes (micro-electrodes) inserted into the tissue - The technique is also referred to as single-cell recordings because typically the data are acquired from single brain cells (neurons) - Because these recordings are invasive (one needs to perform surgery to do them), they are performed in humans only when they undergo brain surgery - What is typically measured is the firing rate (or spike rate) - the frequency of action potential a cell generates

Learning and Memory - Neural Plasticity: from behaviour to genes Environmental enrichment changes the brain

- Enhanced opportunities for learning perceptual and motor skills, social learning - Besides learning complex information increases processing needs, changes in physiology and activity rhythms - Can influence experimental outcomes - Evidence how function changes in specific areas of the brain, for example measuring changes in synaptic density and correlate with behavioural performance and other indicators for cognitive and physical health at different ages - Stuart et al (2017) Journal of Comparative Neurology - Small alterations to the way animals are kept and treated can have quite an effect on the experimental outcome and the comparability between studies, this is why many laboratories try to apply the same standard conditions in which they keep their animals

Learning and Memory - Comparative Research in Neuropsychology and Psychiatry Major limitations for investigating the causal relations between neural substrates and behaviour or psychological processes in human beings:

- Ethical considerations of brain manipulations and measurements - Number of patients with lesions is small, cases do not generalise, coarse damage across functional units, possible compensatory processes (behavioural change, functional reorganisation of brain circuits) - Expensive research-quality data (CT, MRI, behaviour)

Vision - Eye Muscles

- Eyeball held in the orbital cavity by three pairs of extraocular muscles, ligaments and other tissues - The eye muscles are attached to the sclera and jointly move the eye in all directions - The image can be therefore focused on all times onto the fovea in the retina where the photoreceptors are packed most densely - By attaching the muscles to the eyeball shows the muscles can be instructed very quickly how and where to perform a saccade and when to perform a fixation, and move the fovea to specific places quickly

Vision - Humans and many animals have image-forming eyes

- Eyes evolved through a gradual sequence of improvements for detecting directions and forming an image - Advanced types of eyes have evolved several times in the animal kingdom - Fossil records date back to the Cambrian explosion (540 mya) - Faster movement and navigation in animals required better vision - The larger the eye the more receptors can be fitted in and the better the images and the better the spatial resolution and finer detail can be distinguished by the animals and humans which have big lens eyes - However, having big eyes is costly and we find that big eyes are only found in big animals because one then had to add also computational brain power in order to process all the information that is then coming in with much more sophisticated and sharper image

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - Problems that often occur when the brain gets damaged

- Fatigue - Epilepsy, electric activation in the brain around the lesion gets disrupted which leads to seizures - Trouble concentrating - Paralysis - Disinhibition, they start responding to their environment without any control - Language problems - Apraxia / syntax apraxia - Executive problems (problems with behavioural organisation, problems organising particular actions in the right order) - Attentional problems - Emotional regulation problems, changes in the way they respond, emotions can be felt more or less powerfully - Low insight poor insight into their own problems, brain isn't good at detecting its own problems - Personality change - But also: frustration, anger, depression and grief. These can also be found in their immediate social life.

Sex Differences - Phenotypic

- Feminisation and masculinisation - Genotypic sex determines gonadal sex - Gonadal sex determines phenotypic sex Differential exposure to sex steroids during critical periods of development (e.g., foetal development, puberty) causes: - Sexual differentiation of the body - Sexual differentiation of the brain and behaviour - These are permanent effects of organisational effects - Masculinisation and de-feminisation = effect of hormone present early in development promotes later development of anatomical or behavioural characteristic typical of males AMH → internal genitalia DHT → external genitalia - Testosterone → masculinises and de-feminises the rest of the body including the brain

The Cognitive Neuroscience of Addiction - The drugs' influence on processing of rewards (pleasure and incentives (motivation) Dopamine: the brain's 'pleasure' chemical?

- Findings such as the above led to the anhedonia hypothesis (Wise, 1982, 2002) - The hypothesis stated that dopaminergic synapses convey 'goodness' (e.g., in the above experiment, they conveyed to food its 'goodness') - Dopamine antagonists such as pimozide reduce this effect, thus reducing the animal's propensity to work for food - Dopamine became known in the media as the brain's 'pleasure chemical'... - However, soon evidence that contradicted the anhedonia hypothesis started to accumulate

Human Genetic Variation - The Power of Words

- First appearance of term "race" in English language in the late 16th century with the expansion in colonisation by Europeans - Used to describe people in geographical regions (e.g., European, Africans, Asians), sometimes people belonging to certain languages or religions (e.g., Arab, Slavic, Jewish) - "Race" not the same as the scientific term "subspecies", in humans there is no subspecies, the human species is a single species - "Ethnicity", from Greek "ethos" meaning people, often used synonymously to distinguish "others" used since Middle Ages - BAME and BME unclear term and keeps focus on skin colour and on an imposed monolithic label of "otherness". Many prefer to self-identify as BIPoC (Black, Indigenous and Person/People of Colour), as a term that represents diverse cultural identities and a shared experience of systematic racism

Non-Genetic Variance - Example Forests of New Guinea

- Forests of New Guinea you find hut like structures with piles of brightly coloured objects outside the entrance, and some central maypole-like structures with lots of smaller sticks woven around the outside in a clear area at the base of the maypole - When first discovered these structures were assumed to have been built by people - Actually, these structures were produced by the Vogelkop bowerbird, Amblyornis inornata - Produced by the male of species in order to attract females, a display, takes males a long time to build and maintain - Each different type/style of bower is characteristic of the population that is producing them - In one population known as Arfak, the male produces these hut-like bowers, in a different and geographically separated population Farfak they produce the maypole-like bowers - There was initially believed to have been some type of genetic divergence between these populations over time, that they are genetically diverged, and these genes have led to divergence in bowers - However, evidence doesn't support this hypothesis that the difference in bowers is due to genes - There is a clear difference in bower structure however there is also a clear difference in the decorations each male uses to decorate their bower - However, there is extremely low genetic divergence between these two types of bowerbirds, they are very genetically similar - It has been found that young males take 4-7 years to develop typically adult bower style and during that period they spend a lot of time practicing building their own bowers and watching the methods of older males building theirs - It has been suggested then that actually instead of genetic transmission it is actually cultural transmissions, learning cultural traditions of different populations based on those around them

Genes and Behaviour - Some common misunderstandings

- Genetic traits are not 'fixed'/inflexible, express behaviour depend on gene x environment interactions - Learnt behaviour is also genetic, the mechanisms that we have for learning are influenced by genes, mechanisms for learning are envolable the same way tother genetic traits are evolvable - Behavioural flexibility, the behaviour to display different types of behaviour in response to different conditions is a key feature of organisms, biological does not mean inflexible

Vision - Seeing for action: eye-hand coordination

- Guiding hand movements requires two processes: - Deciding which objects to interact with - Interacting with objects skilfully These processes require different type of information from both the dorsal and the ventral streams

Learning and Memory - Different Brain Areas are Involved in Memory Formation

- H.M.'s cognitive abilities were largely preserved, as was short-term memory and episodic memories for past events and information learned before the operation - He could acquire new motoric skills, such as tracing a shape seen in the mirror, but could not recall having performed this task the day before, at the beginning of the task there were a large number of errors however these declined very quickly with each session, over the series of daily session the number of errors was substantially lower and continued to decrease with some fluctuation though he doesn't remember conducting the task - Scoville and Milner (1957) provided the first evidence for the involvement of the hippocampus in memory formation, confirming observations by the Russia neurologist Vladimir Bekhterev in the beginning of the 20th century

Hormones and Behaviour - Social behaviour in meerkats Madden & Clutton-Brock (2010)

- Had 36 meerkats (28 males, 8 females) injected with either oxytocin or a saline control - Treatments were reversed 3-5 days later, those given saline were then given oxytocin and vice versa - Recorded a suite of prosocial behaviour - The oxytocin group [performed more guarding behaviour than the saline control group, when they were given oxytocin hey performed more pup feeding than the saline group, they stayed closer to the pups than those in the control group, and they perform more of the communal digging than the saline group - Could be that oxytocin is just leading to a general increase in activity for all types of behaviours, might not necessarily affect prosociality, they also recorded how often meerkats-initiated aggression against another individual and they found the reverse effect that those given oxytocin were less likely to initiate aggression than those in the control group - The effects only last 30 mins approximately, so it's a relatively short-lived effect, but through this method they could show cause and effect of this hormone of these particular behaviours

Sensory Modalities - Tonotopic arrangement of hair cells

- Hair cells are tuned to narrow range of sound frequencies by their location along the basilar membrane - The vibrations travel from the ossicles to the basal membrane, depending on the frequency of the sound High frequency = basilar membrane deflects close to the base of the cochlear Low frequency = the deflection will occur further away from the base in the so-called apex of the cochlear All along the basal membrane are hair cells called the mechanoreceptors and their sensitivity to a particular sound frequency is purely defined by their location along this membrane, the hair cells are all the same over the base of the membrane and it depends where a sound deflects the basal membrane that will define which neurons transmit the signal that is of the high frequency tone or low frequency tone, this kind of mapping is called tonal topic mapping

Sensory Modalities - Hearing

- Hearing to detect and discriminate locations and movements of sounds sources - Spatial orientation - Echolocation (bats, whales, humans) - Auditory communication and language - Sound - pressure waves, movement of air particles set in motion by vibrating structure - Propagates in three dimensions, alternating compression and rarefaction of air, molecules move back and forth from region of high pressure to low pressure Measures of sound - frequency (reciprocal of wavelength, perceived as pitch) and amplitude (loudness), phase and waveform

Genes and Behaviour - Genetic Mutation Problems with Twin Studies Approach

- Heritability estimates are not comparable across environmental contexts, this can make them problematic and difficult to interpret, e.g., IQ is linked to genetic variance in wealthy families but to environmental variance in poor families - Biased sampling across different family situations (--> confounding factors) e.g., adoptions are rare in low-income families - Comparisons do not clearly separate genetic and environmental effects e.g., monozygotic twins share their environment more than dizygotic twins do

Vision - Segregated rod- and cone-connected pathways in the retina

- Horizontal connections - Horizontal cells - Amacrine cells - Vertical connections Fovea: I cone to I bipolar - Periphery: many cones to I bipolar, many bipolars to I ganglion cell. Same for rods, but connect to rod bipolar cells and other classes of ganglion cells - Cones (or rods) that converge on a bipolar cell form its receptive field. Similarly, the receptive field of a ganglion cell is formed by all converging bipolar cells

Neurons - Molecules in Water Inside and Outside the Neuron

- Human body approx. 60% water, (45%-70%), two thirds of it inside cells (cytoplasm or intracellular fluid), the rest is interstitial fluid, 7% blood plasma, <1% cerebrospinal fluid - Only a few soluble and uncharged molecules (e.g., 02, C02) can pass any cell membrane - Other molecules (nutrients, waste products, proteins, ions) need channels and transporters to move in and out of the cell

Human Genetic Variation - Homo sapiens is a migratory species

- Human populations have been spatially connected and interaction - There are no physiological reproductive barriers preventing admixture - Early and modern humans dispersed and migrated overcoming geographical isolation - Mixed diet, cognitive functions and cultural innovations enabled humans to survive in many different environments and change them

Sensory Modalities - Auditory nerve: Axons of spiking auditory interneurons

- IHC needed for hearing - OHC can change their length to fine tune the organ of Corti - Hair cells are innervated by first--order interneurons (afferent and efferent)

Vision - Lateral Inhibition in the Retina

- If the light falling on the group of retinal neurons is uniform, then their reciprocal inhibitions cancel each other out without further effects - When an edge (dark and light illumination) is created, the cells on both sides of the edge will strongly influence each other, this changes their signals such that a much stronger contrast is coded than physically exists. - More distant cells are not affected, as a result the perception of the edge is enhanced

Sensory Systems - Another type of adaptation in receptors occurs during stimulation

- If you present a very long stimulus, such as a long-lasting tone, your receptor neurons will stop responding - Receptor neurons that show a slow loss of responses are termed tonic receptors - Receptor neurons that show fast loss of response shortly after onset of stimulation are termed phasic receptors Why? - This is because most of the information comes from changes in environment, the brain wants to know is when the stimulus is appearing or disappearing and it doesn't need to have the neurons responding all the time, it can compute that from a combination of phasic and tonic receptors so it just needs to know when the stimulus started and when it ended but not really what happened in between if the stimulus didn't change, this is why a prolonged stimulus which does not change over time causes a reduced neuronal response - This is different from adapting sensitivity range; this is a different type of adaptation that occurs to specific stimuli that are transient (that appear for some time but are quite long-lasting)

The Cognitive Neuroscience of Addiction - Drug taking as self-medication in mental illness A possible role of 'self-medication'

- In addition to the three contributing factors discussed earlier (cue reactivity, tolerance, disruption to reward/motivation circuits), another factor has been proposed - Addicts typically suffer from co-morbidities: psychiatric/psychological disorders, such as anxiety, depression, schizophrenia - Previously these have often been regarded as either vulnerability factors or consequences of addiction - Now there is increasing recognition of the fact that addicts may be using drugs to alleviate the symptoms of mental illness and that this need for 'self-medication' may be a key factor leading to and/or maintaining addiction - There are major factors such as the availability of other meaningful options besides doing the drug

Electrophysiological recordings of brain activity - What information can one extract from an EEG? EEG and Epilepsy

- In epilepsy you get an abnormal/excessive synchronisation of postsynaptic potentials resulting in large amplitude discharges - Such discharges can be observed during seizures (ictal activity) or between seizures (inter-ictal activity) - So, if someone has a grand mal, a severe form of epileptic seizure where the person starts shaking, this is because that rapidly activation has spread to the motor system and the motor cortex, which are now sending strange signals shown an incoherent movements or random stimuli Inter-ictal activity can be seen in between seizures where the activity is present but not bad enough to produce full-blown seizure yet

Neuroimaging - From raw data to functional brain 'activation' maps 2) Collect some data

- In fMRI the scanner collects data in what is called slices, takes somewhere between 2 and 3 seconds to collect what we call a single 'volume', a single 3D image of the brain - Might move down through the brain collecting slices in that order - For each one of those volumes, we divide the image up into cubes, also known as 'voxels', each one of these cubes might be about 3x3x3 mm / 3^3, we refer to each voxel with coordinates (X, Y and Z system) - Sagittal view = looking at the head split down the middle - Coronal view = looking from the back to the front of the brain - Axial/Transverse view = looking down on the top of the brain

Synaptic Sequence - Psychoactive substances: some examples Psychoactive substances: alcohol

- In moderate amounts, alcohol also indirectly increases the release of endorphins - In high doses, the binding of alcohol to GABA channels leads to powerful inhibition and sedation - In very high doses alcohol leads to the destruction of cell membranes and hence, to brain cell death

Learning and Memory - Neural Plasticity: from behaviour to genes Changes at the synapse: more receptors for stronger EPSPs

- In the dendritic spine there are vesicles that contain AMPA receptors in the membrane - If the NMDA receptor open, it lets in Ca2+ from the synaptic cleft - Ca2+ activates proteins that make those vesicles bind with the cell membrane in the synaptic cleft - There are then more AMPA receptors in active zone, so more Na+ will enter each time the neurotransmitter is released - The increased number of AMPA receptors in the cell membrane will last several hours

Genes and Behaviour - Alleles and Genetic Diversity

- Individuals have one or two alleles (variants) of a gene, but multiple alleles can exist in the population - So, for any gene there may be multiple different alleles or variants of that gene, so individuals will have just one or two alleles of a gene but in the population, there may be a range of many different alleles - Human beings are diploid organism, meaning we have two copies of each chromosome, one chromosome from the father and one chromosome from the mother - We can distinguish individuals in terms of their alleles, a homozygous individual is one that has the same allele on both chromosomes (two copies of the same allele meaning no conflict in gene expression) - An individual with two different alleles is referred to as heterozygous e.g., in the case for eye colour brown is dominant over blue so someone who is heterozygous for blue and brown will express brown eyes - Alleles like this are responsible for colouration of various different types in other animals, for example the Agouti gene is an important gene involved in coat patterns and shading of mammals, when upregulated hair follicle melanocytes switch from making black to yellow pigment - Lethal alleles lead to death of homozygous recessive offspring, there are some types of genetic traits where an individual with two copies of the recessive allele will die e.g., yellow-coated mice die as embryos - Quantitative traits often show polygenic inheritance which is where the trait of interest influenced by many genes each with a small effect on the final trait e.g., height, skin colour, sexual orientation etc ...

Motor Control - The Neurobiology of Motor Control Dual Role for the Basal Ganglia

- Inflexible cognitive function as well as motor function in PD - One way of characterizing this is an inflexibility of cognitive control as well as of motor control - Dual gating ole for basal ganglia in cognition and movement - allowing new thoughts and new movements to occur - Motor control and cognitive control rely to some extent on the same neuronal circuits

Human Genetic Variation - Human Genome Project started in 1984

- International collaborative research that aimed to completely map all the genes of human beings Full sequences became available 2001-2004 and cost $2.7 billion - Genome information full available, natural human sequences cannot be patented - 2020: 30th anniversary of the official launch in 1990 - Other initiative focusing on genome diversity: - Human Genome Diversity Project also launched in the 1990s - HapMap Project since 2003 - Genographic Project (National Geographic) since 2005 - 1000 Genomes Project since 2008

Neurons - Electrochemical driving forces act on the ions

- Ion concentration inside the neuron differ from that of the outside medium (extracellular fluid ECF) - The concentration of NA+ and Cl- ions is lower and of K+ ions is higher - Ions move randomly unless there are strong chemical concentration gradients or electrostatic forces of attraction and repulsion - At the membrane the direction of their movement is mainly determined by the electrochemical driving forces - The membrane of the neuron prevents the exchange of ions unless it opens its ion channels to generate neural signals

Neuroimaging - fMRI

- Is non-invasive (innocuous) - Measures (indirect) metabolic correlates of neural activity (blood flow, oxygen consumption) - Has high spatial resolution e.g., 3mm^3 - Has low temporal ... - Extremely expensive, gets cheaper over time

Neurons - When a neuron generates a signal...

- It has to open these ion channels for a very brief period of time - Once it opens the sodium channels and chloride channels, the sodium and chlorine ions will move into the cell - If the potassium channels open, then potassium ions will move out of the cell - Any movement of charged particles generates a very weak electric signal

Learning and Memory - Neural Plasticity: from behaviour to genes Visual Deprivation Causes Structural Changes in the Brain Le Vay, Wiesel, Hubel (1980) Journal of Comparative Neurology

- Kittens are born and have one eye sewn shut - Alternating ocular dominance columns in layer IV of primary visual cortex (V1) receives input from either the right (visible as bright stripes after injection or radioactive dye) or left eye (dark stripes)

Learning and Memory - Neural Plasticity: from behaviour to genes LTP is a postsynaptic mechanism

- LTP - Long term potentiation - LTD - long term depression - Per Andersson (1966), University of Oslo, found that in the perforant pathway of the hippocampus of anesthetized rabbits that during repetitive stimulation an additional strong depolarisation with many fast pulses during few seconds (tetanus) caused an increase in neuronal firing of the postsynaptic cell, during normal stimulation with repeated pulses which are relatively weak the postsynaptic neuron will respond with an EPSP of a certain amplitude which is relatively steady, when a strong depolarizing current is then added on top the EPSPs rises, however as the very strong depolarising ends and the regular pulses continue one would predict that EPSPs fall to the previous level however what was observed was a brief interval of time in which the ESPs continue to be increased although the only stimulation that was provided was these weaker pulses, after some time the EPSPs decline and come down to normal level In his lab, Bliss & Lomo (1973) continued that work and discovered LTP demonstrating that frequency potentiations can be long-lasting LTP has been found in other hippocampus pathways too LTP can last for hours, how? Something must change at the synapse that allows these strong EPSPs to be maintained, research shows that this is due to changes at the postsynaptic membrane

Learning and Memory - The Memory Engram: Where and How Are Memories Stored?

- Lashley (1929,1950), was unsuccessful in his attempts to find a memory engram, a localised trace of memory in the cortex - He concluded that learning and memory is not located in a single area of the rat cortex but is distributed widely across the brain - Maze-learning experiments with rats which had parts of their cerebral cortex surgically removed - Graph of results shows that animals that showed very few errors when retrieving the learned path in the maze, had relatively small lesions to the brain, but these lesions were located all over the cortex and not in a specific area, however animals that made more mistakes tended to have much larger areas of the brain removed

Learning and Memory

- Learning is a ubiquitous feature of behaviour, for humans and all animals - Became clear after studies in early 20th century showed insects are not automata but have a great capacity to learn - E.g., Turner (1907) pioneer in animal behaviour and cognition, published paper showing how ants find back home when they venture to forage, spatial learning in insects, placed leaves in the way of their trajectory, preventing ants being able to find back home, concluded ants learn way back home - E.g. Tinbergen (1937) showed homing behaviour in a Digger Wasps, dig a burrow in which is rears its brood, it leaves burrow and find prey, lay egg on the prey and larvae feed on prey, very important for wasp to know where burrow is because it invested in digging it, wasp hovers and wiggles around the nest area, this was similar to ant and he had similar ideas to Turner, placed a circle of pine cones around nest and when wasp left the burrow he displaced the landmarks and when the wasp returned it was looking for nest in relation to landmarks rather than for the actual nest, shows they learn to get back using the objects around the nest - Density of neurons in 3 months, 2 years, can see across all layers the number of neurons increases dramatically but even more so the connectivity or the number of synapses, this is because the brain is learning and developing, before birth and throughout early development the synaptic densities remain high and eventually start declining again when synaptic pruning occurs or neurons die off, strong decline over first years of life - In adolescence especially in the frontal cortex, there is a strong decline that is related to a substantial restructuring of neurons and brain areas during adolescence

Vision - The Sleep Wake Cycle

- Light levels detected through eye are sent to the SCN (suprachiasmatic nucleus) in the hypothalamus - Special class of ganglion cells in the retina containing photopigment melanopsin (sensitive to short wavelengths) - Keeps the circadian clock in the SCN accurately timed with natural daily light cycles Pineal gland: - Unpaired midline structure near epithalamus - Produced melatonin (derived from serotonin) during darkness

Non-Genetic Variance - Social Learning Mechanisms of Social Learning

- Local enhancement - Stimulus enhancement - Observational conditioning - Imitation - Goal emulation One or more of any of these processes may be operating together in any particular scenario where social learning is involved

Motor Control - The Neurobiology of Motor Control Effects of transcranial direct current stimulation (tDCS) on visuomotor adaptation: dissociation between cerebellum and M1 (primary motor cortex), Galea et al (2011)

- Looked at effects of tDCS on visuomotor adaptation, looked at the difference between tDCS on two different regions = cerebellum and (M1) primary motor cortex - Data showed faster visuomotor adaptation with cerebellum tDCS, slower de-adaptation with M1 tDCS - Slower de-adaptation during stimulation of the primary motor cortex relative to cerebellum - This shows a dissociation between the different functions of the cerebellum and primary motor cortex Cerebellum is important for learning new mapping - Involved in the generation of forward models - Time lag between generation of motor commands and movement initiation - Cerebellum generates prediction of sensory consequences of motor command - Such predictions (forward models) are essential in visuomotor adaptation - errors used to correct future predictions Primary motor cortex (M1) important for consolidating newly learnt mapping

Synaptic Sequence - Psychoactive substances: some examples Example: Alcohol

- Low doses: alcohol is an agonist of the neurotransmitter GABA. - GABA is typically found in inhibitory synapses. Thus, alcohol increases the effectiveness of these synapses, leading to a feeling of relaxation - Alcohol indirectly stimulates dopamine release. - Dopaminergic synapses in certain parts of the brain are associated with reward pleasure and positive motivation (nucleus accumbens and other structures in basal ganglia), hence the euphoria when alcohol is consumed in small to moderate doses - Alcohol acts like a brief stimulant in the beginning and when you take more of it becomes a very inhibitory drug, you feel sluggish, and it affects the motor system etc

Sensory Systems - The intensity range of stimuli often strongly varies over time

- Many stimuli in the environment will change strongly over time such as the illumination of light, light at night has very low levels of intensity, whereas at midday the intensity is much higher (see graph) - So, the range of light intensities that our eye deals with over the course of the day and at night is large, there are much higher light intensities that originate from different energy sources such as the sun or Tungsten Filament - As the light condition changes from night today, moving from a scotopic range during night to a mesopic range at dusk and dawn to the photopic range during the day, our vision has to adapt to these conditions - However, it doesn't have to have receptors for each of these conditions because photopic conditions it is unlikely that we will have conditions that also require scotopic vision - Before human invented artificial light, it was always light during the day and dark at night, so what the visual system had adapted to do is to shift its sensitivity range of the receptors along the intensity axis, this process is called adaptation - We experience this on a daily basis because our use of artificial light represents a daily experiment on our sensory systems

The Cognitive Neuroscience of Addiction - Drug taking as self-medication in mental illness Experimental induction procedures, Mckee et al (2011)

- Mckee et al (2011) had subjects describe the most stressful event to have occurred to them in the last 6 months - This was scripted by a clinician, recorded as an audio file, and later played back to the subjects. - In another session they received a neutral script created in the same way. They then completed an 'abstinence incentive' task where they could smoke in the next 50 min but would earn money for each 5 min period of abstinence. They then smoked ad libitum to determine how much they smoke and how much they enjoy smoking. - stress decreased the delay to initiative smoking in the abstinence incentive task, if you induce stress the delta of the initial smoking is shortened compared to non-stressful - It also made the smoking more rewarding if you're stressed than if you are not stressed

Sensory Systems - Mechanoreceptors differ in their sensitivity

- Merkel's discs and Meissner's corpuscle sense innervate the surface of the skin and are sensitive to stimuli in small areas of the skin (small receptive fields) - Pacinian corpuscles and Ruffini's endings innervate deeper layers of the skin and are sensitive to stimuli over a larger area of the skin (large receptive fields)

Human Genetic Variation - Immunological changes in the genomes of human populations

- Migration exposes groups of humans to new environments and diseases - 60% mortality rate amongst Dutch colonists in Surinam from epidemics in yellow and typhoid fever (de Vries et al 1976, J Immunogenetic 6) - Infectious diseases killed >10,000 individuals in 59 indigenous communities of Amazonia in past 200 years but mortality rate and incidence have decayed over time due to genetic adaptation (Walker et al 2015, sci, Rep 5) - HIV transmission from apes to humans in the 1920s spreading out of Africa from the 1960s. CCR5-Δ32 mutation is involved in HIV-resistance and is found in 14% of European populations but not elsewhere (presumably selected for during plague in middle ages).

Learning and Memory - Contextual and Cued Fear Conditioning

- Mild foot shock elicits freezing and increased blood pressure and heartbeat - Cued conditioning (tone predicts punishment) - Contextual conditioning (box alone predicts punishment)

Neuroimaging - CT

- Moderately invasive - Uses X-rays (ionising radiation) - Inexpensive - Widely available - Low spatial resolution - Useful clinically but not for neuroscience research

Neuroimaging - PET

- Moderately invasive, radioactivity is introduced into the body - Measures indirect metabolic correlates of neural activity (blood flow, glucose metabolism) - Can measure synaptic transmission directly e.g., by labelling receptors - High spatial resolution - Extremely low temporal resolution - Extremely expensive

Neurons - Ion channels and pumps regulate the flux of ions

- Most channels are made from four proteins that assemble themselves to produce a central 'pore' - They have a 'selectivity filter' that only allows ions of a particular type (e.g., charge and size) to pass through, each neuron's membrane contains different classes of ion channels - Nearly all ion channels open for very brief periods of time, only a minority of channels are always open (leak channels) - Pumps are always active to stabilise the concentrations of ions inside and outside the neuron

Vision - Spectrally opponent cells in the LGN

- Most ganglion cells in the LGN fire in response to some wavelengths and are inhibited by other wavelengths - Excited by light from some wavelengths and in inhibited by light from other wavelengths, opponency or colour opponent neuron - These cells are again arranged across the retina and they will code both the object/stimulus and its context and the effects we observed early with the map can also be observed with colour vision

Human Genetic Variation - Genetic variation within the same species Origins of variation of genomes

- Multiple variants (gene alleles, polymorphisms) occur in different frequencies within and between population - DNA changes over time (mutations) ad is recombined during reproduction Migration and admixture between populations change the distribution of alleles and polymorphisms in a population over time

Motor Control - Spinal Cord

- Muscles are controlled by motor neurons in the spinal cord - Motor neurons can have very long axons, up a 1 metre in length - Action potential in a motor neuron triggers the release of acetylcholine, a neurotransmitter that makes muscle fibres contract - The number and frequency of action potentials and the number of muscle fibres determine the force the muscles can generate

Genes and Behaviour - Genetic Mutation The origins of genetic variation

- Mutation is when a particular form of a gene mutates into an alternative form - The effect of a mutation is critically dependent on whether it occur in the germ-line (gametes, sex cells, either sperm of the eggs) or somatic (in the rest of the body) - Somatic mutation only affects the individual in which it occurs, you might see a phenotypic change in that individual but because it is not in their gametes/sex cells it is not transmitted to the next generation - Whereas a germ-line mutation occurs in the sperm or the eggs and effects the entire organisms including their own gametes, so they therefore have the potential to be passed don and affect future generation - Most mutation are harmful or neutral in their effects; only rarely are mutations beneficial - Alleles at >1% frequency termed wild type - Alleles at <1% frequency termed mutant - Gene with one wild-type allele is monomorphic - Gene is >1 wild-type allele is polymorphic - Knockout: lab strain in which a known mutation inactivates ('knocks out') the normal function of that gene

Learning and Memory - Neural Plasticity: from behaviour to genes Temporal Constraints on Plasticity

- Neural plasticity takes many forms - Time courses differ over the lifespan - Important to find mechanisms that enable it and that inhibit it - Learning and memory take place at all stages in life and different experience shape brain plasticity continuously and different environment can have a strong impact - Sensory experience and learning if much more effective early on in life

Neurons - The Nervous System

- Neurons are cells in neuronal tissues (e.g., neurophiles, nervous, chord, brain) where they form interconnected neural networks - CNS = central nervous system (brain and spinal cord) - PNS = peripheral nervous stems (everywhere else in the body) - The neurons of the CNS and PNS interact in many ways, they are interconnected

Neuroimaging - MRI

- Non-invasive (innocuous) - Uses radio frequency (RF) fields to acquire images - Extremely high spatial resolution e.g., <1mm^3 - Number one choice for structural brain imaging in neuroscience

Sex Differences - Sex Differences in Behaviour/Sexual Dimorphism

- On some species their sexual dimorphism is very pronounced, can be seen clearly in the appearance of some animals e.g., lion's male has mane, but female doesn't - Though there are many behaviours that both males and females will perform, there are also some behaviours that we can class as typically male or female - E.g., in many mammal species the female will perform the lordosis response, males don't do that, and it is typically females who do suckling and nursing of young whereas males do the fighting and aggression - E.g., in humans their differences are much less marked and so most of our behaviours we see them in both men and women, and the differences in behaviour are much more subtle, there is also a lot of variation within the sexes also

Synaptic Sequence - Amphetamine and other drugs (cocaine, heroin, marijuana) have a profound effect on dopaminergic pathways in the brain

- One pathway is seen as particularly crucial in explaining the potent effects of these drugs: the projections from the Ventral Tegmental Area (VTA, group of cells in brain stem) to Nucleus Accumbens (group of cells in Basal Ganglia) - VTA and Nucleus Accumbens are thought to be involved in pleasure, reward and motivation - This is important because those two structures, which just involved lots of dopaminergic neurons (dopamine is used a lot in those areas to facilitate transmission) and these systems are involved in your experience of a sense of reward or pleasure and effect your motivational state - So, if you change something in those structures, it is different from affecting the motor system for example, it affects emotional state instead and this plays a big role in why people take these substances in the first place and why they become addicted or find it hard to give them up

The Cognitive Neuroscience of Addiction - The drugs' influence on processing of rewards (pleasure and incentives (motivation) Dopamine: the brain's 'pleasure' chemical relevance to addiction

- One very common finding in addiction is that in long-term drug users (particularly of drugs that affect dopamine transmission, such as cocaine and amphetamines) drug-taking results over time in less and less euphoria - Regular users report a reduction in the 'high' they get from the drug - However, the craving of the drug does not decrease, on the contrary it increases - There appears to be disconnection between 'liking' and 'wanting' ... - Some animal studies have also provided evidence that dopaminergic synapses (particularly those in Nucleus Accumbens) may be primarily processing the incentive (motivational) rather than hedonic (euphoria-related) value of stimuli and that drugs that modulate dopamine influence motivation more than they influence euphoria

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - Neglect Symptoms

- Only attend to thing on the right - More in the opposite direction from you if you come from the neglected side - Problems reading - Ignoring objects in their environment - Problems navigating space - Not using particular limbs - Lack of insight

Learning and Memory - Comparative Research in Neuropsychology and Psychiatry Benefits of animal models:

- Overcome some of the ethical limitations - Replication and precision of lesions - Availability, can keep easily in a lab, and sample sizes (2-3 subjects in primates, more in rodents, many more in non-mammalian models such as the sea hare Aplysia, Drosophila flies or zebrafish larvae) - Systematic study of a wider range of methods, behaviours and psychological processes providing insights at circuit and synaptic level that are different to obtain with human participants

Motor Control - Cortical Motor Regions Cortical Motor Regions: Association motor areas

- Parietal and prefrontal cortex - Parietal = critical for representing space, attention, sensorimotor integration - Lesions produce apraxia, loss of skilled action, also attentional and executive function deficits - Broca's area: speech production - Frontal eye fields = eye movements

Vision - First steps of processing in the retina

- Photoreceptors and bipolar cells: graded receptor potentials - Ganglion cells: long axons (form the optic nerve), actional potentials - The photoreceptor layer is very complex network where information is picked up from incoming light that comes into the eye from the photoreceptors that project onto horizontal and bipolar cells which respond to stimulation with graded receptor potentials, they are non-spiking cells - The ganglion cells are the ones that have long axons and therefore signal has to travel a long way to the brain that leave the eye through the blin spot and these are spiking neurons

Hormones and Behaviour - Social Behaviour in Humans Orgasm

- Plasma oxytocin increases during orgasm - in males and females - Plasma oxytocin levels increase during self-stimulated orgasm - Oxytocin evokes feelings of contentment, reductions in anxiety and feelings of calmness and security around mate (trust and generosity?) - May indicate that sex promotes pair bonding

Learning and Memory - Neural Plasticity: from behaviour to genes A role for adult neurogenesis in spatial long-term memory?

- Precise role of new brain cells born in adulthood unknown, presumable repair and plasticity - Hippocampal neurogenesis (e.g., dental gyrus DG) found in many mammals

Motor Control - Cortical Motor Regions Secondary Motor Area

- Premotor cortex and supplementary motor area (SMA) - Planning and control of movement - Lesions result in apraxia - patients can produce simple gestures but cannot link them into meaningful actions e.g., brushing hair

Sensory Systems - Senses and Perception

- Processing sensory input in order to generate meaningful behaviour or actions (motor output) Motor output and sensory input - The sensory pathways and the motor output pathways overlap in several areas of the brain, there are a lot of cross-connections, this occurs in areas such as the cerebellum close to the thalamus and in the motor cortex located next to the primary somatosensory cortex - Sensory organs and general principles of sensory processing

Hormone Structure and Action - Hormones are chemical messengers that are:

- Produced in endocrine cells - Secreted into the bloodstream - Transported by the bloodstream - Act on specific target cells (typically some distance away from where produced)

Human Genetic Variation - Race is real but it is a social construct

- Race is a social and cultural but not a biological construct. It was historically used to establish social hierarchies and slavery - Modern genetics evinces that concepts of biologically distinct human races are obsolete - "Human genome diversity studies have clearly shown that the large part of genetic variability is due to differences among individuals within population rather than to differences between populations, effectively discrediting a genetic basis of the concept of 'race'" - HM Cann (1998) summarising research from the Human Genome Diversity Project - Genomics research shows that using the term 'race' in discussion about genetic diversity is: - Unnecessary (does not add anything that is not covered by term population or population cluster) - Dangerous because it easily misleads laying the groundwork for dehumanisation and racism

Motor Control - Cortical Motor Regions Primary Motor Cortex (M1)

- Receives input from almost all cortical motor regions - Crossed hemispheric control, means that the left controls the right side of the body, and the right cortex controls the left side of the body - Somatotopic organisation - Lesions to M1 produce hemiplegia, loss of voluntary movements on contralesional side of body - E.g., having a stroke affects one side of the brain, either paralysis of weakness

Sensory Systems - Response thresholds in receptor neurons

- Receptors respond to a stimulus within a limited range of stimulus intensities - The sensitivity of neurons can be plotted in a graph where we show stimulus intensity on the X axis and the response in frequency of action potentials on the Y axis - Merkel's disk = activated by low-level intensity, light touch - Pacinian corpuscle = activated by high-threshold intensity, in contrast responds to stimuli in a much higher range of intensities, does not respond to same range of stimuli as the Merkel's disk - The shape of the curves is roughly similar and just shifted along the stimulus intensity axis - The important point is that every receptor responds to stimuli only within a limited range of stimulus intensities, when the intensity of the stimulus is increased the response of the low-intensity neuron/Merkel's disk does not change and it can't increase its response endlessly - So, it has a certain range within which it can change and vary the frequency of its action potentials and that corresponds to this roughly linear part of the curve - If the brain needs to know about a large range of stimulus intensities it can extract information from the combination of these different receptors that are located in the skin, When sensing two different low-intensity stimuli (violet and green arrows): - Merkel's disc = responds with two different spike rates - Pacinian corpuscle = no spikes The violet arrow shows that estimates of roughly 4.5 elicited a certain response around 80 Hertz, whereas slightly stronger response of 5 units it within the sensitivity range and elicits a higher response The high threshold neuron will not respond to these stimuli because they are below its threshold Within the sensitivity range of this neuron, if the stimulus is stronger it will elicit a stronger response than a weaker stimulus. However, at this intensity range the low-threshold neuron is at saturation so it cannot distinguish between the stimuli in this intensity range, and it will respond with its maximum spike rate

Human Genetic Variation - GWAS: Benefits and limitations Benefits:

- Relies on the smallest possible changes in DNA sequence (single nucleotides) that are frequent in the population (>1%m termed SNP, single-nucleotide polymorphism). For example, a SNP in one individual has the nucleotide cytosine (C) instead of the nucleotide thymine (T) in the same position of the sequence. Ca 90% of sequence variants in humans are SNPs - Looks at the whole genome of many individuals. Huge numbers and stable inheritance make SNPs excellent markers. Associations with polygenic traits more likely to be uncovered to understand variation and for applications SNPs in loci that contain genes can be prioritized during analysis.

Human Genetic Variation - GWAS: Benefits and limitations Limitations:

- Requires fully sequenced genomes of hundreds to thousands of individuals and their relatives (technology limitation) - With hundreds and thousands of loci included, higher change to detect more different associations - 'Dark matter' in the genome: SNPs in non-coding DNA have no functional role or are less important for a polygenic trait

Vision - Spatial layout of retinal ganglion cell projections is preserved

- Retinal ganglion cells project retinotopically to each layer of the LGN - Right and left eye projections are also segregated in the LGN - Retinotopic projection maps, so spatial mapping that originates from the retina - The left and right eye information projections is segregated even though they look at the same part in the visual scene

Hormones and Behaviour - Social behaviour in meerkats Affiliative behaviour

- Rodents and meerkats given supplementary doses of oxytocin spend more time in contact with others - 'Knocking out' oxytocin gene of male mice renders them unable to recognise scent of previously encountered female - 'Knocking out' where a particular strain of the animal lacks that particular gene - Infusing brain with oxytocin cures this amnesia

Vision - Brain circuit for saccadic eye movements

- Saccadic eye-movements directed by midbrain and cortex - Conscious control of eye movements comes from the cortical frontal eye fields (FEF) - Automatic control of eye movements comes from the superior colliculus - Both use input from vision, but also from auditory and somatosensory systems

Vision - Abnormal eye movements in schizophrenia

- Schizophrenia patients have difficulties to track objects with smooth-pursuit eye movements - Eye movements are rapid and jerky - Complex analysis of eye movements using mathematical modelling is possibly a future avenue for developing a diagnostic tool - Patient is looking at a screen and is asked to look at or to track the dot or object and the eye movement is recorded, you have steady responses as the eye follows the dot movement, but you see that the schizophrenia patient shows jerky peaks and can't produce the same eye movement patterns as the control patient Study from Benson et al (2012) where they asked patients with schizophrenia and controls to perform a number of tasks In a fixation tasks the patients are asked to fixate upon a certain point and the control participants are much better at doing this than the patients with schizophrenia, so it has been suggested that with advanced computational modelling it should be possible to accurately make diagnosis based on the eye movement patterns and recognise very early if a person is at risk or already suffering from schizophrenia

Sensory Systems - Somatosensory Pathway

- Segregated projections to different areas of the brainstem, thalamus and cortex (labelled-line principle) - Where possible, information about the spatial location of stimuli is preserved by separating projection that come from receptors in different locations - It is important to know where stimulation occurred in the body (e.g., whether the hand or back was touched) or relative to the body (e.g., whether wind blow into the face or the neck) - The information from the somatosensory receptors across the body are projected to the spinal cord, these projections can be identified as sensory peripheral nerves or spinal nerves - The signals then pass on to the brain stem, and the brain stem receives sensory input from the sensory cranial nerves and these different signals travel separately to the thalamus and then to different areas of the primary sensory cortex - The primary sensory cortex is connected to many higher cortical areas that process different aspects of sensory information and also to association cortices - It is important for the brain to preserve not only the different types of sensory input from different types of receptors, so all receptor information is segregated and separated along the projection pathways, but also to preserve the origin of the receptors (where in the body the stimulus is present)

Vision - Sensory Systems

- Sensory systems are good example to demonstrate main principles how the brain is organised and works - Many sensory pathways connect to the brain - Sensory signals are typically transmitted in a hierarchy of processing steps - Information is filtered, combined or enhanced as it passes from one layer to the next in a serial fashion - Each layer has networks that are composed of input and output neurons as well as many interneurons - The tasks in each layer of the hierarchy become more complex, none of the layers do the same tasks and there is the opportunity to cross connect, there are connections that bypass certain areas and there are connections that can be sent to other layers

Motor Control - Central Pattern Generators Brown and Sherrington (1947)

- Severed the spinal cords of cats and put the cats on a treadmill (below) - Found that even though there were no signals coming from the upper brain regions into the spinal cords they found that cats were able to run on the treadmill, they were able to generate the quite complex sequence of movements needed to run on the treadmill - So, the idea here evolved of central pattern generators essentially neuronal responses that could control these quite complex sequences of movement without any input from higher level cortical and sub-cortical regions - Probably evolved to enable actions essential for survival e.g., running - Useful because being able to run away for example in dangerous situations without having to engage complex brain regions involved in executive control you need to have a fast reflex for that kind of process to occur - But then, if specific motor commands are controlled by spinal cord, what are motor neurons in the brain coding?

Synapses and Networks - Using mathematics to make sense of brains: computational models of neural networks

- Simple neural language rules (summation, multiplication) and binary (0/1) code - Complexity of neural language comes with number of connections, layers and types of connectivity between neurons in networks

Synaptic Sequence - Substances can influence different phases of the synaptic sequences

- Some act as early as the propagation of the action potential, some interact with the axon itself - Others may influence the release of the transmitter, make more or block neurotransmitter coming out of axon - Other modulate how the transmitter interacts with the post-synaptic channels (receptors), might block a receptor for example preventing a neurotransmitter from attaching to it and doing its job or it might look very much like the neurotransmitter and also bind with the receptor but trigger it - Finally, some alter the presence of the transmitter in the synapse by modulating its inactivation and recycling - A lot of human aspects and experience depends on neural activity, if a drug is created altering neural activity it can also alter things about us

Motor Control - Coding of movement direction in primary motor cortex, Georgopoulos et al (1995)

- Some experiments with monkeys looking at coding of movement direction in the primary motor cortex - What he did was trained monkeys to hold a joystick and trained the monkeys to move the lever to one of 8 targets arranged in a circle, the stimulus would flash in one of the areas and the monkeys moved the joystick there - What Georgopoulos et al found was that individual neurons in primary motor cortex show a preferred direction i.e., they fire most strongly when movement is in that direction - Georgopoulos et al were actually recording dropping electrodes into the primary motor cortex and recording the neurons from that brain regions whilst the monkeys carried out the task - They actually found that the neurons of the primary motor cortex seemed to be very hard-wired for a particular movement direction - However, thinking more in-depth about it the interpretation of this experiment could equally be that those neurons were encoding the target location, so to control for this possibility they re-designed the experiment by having the monkeys move the lever to the central location from one of 8 peripheral locations - They found a very similar pattern of firing that the same neuron would respond in these two conditions suggesting that it's not the location of the target that seems to be important for these neurons but it's the direction of movement - This is quite strong evidence that neurons in the primary motor cortex seem to be encoding the direction of movement - The same neurons preferred movements in the same direction, even when the target location was now different

Hormone Structure and Action - Action of steroid hormones

- Steroid hormones, because they are soluble in lipids, can pass through the cell membrane, these hormones diffuse passively into the cell - In order to respond to that particular hormone, the target cell must have the right type of receptor for that cell, the receptors are now within the interior of the cell - The steroid hormone that diffused into the cell will bind with the steroid receptor to form a hormone receptor complex - That complex the travels to the nucleus and binds to the DNA, altering the production of proteins - Steroid hormones are, in contrast to protein or amine hormones, acting on specific receptors inside cells - They act 'slowly' and can take hours - Steroid hormones also have long-lasting effects via transcription of DNA, by causing these changes in the transcription of DNA into proteins - E.g., boost in sex steroids during puberty has a long-lasting effect - As well as particular receptors within the cell, for a cell to respond to steroid hormones it needs a particular type of co-factor which enable the cell to respond, you need the receptor and you need the co- factors, so sensitivity can be altered by presence or absence of co-factors necessary for cells to respond - Steroid cells, unlike protein and amine hormones, steroid cells cannot be stored and must be synthesized on demand

Learning and Memory - Eye-blink Conditioning

- Studied in rabbits but can also be studied in humans - Prior to training -US: air puff -UR: eye blink -CS: tone -CR: tone alone elicits eye blink - Neuronal circuit involves cranial nerves and nuclei, connecting interneurons and the cerebellum - Sensory input US: trigeminal nerve (cranial nerve V) - CS input: auditory nuclei - Motor output: cranial nerves, VI, VII (facial and eye muscles)

The Logic in Neuropsychology - TMS: Temporal Resolution

- Subjects presented with sets of three letters and asked to report the letters one each trial - On each trial, TMS applied over the visual cortex at a slightly different time - TMS clearly capable of telling when the targeted area was involved in processing - - The effects of a single TMS pulse on behaviour are rather brief - Also, the temporal resolution is high

Electrophysiological recordings of brain activity - What information can one extract from an EEG? Using EEG frequency to detect awareness (Cruse et al., 2011, The Lancet)

- Subjects: a group of patients in vegetative state and a group of healthy control subjects - Two experimental conditions, separated into distinct blocks in time Each condition had its own set of auditory instructions: - Condition 1: "every time you hear a beep, try to imagine that you are squeezing your right-hand into a fist then relaxing it. Concentrate on the way your muscles would feel if you were really performing this movement. Try to do this as soon as you hear each beep" - Condition 2: "every time you hear a beep, try to imagine that you are wiggling all of the toes on both your feet, and then relaxing them. Concentrate on the way your muscles would feel if you were really performing this movement. Try to do this as soon as you hear each beep." - Examination of the high frequencies in the EEG over the primary motor cortex showed that: = 3 out of the 16 patients had activated the areas of the motor cortex according to the instructions = Blue = greater activity associated with the 'squeeze hand condition' = Red = greater activity associated with the 'wiggle toes' condition = Strongly suggests presence of conscious awareness in these patients

Electrophysiological recordings of brain activity Determining the source of EEG and ERPs

- The EEG is obtained from the surface of the head - Brain tissue conducts electricity well hence FPs are conducted in all directions - Each point on the head surface reflects cortical activity originating from distant regions - It is very difficult to precisely pinpoint the regions of the brain where particular EEG/ERP activity originates - Researchers have attempted to use sophisticated mathematical and biophysical modelling techniques to overcome this problem - As a result, one can find plausible (reasonable: likely) solutions, but these solutions remain informed guesses Inverse problem: inferring cortical generators from known scalp potentials. Solution: highly uncertain - Have to somehow figure out from all the summary of electrical activity what the origin looks like, the real problem is the lack of information in terms of what the origin is and where it comes from, there are way too many options - Mathematically you cannot work out what kind of cortical activation pattern would result in the EEG signal. Too many possibilities, you cannot really do this at a very precise level

The Logic in Neuropsychology - TMS: other limitations

- The effects of TMS on the brain are limited to the cortex- TMS cannot 'reach' deeper cortical and subcortical regions/structures (e.g., hippocampus, thalamus) - The effects of TMS on behaviour/performance are much more subtle (and hence can be harder to detect) than the effects of neurological damage (in patients) - Although it is generally very safe, it is associated with a small risk of eliciting a seizure. To minimise the risk, low levels of stimulation is used, participants are carefully screened

Vision - How do we see?

- The eye looks at different things, but what happens between the excitation of the photoreceptors and the actual perceptions that require the contribution of higher cortical areas - The projections of images onto the retina of a 3 D world are coded as a 2D image because we have a single layer of receptors and that's highly distorted the further away the image is projected onto the retina - Because there is a single lens the projection is upside down, but we do not see any of these distortions and we see the world as a colourful world in its correct orientation, which is not the case when the receptors respond, there is no colour information just in the photoreceptor responses and that needs to be computed - So, all these different computational steps are done in the retina and the subsequent stages of the visual pathway - Visual conscious perception requires that visual information reaches the V1 so what happens at each of these stages - The most important basic function of the retina is the segregation of objects in a scene or the distinguishing of foregrounds and backgrounds - The segregation of objects needs to happen quickly in the retina, so recognising edges and passing on information to all the different layers is accomplished by the retina

Vision - Controlling the movement of the eyes

- The field of view is defined by the position and orientation of the eyeball, of the head and of the body - We can move eyes and heads separately, many animals cannot move their eyes (insects, birds) and they have to move their head and/or body to be able to see - Show how these three muscles can work together and each muscle pulls in opposite directions but in all three spatial orientations so that the eye can be smoothly moved around to any position in the visual field required

Hormone Structure and Action - Brain and Pituitary Regulation

- The most complex pathway we have is where the pituitary is also involved - Involves a cascade of different hormonal effects - We have the hypothalamus producing a releasing hormone which acts on the pituitary gland and stimulates it to release the tropic hormone - Which then acts on the endocrine cells to produce their specific hormone that acts on the target cells to induce some kind of biological response - Then you have negative feedback acting on both the pituitary gland and the hypothalamus, high levels of that hormone will inhibit further involvement by both of those brain regions Example: temperature regulation, the hypothalamus sense a low environmental temperature, produces thyrotropin-releasing hormone (TRH), one of the releasing hormones that acts on the anterior pituitary gland and stimulates it to produce thyroid stimulating hormone or TSH which acts on the thyroid gland, the thyroid gland is involved in regulation of metabolism and that releases thyroxine which stimulates the activity of lots of cells around the body involved in basic metabolic processes and raises the body's basal metabolic rate or basic rate of energy production, the high levels of thyroxine in the blood inhibit release of these hormones TRH and TSH through this negative feedback process acting on the anterior pituitary and hypothalamus

Electrophysiological recordings of brain activity Micro-electrode Recordings: Advantages and Limitations

- The most direct and precise measure of brain activity - However, because it is invasive, its use is very restricted both in terms of the subjects available and brain areas that can be investigated by patients - However, electric activity in the brain can be measured non-invasively from the surface of the scalp - Using a technique called Electroencephalogram (EEG)

Synaptic Sequence - Depression Side effects:

- The reason they have these side effects is because you are affecting three systems, serotonin, dopamine and noradrenaline, increasing their presence throughout the brain - Increasing their presence can enhance and increase your mood, but they can also do all sorts of things like saliva production and motor function and heart rate and wakefulness and sleepiness - The drugs affect lots of systems because the neurotransmitters are involved in loads of function - This means they can have unwanted side effects - Example: some tricyclic antidepressants for example can give you a dry mouth, and they can make you very sedated at times, so you feel better mood wise, but you have all these other symptoms and effects - This can be true for any drug however it is particularly true for those two because they act on such a wide range of neurotransmitters, so nowadays these drugs are still useful, but the most commonly prescribed antidepressants are the SSRIs like Prozac and Citalopram SSRI = Selective Serotonin Reuptake Inhibitors, this doesn't affect so much the dopamine and the noradrenaline, but it selectively stops the reuptake of serotonin That is better generally speaking because serotonin turns out to be the most important in terms of mood, and so by blocking just serotonin reuptake, breakdown and recycling and therefore increasing serotonin presence in the neuron in the synaptic cleft you get less side effects because you don't affect all the other systems you just affect serotonin (which however does still have side-effects like reducing libido)

Functions of Brain - Some specific groups of neurons include:

- The reticular formation, a complex network of cells in the core of the brainstem involved in the control of arousal and sleep - The suprachiasmatic nucleus (Hypothalamus) controls the circadian (24hr) biological rhythms - The ventromedial nucleus (Hypothalamus) controls the conversion of blood glucose into body fat

Synaptic Sequence - Drugs can influence transmitter inactivation and recycling

- The reuptake of neurotransmitters into the original cell is done by specialized cells: transporters - Cocaine blocks the transporter of noradrenaline and dopamine, thus interfering with their re-uptake and boosting their effect - So, if you stop the reuptake what happens is you can increase dopamine and noradrenaline in the synapse which leads to more activations being triggered by these two neurotransmitters

Vision - Properties of human photopic and scotopic visual systems

- The sunlight that illuminates our environment contains all different wavelengths and it's the amount of that light reflected back that defines how we perceive the colour of objects - E.g., a red object reflects more long wavelengths - Humans have 3 cones that are the basis of our colour vision, and two cones have very close sensitivities in the middle and in the long wavelength range - This is different from many animals that have nicely spaced photoreceptors or even have 4 photoreceptors, e.g., shown in diagram many animals have superior colour vision to humans - Few animals, including humans, filter out UV light using the ocular media

Sex Differences - Gonadal Sexual Differentiation Testosterone

- The testes are also releasing testosterone - Testosterone is a steroid hormone; it is fat-soluble and passes readily through the cell membrane Primary androgen, produced much more in males than in females - Synthesised by Leydig cells in testes Sertoli cells produce AMH In terms of external genitalia, in a similar way you begin with undifferentiated genitalia and then either that develops in the typical male genitalia or the typical female genitalia - That happens under the influence of another hormone called dihydrotestosterone (DHT), in males their testosterone is converted into DHT by the enzyme 5-alpha-reductase, DHT is a more potent form of testosterone and that governs the development of genitalia into characteristic male genitalia In females, they are not producing very much testosterone so the 5-alpha-reductase enzyme does not have any substrate to work on so there is low dht and in that case the external genitalia develop into the female genitalia - Now there are some individuals, a small minority, that have the male genotype (XY) and they produce testosterone but they lack that enzyme 5-alpha-reductase and so they are not producing DHT and so their genitalia do not develop into the typical male genitalia, this is one of the cases of a different pattern of development

Sex Differences - Gonadal Sexual Differentiation During embryonic development in males:

- The testis produces various androgens including testosterone but also another important protein hormone rather than a steroid hormone called anti-Mullerian hormone (AMH) - The androgens lead to the masculinization of many other tissues including the brain, whereas AMH masculinities the internal genitalia - AMH is also known as the Mullerian regression factor because its cause the Mullerian ducts on the diagram to regress - In male individuals the testes are producing AMH causing the Mullerian ducts to regress, so you're left with the Wolffian system and the Wolffian system develops into the characteristic male reproductive anatomy including the Vans deferens, the seminal vesicle etc ... - Whereas in females they are not producing amh and that causes instead the Wolffian ducts to regress, in females the Mullerian system is maintained which then develops into the characteristic female reproductive tract e.g., fallopian tubes and uterus

Synaptic Sequence - Substances can interfere with the release of the transmitter

- The tetanospasmin toxin interferes with the vesicles of the neurotransmitter GABA fusing with the cell membrane - This reduces the amount of GABA released into the synapse - Because GABA is an inhibitory neurotransmitter this results in an imbalance between excitation and inhibition neural signals - This leads to overstimulation of the systems and very strong uncontrollable muscle contractions (tetanus) which are no longer balanced by the inhibitory system which can be lethal

Biology of Stress - Stress Immunisation

- The way individuals respond to stresses is variable, and one of the things that it can depend on is your past experiences - Exposure to stressors early in life can lead to greater resilience later on - E.g., handling of rat pups (Levine et al, 1967, Liu et al 1997, Mirescu et al 2004) - Handling by humans is a mildly stressful event for rat pups - Pups handled earlier in life secrete lower cortisol amounts in response to rang of stressful events as adults - After handling, pups are linked more by their mothers - Offspring of mother who exhibit higher grooming and licking rates are more resilient to stressors as adults - Pups who are deprived of mothers for long periods show elevated stress response, associated with changes in adrenal steroid receptors in brain

Brain subdivisions

- Then there are further subdivisions beyond that - Brain can be subdivided into regions loosely associated with particular functions - The brains of humans and other vertebrates share similar gross structure - The relative size of different brain areas indicates the functional specialisations of the animal, reflecting its ecology

Sex Differences - Sex Differences in the Brain Brain Size

- There are actually measurable differences between the brains of men and women - On average male brains are 120-160g (10-15%) heavier than female brains - Also, heavier relative to body size, men's bodies are bigger and heavier and controlling for that defect brain sizes are heavier in men - Difference present at birth despite equal body weights What does it mean (functional significance)? - Are female brains more "efficient"? Is bigger necessarily better? - Is the extra weight due to extra neurons or supporting cells, or water? - Is there a correlation between brain weight and performance in specific domains?

Hormone Structure and Action - Brain regulation

- There are more complex hormone regulation pathways that also involve the brain - Particular parts that play a key role here are the hypothalamus and the pituitary gland - There are some pathways only involving the hypothalamus, so where you have neural or hormonal stimulation of endocrine cells by the hypothalamus to release a particular hormone which have their effect on target cells and effect some biological response, and that biological response then feeds back onto the hypothalamus to inhibit further stimulation Example: the alarm response, in reaction to a threat or stressor, hypothalamus detects an alarming stimulus which stimulates some cells in the adrenal medulla (central part of the adrenal gland) which release adrenaline into the bloodstream which has some effects such as faster heart rate (fight or flight) which are designed to combat the threat, this physiological effect then causes the hypothalamus to stop stimulating the adrenal medulla through this negative feedback process, perhaps when the individual moves away from the threatening situation

Human Genetic Variation - Geographic clustering of mtDNA haplotypes

- These haplotypes have allowed us to trace back the migration patterns of the human species since about 50,000 years ago - Oldest mtDNA haplogroups in Africa - Haplogroup L3 is ancestral to haplo-groups M and N which arose in North-East Africa and is found in Europe and Asia - Haplogroups H, I, J, N1b, T, U, V, W and X derived from haplogroup N in Europe - Haplogroups A, B, C, D, F and G were derived from M and N in Asia - Haplogroups A, B, C and D are frequent among Native Americans

Sensory Systems - From receptor potential to sensory information

- This is useful because every behaviour is composed of a number of actions for each behaviour the movement needs to be tightly controlled - All the receptors together can provide a range of information to the brain that then controls the ongoing movement of the hand and the fingers while holding the cup for example

Neurons - Main functions of the nervous system

- To monitor regulate and coordinate inner systems and organs, release chemical messengers, change internal states (sleep, hunger, emotions), these are fundamental processes that keep the organism alive to allow to mate and produce offspring - To acquire and analyse information from the environment and from inside the body, making decisions (sensing, thinking, cognition) - To generate, coordinate and control motor patterns (movement, behavioural responses, signals, vocalisations and language, organ activity), also process in which the nervous system is critically involved

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal Tolerance

- Tolerance is a complicated thing which is to do with the brains balancing and trying to get back to equilibrium - The conditioned compensatory response is a form of tolerance to the effects of the drug The effects of tolerance are complex - One the one hand, this is a form of homeostatic protection to reduce the potentially harmful effects of the rug - On the other hand, tolerance can lead to overdose if the conditions necessary for it to work (e.g., contextual cues) are absent Tolerance also often results in an increase in overdose - because larger and larger doses are required to achieve the desired effect It is 'ironic' that homeostatic protection mechanisms that underlie tolerance can increase the addictive potential of a drug This is because the physiological mechanisms that underlie tolerance can contribute to withdrawal symptoms A withdrawal symptom is kind of like if you and your system have adapted to the drug, if you then don't take the drug you start feeling really hyper because what your brain normally does is up the heart rate, so you start to feel restless which is unpleasant, you then feel the need to take the drug again because we've associated the state of mind with the onset of the drug

Sensory Systems - Mechanoreceptors

- Touch and pain: diverse receptors in the skin and body - Posture control: proprioceptors in the body (muscles, joints) - Hearing: hair cells in the inner ear - Balance control: vestibular receptors in the vestibular apparatus Each type of mechanoreceptors (stretch, vibration, pain, touch) has a distinct pathway to the brain, so different qualities of skin stimulation can be communicated to distinct places in the brain.

Learning and Memory - Surgical Lesions Vary in Precision

- Traditional method in experimental neuroscience to causally infer function of brain areas - Neurons are ablated applying physical (e.g., suction) or pharmacological methods (e.g., injections of neurotoxins or pathologically high concentrations of neurotransmitter) - Loss of neurons is permanent, significant damage of non-target tissues in surrounding areas - E.g., in monkeys the hippocampus is usually removed by aspiration via the inferior surface of the brain, thus destroying substantial amounts of the rhinal cortex - E.g., in rats aspiration of the hippocampus is usually performed via the dorsal surface of the brain, thus destroying small amounts of the parietal neocortex

Learning and Memory - LTM in non-associative learning

- Training sessions over 4 days (T1-T4) - Memory recall test on the next day (R1) - Test a week later (R2) Memory was retained for three weeks.

The Logic in Neuropsychology - TMS: Spatial Resolution

- Typically, 10-20mm; 5-10mm at best - TMS has a very high spatial resolution - Influenced by: distance from the scalp, connectivity between target region and adjacent regions

Electrophysiological recordings of brain activity The Physiological Basis of EEG

- Unlike micro-electrode recordings which can detect spiking activity in neurons, EEG is not sensitive to the spikes (also referred to as action potentials) - This is because the spatial extent of action potentials is too small and the time too short for them to be reflected in the EEG - And the shape of the electrical fields they elicit does not allow it, and the time is too short for it to occur If lots of neurons are very active you see a change in electrical signals in the EEG - Can tell you the activation of the overall summary activation of lots of different groups The main reason is by the time all that activation reaches that electrode it has all merged, you can't differentiate between the elements - EEG is most sensitive to the activity in cortical tissue, which is nearest to the surface of the scalp, any electrical activity coming from deeper has to travel further and gets weaker - The cortical surface activation is what EEG picks up bets, however it is possible to study deeper areas with the correct experimental setup - Because electrical fields diminish with distance, the EEG is less sensitive to brain structures that are further down from the scalp - However, it can still detect some activity from some such structures, e.g., the hippocampus

Hormones and Behaviour - Social Behaviour in Humans Social Sensitivity, Marsh et al (2010)

- Used well-validated set of photos of facial expression - Blended with neutral expression to create varying emotional intensity - Participants classified expression 35 mins after oxytocin vs control nasal spray - Results are interesting because it's only when they are rating faces that vary in the degree of happiness that you see a difference between the oxytocin and the placebo group - When they are judging which particular emotion a face is showing, anger disgust or fear, the oxytocin and placebo groups were equally good at doing that, for happiness having a dose of oxytocin first made the subjects better able to distinguish that particular emotion - Oxytocin appears to increase sensitivity to these specific positive emotional expressions

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal Conditioned compensatory response - Overdoses

- Victims of heroin overdose are seldom novices - thus, repeated use leads to a conditioned compensatory response - Often cases of overdose involve some significant change in the context in which the drug is taken (e.g., Rockstar overdoses in an unfamiliar hotel in an unfamiliar city) - Alcohol has a stronger effect when consumed as part of exotic drinks and cocktails than when it is part of familiar drinks, because the change in taste reduced the conditioned compensatory response - One tends to get drunk more easily in the company of unfamiliar people compared to that of old friends ... because the change of company reduced the conditioned compensatory response

Vision - Responses of neurons in the orientation columns of VI

- When recording from neurons of a particular orientation column, some neurons respond to orientation columns only within a small part of the visual field which corresponds to their receptive field - Different to the retinal ganglion cells, these neurons fire at the maximal spike rate when a bar stimulus shows their preferred orientation - Other cortical cells in VI respond with the maximal spike rate to a preferred direction of motion of bars or patterns

Vision - Responses of ON- and OFF- centre bipolar and ganglion cells

- When the cones in the centre of the receptive fields are stimulated with light - These many connections between the photoreceptor bipolar cells and ganglion cells allow for a number of modulations involving both excitatory synapses between the photoreceptor horizontal cells and bipolar cells and excitatory ones - It has been found that very early on at this level of synapses many bipolar cells have structured receptive fields, that means that the input from the cones that connect onto bipolar cells can be mediated by both excitatory and inhibitory connections that are distributed in a centre-surround fashion - Cones that will project with an excitation onto the bipolar cell form the ON centre of such centre-surround receptive field and the signals of its neighbours around it which therefore form centred around/centre-surround, those sinuses from the neighbours and the surround are inhibitory - When these signals arrive at the same time the EPSPs and the IPSPs will sum up and depending how much excitatory input or inhibitory input is reaching the bipolar cell, the resulting signal will be weaker or stronger - So, the signal that is transmitted from the bipolar cell to the ganglion cell is influenced by both these excitatory connections from the central cone and its neighbours that send inhibitory signals - When there is light the photoreceptors stop releasing the neurotransmitter glutamate in this case, and they become hyperpolarized and when there's no light they become excited so depolarized and they start releasing transmitters, an inverse relationship which is re-established to normal by the type of receptors that are found in the dendrites of the bipolar cells - Though the release of the neurotransmitter is inverse at these synapses, the way it is coded re-establishes that when there is light there is excitatory and EPSP building in the cell, and when there's no light there will be a hyperpolarized great potential building in the bipolar cell - Bipolar cells can respond with a depolarization or a hyperpolarization and how strong these are will depend on the exact summation in the receptive field - There are two parallel pathways, so each bipolar cell with an ON / OFF centre surrounded by receptive field will have a sister bipolar cell that is connected to exactly the same photoreceptors but now codes the signals as inhibitory synapses from the central cone and the neighbours are connected with excitatory synapses so it's the opposite connectivity pattern so obviously these two cells respond to the light stimulus in the opposite way - When the cones in the centre of the receptive field are stimulated with light - Objects can be dark against a bright background, or bright against a dark background - This is a smart way to build a filter that already codes the direction of the edge

Learning and Memory - Neural Plasticity: from behaviour to genes Ageing-Relating Changes of Memory

- With ageing humans experience decreases of different types of memory, including spatial memory and navigational skills due to loss of neurons and connections - Memory impairment as a symptom of neurodegenerative diseases - Evidence for reduction of cholinergic inputs to hippocampus and cortex - White matter can change in older subjects to allow for task-independent learning in specific regions, different to younger subjects Spreng et al (2010), Yotsumoto et al (2014), Katsimparido &Lledo (2018), Rehfeld et al (2018)

Sex Differences - Difference in behaviours in humans

- e.g., homicide rates, US homicide reports 1976-1999, classified according to sex of victim and perpetrator, can see the vast majority of homicides were men killing other men - there are hardly any where women kill women, looking at same sex homicides there is a large difference between the sexes - this is relatively stable across the time period, there can also be a characteristic pattern seen with age, peak in homicides at ages of late teens to 30s the age crime curve - this is the case for both victims and offenders, much higher in males than females - looking at location we can see the proportion of homicides man killing man is remarkably consistent, and even across the world, cultures and times - Men kill men much more frequently than women kill women - Most victims and offenders are young men - This pattern is stable across cultures and over time - This is evidence in humans that there are clear sex differences in behaviour that doesn't seem to be a recent cultural phenomenon and suggests it may have deeper biological roots

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal Conditioned compensatory response, Siegel et al (1982)

- injected three groups of rats with a large dose of heroin - The first group received previously a small dose of heron in exactly the same setting ('same-tested' condition) - The second group previously received a small does in a different cage and room ('different-tested' condition) - The rats from the third group were heroin-naive ('first-time tested' condition). The figure below shows the percentage of rats that had fatal overdose in each condition. - The key comparison here is between the 'same' and 'different' conditions: this difference can only be explained by the effect of contextual cues - You can see from the results that if you give the rat the first-time tested there are lots and lots of overdoses, if you've given them the drug before but somewhere else/different setting you see a reduction in overdoses because already a tolerance is building, and finally the most tolerance occurs when you gave the drug in the same tested system because the system is anticipating the presence of heroin in that context and so it's already preparing its system to deal with the onset of the heroin making it less likely for the rat to overdose

Sensory Systems - Sensory receptors have specialised structures to detect stimuli Sensory receptor neurons:

1) are specialised neurons that detect internal and external stimuli of a particular sensory modality 2) input zone usually contains accessory structures, receptor molecules and/or specialised ion channels instead of dendrites 3) transforming stimulus energy into neural signals (= transduction) that are transmitted to sensory interneurons 4) filtering stimulus energy because they have a defined affinity and sensitivity range

Motor Control - Subcortical motor structures: Brainstem

12 cranial nerves = reflexes associated with eating, breathing, facial expressions Extrapyramidal tracts = direct pathways from brainstem nuclei, including substantia nigra, down spinal cord to control posture, muscle tone, movement speed

Human Genetic Variation - How is genetic variation measured?

19th century = Darwin's theory of evolution, Mendelian inheritance laws, biometry, 20th century = quantitative genetics, biometry, emergence of molecular genetics (PCR in 1980) 1980-21st century = PCR test, age of genomics Prior to the 20th century nothing much was known about genes, mainly there were observations of traits and pedigrees, assumptions were made about a substance in the body ensuring offspring resemble parents, biomedical genetic to record observations of traits Mendel discovers the laws of inheritance experimenting with pea plants and this work is rediscovered in 1900s and influences quantitative genetics field 20th century is largely dominated in the first half by quantitative genetics and with the discovery of the structure of the DNA we see the emergence of molecular genetics in the second half of the 20th century By 1980 the PCR test is invented and is well-known, it allows us to sequence DNA, other sequencing techniques are also developing at the time leading to the age of genomics, so from 1980s onwards the age of genomics tests many theories and assumptions made by quantitative geneticists

Hormones and Behaviour - Alloparental Care (young of others)

= Neonate female prairie voles injected with oxytocin are less likely to attract novel stimulus pups Neonate male prairie voles injected with an oxytocin antagonist show reduced alloparental care

Synaptic Sequence - competitive/non-competitive

= agonists or antagonists that bind to the same (competitive) or different (non-competitive) sits on the ion channel (or receptor) as the transmitter

Non-Genetic Variance - Social learning

= learning that is facilitated by observation of, or interaction with, another individual or its products (Hoppitt & Laland, 2013), 'observer' individual learns from 'demonstrator' individual, differs from individual learning because it is heritable

Sensory Systems - Sensory modalities

= sensory systems are classified into several groups depending on the type of stimuli that they are sensitive for e.g., mechanical, visual, thermal, chemical, electrical

The Logic in Neuropsychology - The Effects of TMS on Performance

A TMS pulse typically induces a brief chaotic increase in neural activity often followed by a more sustained reaction in excitability This inevitably results in a disorganisation of neural activity, typically resulting in impaired performance This the effect is similar to that of neurological lesion, only mild, reversible and safe For the reasons above, TMS is often referred to as a virtual lesion technique

The Logic in Neuropsychology - Transcranial Magnetic Stimulation (TMS)

A non-invasive magnetic stimulation of human motor cortex The Neurophysiology of TMS A large current is briefly discharged into a coil of wire held on the subject's head The current generates a rapidly changing (increasing) magnetic field around the coil of wire and this field passes into the brain If you do this over a small area you can briefly stimulate axons, the connections coming from neurons, and they start to depolarise, start firing In the cortex, the magnetic field generates electric (ionic) current through neurons membranes The neurons start sending signals, but they are RANDOM signals Conducting TMS over the primary motor cortex induces muscle contractions resulting in finger twitches Conducting TMS over the primary or secondary visual cortex results in the perceptions of flashing patterns 'phosphenes', the shape and size of the phosphenes are thought to depend on the exact size, strength, curation and timing of stimulation

Biology of Stress - 'Stress' is a confusing term, with multiple meanings

A threatening/demanding event or situation is called a stressor e.g., presence of a predator; social competition; extreme weather conditions This often triggers a suite or coordinated physiological, psychological and behavioural changes, known collectively as the stress response The physiological things occurring in organisms may be very different however they are all showing this characteristic response to a particular stressor In vertebrates the stress response involves activation of two neuroendocrine protection systems: The sympatho-adrenergic systems (SAS) = rapid, short-term response; mediated by catecholamines (adrenaline, noradrenaline) Hypothalamic-pituitary-adrenal (HPA) axis = longer-term response; mediated by glucocorticoids (e.g., cortisol) Together these systems orchestrate the response to potentially harmful or even life-threatening situations Involves bi-directional brain-body communication

Learning and Memory - Change of Connectivity During Encoding and Consolidation

A) ENCODING = Hippocampus-dependent encoding of interconnected sensory attributes (stimulus and context), events to be stored in memory have various interlinked sensory attributes B) RETRIEVAL OF MEMORY BEFORE IT IS CONSOLIDATED = hippocampus-dependent retrieval of learned information C) RETRIEVAL OF CONSOLIDATED MEMORY = retrieval without the involvement of the hippocampus

Learning and Memory - Neural Plasticity: from behaviour to genes Recruiting new brain areas when one of the sensory systems does not develop:

A) cross modal changes following blindness (recruitment of occipital visual cortex) B) cross modal changes following deafness (recruitment of auditory cortex) Cross modal recruitment of occipital cortex in the blind and auditory cortex in the deaf have been reported A) occipital recruitment for tactile processing such as Braille reading, sound localisation and verbal memory B) recruitment of auditory and language-related areas for viewing sign language, peripheral visual processing and vibro-tactile stimulation Merabet and Pascual-Leone (2010) Nature Reviews Neuroscience

Learning and Memory - Neural Plasticity: from behaviour to genes CA1 Neurons Also Have NMDA Receptors in their Dendrites

AMPA receptors are ionotropic receptors (ligand-gated ion channels) NMDA receptors are both ligand- and voltage-gated When the cell is at rest NMDA receptors are blocked by Mg2+ Binding of the neurotransmitter glutamate is necessary but on its own not sufficient to open them

Vision - Colour Constancy

Ability to recognise colours under different illuminations Sunlight is slightly coloured during dusk and dawn Visual system compensates for such slow changes by global adaptation During visual search in a natural scene, the visual systems can also adapt quickly but within the spatially restricted area(s) of visual search The daylight changes in colour as the sun rises and sets, the light scatters differently in the atmosphere and means one is absorbed and not all wavelengths reach the surface the same as during the day, this changes the signals of the cone and the colours it then sees, so the vision system has to be calibrated the sun changes across the day This is called global adaptation because it involves the whole retina

Evolution of the Brain - Comparative Neuroanatomy

Across animal groups great variation in sizes of brain regions Brain tissue is energetically very expensive, and yet is responsible for 20% of energy we use, so energetically expensive so particular brain regions only evolve to bigger size if provides important benefits Brain evolution depends on animal anatomy and ecology Sizes of different brain regions should tell us about animals' abilities, what is important, priorities Cerebral cortex size is related to importance of information it processes Despite specialised differences our brains are similar to other animals because of our shared ancestors Studying other animals helps us understand how our own brains work

Analyse the Data - Region of interest (ROI) analysis

Advantages: - Hypothesis driven, avoids meaningless 'laundry lists' of activated regions - Avoids multiple comparisons problem, data summarised in a single number per subject reflecting mean activation across voxels in ROI - Simple, data can be exported and treated as any other type of data, requiring no special software for further analysis - Generalisable, data can easily be compared across studies e.g., for meta-analysis Disadvantages: - Easy to miss things going on elsewhere in the brain - Not always simple how to define ROIs

Analyse the Data - Whole brain analysis

Advantages: - Requires no prior hypotheses about areas involved - Includes entire brain Disadvantages - Can lose spatial resolution with inter-subject averaging - Can produce meaningless "laundry lists of areas" that are difficult to interpret - Depends highly on statistics and threshold selected - Multiple comparisons problem

Neurons - Ion channels vary in different parts of the neuron

All neurons have: - Input zone (soma, dendrites), where neurons collect and integrate information, either from the environment or from other cells - Integration zone (between soma and axon), where the decision to produce a neural signal is made - Conduction zone (axon), where information can be transmitted over great distances - Output zone (axon terminals), where the neuron transfers information to other cells - Neural signals always travel in one direction - from input zone towards the output zone - Ion channels in the axon differ from those in the dendrites/soma and the axonal endings This is important for the generation of two types of signal, the action potential and the graded potential

Hormone Structure and Action -

Amine hormones - Modified single amino acid (a.k.a. Monoamine hormones) - Smaller and simpler than protein hormones - Well-known amine hormones include: - Adrenaline (epinephrine), noradrenaline (norepinephrine) and thyroid hormones which are related to metabolism and body function - Melatonin

Hormones and Behaviour - Nervous system

An action potential travelling along the presynaptic neuron Stimulates release of neurotransmitters Neurotransmitters travel across the synaptic cleft and bind with receptors on post-synaptic membrane

The Cognitive Neuroscience of Addiction - Causes of Addiction Relapse - a learning-based explanation

An extinction trial is where that cue is present, but the reward is no longer present When Sharon stopped smoking, she started the process of extinction-reducing the strength of the association between various smoking cues and smoking Because she changed her job, the company of the old friends (a potent cue) has been taken 'out of the equation': it has not been extinguished The re-exposure to this cue elicited the conditioned response of smoking Context-driven relapse has been extensively documented in rehabilitation Extinction procedures that involve exposure to multiple cues without the reward can be effective, because one reduced their potency in triggering the relapse. But they can be hard to pull off Research suggests that extinction treatments limited to rehabilitation centres are less effective, long term, than treatments carried out in contexts equivalent or similar to those in which addiction developed (e.g., where the addict lives)

Neuroimaging - Analyse the data

Analysis: Multiple regression is used to determine the effect of a number of independent variables (our conditions) on single dependent variable (brain activation) For each voxel we use multiple regression to estimate how closely the BOLD signal correlates with the time course of each condition Finally perform a contrast - simply a t-test comparing beta condition 1 beta values to condition 2 beta values Beta values are the estimate of how closely the activation in a voxel correlates with our model We see whether the beta values in condition 1 more closely fit our model than condition 2. We must decide on a threshold, we have to decide what we accept as a significant difference in activation between our two conditions. The threshold we apply defined what we accept as a significant difference in activation between our 2 conditions. What alpha level, what threshold we select, is essentially arbitrary (as it is in any statistical procedure). The standard p value/alpha level that we use in psychological research is p<0.05. (we accept a 5% rate of false positives). The problem here is that if we're doing so many different T tests, when we do all of these comparisons, we massively increase our chances of a type 1 error.

Vision - Decomposition of images in different spatial frequency channels

Another class of neurons is also responsive to the spatial frequency Higher cycles per degree = more edges in an image Lower cycles per degree = less edges in an image The existence of these neurons suggests that there is a lot of information the brain can extract from these characteristics in images, and it can use the same input from ganglion cell with centres around receptive field to generate neurons with high sensitivity for these sinusoidal wave patterns They could allow to make very quick judgements based on the high or low spatial contrast content in an image without having to reconstruct specific objects, so there could be important information carried, for example emotional responses where recognition might be very fast using low spatial frequencies you can quickly identify if face is happy or sad

Learning and Memory - Neural Plasticity: from behaviour to genes Modulatory interneurons can influence how much and for how long neurotransmitter is released

Another example of presynaptic facilitation - Studies in Aplysia also showed that the connector which connects to the sensory and motor gill is quite complex and it involves some interneurons, some of these interneurons form axonal synapses - Example: Shows that before the training the activity in this facilitatory interneuron does not influence neurotransmitter release at the gill synapse, after training the facilitatory interneuron will influence the activity of the sensory cell in such a way that it instructs the cell to release more neurotransmitter using a number of biochemical cascades in the presynaptic end of the cell - The result is the same one, the neurotransmitter is released when required for the response and an increase postsynaptic potential is generated in the motor neuron - Modulation causes an increase in neurotransmitter release

Neurons - Bioelectricity in Giant Squid Example

The discovery of how neurons generate bioelectric current goes back to the Common Squid (loligo forbesi), John Young discovered giant neurons in the mantle of the squid in the 1930s. He discovered that they had giant neurons that innovated the muscles of the mantle here, this is how the animal moves, it moves the mantle and can propel it very quickly to escape or swim quickly. To do this it has to contract all the muscles very quickly and at the same time, therefore it needs very big neurons which the signal can be travelled and distributed very quickly to many motor neurons. The way neurons generate eclectic signals was discovered only 70 years ago Squid giant axons can be up to 1mm in diameter, much larger than mammalian They innervate the mantle muscle and ensure rapid and simultaneous contraction of all muscles Hodgkin and Huxley 1940s and 50s, started to record more systematically from the giant axon of the squid, they received the Nobel prize for their theory of the action potential, their work marks the start of computer-based quantitative modelling in neuroscience research

Brain Function and Localisation - Challenges for Localising Function

The dorso-lateral prefrontal cortex is the region of the brain which expanded more than any other in the course evolution of primates Yet patients with lesions to this region rarely show selective/specific deficit, problem is thee but is not immediately obvious, form of problems with emotional regulation or organisation of behaviour Evolution shows PFC it is clearly important? What might it be doing? Based on examples it may seem that localisation of function in the brain is relatively straightforward, it is just a question of time before the specialization of all areas is revealed Scanner to test the density of fibrous connections between areas, which areas are connected to what, areas that those areas are part of which are related to function

Evolution of the Brain - around 500,000000 (500 million) yrs ago

The emergence of first animal, metazoa, now after cell is divided, they cells stick together to form multicellular organism, now different cells within same organism can specialise for different functions

Hormone Structure and Action - Endocrine system subdivisions

The endocrine (only) system appears very simple as it typically responds to levels of chemical in the blood and is not directly controlled by the nervous system Within the neuroendocrine system there are more complex levels of organisation where there also an involvement of the nervous system, particularly the hypothalamus and the pituitary gland The neuroendocrine system ends to evolve faster responses than the more standard endocrine system, which is slower to act but longer lasting in many cases The neuroendocrine system is where the nervous system and the endocrine system come together, and you have more rapid initiation of hormone production by the involvement of the nervous systems through the hypothalamus and pituitary gland

Evolution of the Brain - 525 million years go

The first vertebrate animals, first bones, bones around brain area and down neural cord to protect nervous tissue, forebrain a midbrain and a hindbrain here, may not be the first to have them but did have these three divisions

Vision - Functions of simple and complex cells

The functions of simple and complex cells indicate that everyone is important for object recognition, but we also know it is important for conscious vision and perception Analysis of contours and boundaries analysis of objects Shape and positional invariance Contour enhancement for objects identification VI is fundamentally important for conscious vision and perception

The Logic in Neuropsychology - Single Case vs Group Studies

The gold standard of experimental psychology (be it in behavioural or imaging studies) is to analyse the data at the level of groups of subjects rather than individuals Group-level analysis reduces the contribution of irrelevant factors (idiosyncrasies associated with individual stimuli or individual participants) and emphasises the effect of the experimental manipulation Modern structural brain imaging enables one to identify the degree of overlap between the regions of damage in different patients and compute the area of maximal overlap However, group-level analysis may not always be possible in neuropsychology Suppose one finds individual patients with very specific effects of brain damage and other similar cases are very rare In such circumstances, it seems appropriate to report single-case studies, in which the pattern of performance in one or a small number of individual patients are reported at least until other similar cases are identified

The Cognitive Neuroscience of Addiction - Causes of Addiction Cue reactivity can be clearly detected in brain activity in addicts

The idea that your brain responds to a smoking cue or another drug cue has been very well studies in the brain You can see you can detect it is in all addicts, even gambling addicts shows you can have gambling cues and what you do is you show in a scanner for example pictures of smoking stimuli versus matched pictures of something else, similar size and similar colouring You present both of them and then lots of them and you take the average brain activity related to the smoking stimuli and the average brain activity related to the neutral stimuli and you deduct them from each other, and then you get a whole bunch of brain areas (usually in the reward areas of the brain) that are more active in an addict when seeing a drug/smoking/etc cue that when seeing a regular cue And when you do this experiment with people that aren't addicted you don't get a difference

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - We do not know what is happening in neglect

The lateralisation to the left side of the visual field suggest to some to indicate that attention is inherently biased to the right and that some function bringing it leftwards is impaired Another possibility is that something has gone wrong in the internal representation of space in the brain (some of it is missing and therefore not used) Another possibility is that imitation of the motor system in certain directions is impaired It is possible that neglect is caused by a multitude of problems

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - Determining Causality

The only definitive solution is to examine whether behaviour/performance is affected when the brain activity is disrupted in a particular area. In animals, lesions can be produced experimentally e.g., in rats or monkeys In humans one can examine the effect of: Neurosurgery - removal of brain tissue for treatment of neurological or psychiatric disorders, most often epilepsy, try to determine where the course of the seizure activity in the brain is as it very often starts in a particular place then spreads through the system, they them remove that Stroke - cerebrovascular accident resulting in the disruption of blood circulation in the brain and/or brain haemorrhage, either a blockage which prevents oxygen supply to the brain, or you can have a bleed, either one leads to a particular brain damage, can observe consequence in behaviour Brain trauma or tumours Neurodegeneration - degeneration of brain tissue and dementia e.g., Parkinson's Infection - of brain tissue e.g. Some infections can cause severe brain damage such as meningitis or syphilis

The Cognitive Neuroscience of Addiction - Drug taking as self-medication in mental illness Comorbidity

The probability of a diagnosis of drug or alcohol dependence increases with the severity of mental illness (including mood disorders (e.g., depression), anxiety disorders (e.g., panic disorder), eating disorders, intermittent explosive disorder, or psychotic symptoms (e.g., schizophrenia)

Vision - LGN neurons project to VI

The projections from the LGN, you have the output neurons/new interneurons that start in the LGN and they send signals along the synapse to the V1 The V1 is 6 layers that are numbered 1, 2, 4A, 4B, 4C, 5 and 6 These layers are important because all the projections are kept separate so via the LGN these P- and M-ganglion cells project to different LGN layers and different layers in the visual cortex

Neurons - Unidirectional transmission of the action potential

The recovery period is very important because it allows the unidirectional transmission of the action potential from one end of the axon to the other end of the axon Due to the refractory period, the voltage gated Na+ channels can open on only one side The action potential travels along the axon away towards the output zone Na+ entry locally depolarizes the axon, sufficiently depolarising the adjacent region to open more of the voltage-gated Na+ channels, re-creating the action potential there and so on down the axon. The patch of Na+ channels behind the action potential are temporarily refractory

Neurons - Action potential: an all or nothing response

The stronger the above-threshold excitation, the higher the frequency of action potentials (measured in Hertz as the number of action potentials per second)

Non-Genetic Variance - Symbolic representation

The use of arbitrary symbols to represent (or stand for) objects and actions Example: - Human language - Using letters and words to represent particular objects, actions and concepts - When two initially unrelated stimuli are associated with the same event, an emergent relation can develop such that they become interchangeable in other contexts - Command and warnings can be understood equate of an association between that particular sign or symbol and the situation that it referring to - Human language allows information to be stored and retrieved and persist across and over long periods of time - Is this uniquely human? Though we know human language is far advanced beyond anything we see in other species, do animals show something that could be regarded as a simple form of symbolic representation? - E.g., there have been examples of studies where animals have been taught to use symbolic representation in a similar way to some aspects of human language e.g., Alex the grey parrot, chimpanzees using sign language - E.g., there are some examples where other animals appear to use some form of symbolic communication in their natural behaviour in the wild, Vervet monkeys have different alarm calls for different predatory threats e.g., different for airborne or on ground and different responses to each type of predator - E.g., honeybees performing the so-called waggle dance, a bee out foraging and returning to hive communicates the location of food and how far away using the waggle dance to indicate information about the food, the speed and vigour of the waggle indicates how close the food source is and the angle relative to the vertical direction indicates where that food source is in relation to the sun

The brain's sensory communication in animals

Therefore sensory and communication systems are similar to what we see in other animals. Structure of human brain shares many similarities with structure of brains in other animals. Mammalian brains have all the same regions you see in human brains but the shape and appearance of them might look very different. In order to understand similarities and differences we must take an evolutionary perspective, can't consider humans in isolation from other animals.

Biology of Stress - Eustress vs Distress, Engelmann et al (2004)

They pointed out that there might be varying degrees of disturbance to our bodies physiological systems moving from homeostasis through to a certain degree of disturbance (eustress) and then really extreme disturbance and more damaging consequences (distress) Eustress = perturbation can be dealt with effectively; (beneficial) stress response quickly terminated once homeostasis restored Distress = chronic hypo-/hyperactivation of HPA axis; may be harmful and lead to abnormal behaviour

Neurons - Resting Potential

They separated the giant neuron out of the body, and it was bing/1mm in diameter so they could see it with bare eyes, the positioned that within the sea water bath They had two sharp microelectrodes filled with salty solution so they can conduct electricity and they placed one electrode in the bath and the other next to the neuron, both connect to a computer and to an oscillograph with an amplifier because the signals are very small and need to be amplified to be detected and picked up by the measuring apparatus As long as both electrodes are outside the neuron there is 0 potential difference that is picked up between these two electrodes, so the voltage that is measured is 0 This is because ions will distribute equally due to the fusion in the bath When the ion channels are closed, there are always: negative ions on the inside and positive ions on the outside, accumulated along the membrane due to electrochemical driving forces Resting potential = membrane potential when no signals transmitted (around -70mV) Once the electrode is inserted inside the axon, it records a negative potential (the inside of the axon is more negative than the outside)

The Cognitive Neuroscience of Addiction - The drugs' influence on processing of rewards (pleasure and incentives (motivation) Incentive Salience Theory

This has led to an alternative to the anhedonia hypothesis - the incentive salience hypothesis, which states that dopaminergic circuit involving NA and VTA is not so much responsible for the pleasure obtained from a drug, but for the motivation to obtain it The proponents of this theory do not dispute that euphoria induced by drugs of abuse contributes to their consumption (they also do not context the important of cue reactivity or withdrawal avoidance in eliciting or maintaining drug use) However, they claim that these factors are not sufficient to explain addiction in long-term users and relapse after therapy The theory proposes that addicts become sensitised to drugs (such as heroin, cocaine, alcohol, amphetamines) because their use strongly stimulates these motivation-related dopaminergic synapses in the brain with repeated use of the drug leading to greater responses to the dopamine circuit, independently from the effects of the drug on euphoria

Vision - Identifying spatial relationships and properties of objects

This is useful because it helps to enhance the edges and direct attention of the eye automatically to areas of high contrast and because contrast of light information is not sharped edged but in natural environments there will be a lot of scatter it is important that when edges are extracted, they are reliable and important One important information of objects in the individual field is how they're orientated, and shades can help to determine if a 3d object is the right way up and where it is facing - Without context cues, we perceive the physical reflectance of the surfaces which carries little information - Edges and shadows provide context information about the spatial structure of objects or spatial relationship between objects

Hormone Structure and Action - Autocrine Feedback

This is where we have production of some hormone by endocrine cells stimulating the target cells that have the receptor for that particular hormone When there are excessive amounts of that hormone in the bloodstream that then feeds back on the target cells that produce that hormone in the first place Negative feedback inhibits further production Example: the role of prostaglandin in regulating acid secretion in the stomach, when you consume a meal the Parietal cells in the stomach secrete hydrochloric acid to help you break down the food in the stomach, others cells in the wall of the stomach secrete prostaglandin which inhibits further production of hydrochloric acid by those cells, when the levels of prostaglandin rise that then acts through negative feedback on those stomach wall cells to inhibit further release of prostaglandin and allow the parietal cells to produce hydrochloric acid again

Learning and Memory - Stimulus-response Learning

Thorndike (1898) proposed that animals learn based on the outcomes of their actions (law of effect) According to his Law of Effect, when a response is followed by a reinforced, then a stimulus-response (S-R) connection is strengthened Thorndike's Puzzle Box Latency to open the door by operating the object correcting mechanisms in the box, cat must pull down object to open the door, first will explore the box and then will eventually associate the opening of the door with the pulling of this object The animal is rewarded and then placed back in the box to be tested again, Thorndike observed a decrease in latency with the number of trials, the more often the cat was placed in the box the faster it would operate the mechanism to open the door and escape

Learning and Memory - Neural Plasticity: from behaviour to genes Hippocampus is involved in spatial memory formation

Three main pathways: 1) perforant pathway (input from entorhinal cortex) 2) mossy fibre pathway (dentate gyrus to CA3 pyramidal cells) 3) Schaffer collateral pathway (CA3 to CA1 pyramidal cells) - Neurotransmitter: Glutamate - Can take slice from hippocampus that preserve a functioning network, they can be kept alive, and recordings are performed ex vito - The hippocampus is composed of many different cell types, major groups of cells form very prominent fibres

Genes and Behaviour - Gene products: proteins The Human Genome Project

Through alternative splicing, one gene can produce multiple proteins (Human Genome Project) "The old axiom 'one gene, one protein' no longer holds true. The more complex an organism, the more likely it became that way by extracting multiple proteins meanings from individual genes." - Ast (2005) Most of the vertebrae genome does not code for proteins, there is only a small fraction that we could refer to as the gene and protein coding regions Most of the genome is not really coding for anything in particular There is also no consistent relationship between amount of chromosomal DNA and organism's 'complexity' Two humans share 99.8% of their DNA, we are overwhelming similar to each other within our DNA, if we compare us with other organisms' humans share 98% of our genes with chimpanzees, and humans and mice share 92% of their genes

Human Genetic Variation - Genes have two important functions:

To make sure that cells operate and work at all times during life, genes are active and turned on or off at any moment in time (SOMATIC FUNCTIONS OF GENES) Reproductive cells, carrying information from one generation to the other, chromosomes that contain the instruction to develop the organism to grow a new individual, these genes are expressed in the germ-line cells, All the cells, the somatic and germ-line cells are acting in a physical social environment, they receive different nutrients, different amounts of nutrients, and the DNA mutates these, and the genes are embedded in the architecture of non-coding DNA

Genes and Behaviour - Gene expression: transcription + translation

Transcription = where the DNA double-stranded helix is 'unzipped' and a new molecule mRNA is produced and produces a copy of the DNA, said that the DNA is transcribed into messenger RNA (mRNA) Translation = that mRNA is then transported out into cytoplasm, outside nucleus but still inside of cell, and mRNA is then translated into a protein

Neuroimaging - Alternative to block-related design = Event Related Design

Trials of different conditions are randomly intermixed and occur close together in time Originally researchers thought this wouldn't be possible because what we have is two different conditions, can see that if the BOLD signal increases in one condition, if you have another trial occurring only a couple of seconds after that condition this doesn't allow the BOLD signal to return to baseline before your next trial occurs But researchers devised a method to disentangle the BOLD signal relating to different trial times and what they realised what that this was only a problem if you had alternating trials, you could never disentangle the BOLD signal and you could never tell which trial type was leading to an increase in the BOLD signal because they're all overlapping like this What they realised what that if you presented the trials of different conditions in a completely random order then you could disentangle the BOLD signal to different trial types and you could predict which condition was leading to an increase in BOLD signal

Genes and Behaviour - Genetic Mutation Twin Studies

Twin and adoption studies investigate the genetic and environmental influences on human behaviour and cognition The basic idea is that by studying pairs of twins and adopted children we might be able to disentangle the genetic and environmental factors

Biology of Stress - Coping and Cognitive Appraisal Cognitive appraisal

Two forms of appraisal: - Primary appraisal = significance in terms of personal goals, values, self-beliefs, is the situation irrelevant, beneficial or threatening/challenging for me? - Secondary appraisal = ability to control situation and importance for wellbeing, what can/should I do about it? Involves taking into account: - Personal factors = goals, personal resources, beliefs about oneself and the world - Situational factors - demands, constraints, opportunities and culture

Human Genetic Variation - Climate matters: the untold story of the early Modern humans in Africa

Typical Modern human features emerge in a mosaic-like fashion within the H.Sapiens clade Genomic studies show that early homo sapiens comprised several populations across Africa that were interlinked and with connectivity changing through time prior and after main OOA migration wave Evidence that climate varied greatly, and periods of relatively increased aridity to humidity were asynchronous across Africa

Synapses and Networks - Signal generation and transmission are determined by the nature of ion channels in the neural membrane

Typical locations of ion channels (in varying numbers and densities) - Voltage-gated channels (Na+, K+), axonal hillock (integration zone of the axon) and axon (conduction zone) - Leak channels and ion pumps: entire neural membrane Voltage-gated Ca2+ channels: axon terminals (output zone) - Ligand-gated channels: dendrites and soma (input zone) At a synapse signals are transmitted to another neuron or to tissues that are under direct neuronal control (muscles, glands).

Electrophysiological recordings of brain activity - What information can one extract from an EEG? Using EEG frequency to detect conscious awareness

Typically, higher frequency activity in the EEG is associated with greater cortical activity Recently, researcher have recorded high-frequency EEG over the motor cortex to assess conscious awareness in patients with vegetative state fMRI can be used for this purpose But - EEG is much cheaper, more portable - can be easily deployed to the patient's bedside Diagnostic criteria for 'vegetative state': someone who has had brain trauma, no overt motor responses to commands, no elaborate 'voluntary' or 'willed' behaviour from the upper or lower limbs, no evidence of visual orientation, no eye fixation greater than 5 seconds or tracking of visual or auditory stimuli

Synapses and Networks - Transmission of neural signals over short and large distances: Non-spiking Neurons

Typically, neurons with short axons or no axons Neurons with short axons or no axons do not generate action potentials, the signal spreads passively to the output zone These are two types or two mechanisms the brain and nervous system can employ depending on how far the signal has to travel

Synaptic Sequence - Drugs and Synapse

Various substances (naturally occurring toxins, chemicals, drugs) alter synaptic transmission 1) Which phases of the synaptic sequence can drugs alter? 2) psychoactive substances: some examples 3) psychoactive substances used to treat psychiatric conditions

Non-Genetic Variance - Vertical vs horizontal transmission

Vertical transmission = transmission between generation, parents to offspring, similar pattern to genetic inheritance, in some cases may skip generations (unlike genetic inheritance) Horizontal transmission = within generations, peer to peer, not possible with genetic inheritance

Sensory Systems - Mechanically-gated ion channels

Vibration or pressure on skin deforms the corpuscle and stretches the tip of the axon opening mechanically gated ion channels What happens when vibration is applied to the area in which this particular receptor is sensitive? - The vibrations will be amplified by the concentric layers around the axonal tip, and they will stretch open the ion channels - So, what all mechanoreceptors have in common is that the mechanism to open their ion channels and allow ions to flow into the cell is just brutal force, the membrane is stretched and just by mechanical force the ion channels are stretched open - The influx in this example of sodium ions, creates a greater potential and if their greater potential is strong enough/ enough force is applied in the integration zone of the axon, the action potentials will be generated and travelled down the axon towards the spinal cord

Vision - Projections of light onto the retina

Vision starts with the formation and processing of images in the eye - Rod and cone cells forma 2D-array in the retina - The light in the retina has to travel through layers of neurons because the photoreceptors are oriented towards the back of the retina where the eyeball is aligned with the pigmented epithelium - The receptors are more or less upside down, so the light has to travel through these layers of soma and axons before reaching the input zone of these photoreceptors which are extensions of the membrane which have been folded into disc shaped structures - The rod cells of which we have approximately 100 million in the retina, have a much larger surface areas because they have many more of these discs are much bigger and they can fit much more photo pigment, this makes them much more sensitive - The cones have a smaller area that contains the photopigment in the membrane, which then catch the light quanta that are reaching the back of the eye - These photoreceptors absorb light and create 2D images on the retina, so though we look at the 3D world, the image on the retina is 2D

Brain Anatomy and Localisation: Perception - Visual Perception

Visual perception: hierarchical organisation, visual processing is segregated into: - A pathway specialised in the analysis of the stimulus features (colour, shape), the 'what' pathway - A pathway specialized in rapid detection of stimulus location and motion, the 'where' pathway Visual processing in the Fusiform gyrus, cells in the inferior temporal lobe (the Fusiform gyrus) seem to respond to highly complex visual stimuli, there is an area in the Fusiform that seems to specialise in face recognition (Fusiform Face Area, FFA), neuroimaging studies of face processing consistently find FFA activation, damage to FFA or cell loss in FFA due to degeneration often result in impaired face recognition e.g., prosopagnosia

Learning and Memory - Operant (or instrumental) Conditioning

Watson and Skinner strongly influence ideas that lead to the emergence of behaviourism in the 1920s as research field dedicated to the study of operant conditioning Reinforcement learning: if a behaviour is reinforced, it will be repeated, if not it will be extinguished Animals are mainly tested in boxes (Skinner box) Rat in the Skinner box has learned to press the lever in order to receive a food pellet, the lever is the stimulus and pressing the lever is the response Reward-seeking behaviour in addiction (e.g., self-administration of morphine), you can train animals to associate pressing lever with them feeling better and they get addicted

Learning and Memory - Neural Plasticity: from behaviour to genes Sensory information reaches the hippocampus via multiple routes:

We have discussed many examples where hippocampus is important in learning and mediates memory formation, not just one type of memory but different types of memory and because it is interconnected with many different brain areas it has many functions One of the tasks of the hippocampus is to code and map out spatial location, from a group of cells found in the entorhinal cortex

Evolution of the Brain - 430 million years ago

We have first jawed fishes, had many important innovations, first animals to have teeth which allows animal to take in food bigger than its mouth and larger prey, can break down before digestion, can take on more energy which allows them to build bigger brain, eye muscles to allow them to move eyes independently form where facing, semi-circular canals in ear which allow to sense orientation of head for balance and stabilisation, appearance of cerebellum which is involved in movement of eye and keeping head stable based on movement from semi-circular canals, more efficient and ferocious predators

Sex Differences - Sex Differences in the Brain Brain lateralisation

We know that different hemispheres of the brain are differentially involved with particular tasks - Left hemisphere = movement on right side of body - Right hemisphere = movement on left side of body Female brains are less strongly lateralized with respect to various functions than male brains Anatomical lateralisation of the cerebral hemispheres appears to be more marked in males

The Cognitive Neuroscience of Addiction - Drug taking as self-medication in mental illness Drugs cause mental illness

We've already seen at the beginning of the lecture that drugs are associated with an increased risk of neuropathology There is also substantial evidence that drug use causes mental illness

Learning and Memory - Neural Plasticity: from behaviour to genes Synaptic plasticity in learning and memory

What can change in the presynaptic neuron? Gain control (change in the amount of neurotransmitter that is released for a given signal) Temporal filtering (change in selectivity for the frequency range of spike arriving in the axon terminal) It has been shown that for short term plasticity the presynaptic neuron can release temporarily more neurotransmitter, when more neurotransmitter is released a stronger EPSP can be formed, so by releasing more neurotransmitter here it is also possible to have mechanisms at the solo terminal that will change the selectivity for the frequency of spike that arrive so they may respond with more neurotransmitter release to the same spike frequency, this way creating temporal filters that can also lead to an increase in neurotransmitter Short term facilitation (very brief, milliseconds) or potentiation (few seconds to minutes) Short-term depression (opposite effect, decreases PSP) Enhancement of synaptic transmission: e.g., presynaptic facilitation (Aplysia's gill synapse)

Synapses and Networks - Type of neurotransmitter and receptor defines whether a postsynaptic potential is excitatory or inhibitory

When an excitatory presynaptic neuron fires it shows a normal action potential and causes depolarisation (EPSP) in the postsynaptic neuron Typical transmitters at excitatory synapses: - Glutamate aspartate - Nicotine acetylcholine (nACH) When an inhibitory presynaptic neuron fires it also shows a normal action potential, but it causes hyperpolarization (IPSP) in the postsynaptic neuron At inhibitory synapses: - GABA - Glycine - Muscarinic acetylcholine

Neuroimaging - Blood Oxygen Level Dependent (BOLD) signal

When neurons become active, blood flows to the part of the brain to provide oxygen to fuel the cells Haemoglobin (the iron-containing oxygen transporting protein present in blood) differs in how it responds to magnetic fields, depending on whether it has a bound oxygen molecule The MRI scanner, which is basically a giant magnet, detects these small changes in the magnetic field With fMRI we are not directly measuring brain activity We are measuring blood flow (more precisely, the magnetic properties of oxygenated vs deoxygenated blood) Difference in the magnetic properties of blood when that blood has become deoxygenated, when it's flowed into a particular brain region the oxygen has been extracted for fuelled and that's caused some different in the magnetic field

Vision - Ganglion cells do not respond to uniform illumination

When the light spot covers the whole ON-centre, the ganglion cell responds with its highest spike rate When a ring of light covers all of the surround but not the ON-centre, the ganglion cell responds with the lowest spike rate or even no spikes at all When the whole receptive field is equally stimulated, the ganglion cell is at rest and fires with a spontaneous frequency So, in this case the fact that it's not firing tells the brain that there is maximum inhibition

Synapses and Networks - The vocabulary of neural language

When the neuron receives information from a single neuron it responds in a binary code, essentially the neuron has to make a decision whether it transmits or not: yes or no decision YES = The signal gets transmitted inside neuron to output zone and sufficient neurotransmitter is released NO = Signal does not reach output zone or is too weak to release sufficient neurotransmitter, therefore signal is not transmitted

Brain Function and Localisation - The 'multiple demand' brain areas

When there is a task at hand where things have to be one in certain way in certain order or multiple things done Activity in MD regions across multiple tasks Broca's area, to do with language, Broca's aphasia or trouble speaking if damaged, was thought of as a purely language area but has been challenged because of evidence it may be important for other things also, bits of Broca's are dedicated to language and bits dedicated to language and other things also,

Neuroimaging - Preprocessing Steps 4 - Co-registration

Whenever we do an fMRI experiment in a single subject, quite often we will collect a lot of functional images and a high-resolution structural image of that subject's brain and what we want to be able to do is overlay any kind of functional activations onto a structural image so we can see precisely which area of the brain is activated An important step is to co-register those two images, they might be acquired at two very different times, the head may have moved substantially between collecting the functional data and the structural data, may even be acquired in different sections, we might collect the functional data first then the structural data later Simple process because as we are dealing with the same brain, we have the same dimensions, size and shape, all we need to do is take the functional images and make sure they are in the same space as the structural images

Non-Genetic Variance - Cultural transmission

Where behavioural techniques are transmitted socially and persist over generations Example: washing sweet potatoes in Macaques One particular macaque in the long-term study started washing the potato before eating it This behaviour spread initially to her closely associated and then through the macaque population This then became an established tradition within this particular population

Hormone Structure and Action - Target Cell Feedback

Where endocrine cells produce a particular hormone that affects a biological response by the target cells, not biological response itself, inhibits further production of the hormone through negative feedback. Example: insulin pathway which regulates levels of sugar/glucose in the blood, they release insulin which acts on muscles and fat cells to take up glucose from the blood, but then a drop in circulating glucose as a result of this glucose uptake through negative feedback then acts on the pancreas to stop producing further insulin, enabling the level of blood glucose in the blood to be kept at the right level

Non-Genetic Variance - Mechanisms of Social Learning 4. Imitation

Where the observer copies the topography of demonstrator's behaviour Seen in humans very much and especially from a very young age Example of imitative behaviour

Non-Genetic Variance - Mechanisms of Social Learning 3. Observational conditioning

Where the observer learn association between stimulus and demonstrator's behaviour Thought to be important in learning which elements of the environment to be afraid of E.g., monkeys learning to be afraid of snakes

Hormones and Behaviour - The neuroendocrine system

Where the two systems interact with each other In particular when you have these more complex hormonal pathways involving the hypothalamus and the pituitary gland then that involves the production of releasing hormones often from neuroendocrine cells that then act on the pituitary to produce tropic hormones that stimulate further endocrine gland around the body to produce the hormones that have their effect on target organs This allows a fast initial response, important in situations which require a faster hormonal response Can be prolonged action if that is required Enables regulation and control of homeostasis - CNS - ANS - SNS and PSNS Ensures the appropriate response is given to a stimulus

The Cognitive Neuroscience of Addiction - The drugs' influence on processing of rewards (pleasure and incentives (motivation) Drugs as rewards

Whilst drug-related cues and avoidance of withdrawal can go some way in explaining the addictive potential of drugs of abuse, they do not seem to capture the whole picture of addiction For instance, they'd not explain why someone who stopped taking drugs a relatively long time ago and does not experience severe withdrawal or is not exposed to drug-related cues, may still relapse conditioning -based models of addiction also find it hard to account on their own for the fact that drugs of abuse become increasingly desired with use (unlike natural reinforcers like food, sex, etc...) These limitation of cue reactivity and withdrawal models, along with the discovery of the dopaminergic circuits and their importance for processing naturally rewarding stimuli, gave rise to the idea that drugs of abuse may be addictive because they are exceptionally rewarding

Human Genetic Variation - mtDNA tests: Who are your relatives? Who are your ancestors?

Whole-genome sequencing for an individual is expensive (although getting cheaper with technological advancement). Mitochondrial (mtDNA) sequencing is cost-effective Benefits of mtDNA sequencing - High number of copies in a cell - Inherited from egg parent - No recombination - High mutation rate - We share very similar mtDNA with all of our close relatives mtDNA is an important genetic marker in forensics, anthropology, medicine and evolutionary research Using mtDNA tests we can ask both the question who are your ancestors and who are you relatives Nuclear genome: 3.3 billion DNA base pairs (93% non-coding DNA) Mitochondrial genome: 16,569 DNA base pairs (3% non-coding)

Vision - Coping with changing light levels

Why have two types of visual receptors? - This is in order to increase the range in which our vision can effectively operate, so out cones are active during the day (the photopic range of vision) and rods take over as soon as it gets darker and during the night (the mesopic and scotopic time periods) and during this time the cones are negative and it's the much more sensitive rods that operate our vision - Duplex retina in the vertebrate eye - Cones are specialised for vision during the day (1-100 million times brighter in sunlight than moonlight) Rods are specialised for vision during the night Two types of visual receptors: rod and cone cells - Both types of receptors detect light in largely the same way (opsins, metabotropic transduction), but tods are more sensitive than cones - Both receptors have the opsins inserted in the membrane discs in the input zone in these accessory structures Opsin - light-sensitive protein (G-protein coupled receptor molecule) in the membrane of photoreceptors which is bound to the chromophore retinal (needed for transduction) - Opsins come in different classes and so different cones express different types of opsins Three functional classes of cones (S-,M- and L- cones): Cone opsins differ in their wavelength-specific affinity to absorb light (S,M and L) opsins). Only one opsin type is expressed per cone. One functional class of rods: all rods express the same type of opsin (RHI, or rhodopsin), the rods are much more sensitive because they have much more photopigment densely packed in these membrane discs and this because during night there's less light, so they need more photopigment to capture light

Vision - Colour vision deficiencies: 5-8%m, 0.5% f

X-chromosome recombination causes colour vision defects S gene on chromosome 7, M and L gene on X Colour deficiency (mild) trichromats Colour blindness (severe deficiency) dichromats and truly colour blind

The Logic in Neuropsychology - Neuroimaging: key approaches

You may want to run imagining experiments to see WHERE a certain task/function is localised in the brain Or you may be interested in weather a certain task/condition has a qualitatively different pattern of activation from another condition - REGARDLESS of precisely which areas happen to be activated Some argue this approach is more useful for psychologists because it can tell one whether two experimental conditions rely on the same processes or on qualitatively different processes The same two approaches can also be distinguished in neuropsychology Some research is concerned primarily with localisation This approach is often referred to as classical neuropsychology tradition Other research is primarily concerned with determining the cognitive architecture by identifying behavioural performance that relies on qualitatively similar or on qualitatively different processes, regardless of the exact location of damage This approach is often referred to as a cognitive neuropsychology and it relies on part of the logic of dissociations

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - Neglect Tests

You might get someone for example to cross out symbols on a piece of paper and notice that they only cross out the ones on the right Even if you ask them to describe the street, they live on from one side to the other they will only describe one side of the street and completely ignore the other side, they if you say to then go and stand on the other side, they report the other side of the street and not the one they said before What we learn from that is that most of these occurring right sided parietal injuries here is somehow essential for attention to the left visual field

The Cognitive Neuroscience of Addiction - Neuropathology Cannabis

Yucel et al (2008) - carefully selected long-term (>10 years) heavy (>5 joints daily) cannabis-using men with an average of 19.7 years of use no history of other neurologic/mental health complications, and contrasted them with 16 control subjects Brain volume was reduced in users in the hippocampus and the amygdala

Learning and Memory - Behavioural Models of System Consolidation in Rodents

a. Contextual fear conditioning (classical conditioning of freezing response) - single-trial training can generate life-lasting memory in the same context b. Food preference learning (social conditioning of food preference) Hippocampus lesion causes temporally graded retrograde amnesia Frankland & Bontempi (2005) If the surgery is delayed 14 days after training then the difference seen is still visible, however very late surgery showed that removing the hippocampus would have no effect on the responses and these animals will respond in the same way as non-lesioned animals Similar effect shown in two curves in a different paradigm in which the demonstrator rat exchanges information with the naive rat which will then show preference for the food that the demonstrator has eaten, so this is food preference learning task in which the food preference is conditioned with the help of a demonstrator and therefore is called social conditioning

Genes and Behaviour - Selective Breeding for Behaviour Artificial selection: mice selected for different levels of nest building

control: randomly mated mice Artificial selection experiments create mice that differ strongly in their nesting behaviour Indicative of the heritable basis of the trait

Interpret Results - Limitations of fMRI

fMRI data is correlative; therefore, we can't say that that region activated during a task/function is essential for that task/function. Need converging evidence from TMS/neuropsychology to make stronger inferences about causation Temporal resolution of fMRI is low - Need converging evidence from EEG/TMS to provide finer grained temporal information

fMRI scanner

functional Magnetic Resonance Imaging, with fMRI we use an MRI scanner, the same kind of scanner you would use in hospital to measure brain damage

MRI scanner

originally developed for structural imaging, more recently also used for functional brain imaging

Non-Genetic Variance - Mechanisms of Social Learning 2. Stimulus enhancement

presence/behaviour of demonstrator draws observer's attention to particular object or stimulus which is then generalised to other objects/stimuli in the environment Example: the red observer bird has its attention drawn to the pinecone which makes it more likely to visit this particular pinecone and other pinecones in the environment and once there it may be more likely to acquire that behaviour itself These processes of local and stimulus enhancement are suggested to have been important in the spread of the milk-bottle opening behaviour in the tit species of the UK Example: the naive observer tits have their attention drawn to the milk bottle tops by a demonstrator and some of which may have been opened by the demonstrators, they then travel there, and they gain the reward through that opened bottle top and their attention is then generalized to other milk-bottle tops in the areas and through individual learning learn to peck through the top

Electrophysiological recordings of brain activity Micro-electrode recordings in humans, R. Quian Quiroga et al (2005, Nature)

recorded spike rates of cells in the medial temporal lobe (in and around the Hippocampus in patients undergoing monitoring for surgery, many showed selective responses to a specific item (e.g., face) irresponsive of view, size, etc ... showed them pictures of famous people and pictures of famous buildings, regardless of which angle the person has been photographed at the neurons spike this is a great challenge in photograph technology considering how people recognise faces even if the experience is different such as different angles or lighting it seems that the processing of the brain has successfully deducted everything that is similar between the things and come to the conclusion that it is represented to the activation of that one cell that is that person (e.g., Jennifer Aniston) Some cells that responded to the face also responded to the name of that person, showing that they were not simply coding for visual appearance See that in higher order areas the cells are not only coding for visual field such as colour, but also, they are coding for particular visual information and where it ties into my already existing knowledge, the cell representing the existing knowledge The same worked for famous buildings This pattern of very selective responses was not only seen for faces, but also for other pictures e.g., famous buildings The 'Sydney Opera House' could be used as a name or as a picture and there are cells that would code for both, that's where the knowledge of what that building is or all the things you know about the building come together Every stimulus that comes to you that relates to that thing/person/building activates that cell

Corpus callosum

white matter tracts (numerous axons) connecting the two hemispheres, the electrical impulses that travel from neurons in one hemisphere and reach neurons in the other hemisphere via corpus callosum are referred to as intercallosal transfer, primary function to communicate information from one side of brain to the other

Human Genetic Variation - Genes are pooled in populations after few generations

· Construction of ancestry profiles typically evidence history of interactions between populations not an individual's family history

Human Genetic Variation - Measuring correlations between traits prior to the genomic age Modern Eugenics

· Francis Galton coined the term in 1883, in 1896 he concluded from studying pedigrees of rich families in Britain that 'superior intelligence and abilities" are heritable · Racial segregation was believed to be a necessary mechanism to maintain those in the population · Study of pedigrees of "defective" families (socially deviant, problematic) was widely accepted part of eugenic family studies · Imagery of pedigree chart propelled board misuses in professional sphere to general popular culture

Non-Genetic Variance - Social Learning Why learn from others?

· May be less time-consuming than individual learning · May allow exploitation of new resources e.g., by overcoming neophobia (the fear of novel objects or substances) · May be less risky than individual trial-and-error learning

Non-Genetic Variance - Social Learning So why not learn from others all the time?

· May be more time consuming to wait for conspecific than find out for yourself · Actions of others may be outdated or not relevant to your needs · Individual learning can sometimes yield higher pay-offs

Biology of Stress - The two possible routes out of the resistance stage:

· Recovery = where you were successfully able to deal with that stressor and your physiological systems then return to their baseline homeostatic levels · Exhaustion stage = experience a chronic stress response

Sensory Systems - Combining receptor neurons with different sensitivities

· Sensory systems can combine receptor neurons with different sensitivities (=different thresholds) · This can be useful for extending the range of intensities (e.g., gentle touch to strong pressure) · Graph here refers to summation of receptor signals to measure intensity over a large range (but sensory systems often also compare different receptor signals (subtraction of signals) to differentiate between stimuli) · The combination of these such receptors was low, medium and highly sensitive ranges, which increases the range of stimuli that can be coded so they can now reach from 20 down to close to 0 as compared to the responses of a low threshold neuron alone which would only range from 2-6 on this hypothetical axis · Combining the responses of different types of collocate receptors has the advantage that it is possible to conduct a number of computational operations in order to extract information

Neuroimaging - From raw data to functional brain 'activation' maps 1) Design a task to be used in the scanner

· the scanner is a constrained environment, · subject may have a button box on stomach to respond to task, · may also have an emergency button if they get claustrophobic, also need a screen either at feet or head, need a projector to project images onto screen from outside scan room because there can be no metal inside scan room, · this can project onto mirror above subjects' eyes then directly into their eyes, subject must also remain motionless throughout the scan, scanner is also loud so auditory experiments are limited, · all means we are fairly limited in the tasks we can perform from inside the scanner,

Biology of Stress - What triggers the stress response?

Any stimulus can be a stressor if it is perceived to threaten homeostasis and activates the HPA axis Systemic stressors (actual threats) detected through: - Visceral nociceptors - Somatic nociceptors - Inflammatory signals Stimulation of barocreceotrd or osmoreceptors Neurogenic stressors (anticipated threats) lead to HPA activation in the absence of physiological challenge: - Anticipation/recognition of predators - Dangers associated with the novel environment Most naturally occurring stressors involve a combination of both factors In some animals, the main stressors are interactions with conspecifics E.g., dominance interactions in baboons (Sapolsky, 2005) - Dominant male's testosterone recovered more rapidly after stressful event - Subordinate males display higher levels of circulating cortisol - Dominance behaviour often subtle - threats rather than direct aggression Other subtle stressors: - E.g., begging by meerkat pups (Carlson et al 2006) - Adults' long-term contributions to pup feeding are positively correlated with plasma levels of cortisol - Pup begging both increases plasma cortisol levels and increases pup feeding by male helpers Stressors in modern environment can be difficult to avoid, leading to high rates of chronic stress e.g. - Job related (high pressure, long hours, inconvenient shifts) - Financial worries - Transport (traffic jams, dangerous driving, public transport) - Global pandemic, environmental destruction, racial inequality etc ...

Sensory Systems - Sensory Systems

Are good example to demonstrate main principles how the brain in organised and works: - Many sensory pathways are connected to the brain Sensory signals are typically transmitted in a hierarchy or processing steps - Starts with receptors which are located either in body systems or in sensory organs sometimes involving interneurons - This information then travels to the thalamic nuclei where again that process in different parts of the thalamic nuclei they can be interlinked, it is an important sensory relay station but also it can mediate interactions between different sensory pathways from the primary sensory cortex and from there to higher cortices - The arrangements of different layers and networks in sensory organs and the brain serial connectivity Information is filtered, combined or enhanced as it passes from one layer to the next in a serial fashion - Each layer has networks that are composed of input and output neurons as well as many interneurons

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal Tolerance and Withdrawal

As mentioned earlier, heroin reduced heart rate and blood pressure In heroin users, tolerance results in raising the blood pressure and heart rate When the drug is discontinued, this leads to abnormally high blood pressure and heart rate (as well as insomnia, and other signs of hyperactivity in the central nervous system Thus, withdrawal symptoms are caused by the prior adjustments in the nervous system to combat the effects of a drug when the drug is no longer there This also gives rise to craving, a motivational state akin to hunger, your adapted system is motivating you to see the drug Avoiding withdrawal & cravings are believed to be one of the primary factors promoting addiction

Synapses and Networks - Axon myelinisation with gaps for saltatory transmission of action potentials:

As mentioned, the Schwann cells wrap themselves around the axons, but they leave small areas open known as the Nodes of Ranvier - These Nodes of Ranvier are populated with ion channels, voltage-gated sodium and potassium channels - The neural membrane is exposed at the nodes of Ranvier for ion conductance through voltage-gated channels - Saltatory conduction of action potentials increases transmission speed

Neuroimaging - From raw data to functional brain 'activation' maps 1) Design a task to be used in the scanner FMRI: experimental design

BOLD signal is arbitrary, has no stable baseline The MRI scanner will vary fairly randomly from one day to the next or from one hour to the next in terms of its baseline BOLD signal therefore, the most important aspect of any fMRI experiment is that we have to provide both a) an experimental condition and b) a baseline condition We must perform some comparison between those two conditions then Ultimately brain activation maps represent is the difference in activation between these two conditions Is not pure activation, it's not just measuring overall level of activation, we are always looking at with activation maps is the difference in activation between our experimental condition and our control condition, so these brain activation maps are only as good as the contrast that we perform here

Learning and Memory - Non-dissociative learning: habituation and sensitisation

Best example of non-dissociative learning comes from an invertebrate, the sea slug Aplysia, habituation and sensitisation can be observed when the mantle or the siphon is touches Habituation: response weakens with repeated stimulus presentation due to repetition but not due to adaptation of sense or fatigue. Not an extinction of associations acquired through learning The repeated tactile stimulation of the siphon leads to a reduced gill withdrawal response, the response is reinstated after stimulation by a different stimulus (dishabituation)

Evolution of the Brain - 555 million years ago

Bilateria, bilaterally symmetric, central line of symmetry with left and right side, these organisms separated digestive tract to form mouth and anus to allow more efficient digestion and energy use, sensory organs become concentrated at front end of body, beginnings of brain and muscles to move more efficiently, around same time Cambrian explosion of different body types

Learning and Memory - Brain damage

Brain damage often causes memory loss for earlier events, retrograde amnesia, within a limited time period of hours, days, sometimes up to a year - Patient H.M. (1926-2008), after his death was known by his full name Henry Molaison, had severe epilepsy and underwent a bilateral medial temporal lobotomy - After the operation he suffered from anterograde amnesia, long-term memory loss for new events and newly learned information first reported by Scoville and Milner (1957) - Most of H. M's hippocampus and amygdala, subcortical regions, and the entorhinal cortex was damaged, but some parts probably spared, the Para hippocampal cortex was fully removed - Lost the capacity to form episodic memories, his cognitive abilities were largely preserved for example short term memory and he was able to acquire new motor skills though he couldn't consciously remember doing the task the day before

Brain and Nervous System Structures

Brain divided into brainstem and cerebral hemispheres (cortex of each side, subcortical structures and white matter tracts) Brain stem has all our vital functions in it, keeps you conscious, keeps your heart going and your organs going, also has nuclei producing dopamine etc ... Corpus callosum = white matter tracts (numerous axons) connecting the two hemispheres Grey matter = the outer part of the brain: cerebral cortex, at the level of micro-structure, the cortex is made of bodies of nerve cells-neurons White matter = situated under the grey matter, white matter is made of the long-elongated part of the nerve cells - axon Gyrus (plural gyri): plateau on cortical surface Sulcus (plural sulci): fold/ditch in cortical surface, major sulci are often referred to as fissures Body or soma of a neuron (protrusions are called dendrites): part of the grey matter Axon of a neuron: part of the white matter, axons are covered in a protective layer of myelin, the (white) appearance of white matter comes from the light colour of myelin

Brain takes _______________ from external and internal sources, then communicates with other part of body to ___________________________________ .

Brain takes sensory input from external and internal sources, then communicates with other part of body to guide actions and regulate internal processes

Motor Control - The Neurobiology of Motor Control Brain-Machine Interfaces, Chapin et al (1999)

Brain-machine interfaces = neural prosthetics Chapin et al (1999) - trained rats to press lever for reward, they dropped an electrode array into the rat's brain while they carried out task - They are recording from multiple neurons at the same time whilst the rat carries out this task and while the rat gets rewarded - They then hooked a=up a neural network algorithm that learns about patterns in neuronal activation and allowed it to learn the patterns of activation predicting the different forces exerted on the elver measured multiple neuron responses in motor cortex - However, what they then did is something quite clever and instead of having the reward controlled by the rat's lever press, they then switched the input to reward delivery system from lever to neuronal population vector - Mice eventually stopped pressing the lever as they learn about the lack of precise correlation between force exerted and reward - Mice continued to produce cortical signals necessary for moving the lever - What is happening is the mice are stopping pressing but they are still generating the brain signals that would be associated with those pressing responses and that's still enabling them to receive the reward, this is a kind of rudimentary form of brain-machine interface and these kinds of processes where you teach a pattern classifier to learn about the patterns of neuronal activation associated with a particular movement and you can then use that pattern classifier to interpret the brain/neuronal signals to the control a prosthesis

Examples of when studying brain has helped understand the brain - Memory Example

Brenda Milner (1918) studied temporal lobe amnesia in Patient HM - To treat severe epilepsy at age 27 he received bilateral (both hemispheres), medial temporal lobe resection After surgery the epilepsy was greatly improved but H.M. showed a nearly total, profound amnesia that persisted for his entire life - This part of the brain is apparently incredibly important because if you lose it you suffer anterograde amnesia, inability to form new memories, many people with this kind of injury do remember the past to a degree but they have an inability to form new memories - Similarly, we know that alcohol inhibits hippocampal activation, and we know that if you drink a lot of alcohol you don't remember things very well the next day, this is because the hippocampus has been stopped from formulating new memories and laying down new memories in the longer-term memory tracks Temporal Lobe Amnesia - H.M. had profound anterograde amnesia, he formed almost no new episodic memories following the surgery. Despite years of memory testing experiments, he had no memory of them - H.M. had partial retrograde amnesia; he recalled his early childhood but not the years immediately before the surgery - He could recall early childhood, suggesting that the ability to retrieve memories might have been spared - Working memory was relatively normal, 6 numbers could be remembered with constant, uninterrupted rehearsal - His procedural memory and lexical memory (which support skills such as writing and the memory for words) were close to normal - Clive Wearing: concert pianist who had an infection in his brain, had the same issue, everyday sees his wife but feels he hasn't seen her in 10 years, can't remember what a piano is but if he sits behind one, he can play well, the procedural memory is intact, but his episodic memory and some other forms of memory are disrupted, in particular his ability to form new memories

Examples of when studying brain has helped understand the brain - Language

Broca's area and Wernicke's area Language system in the left hemisphere, language tends to be lateral on the left, in most people not everyone Wernicke's area where a construct of words is chosen, and things are formulated Moves on to Broca's area where you get more the building of the language and the actual sentence, how to organise and pronounce things Then goes on to the motor cortex where the facial area of the brain will then execute this Broca's area and speech: Broca's studied brains of patients who had impaired speech (aphasia), one of his patients was nicknamed 'Tan' for his inability to utter anything other than 'tan', in 1861 through post-mortem autopsy Broca determined that Tan had a lesion caused by syphilis in the left inferior frontal lobe, subsequent research has confirmed that lesions in this area are indeed often the resulting in language impairments Wernicke's aphasia: the ability to comprehend the meaning in words is highly impaired, reading and writing often is as well, they often use sentences but with the wrong words or non-existent words, individual may not have good insight into what is happening and won't realise anything is wrong Wernicke's area is in the temporal lobe, where there is recognition, memory, categories and more language content Broca's area is no longer so much about content but is more about the 'how'

Synaptic Sequence - Cocaine as well as Amphetamine and its derivatives

By increasing dopaminergic transmission, they can induce schizophrenia-like symptoms in high doses So, taking high doses means that sometimes people start to get paranoid, and they start to feel very fearful, at first it seems mostly pleasurable and then as you begin to take more it starts to act like some of the schizophrenia symptoms because your dopamine levels are largely out of balance You either already have too much dopamine or you artificially enhance it with drugs

Synaptic Sequence - Psychoactive substances: some examples Example: coffee?

Caffeine (effective ingredient) - Many of the neurons that release substances like dopamine and adrenaline (catecholamines) also release a self-inhibiting transmitter - adenosine - Adenosine binds to its receptors in the pre-synaptic neuron and inhibits the release of catecholamines - Caffeine competes with adenosine for its receptors (it is an antagonist), blocking adenosine and this reducing its inhibitory effect - However, it does not give you energy, all it does it block the systems that give you the motivation to sleep or to eat which are preparatory or in nature they work in advance of actually running out of energy to prevent you ever actually running out of energy, don't actually give energy they just turn off the other side of the balance - Caffeine also has a non-synaptic effect in neurons It acta on cyclic adenosine monophosphate (cAMP) cAMP controls the energy levels in the cell via the regulation of glucose metabolism - Caffeine inhibits the enzyme that breaks down cAMP, thus increasing glucose metabolism, consuming more energy not giving more energy, cell becomes more active and costumes more energy than it would otherwise

Synapses and Networks - Early theories on brain organisation: diffuse reticular syncytium of neural matter

Camillo Golgi (1843-1926) - histological solver stainings of neurons (bathing tissue in potassium chromate and silver nitrate solution) Santiago Ramón y Cajal (1853-1934) - 'the father of neuroscience', brilliant neuroanatomist and artist who drew the microscopic structures of brains. They shared the Nobel prize in Medicine and Physiology in 1906

Electrophysiological recordings of brain activity When we read words do we access their meaning automatically?

Can we use the ERP to assess whether when we read words is the meaning just instant and automatically retrieved or is there some sort of mental effort involved? Does the brain need time to do this? - Lien et al (2008) used the Psychological Refractory Period (PRP) paradigm: present two tasks in rapid succession - On some trials the interval between the stimuli from the two tasks (SOA) is very short - Task 1: tone task-discriminate between two tones - Task 2: word task-decide if target word is related to context word - We have a fixation screen and then you have the two tasks - You do this and you vary the stimulus onset asynchrony (the time between task 1 and task 2) (SOA), you vary the time between tasks - If the meaning is accessed automatically (does noy require extra attention) the related vs unrelated difference should not be affected by Task 1 (tone discrimination) - If Lien et al's study the related vs unrelated difference was reduced at short SOAs, the N400 is not there which suggests the other task is getting in the way, meaning the second task is completed less well because of the first - When SOA is quite far away it can do the processing because we know that N400 is related to that semantic processing, it has plenty of time you see a strong N400 and you also see shorter reaction times - This means that there is something in the brain to do with potential resources that you need to have available in order to do this task properly, if you give lots of time that is the case however if you don't give lots of time it is not - This suggests that the processing in Task 1 does interfere with the processing of the target meaning in Task 2 - Difference between unrelated and related conditions in one parietal electrode (difference wave)

Synaptic Sequence - Substances can alter how the transmitter interacts with its receptors

Certain substances simply bind to receptors (blocking the way of the neurotransmitter) but without opening the channel E.g., the plant toxin curare in South America occupies acetylcholine's receptors in excitatory (nicotinic) synapses, blocking them and causing paralysis Curare here acts as an antagonist (occupies channel, but does not open it i.e., blocking) Curare is used in surgery as an anaesthetic agent In contrast to antagonists, agonists imitate the behaviour of the neurotransmitter, thus increasing its effect Heroin is an artificially modified form of morphine (contained in opium) Heroin is an agonist of endorphins - natural body chemicals that bind to opiate receptors and reduced pain and induces relaxation So, if you stimulate an endorphin function in the synapse, you get that people feel more relaxed and it reduces pain, hence morphine and heroin both have very strong anti-pain properties because they're agonists of endorphins, they bind to the opiate receptors and act like the endorphins Marijuana (Cannabis) contains THC, an agonist of anandamide - natural body chemical which binds to cannabinoid receptors Anandamide is involved in emotion, pain, appetite and memory Tobacco contains nicotine, which stimulates nicotinic receptors (it is an agonist for acetylcholine) This has a short-lived generalised excitatory effect, e.g., it increases blood adrenaline level Nicotine is a brief acting stimulant

Human Genetic Variation - Big data: new ethical challenges for application and research

Chance for bias in sampling rules or population or categorisation of individuals Expanded precision and tools for genetic inference Ethics and morality: Which traits are healthy or 'normal'? Prediction errors: who is a carrier and who will be affected by a predicted risk under which conditions? How, when and where is this most detailed genetic "fingerprint" of an individual used?

Synaptic Sequence - Psychoactive substances: some examples Example: chocolate?

Chocolate has been found to contain several psychoactive compounds - One of them is anandamide - the neurotransmitter produced naturally by the brain, whose agonist is thc (contained in cannabis) - Another is phenylethylamine - a compound closely related to amphetamine However, chocolate contains these in such small amounts that I would not cause a noticeable effect (e.g., to obtain an effect similar to that of marijuana, one would have to consume half their body weight in chocolate) So why does one become "addicted" to chocolate? This may be down to its taste

Evolution of the Brain - 535 million years ago

Chordates emerged, notochord and tail for movement, neural tube for communication along body and improved means of sending signals, later evolves into spinal cord, which is important for controlling movement,

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - Clinical Neuropsychology

Clinical neuropsychology is the applied clinical variant of neuropsychology They are experts in the behavioural and emotional consequences of brain damage Clinical neuropsychologists assessing the effect of brain damage in patients. Diagnosing neural disorders and helping patients and family adjust. They work in hospitals, care homes and rehabilitation centres Help people with brain damage by helping them understand the environment and understand better what has happened to them

The Cognitive Neuroscience of Addiction - Neuropathology Cocaine

Cocaine addiction is associated with a number of brain damage risks appearing minutes to hours after cocaine consumption, including stroke in young adults in their early thirties, seizures, lesions resulting in movement disorders More subtle pathology includes reduced volume of the inferior portion of the frontal lobe The volume of cell masses is reduced after cocaine use over a prolonged period of time

Synaptic Sequence - Cocaine

Cocaine blocks the transporter of noradrenaline and dopamine, thus interfering with their re-uptake and boosting their effect

Vision - Colour-sensitive P ganglion cells in the retina

Colour-coding P ganglion cells subtract cone signals - S-(L+M) (all mammals) - And in addition, in trichromatic primates and humans also L-M Brightness-coding P ganglion cells sum cone signals - L+M

Sensory Systems - Receptors are diverse in their response properties

Combing slow and fast adapting receptors can help to extract more information about the stimulus, the type of stimulus, the duration of stimulus, and is a way that the brain obtains this information Example: - slow adapting tonic receptors are the Merkel's disc and the Ruffini's ending, fast adapting receptors are the Meissner's corpuscles and the Pacinian corpuscles - they also differ in their receptive field size so that you have 4 types of receptors collocated in the same area of the skin that code for very different aspects of touch stimuli

The Cognitive Neuroscience of Addiction - Drug taking as self-medication in mental illness Cause and Effect

Comorbidity between drug dependence and mental illness does not clarify the direction of causality Drug use could cause mental illness through neurotoxicity Mental illness could cause drug dependence through self-medication Both causal mechanisms might exist and be reciprocal

Hormones and Behaviour - Pair Bonding

Comparative studies have looked at differences between the prairie and meadow voles, the have very different mating systems Prairie vole - Microtus ochrogaster - Monogamous (male mates with one female) - Oxytocin injections promote pair bonding - Dense collection of vasopressin receptors (vasopressin = OT analogue) Meadow vole - Microtus pennsylvanicus - Polygynous (male mates with multiple females) - No pair-bonding - Few vasopressin receptors There is a link here between the behaviour that they show in pair bonding and their physiological density of these hormone receptors

Hormone Structure and Action - Protein hormones

Composed of a chain of amino acids Peptide hormones have a short chain compared to protein hormones Well-known protein hormones include: - Oxytocin, vasopressin and prolactin related to social bonding and parental care - Insulin and glucagon are related to the metabolism - Growth hormone (GH) - Thyroid-stimulating hormone (TSH) - Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) which are related to the female oestrous cycle - Releasing hormones, incl. Corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH)

Examples of when studying brain has helped understand the brain - Connectivity

Corpus callosum is the bridge between the two brain hemispheres, the white matter tracts (numerous axons) connecting the hemisphere Split Brain Research Roger Sperry (1913-1994) American neuropsychologist and Winner of the Nobel Prize in medicine in 1981 for his research with Gazzaniga in split-brain patients Michael Gazzaniga (1939) American neuropsychologist student and collaborator of Sperry Did some experiments with people whose corpus callosum has been severed, known as a callosotomy, the cutting through or severing of the Corpus callosum to limit the spread of epileptic activity from one brain hemisphere to the other This is fairly radical however epilepsy is very debilitating, and this procedure would severely reduce the symptoms of epilepsy in the individual, it also gives the opportunity for investigation into what happens when the corpus callosum is severed Example: show a horse in the left visual field, the left visual field is processed by the right hemisphere and the right visual field is processed by the left hemisphere, left hemisphere is dominating language and the right hemisphere doesn't really have much language ability, someone with a split brain cannot answer the question 'what is that' with the horse in the left visual field because the brain in the right hemisphere does not have access to language skills to produce that answer, but if you then let them draw something with their left hand to answer the question (something non-verbal) then they might draw something like a saddle, the brain has recognised the horse, the right motor cortex can do something visual and can create a drawing like that with the left arm but it can't produce language You can also do experiments where you put a part of the brain to sleep and not the other part for the brain, this is more where you are manipulating the brain in a reversible way rather than using surgery, The Wada Test where you use some chemicals to put the left side of the brain in a sleeping state, reversible numbing of the left hemisphere via a sodium amytal injection, then present a spoon to the left hand (left hand controlled by right hemisphere) the right hemisphere will know it's a spoon, if you ask these people what did I give you they cannot answer the question because the left language side of the brain is asleep so brain can't access that ability, however if you showed a picture to the left visual field (the right active brain area) they can point out what it is they just felt Split-brain studies and Wada test studies have shown that the linguistic competence of the right hemisphere is very limited However, this is not necessarily true for all people, you do get patients such as stroke patients for example, who have damage to the right hemisphere and actually have an aphasia of some sort, it does happen, this is because in some people the lateralisation between the hemispheres is not as distinct Another form of connectivity problem is Contusion and frontal lobe disorder, brain damage as a consequence of a blow to the head, severe axonal damage and frontal cell damage, swelling and bleeding, symptoms include: Disorientation, memory loss, disinhibition, problems with emotional regulation, planning problems/goal directed behaviour, highly distractible

Neuroimaging - From raw data to functional brain 'activation' maps 3. Pre-process the data

Correcting for non-task-related variability in experimental data, getting rid of the 'noise'

Human Genetic Variation - Skin colour variation highest in Africa

Correlation with UV-levels suggests adaptive selection for lighter skin when modern humans migrated to high latitudes Studies of the genetics in skin pigmentation mainly in European populations focussing on the derived alleles strongly affected by selection for lighter skin in low ultraviolet radiation (UVR) regions This had led to the mistaken idea that only a small number of genes has large effects on skin pigmentation. Research of skin colour variation in Africans has identified novel and canonical pigmentation genes Spectrophotometry to determine melanin levels more accurately from upper underarm area (unexposed to sun) San of South Africa who have the oldest genetic lineages in Africa have very lightly pigmented skin

Brain Anatomy and Localisation of Function

Cortex also divided into different lobes e.g., frontal, temporal, parietal, occipital, this is because there are major sulci between those areas (e.g., central sulcus/fissure of Rolando, parieto-occipital sulcus, Sylvian or lateral fissure) Cerebral hemisphere is divided into 4 lobes, separated by 3 major sulci: the central, lateral and parietal-occipital lobe Major gyri, superior, medial and inferior temporal gyrus or superior, medial and inferior frontal gyrus Coordinates and orientations, Superior (dorsal), Anterior (Rostral), Posterior (Caudal) and Inferior (Ventral), medial superior, lateral (left/right), medial inferior, orientation of slices

Functions of brain - The Brain

Cortex covers most of the surface of the brain - Ridges = gyrus - fold/valley = sulcus Beneath the cortex there are many brain regions with a variety of functions

Sensory Systems - Experience-dependent plastic reorganisation of cortical maps

Cortical representations can change with use - Owl monkey trained for several months at task using fingers 2-4, before the training the researchers record the individual mapping of each digit in the somatosensory cortex - After several, months they remeasured these mapping and they found that the areas were increase for the digit 2 and 4 that were trained, and a reduction in the areas for the 5th digit that was used less, there was a slight increase for the thumb and 3rd digit even though it was not trained - This is because the completion of the task required more refined movements from digit 2 and 4 but also digits 1 and 3 were moved more frequently in combination with 2 and 4, whereas the 5th digit was not used at all and so area was reduced because of lack of use - When some body parts are used more than others the brain can reorganise these maps Experience-dependent plastic reorganisation of cortical maps - Used MRI to measure the somatotopic maps for the digits of the right and left hand in strong players and in controls - They measured the distance between areas that were activated when the 5th digit was moved and plotted it for the left hand and the right hand - You can see in the graph that string players had longer distances as one would expect because in string playing it is the left hand where the fingers are moved frequently and have to be placed accurately, as compared to controls - The right hand in contrast overlapped very strongly, there were some control individuals that had quite large separation between the 1st and 5th digit as can be seen, some strong players had larger distances but there were also others that had shorter distances, so overall there is some variation with more distances observed in the left-hand side - The activation of the areas of the 5th finger is particularly prominent in players that started playing strings at a young age, there may be a relationship between the age at which one began musical practice and the relative strength of activation for that 5th digit - When the body part is lost such as after amputation the area of the somatosensory cortex is preoccupied by other typically adjacent brain areas e.g. hand amputation leads to reorganisation where the brain will allocate a large areas to processing information coming from face

Human Genetic Variation - Why decolonizes psychology?

Critical questions - Eurocentric views - Application of western theories cross-culturally - Number of citation in first/last authorship, conducted and taught research and staff involved in research, education and professional training

Hormones and Behaviour - Reproductive Behaviour Mammalian oestrous cycle

Cyclic patterns of gonadotropin secretion (FSH, LH), present only in females, prompted by surge in GnRH (from hypothalamus) above tonic levels In response to GnRH the anterior pituitary gland is releasing FSH which stimulates growth and development of follicle containing females' egg, and as this grows and developed, we see riding oestrogen levels There's a second hormone luteinising hormone which causes the follicle to rupture and release the egg, which is referred to as ovulation, the leftover part of the follicle becomes the corpus luteum that releases progesterone, this prepares the wall of the uterus for successful implantation of the egg Pro-oestrus: follicular development and ovulation Oestrus: receptive period during which fertilisation is most likely to lead to pregnancy E.g., in female candis they have a blood-stained discharge from the vulva that changes to a straw-coloured one which attracts males E.g., female cats at night, roll and treat the carpet and stand firm when pressure is placed on the pelvic region (lordosis response) E.g., rats show the lordosis response when in oestrus, mount other females and are more active than normal E.g., many primates have conscious sexual swellings often occurring when female is in oestrus phase

Neuroimaging - Preprocessing Steps 3 - Slice Time Correction

Data in the fMRI is collected in slices, the top slice collected first and then over 2-3 seconds the remaining slices are collected This means a slice towards the top of the brain will be acquired around 1.5 seconds before a slice at the bottom of the brain, there's a discrepancy in the timing If we want to relate brain activation at particular points back to particular trials or particular portion of the trials with some accuracy, we need to know more precisely which slice is collected when In the temporal plane we can then to correct this just move those slices back into alignment temporarily, perform a simple temporal correction on the data to make sure that those slices are aligned temperately

Learning and Memory - Memory Requires both Cortical and Subcortical Brain Regions:

Declarative memories, memories about facts, information, knowing what something is or an event that happened, general knowledge, but also how events or facts relate in terms of familiarity and knowing that some events in the past happened to you Facts and events can be learned, memorised and recalled, we have seen examples that the medial temporal lobes are important, particularly the hippocampus but also other adjacent areas such as the mamillary bodies (patient N.A. and Korsakoff syndrome) The other type of memories are non-declarative or procedural memories, these are memories of how, how do you do something, how do you respond to a situation Learning: process of acquiring new information Memory: ability to store and retrieve information Learning processes are divided into two different forms of how a subject is exposed to stimuli, how often and which time intervals, and whether it interacts with the stimuli or it is a passive exposure One example of passive exposure learning during passive exposure is priming, priming occurs when the subject is exposed to a stimulus and they respond much faster to the same or very similar stimulus Non-declarative: - Priming = neocortex - Non-associative = reflex pathways - Procedural = striatum Classical conditioning = emotional (amygdala) and somatic (cerebellum) We first look at non-associative learning and in humans it's the startle response that can be conditioned, it involves the brain stem and some parts of the cerebellum

Genes and Behaviour - To what extent is behaviour transmitted by genes? Burrow structure in Peromyscus mice, Weber et al (2013)

Deer mouse (P. maniculatus) = lives in grassy/forest habitat, builds burrows with short entrance tunnel and no escape tunnel Oldfield mouse (P. polionotus) = lives in open habitats (beaches, fields), builds burrows with long entrance tunnel and escape tunnel Some animals build an escape tunnel which doesn't quite reach the surface but if an animal that presents a threat such as a snake enters then it can escape out the back door and burst through to the surface This escape tunnel is a key difference between these two species of mice, the oldfield mouse includes an escape tunnel because its more at risk from predation in its open habitat Captive-reared mice placed in sand-filled arena for first time, builds a species-typical burrow e.g., maniculatus did not build an escape tunnel but polionotus all built escape tunnel Interested particularly in captive reared mice because they wouldn't have had experience building any type of burrows in the wild F1 OFFSPRING of maniculatus x polionotus = hybrid, among those 100% of them build the escape tunnels (following behaviour of polionotus parent) Backcrossed F1 hybrid x maniculatus (¾ genetic material from maniculatus and ¼ from polionotus) and among this half of them build escape tunnels and half didn't This is really useful because this tells us about the genetic basis of the trait, suggests that this behaviour is controlled by a fairly simple genetic basis of a single dominant locus controlling building of escape tunnel

Non-Genetic Variance - Social Learning Example: Social transmission of food preference in rats Galef & Wigmore (1983)

Demonstrator rat is exposed to particular type of food, in this case chocolate, and another demonstrator rat is given cinnamon flavoured food Then naive observer rats not exposed to either food type is then allowed to interact with this demonstrator (chocolate), and when you remove the demonstrator then give the observers the chance to choose between cinnamon and chocolate flavoured food, they will then choose the chocolate You could do the reverse experiment where you expose the observers to the cinnamon experienced demonstrator, and they will show a preference to cinnamon flavoured food To the preference is really passed on from the demonstrator individual to the observers which happens through the odour that they can detect on the demonstrator rat's breath

Synapses and Networks - Signal transmission involves mostly chemical synapses Signal transmission within a spiking neuron

Depolarisation (graded potential before reaching threshold) when the neuron is excited (received signal) Action potentials (spikes) are generated in the integration zone if depolarisation reaches threshold, signal transmission inside neuron Signal transmission to next neuron starts when action potentials reach the output zone and neurotransmitter is released (chemical synapse) Signal transmission is accomplished if a graded potential in the input zone of the postsynaptic neuron is elicited Serial electron microscopy reconstruction of axonal inputs (various colours) onto a small segment of the apical dendrite.

Synaptic Sequence - Depression

Depression is associated with reduced monoamine (serotonin, dopamine, noradrenaline) transmission MAO inhibitors: interfere with the enzyme MAO, which breaks down serotonin, dopamine and noradrenaline Tricyclic Antidepressants: inhibit the transporter of serotonin, dopamine and noradrenaline (prevent reuptake), same effect you get an increase in serotonin, dopamine and noradrenaline leading to quite a substantial effect in reducing anxiety and depression but also with a lot of side effects

Hormone Structure and Action - Steroid hormones

Derived from cholesterol Made from four interconnected carbon rings Soluble in lipids/fats Well-known hormones - Oestrogen, progestins and androgens (e.g., testosterone) are sex hormones - Glucocorticoids which are stress hormones

Vision - What is vision?

Detecting and interpreting patterns of electromagnetic radiation - Image-forming eye and visual pathways - Visible light is a part of the electromagnetic radiation that is emitted by the sun, it is characterised by its wavelengths between 400-700 nanometres - Between 300-400 nanometres there is ultraviolet light that is filtered out by our lens in the eye, our short wavelength receptors are sensitive to ultraviolet, but it is filtered out by our eye in particular the lens - That leaves us with a visible spectrum between 400-700 nanometres, beyond 700 nanometres we have infrared which we perceive as heat, one cannot see infrared rays, but some animals can reconstruct spatial images from infrared sensations - The wavelength range in which visual systems are based on opposite ends of the photopigments pick up light between the ultraviolet and the visible light spectrum - One task of the visual system is to detect differences in wavelengths in the spectral composition of the light that is emitted by the sun and then reflected from objects in a particular pattern and that is why we perceive object as being for example blue or red colour - The other task is to detect differences in intensity or what we call brightness differences, this is shown that the daylight intensity varies a lot between the photopic phase, the mesotopic phase and scotopic phase in the night, and our eye is able to deal with this huge range of light intensities that change over the days and nights Within that each object will reflect in a different and particular way the light intensities so that there is colour but there is also light intensity and its part of the information that the eye detects and discriminates

Sex Differences - Sex Differences in the Brain Sexually Dimorphic Brain Structures

E.g., in songbird, song control region in zebra finches, it is 5-6x larger in males than in females, the male does nearly all the singing, and it gets bigger in females given supplementary testosterone as hatchlings E.g., rat hypothalamus: sexually dimorphic nucleus of pre-optic area (SDN-POA), smaller in males castrated at birth, bigger in females given testosterone at birth, no effect of castration/testosterone treatment in adults

Electrophysiological recordings of brain activity EEG: strengths and weaknesses

EEG/ERP has high temporal resolution: it can provide detailed temporal information about the processing of a stimulus The time-course of a particular component (peak) in the ERP along with it scalp topography (map) can be seen as a spatio-temporal 'signature' of a certain process or set of processes However, it has limited spatial resolution (it cannot localise activity in the brain with precision or confidence), due to the complexity of the inverse problem

Electrophysiological recordings of brain activity ERP Components

ERP components: features in the waveform (e.g., peaks) - Labelled by order (P1 - first positive peak) or latency (P100-positive, at 100ms after stimulus) - The size (amplitude) of these peaks is related to stimuli/tasks (e.g., P1 and N1 reflect perceptual analysis and attention; P3 is associated with a decision about the stimulus etc...)

Electrophysiological recordings of brain activity Event-Related Potentials (ERPs)

ERPs as a way of analysing EEG - ERP refers to a methodology of analysing EEG recordings by extracting from the EEG segments time-locked to specific "events" (stimuli or responses) that were recorded by the EEG when a particular thing happens - Analysing the part of the EEG hat relates to something being presented to participant or they had to do a particular task, processing that particular stimulus It is those parts of the raw EEG that are tied in time to a particular event - What happens to the EEG pattern when I give a particular stimulus?

Synapses and Networks - Neurons can collect information from few to hundreds of other neurons. When and which signal is picked up by a neuron depends on the:

Each neuron forms many synapses: - Type of neurotransmitter - Duration of neurotransmitter release

The Cognitive Neuroscience of Addiction - Causes of Addiction

Effects of drug-related cues - cue reactivity Effects of drug tolerance and withdrawal The drugs influence on processing of rewards (pleasure and incentives (motivation)) Drug taking as self-medication in mental illness A vast amount of research has been carried out into the causes of addiction to drugs of abuse it is clear by now is that there is large inter-individual variability in susceptibility to addiction About 10-20% of individuals who regularly use drugs of abuse become addicted to them; the precise figures vary depending on the specific drug Similar estimates have been drawn from research on animal (rat and mouse) models of addiction: a similar percentage of animals who are systemically administered potent drugs end up preferring them to sucrose It is estimated that the genetic contribution to addiction is about 50%, genetic predisposition to being addicted

Learning and Memory - Neural Plasticity: from behaviour to genes What can change in the postsynaptic neuron?

Evidence provided by studies investigating the mechanisms of associative (classical and operant conditioning) and spatial learning There can also be changes in the postsynaptic neuron where its dendritic membrane becomes more sensitive and has more receptors so that the same amount of neurotransmitter without changes in the presynaptic cell can lead to a stronger postsynaptic potential It is also possible that at some synapses both pre and postsynaptic cell change, you can have presynaptic processes leading to more neurotransmitter release and that the postsynaptic neuron membrane is more sensitive, has more reports or activates more different receptors These changes in the postsynaptic neuron have been mainly studies in experiments that involve associative learning, classical/operant conditioning and spatial learning

Non-Genetic Variance - Social learning can lead to: Horizontal transmission

Example: e.g., birdsong between territorial neighbours in song sparrows, Melospiza melodia This allows non-genetic transmission to occur much more widely and more rapidly than could be achieved through purely genetic transmission Two territorial neighbours have very different song types but there are also many similarities between then because to a certain extent they begin to copy each other's song elements and incorporate elements of each other's songs There are still some differences, but also a great deal of similarity, so two territorial neighbours will be much more similar in their song types than two birds who are much further apart They don't produce an exact copy of behaviour and there are some errors which could be thought of as non-genetic mutations that generate variation, so here you see some of the non-shared song elements

Non-Genetic Variance - Social learning can lead to: Vertical transmission

Example: e.g., birdsong from father to son in zebra finch, Taeniopygia guttata Wilbrecht et al (2002) In songbirds it is the males who do most of the singing, and male birds learn the song by listening to their father If you look at sonograms there are very strong similarities between father and sons' songs, however this could also be expected if there were genetic transmissions Non-genetic transmission can mimic genetic transmission However, we known that this is not genetic transmission in this case because of experiments where they have surgically deafened a particular male, so he is unable to hear father's song, and then you don't see any resemblance between the two birds' songs The underlying mechanisms that allow the learning to take place are strongly influenced by the genes that the individual has but the particular song type ale produces is something acquired by learning rather than transmission

Synapses and Networks - Neurotransmitters are synthesised and stored in vesicles in a neuron's output zone Ionotropic receptors (fast, signal transmission)

Examples: - Amins: Acetylcholine (nicotine, nACH receptors, serotonin (5-HT) - Amino acids: glutamate (e.g., NMDA and AMPA receptors), gamma-aminobutyric acid (GABA A), glycine, aspartate

Synapses and Networks - Neurotransmitters are synthesised and stored in vesicles in a neuron's output zone Metabotropic receptors (slow, long-lasting, more varied effects, neuronal modulation)

Examples: - Amins: acetylcholine (muscarinic), dopamine, norepinephrine, serotonin, octopamine. - Amino acids: glutamate, GABA B, glycine - Neuroactive peptides: vasopressin (also known as antidiuretic hormone ADH), oxytocin - Higher vasopressin receptor densities in the prairie vole are linked to its unusual monogamic behaviour as compared to polygamic vole species (Winslow et al 1993, Nature)

Neurons - A second pair of electrodes added generating electric currents (I) to excite the neuron

Experimental manipulations to determine which ion movements contribute to the generation of the neural signal. The strength and direction of stimulus current (I, milliAmper) with the second pair of electrodes was varied (tip of sharp electrodes is filled with a conducting fluid, for example KCI) At the same time, they measured the membrane potential with the first pair of electrodes (V,milliVolt) In other experiments they manipulated the concentration of ions in the saline bath and observed how the membrane potential changed.

Non-Genetic Variance - Non-genetic inheritance

Factors in one individual influence the behaviour or development of another individual (without passing on genes) who, in turn, may pass on these influences on another ... Vertical vs horizontal transmission Mechanism of non-genetic inheritance - Maternal effects - Social learning - Symbolic representation Genetic vs non-genetic transmission of behaviour

Motor Control - The Neurobiology of Motor Control Treating Parkinson's Disease

First line treatment for Parkinson's Disease in Levodopa (L-dopa), a dopamine precursor - Crosses the blood-brain barrier, enters the CNS and is converted into dopamine - Effective up to a point but people tend to adapt to it over time - Does also have side-effects, interesting and problematic, associated with compulsive behaviour More recently, researcher have investigated effects of deep brain stimulation (DBS) on Parkinson's disease - Little electrical stimulation pack patients can turn on when feeling symptoms and this can have dramatic effects

Evolution of the Brain - 225 million year ago

First mammals emerged, differentiated teeth, different teeth for different purposes, e.g. Molars, diversification reflects dietary differences, allows even more efficient digestion but needs fine motor control, early mammals had big development of motor cortex to control fine movement, further development of sensory systems e.g. whiskers, improved hearing with additional bones in ear to connect ear drum to membranes, extended parental care where offspring stay and learn from parents, cortex changes

Vision - Retina is a complex neuropile with many circuits

First stage of visual pathway: photoreceptors and retinal neurons - Retina performs first filtering and decomposition of scene, codes local and global contrasts and enhances features such as edges - Lateral inhibition and vertical+horizontal connectivity from circuits for these tasks - These early pre-processing circuits (e.g. centre-surround receptive fields) help to separate the coding of visual features in parallel streams within the visual pathway - We do not notice these processes but, paradoxically, with some effort (creating visual illusions) we can become aware of these otherwise effortless (because automated) processes.

Hormone Structure and Action - Transmission of endocrine signals

First, we have some stimulus acting on an endocrine cell, this could be a nervous signal, a neurotransmitter released by a neuron, or it could be a releasing hormone released from one of these neuroendocrine cells This induces the endocrine cell to release hormones into the bloodstream which travels widely around the body and contracts target cells anywhere in the body Those target cells have the receptor for that hormone and will then respond, so the action of hormones is really determined by the type of receptors that the target cells have

The Cognitive Neuroscience of Addiction - The drugs' influence on processing of rewards (pleasure and incentives (motivation) Dopamine as 'work motivator'

For example, in one experiment, two groups of rats were trained to press a lever for sugar pellets. Then one group had their dopamine synapses in Nucleus Accumbens disrupted. The experimenters compared food preferences and lever pressing in the two groups after training Rats from both groups preferred the sugar pellets to less tasty food when both foods were freely available However, when the animals had to press the lever, only the healthy rats were willing to work for it, whereas the rats with impaired dopamine transmission were happy to settle for the less tasty food

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal Conditioned compensatory response to alcohol

For example, tolerance to alcohol is based on the desensitisation of GABA receptors where alcohol is an agonist Whilst this has a protective role when alcohol is consumed, when consumption is ceased it leads to imbalance between excitation and inhibition in the brain resulting in psychological and motor agitation characteristic of alcohol withdrawal To prevent excess inhibition, the organism compensates by reducing the sensitivity of GABA receptors in inhibitory synapses and by increasing activity in excitatory synapses

Brain and Nervous System Structures - Brodmann (1868-1918)

Found that cortical regions vary in the detailed cellular structure (types of neurons) and cellular arrangement (number of layers, density), this is referred to as cytoarchitecture Using this criterion Brodmann divided the cortex into a number of areas Many of these areas turned out to serve specific functions e.g., primary visual and auditory cortices, primary motor cortex

Electrophysiological recordings of brain activity - What information can one extract from an EEG? Frequency:

Frequency refers to the number of oscillations per unit of time (e.g., 4 times per second is 4Hz) EEG has a complex pattern of frequencies For example, several frequencies can be notices in the idealised waveform

Vision - Complex structure of vertebrate retina

Functional classes of cells in the retina: - 4 classes of photoreceptors (3 cone types and rods) - 50-70 classes of horizontal, bipolar and amacrine cells - 20-30 classes of ganglion cells First stages of visual processing - Edge detection in visual scenes - Edge enhancement in patterns - Filtering of spatial, wavelength, movement and directional information Amacrine cells that connect between bipolar cells and ganglion cells - We see two types of connection that are vertical serial connections from the photoreceptors with bipolar cell to the ganglion cell, and there are horizontal connections that are not serial but are interconnected between these serial stages - These are the horizontal cells between the photoreceptors in bipolar cells and the amacrine cells between the bipolar and the ganglion cells - There is a very strong conversion observed from the high number of photoreceptors (100 million) approximately a million ganglion cells, so a lot of processing occurs before the information is passed to next level

The Logic in Neuropsychology - What can one infer from the effects of TMS?

Functional-anatomical inference: is cortical area x essential for performing a given task Chronometric (temporal) inference: at what time it does stimulation affect performance relying on a hypothetical psychological process x? Process interaction inference: if disrupting process x increase effectiveness of process, it shows the two processes normally compete

Learning and Memory - Neural Plasticity: from behaviour to genes Continuing the search for the memory engram

Fundamental principles of the cellular and molecular mechanisms underlying learning and memory were uncovered in Aplysia Signals transmitted a few, individually identified sensorimotor synapses control the gill withdrawal response Eric Kandel and his team dissected the whole neural network that steers the motor neurons of the gill muscles Small number of neurons with their large-sized soma and axons Possible to measure and manipulate neural signals in swindle sensory and motor neurons (pre- and postsynaptic cells of the sensorimotor synapse) during acquisition, memory formation and memory recall

Sex Differences - Phenotypic Puberty

Further organisational effects of hormones at puberty: - Anterior pituitary releases growth hormone, gonadotropic hormone and adrenocorticotropic hormone - These have some important effects, growth hormone acts directly on the bones and tissues to stimulate further growth, gonadotropic hormone acts on the gonads (e.g., testes in males to make testosterone, ovaries in female to initiate cyclic production of follicle stimulating hormone and luteinising hormone together to coordinate the menstrual cycle) - And in both sexes adrenocorticotropic hormone (ACTH) stimulates the adrenal cortex in the outer part of the adrenal glands to release adrenal hormones - Leads to development of secondary sexual characteristics (sexual differences not present at birth) - Ones present at birth are referred to as primary sexual characteristics, secondary sexual characteristics are the differences that develop later on Some secondary characteristics include: acne appears, facial and body hair appears, pubic hair appears, growth spurt occurs etc ...

Genes and Behaviour - To what extent is behaviour transmitted by genes? How do genes contribute to behaviour?

Gene expression acts at different phenotypic levels Expression of a gene can influence: - Expression of other genes - Activity of the cell, other tissues and organs - Developmental processes - Activity of brain, muscles, messenger systems ---> expression of behaviour - environmental influences act on gene expression and or on phenotype - this interaction between genes and environment happens at every stage through this pathway from initial gene expression to behaviour

Biology of Stress - Stages of the Stress Response - Hans Selye (1907-1982)

General Adaptation Syndrome (Selye, 1932) Homeostasis, when our bodies are not exposed to a stressor and are maintaining homeostasis, a steady state and usually bodily processes function in a controlled way The appearance of a stressor upsets that balance and puts us in the stressed state 1) ALARM REACTION The stressor is perceived by the pituitary-adrenal system SAS system prepares body for action: "fight or flight" HPA system releases energy stores 2) RESISTANCE STAGE Body attempts to re-establish physiological balance If stressor persists, stress hormones and arousal remain high Hopefully you can successfully counter stress, if stress is successfully handled by your responses then you've recovered from that threat and re-established homeostasis 3) EXHAUSTION STAGE If you are unable to counter stress and handle the stressor effectively Prolonged stress eventually depletes resources and exhausts body's defences Stress-related illnesses develop

Human Genetic Variation - What's in the DNA?

Genes = 2% protein-coding DNA sequences Non-coding DNA (also known as junk DNA) 98%, functionally important, contributes to complex genetic architectures in which genes are embedded

Genes and Behaviour -

Genes produce proteins, not behaviour But genes can influence behaviour through the effects of those proteins on neurons, hormones, brains, muscles, etc ... The resulting behaviour is affected by the environmental conditions in which it develops (gene x environment interaction)

Sex Differences - Sexual Differentiation Genotypic

Genetic Basis of Sex Differentiation - DNA is present in the nucleus of every cell, expect red blood cells (anucleate) - DNA is packaged up into chromosomes/units of genetic material - Sex is fundamentally initially determined at the start of your life genetically - Diploid human cells contain 46 chromosomes (23 matched pairs), 22 pairs of autosomes and 1 single pair of sex chromosomes (XX = FEMALES, XY = MALES) - Gametes are haploid: just one copy of each chromosome, in females you get two X chromosome bearing eggs whereas in males you have an X bearing sperm and a Y bearing sperm - Gametes fuse to create diploid offspring when they fuse together, then there are the 4 possible combinations as a result: XY,XX,XX,XY - Then the process will repeat within the next generation - Note that there are many ways of doing this across the animal kingdom, humans have male heterogamety, whereas in birds they have female heterogamety, in some fish you have polygenic sex determination, there are some organisms where sex is determined by temperature, some fish have sequential hermaphroditism - So, the sex of the offspring is determined by the male's gametes (sperm), whether it is an X bearing sperm or a Y bearing sperm that fertilises the egg, this comes down to a certain region of the Y chromosome which is referred to as the sex determining region SRY (sex determining region Y) genes, also known as the tests determining factor (TDF) gene - The differentiation then starts in the very first few weeks of pregnancy, beginning right at the start, and is associated with the function of this particular gene, due to those genetic instructions received from the gametes fusing to create that offspring

Human Genetic Variation - Genetic Variation and Health

Genetic and epigenetic changes in different environments and admixture in human populations explains patterns of susceptibility to human pathologies Health conditions can impact on capacity of individuals to respond to health threats that arise from fastly evolving microorganisms and viruses Given the expanded life span, aging processes have a yet poorly understood impact on cognition and mental disorders that can involve different susceptibilities based on the genetic signatures in individuals Drive towards personalised medicine based on genetic profiling which possible due to modern technologies that are becoming cheaper and widely accessible The recent Covid-19 pandemic has shown that the prevalence of different chronic health conditions varies with a number of factors that are correlated with race as a social construct, and therefore certain individuals are more adversely affected by covid e.g., black or Asian minorities

Vision - Visual pathways: projections from the retina to other brain areas

Geniculate-striate pathway: Retina - LGN (lateral geniculate nucleus) of the thalamus - VI (primary visual cortex) - areas of the higher visual cortex (90% of retinal projections), VI required for conscious visual experiences Extrageniculate pathways - For example: retina - superior colliculus (SC) - several projections to areas of the higher visual cortex and the pulvinar nucleus of the thalamus (eye movement control and visual attention) (10% of retinal projections) - Accordingly, the axons of the ganglion cells that are located in the basal area of both eyes have to cross over forming this optic chiasm, just behind the optic chiasm is the SCN which regulates sleep wake cycles - Further down are the superior and pulvinar nucleus which are important for controlling automatic processing of visual attention and eye movement, they don't require direct control by the cortex, but it can modulate eye movement - Another important layer is the lateral geniculate nucleus which is first relay station to which the axons of the ganglion cells project the projections between the retina and the LGN to form the optic nerve - From the LGN these signals again, spiking interneurons which travel to the visual cortex over long distance

Hormones and Behaviour - Eating

Ghrelin - 20-amino-acid peptide secreted by cells in stomach epithelium - Stimulates feeding - Stimulates release of growth hormone (GH) from pituitary - Ghrelin-secreting neurons in the brain involved in control of feeding Ghrelin is a powerful appetite stimulant - Circulating levels: rise prior to mealtimes and at night, drop following a meal - Treatment of people with exogenous ghrelin provokes increased appetite Obese people - Have lower ghrelin before eating But following a meal their levels do not drop - A ghrelin system unresponsive to feeding and therefore always hungry has been suggested

Vision - Disproportionate large foveal projection area in VI

Given the higher density of cones in VI (higher acuity), more processing power is required for information originating from the fovea Foveal magnification in the primary visual cortex because the densely packed receptors here processed a lot of information that's requires a lot of processing neurons in this part of the brain

Hormones and Behaviour - Social Behaviour in Humans Social Effects of Oxytocin in Humans, Bartz et al (2011)

Gives a nice overview of the studies in humans that have use exogenous oxytocin administration, giving a dose of extra oxytocin to people and investigating how that affects their behaviour and cognition as well as psychological mechanisms underlying it

Sex Differences - Sexual Differentiation Gonadal

Gonadal Sexual Differentiation - In the very early part of development (in the first 6 weeks or so of gestation) the gonads look very much the same in male and female individuals, known as undifferentiated or primordial Mullerian Ducts and the Wolffian Ducts - From 6 weeks or so after conception we then begin to see the gonads starting to differentiate Within the primordial gonad they don't have a Y chromosome and so in that citation the cortex/outer part develops into an ovary - Whereas in male individuals, the Y chromosome causes the medulla to develop into testes - This happens because of the SRY gene which produces SRY protein which causes these initial changes So, the undifferentiated gonad in females develops into an ovary which happens in the absence of SRY proteins, there is no Y chromosome therefore not SRY gene so no SRY protein In the absence of SRY protein, the gonad just develops into its default state, which is to become an ovary, females are default sex In males there is the presence of a Y chromosome and therefore the SRY genes and SRY proteins which causes a different pattern of development, leading the primordial gonad to become a testis - This sets of a chain of events that usually in the vast majority of individuals results in either a female or male individual

Neurons - Signals differ in the input and conduction zones of the neuron

Graded potentials are generated in the soma and dendrites and travel towards the integration zone Action potentials are generated at the integration zone and travel along the axon to the axonal terminals

Hormone Structure and Action - Hormones Acting Within the Body Long-term effects

Growth hormone (GH or somatotropin): regulation of bone growth - Involves the hypothalamus and the anterior pituitary - Releasing hormone somatocrinin which then stimulates the anterior pituitary to release growth hormone and growth hormone affects bone growth - Sleep is a very important stimulus for this, when you sleep that stimulates further release of somatocrinin and therefore growth hormone and leads to enhanced bone growth - However, under conditions of stress or overexercise there is inhibition of that same pathway to somatocrinin release, inhibited growth hormone release and then inhibited or retarded bone growth as a result - These are much longer-term effects than the short-term milk letdown reflex - Long-term effects can be reversed e.g., psychosocial dwarfism, where a child is put into a very stressful situation has reduced bone growth as a result, but when they are removed from the situation there are periods of accelerated growth to catch up

The Logic in Neuropsychology - Double Dissociation

Hanley (1994) identified a patient who made more spelling errors in consonants than vowels - The existence of such opposite patterns if referred to as double dissociation - A double dissociation is hard to explain as a quantitative different, where one type of item (here vowels or consonants) is generally more resilient to the effects of damage - This really suggests that that there is a qualitative difference in the way those two letter types are being processed

Hormone Structure and Action - Thyroid Gland Cross-Section

Has a characteristic structure, arrangement of follicular cells surrounding the central space the lumen, also has tiny blood vessels known as capillaries which have walls only 1 cell thick This gland is richly permeated with many tiny blood cells meaning it is perfect for getting hormones into the bloodstream The follicular cells secrete the hormone into the central space, the lumen, from there the hormone crosses the thin wall of the capillary into the bloodstream to the rest of the body A feature of the endocrine gland is they are so-called ductless, they are passing directly across the cellular space into the bloodstream. This is in contrast to the other main type of gland, the exocrine glands, which have ducts that carry the produced substance onto the particular body surface An example of an exocrine gland is things such as sweat glands and salivary glands and tear ducts where substances are secreted directly onto the surface of the body In the case of endocrine glands, it is very different because the substance produced/the hormone passes from cells into the bloodstream and flows around the body into the bloodstream

Learning and Memory - Reconsolidation of memories

Have looked at memories from coding stage through to consolidation stage, during consolidation memories can be disrupted After the end of consolidation when the memories are activated again or recalled, and the animal performs the learned task, the memory undergoes a transformation and becomes unstable and needs to be consolidated again, during reconsolidation it can be altered again or updated In the unstable state memories can be degraded or strengthened but also modified (e.g., false memories) Behavioural modifiers = interference, extinction Pharmacology: e.g., protein-synthesis blockers NIBS: non-invasive brain stimulation techniques (e.g., rTMS)

Examples of when studying brain has helped understand the brain - Attention Example:

Hemi spatial neglect, inattention to parts of the visual field, they can see everything however they just don't attend to parts of the visual field, this can be slightly or a lot of the visual field, affects up to ⅔ of right hemispheric stroke patients, can differ from very mild to almost complete, can strongly affect one's independence, crucially different from blindness and cortical blindness Patient may be given a plate of food and only eat half of it, then you turn the plate around and they aren't surprised because they have seen the food, they just haven't attended to it and then they will eat the rest If you come up to someone and come into the neglected area and speak, instead of turning straight towards they will turn all the other way around This can be incredibly debilitating because if you know you are blind in one of your visual field then you begin compensating, reading also becomes incredibly difficult because you may begin mid-sentence, it is difficult for people to compensate for this because they don't know what is wrong

Neuroimaging - Preprocessing Steps 2 - Motion correction

Here we have to correct for head motion movement in the scanner It is important subjects stay as still as possible in the scanner; this is difficult to do however May move for a variety of reasons, falling asleep and waking up, speaking over intercom, being told not to move so they tense up, head motion is inevitable We can keep track of this head motion; however, we can get an output using six different parameters how the head has moved within the scanner Using these 6 parameters we can get a precise estimate of the head position at any point in time and whether it's drifted over time Occasionally we have to throw out data from participants who have moved their heads too much over the course of the scan, this depends sometimes on which part of the brain you are interested in whether it is a precise area or not For subjects that don't move their heads too much we can codirect their head motion, all we do is take each volume and move it back into alignment with the original volume, this is not done manually it is done using an algorithm

Genes and Behaviour - To what extent is behaviour transmitted by genes? Artificial selection on heritable traits

Heritability is a useful measure because it gives an indication of how a trait is likely to respond to selection

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal This can lead to overdose

Heroin tends to suppress activity in the central nervous system It also has other strong effects: it reduced heart rate, respiration rate and blood pressure Because heroin reduces heart rate, blood pressure, etc ... the organism learns to compensate by raising the heart rate, blood pressure etc ... - a conditioned compensatory response In the absence of this response, the effect of the drug is stronger hence the potential for overdose If you use heroin in a new environment, the CSs that has elicited the conditioned compensatory response to heroin is removed If you go to a different environment then you don't have a compensatory response and you have a much higher risk of overdose because you are now somewhere else, you take the dosage you are used to taking at home, but your body is not used to it The lack of a conditioned compensatory response to heroin means that the effect of morphine (lowering heart rate and blood pressure) is stronger which can lead to heroin overdose

The Cognitive Neuroscience of Addiction - Neuropathology Heroin

Heroin use is associated with a broad range of neuropathologies including reduction in grey matter, brain hypoxia (reduced oxygen availability), cerebral oedema (water saturation), stroke (loss of blood supply), spongiform leukoencephalopathy (general loss of brain white matter - axons) and myelopathy (paralysis produced by spinal lesions) Red blobs indicate frontal and temporal regions where heroin-dependent individuals have reduced grey after density. The scatterplot shows the correlation between reduction in grey matter density associated with longer duration of heroin use.

Learning and Memory - Neural Plasticity: from behaviour to genes Strongest LTM Effect: Growth of New Dendritic Spines with Synapses

High influx of Ca2+ activates intracellular enzymes, protein kinases. Of those, PKA, PKC and CaMKII (calcium-calmodulin dependent protein kinase II) activates transcription factor CREB (cAMP response element binding protein) CREB targets many genes that are required for growing new dendritic spines and synapses

Synapses and Networks - Signal transformation during synaptic transmission

Hill et al (2008) Animal Physiology - Presynaptic neuron: depolarisation of the axon terminal membrane opens Ca2+ channels and Ca2+ ions enter the terminal - The arrival of an action potential, them causes depolarisation of the membrane, in the axon terminal opens Ca2+ channels - Presynaptic neuron: the increase in Ca2+ concentration stimulates the release of neurotransmitter that is stored in vesicles, when these vesicles fuse with presynaptic membrane the neurotransmitter diffuses into the synaptic cleft - Postsynaptic neuron: the neurotransmitter either crosses the synaptic cleft and interacts with ionotropic receptors that are embedded in the membrane of the dendrite or soma (typically)of the postsynaptic neuron - The arrival of an action potential in the axon terminal opens Ca2+ channels, Ca2+ triggers vesicle fusion and transmitter release, neurotransmitter can bind to ionotropic receptors, opening their ion channels

Learning and Memory - Targeted Lesions in the Medial Temporal Lobe

Hippocampus involved in encoding specific items in context during long-term memory formation Squire & Zola-Morgan (1991) studies reported, and it was shown that when the hippocampus alone is lesioned the animals performed nearly as well as the control group, when the hippocampus lesion is extended to include the entorhinal cortex and parahippocampal cortices there was a substantial impairment, and they were not able to retrieve memories when the hippocampus lesion was extended to include the anterior entorhinal and perirhinal cortices This study suggests the perirhinal cortex important for sense of familiarity and the parahippocampal encodes context representations The hippocampus is important to bind the specific items to context during memory formation

The Logic in Neuropsychology - Single Dissociation

However, at close scrutiny the above single dissociation is not sufficient for drawing the conclusion that there is a qualitative difference between how the mind represents vowels and consonants For instance, it is possible that the same mental computations are used for both, but suppose that consonant letters are easier to differentiate visually from each other than vowel letters This could make consonants more resilient to the effects of brain damage, but would not necessarily demonstrate a qualitative difference in the way they are processed But if consonants are generally more resilient to the effects of brain damage, then one should not find any patients with impaired processing of consonants and relatively spared processing of vowels

Vision - The receptive field of a simple cell in VI (striate cortex)

Hubel and Weisel proposed that simple cells in the orientation columns receive input from several neighbouring retinal ganglion cells They proposed that the different LGN neurons with the same centre-surround receptive field type have an excitatory connection to the simple cortical cell in the orientation column depending on which spatial locations they pick up the resulting bar will be more inclined in one direction or another The spatial arrangement of these receptive fields defines how sensitive this cortical cell will be to a particular orientation They also discovered another type of cell called complex cortical cells which also have a preferred inclination to which they respond more strongly, but differently to the cortical cells it doesn't matter where in the visual field the bar is projected and they would respond always to the orientation, whereas simple cells are also sensitive to the specific location on the retina of the bar Hubel and Weisel proposed that this could result from a larger receptive field where now a number of simple cortical cells converge onto the complex cortical cell, and the model can explain the responses that are position variant, and therefore the complex cell being able to respond to the bar in its preferred orientation in any part of the visual field These recorded responses from cortical neurons could explain how the brain is reconstructing more complex features from the highly decomposed retinal image that is transmitted from the filters spatial and other filters in the retina

Hormones and Behaviour - In humans, ovulation is concealed, or is it?

Human female menstrual cycle the fertile window is when conception is only likely if sperm is present in the reproductive tract when ovulation takes place period leading up to ovulation can lead to physiological changes e.g., lining of uterus these hormones affect behavioural changes Beall & Tracy (2013) where they recruited 124 normally ovulating women aged 17-47 were asked on-line what colour shirt they were wearing each respondent was classified as high or low fertility based on reported time since last period found that in fact among those who were wearing a red or pink coloured short a higher percentage of those were in the high fertility category/higher conception risk a smaller percentage of high conception risk amongst women wearing different shirts so across both the sample there was a very subtle change in behaviour that affects what people decide to wear and what king of colours they decide to dress in in this period of high fertility Miller et al (2007) Recorded tip earning by dancers in lap-dancing club Dancer provided information on their menstrual cycle and use of hormonal contraception Among the dancer who were in the luteal phase of their menstrual cycle the average amount of tip earning was 260 dollars During the fertile phase this increased to 335 dollars And in the subsequent phase, the menstrual phase of the cycle, that went down to 185 dollars These are the amounts seen in normally cycling women whereas those who are taking hormonal contraception did not show that same kind of pattern Interesting evidence that suggested the number of tips for these dancer sis related to their menstrual cycle Could men sense this directly? Did women dance differently when being in different stages of the cycle. Two pieces of evidence suggesting that ovulation in humans may not be completely concealed and does produces some behavioural changes

Synapses and Networks - The neurotransmitter and receptors can either cause a depolarisation (EPSP) or hyperpolarization (IPSP) at the postsynaptic membrane.

If the neurotransmitter is released for a longer time into the synaptic cleft, then the postsynaptic potential is stronger (temporal summation). Suppose two excitatory or two inhibitory synapses are activated at the same time by two different stimuli. If postsynaptic potentials arrive together in the integration they are summed up (spatial summation). Spiking neurons: if the membrane at the integration zone is depolarised above threshold an action potential will be generated. The more excitatory input arrives, the stronger the output signal. At the same integration zone EPSPs and IPSPs that arrive at the same time or within a small-time window are summed up. The more inhibitory input arrives, the weaker the output signal and the neuron may even not transmit any output signal.

Genes and Behaviour - To what extent is behaviour transmitted by genes? Foraging in fruit-fly larvae

If you place fruit fly larvae on a petri dish in a lab with two patches of food (yeast) you notice two very different types of behaviour: Rover = larvae will roam around and happily feed off different yeast patches Sitter = initially placed on one patch of yeast they will just stay there If you place them on a petri dish where there is yeast everywhere, they trace out the path they move in and you can see that the Rover type have a tendency to travel much further than the sitter type, this is a specific behaviour associated with searching for new sources of food And in the wild these types exist also, there is variation in the amount of foraging exploration they do, there is some overlap but there are still two fairly prominent groups, in the wild there is approx. 30% sitter type and 70% rover type What is the genetic basis of this behaviour? This is explored using breeding experiments: Two parents who are both homozygous, the male is homozygous for rover allele and the female is homozygous for sitter alleles F1 OFFSPRING of female sitter x male rover = essentially all the same phenotype ROVER F2 OFFSPRING of female F1 x male F1 = 3:1 phenotypic ratio rover to sitter We end up with 4 different potential genetic combinations and offspring and because the rover allele is dominant over the sitter's allele all of these will show the rover behaviour and the only ones showing sitter behaviour are those homozygous for the sitter allele because that's the recessive allele That explains why we get this ratio of three to one in the F2 generation This tells us that the genetic basis of this behaviour is simple and appears to be controlled by a single genetic locus influences expression of behaviour (but does not encode it) and we have the rover allele dominant over the sitter allele de Belle et al (1989) - For gene encodes protein kinase G, which affects neuronal activity (short- and long-term memory) - Sitters homozygous for recessive allele fors - Rovers have at least one copy of dominant allele forR

Vision - Columnar structure of VI

In addition to the six horizontal layers, the neurons in VI are further segregated into functionally distinct hypercolumns (ca 1mm2) Hypercolumn (appx 1mm2) is composed by: - Left and right eye ocular dominance columns (L,R) - Orientation columns (rainbow colours) - Blobs (drawn as cylinders) - Retinotopic organisation: the spatial mapping arising from the projection of the image onto the retina is preserved in VI - 6 layers shown but also vertical structure called hypercolumns which contain neurons that are functionally distinct, but they are highly mapped, they are retinotopically mapped and they preserve the input from the right and left eye - This is shown in the diagram, there are two hypercolumns which are receiving input from the same part of the visual field from the right and from the left eye, these are the ocular dominance columns - To develop a regular pattern both eyes need continuous stimulation across the sensitive periods of development in order to produce these stable neuronal connections - Orientation columns are cellularly interesting, when an electrode is passed the neurons will change their orientation selectivity for bars of a certain inclination, this is shown in the diagram, the neurons sitting in the hypercolumn shown in red will be maximally sensitive to bars shown to the eye that are orientated horizontally, further down there is a layer that is maximally sensitive to vertically sensitive bars but in between you have a layer a regular pattern that you slowing increase the orientation and the neighbouring layer will have maximal sensitivity for this slight change in orientation, if you change it again a little bit more and go deeper into next layer then they could record neurons that were sensitive to this orientation of the bar - All the different possible orientations from 0-180 degree are covered by these highly ordered layers of neurons, which are called orientation columns

Neuroimaging - From raw data to functional brain 'activation' maps 1) Design a task to be used in the scanner Advantages of Event-Related Designs

In freeing us from the necessity of block designs, event-related fMRI enables us to design more complex and novel experiments. 1) Flexibility and randomization Eliminate predictability of block designs Avoid practice effects 2) Post hoc sorting (e.g., correct vs incorrect, aware vs unaware, remembered vs forgotten items, fast vs slow RTs) 3) Can look at novelty and priming - rare or unpredictable events can be measured E.g., P300 4) Can look at temporal dynamics of response Dissociation of motion artifacts from activation Dissociate components of delay tasks Mental chronometry

Neurons - Neurons Generate Bioelectricity

In the neuron the cell membrane has a further function, it does not only act as a barrier and controls the movement of different molecules, but it also generates bioelectric signals In the neuron the cell membrane does not only act as a barrier, but it is also slightly polarised and selectively permeable (because it contains specialised types of ion channels that allow the flux or exchange of intra and extra cellular fluid for a brief period of time and within the exchange or flux of items) Ion channels distributed along the neural membrane Movement of ions across the neural membrane generates tiny localised bioelectric currents, the membrane especially because it is equipped with a special class of ion channels which are not found in other cells These ion channels have the task of allowing the movement and flux of ions across the membrane from inside to outside or outside to inside, and this is what generates tiny localised bioelectric current which we call neural signals

Motor Control - The Neurobiology of Motor Control Effect of transcranial magnetic stimulation of the cerebellum on forward models, Miall et al (2007)

In this experiment subjects were required to sit and move their hand to the side but when they heard a tone and saw a target appear in front of them, they had to stop moving to the side and reach for the target in front of them Move hand to side, hear tone, then usually a couple of hundred milliseconds between hearing tone and responding and that is when they make their response Miall et al looked at the effects of transcranial magnetic stimulation on performance on this task See is that when there is no TMS of the cerebellum (TMS is transiently disrupting neuronal activity) people are more accurate and closer to the target, and when there is TMS of the cerebellum subjects are much less accurate in terms of their reaching trajectory Using this method researchers concluded that the average directional errors in the TMS conditions were actually consistent with reaching movements being planning and initiated from an estimated hand position that was a 138 milliseconds out date, clearly TMS of the cerebellum was actually disrupting the brain's ability to predict the sensory consequences of a motor command and to therefore produce the direct response according to that prediction When you don't have the forward model or ability to predict, your movement trajectory becomes inaccurate Forward model generated by cerebellum uses information about future position of limb to compute the trajectory to hit the target

Synapses and Networks - Signal transmission involves mostly chemical synapses Electric synapse: gap junctions connect the cytoplasms of two neurons

Instantaneous current flow (very fast transmission of electric signal across connexons producing a coupling effect, e.g., there are virtually no time delays Gap between membrane as little as 20-40nm They are found where fast response and/or synchronisation of activity is required Fast action: commanding escape responses (crayfish, fish) Synchronised activity: inhibitory neurons in mammalian brain, eye-moving muscles

Neurons - Three classes of ion channels

Ion channels differ in their selectivity for certain types of ions. Gated ion channels remain closed until activation for a very brief period of time, either by electrical signals (voltage-gated) or by drugs and neurotransmitters (ligand-gated) Ion pumps actively transport ions (Na+, K+ or Ca2+) from one side of the membrane to the other and carry them across to the other side against the concentration gradient. This is costly (most of the brain's energy consumption) Leak channels allow a specific ion type to freely diffuse (e.g., they are always open and let K+ through but not Na+)

Vision - Simultaneous contrast effect

Koffka-ring illusion - Grey ring on a dark and bright background - A white bar separates the two halves of the ring. Do the two halves of the ring appear to be identical in brightness? - The right half has been moved in a vertical direction, do the halves look identical?

Neurons - Electric currents in neurons are generated by ions

Life evolved in the sea and sea water contains a large amount of different ions including sodium chloride, potassium, calcium Some are positively charged/positive ions, and some are negatively charged It is this property of the fluids in the body that the neurons exploit to generate bio electric currents

Synapses and Networks - Ionotropic receptors are ligand-gated ion channels

Ligand-gated ion channels open when bound by neurotransmitter molecules There are different types of ionotropic receptors which vary in their affinity for a particular neurotransmitter or drug Reuptake = transmitter is taken up into the presynaptic cell Some neurotransmitter molecules do not cross the cleft, they bind to auto receptors that inform the presynaptic cell about the net Postsynaptic neuron: the neurotransmitter can also interact with metabotropic receptors Metabotropic receptors are ion channels that need the activation from other molecules in the membrane, so called g protein receptors

Sensory Modalities - Points

Light and sound propagate as waves that differ in frequency and intensity To locate sound sources, animals compare the sound information processed by both ears Whilst light is absorbed by photoreceptor as quanta, sound vibrates the internal structures of the ear Hair cells have stereocilia and ion channels that are open by mechanical forces. Inner hair cells release glutamate to excite afferent first-order auditory interneurons that transmit the signal to the cochlear nucleus and brainstem Signal coding is modulated by outer hair cells and efferent interneurons (top-down control) The auditory pathway has parallel and serial connections, similar to vision. Tonotopic maps are found in each stage of the auditory pathway Audiograms allow comparisons between species to determine how hearing can be adapted to different tasks and ecological needs

Vision - Regulation of physiological processes during day and night

Light is significant in the cycles of any organism in an environment that experiences daily life changes Some part for the visual brain is devoted to regulating sleep-wake cycles, this is called the suprachiasmatic nucleus, which receives input from some ganglion cells in the retina and sits just behind the optic chiasm Light levels that are detected by these specialised ganglion cells in the eye send their signals to the SCN, these retina cells contain a photo pigment called melanopsin and that is sensitive to short wavelengths The circadian clock that is located in the cells of the SCN keeps our cycles, it runs approx. 24 hrs in humans, and it evolved to be accurately in line with the daily life cycles of approx. half of the time being day and half night with some changes over the season where the circadian clock can retrain and be adjusted We have a pineal gland that is important for producing melatonin which it does during the darkness, this is the sleep hormone these cycles are regulated by these specialised cells in the retina that are sensitive in the blue range of the spectrum or the short-wave section of the spectrum, light waves that are emitted by the sun across the whole septum have shorter wavelengths in what we perceive as blue and violet colours, and longer wavelengths have longer distances The short wavelengths contain very high levels of energy, so each photon in this light wave contains a high amount of energy that interacts with the photopigment and therefore it is particularly able to quickly activate corresponding neural circuits So, absorption is very easy because it's such a high energy light but of course it can be sometimes damaging if you get too much of it As humans invented artificial light, especially LED light (white LEDs have the maximum emission in the blue light range) it messes around with our physiology and sleep wake cycles because it blocks melatonin our sleep hormone and it is suspected to play a substantial role in the symptoms we experience now where we are stuck on monitors and phones There is good evidence that exposure to supernormal levels of blue light causes digital eye strain and tiredness, so not all blue light is bad as it is part of normal daylight and our physiology is adapted to this, it is excess light that is difficult However, sometimes people are recommended to consume extra levels of blue light where there is very little light in their environment, as this can cause Seasonal Affective Disorder (SAD) in particular in the high north an arctic areas where people experience constant darkness

Evolution of the Brain - Around 2 billion yrs ago

Major transition to Eukaryotic organisms, everything within cell more compartmentalised, DNA in central nucleus, mitochondria to produce energy so more efficient, cell membrane performs phagocytosis and secretion which is the basis of cellular communication, also microtubule network which allows more complex structure and shapes of cells, also specialised areas for sensing external condition cilia and microvilli

Neuroimaging - Pre-processing fMRI Data

Means that rather than looking for the variability in experimental data that is related to our task, to what the subject is doing, with processing what we're trying to do is correct for non-task related variability in our experimental data In fMRI data there is a lot of noise and variability in the data, that's just related to factors we aren't interested in, and what we are trying to do in fMRI experiments is to detect the signal in the noise and get rid of as much of this 'noise' as possible

Human Genetic Variation - Trade, colonization and slavery: historical evidence of inter-ethnic families

Mixed families in the 1930s were not a rare sight, London, Liverpool (as cited in Caballero 2019), Genealogy, 3(2),21). Mixed families and people documented since Tudor times in the 1600s Miranda Kaufmann (2017): Black Tudors - the untold story Africans already known to live in Roman Britain Las castas, 18th century, anonymous, Mexico, depicts the admixtures present in the Americas Human and historical record shows that in more recent times humans have a different physical appearance have/had mixed race or intermixed children

Human Genetic Variation - Inheritance is not simply blending the characteristics of the egg parent and the sperm parent

Modern genomics: most human trait variations are polygenic and Mendelian trait variations are very rare Human skin colour is a highly variable and complex trait Skin colour is not uniformly distributed across the body Variation also due to biological sex, changes in different environments, during disease or pregnancy Complex tangled relationship between genes determining polygenic inheritance. Some gene have several alleles, not always dominant recessive 15 genes regulating amount of melanin in the melanocytes of the skin explain only some of the variations in skin colour

Learning and Memory - Neural Plasticity: from behaviour to genes Hippocampus lesions prior to training do not specifically impair working or reference memory, but spatial memory

Morris et al (1982) - Control group: brain is intact Hippocampal lesion: these animals are still searching for a relatively long time compared to the control and have not established a memory for the location of the platform - Another control group: cortical lesion, this group showed very quick learning, similar to the control group - This shows it is specifically spatial memory that is impaired by the hippocampus lesion but not other types of memory such as reference or working memory - Lesions after training had a less strong effect on spatial memory, again showing hippocampus has a time-limited role in the formation and recall of memories - First phase: hidden platform - Second phase: platform hidden but marked with a beacon (cue-based navigation). All rats showed the same escape latency - Third phase: reversal to hidden platform. Rats with hippocampal lesions performed poorly again

Sensory Modalities - Auditory pathway: from receptor to primary cortex

Most projections from the cochlear project to the contralateral cortex Each superior olivary nuclei of the brainstem receives inputs from both cochlear nuclei for first stage of binaural analysis of sound-source location The information is then passed on to the Inferior colliculi are located in the dorsal midbrain, from there it is projected to the medial geniculate nuclei of the thalamus The next station is the primary auditory cortex called A1

Motor Control - The Neurobiology of Motor Control Visuomotor learning and adaptation

Motor system is able to continually learn new movements and adapt to changing sensory inputs - how? Visuomotor adaptation = the ability to adapt out movements according to new sensory information Coordinating sense of vision with bodies Babies have to learn where things are and what to do to grab them Even the simplest movement depend on accurate guidance from eyes Adapt to wearing the goggles and over a long period of time the degree of adaptation is remarkable Studies using controlled methods in a laboratory, hands under table so can't see it and visual display of their hand s produced accurately or inaccurately

Vision - Stabilising the gaze for better vision

Movement can be described as a combination of three direction of translation and three directions of rotation - Large and faster movements of the head renders vision blurry when the eyes cannot compensate - Show that we move our head as well in addition to eye movements, these need to be tightly coordinated, the larger and faster movements of the head cause much more blur than tiny eye movements, these tiny movements are then compensated by different types of eye movements in order to stabilise the gaze

Hormone Structure and Action - Chemical communication in living organisms

Multiple forms of chemical communication (from those with nearby effects to those with more distant effects) - Autocrine communication = chemical released by cell affects its own activity - Neurocrine(synaptic) communication = chemical released by neuron diffuses across synaptic cleft and affects postsynaptic membrane - Paracrine communication = chemical released into extracellular environment and effects nearby target cells - Endocrine (hormone) communication = chemical released into bloodstream and selectively affects (distant) organs - Pheromone communication = chemical released into external environment and affects conspecifics - Allomone communication = chemical released into external environment and effects heterospecifics

Functions of Brain

Needs to regulate bodily functions e.g., blood pressure, heart rate, create motivational functions of emotional states such as hunger, thirst and social needs, produce language... Phrenology, school of thought that attempted to localise mental processes anatomically, Gall (1758-1828) Jean Pierre Flourens (1794-1876), proponents of the idea that cognitive functions are no localised but diffusely distributed in the brain, following experiments on animal concluded that basic physiological regulation and motor function ire localised in the brain stem and control of balance in the cerebellum Basic physiological and metabolic processes are controlled by groups of neurons in the brainstem, including thalamus and hypothalamus These are functions such as respiration, digestion, glucose metabolism, arousal, regulation of body temperature, blood pressure, swallowing, coughing, sneezing, vomiting, circadian rhythms etc ... The Reticular Formation, Thalamus and Hypothalamus, the Reticular Activating System (RAS) determines the level of alertness

Synaptic Sequence -

Neurons sense a stimulus This stimulates the next neuron If that stimulation is strong enough it leads to action potential That action potential one travels down the axon towards the next neuron You have your sodium potassium pumps going and pumping both in and out, making the electric transmission drug go through the axon and arm these myelin segments around it that facilitate transmission, especially in longer axons If that then reaches the end and there's enough build-up of stimulation you get an action potential in the next neuron and so on and so on If it starts in the motor cortex and it travels down a bunch of neurons and all the axons and if it's strong enough, I might make my fingers move When the action potential reaches the axon terminal, this initiates synaptic transmission, when that signal reaches the end it reaches the synapse and that is where the transfer happens of activation from one cell to the other When the action potential reaches the axon terminal, it interacts with neurotransmitter vesicles (storage units of neurotransmitters), pushing them towards the membrane Once the vesicles containing the neurotransmitter reach the membrane, they open up and the neurotransmitter is released into the 'synaptic cleft' The neurotransmitter then binds to its receptors in the postsynaptic neuron. If these receptors are themselves ion-channels, they open when the neurotransmitter interacts with them If the receptors are not ion channels, they interact with specific ion channels and eventually open then As a consequence, ions enter the postsynaptic neuron, resulting in a Post-Synaptic Potential

Synapses and Networks - Transmission of neural signals over short and large distances: Spiking Neuron

Neurons with long axons transmit the signal with action potentials along the axon The signal is sustained effectively by the population of voltage-gated ion channels in the axonal membrane In spiking neurons, graded potentials set up trains of action potentials, the frequency of which encodes the amplitude of the graded potential The action potentials propagate to the axon terminal and evoke graded neurotransmitter release in proportion to action-potential frequency

The Logic in Neuropsychology - The Logic of Dissociations

Neuropsychological data can be used to test theories about the architecture of psychological processes even without knowing the exact location of the damage Suppose one wants to investigate the psychological processes involved in the recognition and writing of graphemes - letters One key question that can be asked is whether the recognition and writing of vowels (e.g., a, e) rely on different psychological processes from the recognition and writing of consonants (e.g., t, r) Say, brain damage impairs processing of vowel letters but spares processing of consonant letters This dissociation may indicate that the two classes of letters are processed differently Note that determining the exact location of damage in the brain is not crucial for the above inference The Italian neuropsychologist Roberto Cubelli (Cubelli 1991) found this pattern in two patients One of them could write consonants, but left gaps where there were vowels The other made spelling errors mostly on vowels, but had no problem with consonants Suggests there are two different types of processing for those two different types of letters

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - What is neuropsychology?

Neuropsychology is the area of psychology that examines the effects of brain damage on abilities and behaviour If damage to a particular brain region/structure is systematically associated with a certain cognitive impairment, that region/structure is NECESSARY for the cognitive process to function Example: the primary motor cortex, a lot of the time when people gave stroke you see they have left paralysis for example right arm paralysis, this is common in strokes because of the major arteries there, they are often the cause of various kinds of stroke, and so if that part of the brain gets damaged the hand and arm area are vulnerable, because of this we know for a fact that the primary motor cortex is essential for moving your arm and we can make a clear causal link Therefore, the brain region must be (part of) the anatomical substrate for the given cognitive process Neuropsychology is thought to have emerged in the 19th century when the French neurologist Paul Broca (19th cent) identified post-mortem that damage to an area of the inferior frontal cortex (now referred to as Broca's area) was the likely cause of a severe language impairment in one of these patients

Electrophysiological recordings of brain activity Electroencephalogram (EEG)

Non-invasive electrophysiology - The cap put on the head very precisely, top of cap is above a certain point and a certain distance from top of nose, certain electrodes need to be in more or less the same space, each electrode collects lots of information on lots of neurons - Someone comes with a syringe with fluid which is injected into the electrodes, it is conductive gel which is put to the electrodes and it gets between the scalp and the electrodes through your hair, it is to facilitate conductivity between the scalp and those electrodes - EEG is the change in voltage (electricity) recorded from sensors on the scalp, each of these lines is a differential between one electrode and the reference - The reference is an electrode that is put somewhere near the scalp e.g., the earlobes, where they are no longer reading electricity because it is too far from the brain. But there is lots of other activity in the world, a reference picks up the background noise so make sure it doesn't go in the EEG, it is a way of comparing the relative activation between one electrode and the reference, the difference is brain activity. - Since the reference electrode has all the activity that's in the room in it, just like the other electrodes, but the other electrodes have the brain also, so deducting one of the other gives us the activity related to the brain - Each location of the electrode has a name e.g., FB1, these are worldwide codes used - Each of the electrodes and the different c score between the wave is the difference at a millisecond between each electrode and the reference, it is the amount of activation happening in the brain

Neuroimaging - Preprocessing Steps 6 - Spatial Smoothing

Not always done, but has formed an important part of the pre-processing step over many years Application of Gaussian kernel Means that for every voxel in the brain, we take this filter, and we change the values of the central voxels according to the values of the surrounding voxels The voxels that are further away contribute less and less as we move further and further away The kernel essentially reflects how much of a contribution each surrounding voxel makes to the central voxel's signal We do this because we are trying to take into account the fact that neurons don't fire in isolation, we know that when a neuron fires the neurons around it will tend to fire as well Similarly, it's trying to appreciate the fact that if a particular voxel in the brain shows an increase in activation the voxels around it are also likely to show an increase in activation Why smooth? Because neurons do not fire in isolation If a neuron fires, neurons close to it will tend to fire as well Smoothing attempts to model the data according to this property of neurons The amount of smoothing that we do in each experiment will depend on, again, which brain areas we're interested in, for example if we are interested in small precise areas of the brain, subcortical structures that are well defined, we might do minimal smoothing But if we are interested in quite large areas of the cortex, for example the prefrontal cortex, where there isn't such precise anatomical delineation of structures then we might apply a broader smoothing kernel

Vision - Object recognition

Object recognition can be very fast and have lag times of less than 200 milliseconds to decide whether object you see belong to one category or to another They're also invariant to the position viewpoint and object size or visual context, so they are heavily implied in categorization of objects, this is thought to involve the anterior area of the IT

Non-Genetic Variance - Mechanisms of Social Learning 5. Goal emulation

Observer attends to consequences of demonstrator's action and uses own method to achieve the same goal

Non-Genetic Variance - Maternal Effects POST-BIRTH

Occurs outside the womb Example: cabbage white butterfly, Pieris spp Species that was studied by Charles Darwin The caterpillars of these will be laid on a host plant so they very first food that the caterpillars eat will be that of the host plant where the mother decided to lay her eggs So, the choice of the mother that determines what food type the caterpillars are exposed to when they hatch out of those eggs, female lays eggs on host plant and caterpillars develop there Darwin showed this by putting eggs on different cabbage plants, putting the caterpillars on certain types of cabbage plant means that the adults will grow and develop to have a particular preference for that type of cabbage So, it's the post-birth environment they experience after hatching determining their preferences

Non-Genetic Variance - Maternal Effects PRE-BIRTH

Occurs when inside the womb Example: the transmission of food preferences in rabbits Rabbits have litters of multiple offspring called kits The food preference of offspring is determined by what mother eats during pregnancy Bilko et al (1994), two types of mothers fed two different types of food during pregnancy, the rabbits were randomly allocated to these treatments, experimenters then looked at the preference of the offspring born to those mothers later in life, kits a choice between juniper flavoured food and control food Kits born to mothers who had been fed control food during pregnancy tended to prefer the control food over the juniper flavoured food Those kits born to mothers flavoured juniper flavoured food had a preference to juniper flavoured food As these diets were allocated as part of the experiment this shows that the kit's preferences were affected directly by the mother's diet via prenatal environment Can also be found that this is more complex, it is not just the food the mother consumes during pregnancy (pre-natal or pre-birth maternal effect) but it's also important what happens outside the womb This was shown in Bilko et al's further experiments where they cross-fostered offspring from one mother to another after birth, they took the offspring from a juniper-fed mother and gave them to a control-fed mother, when these offspring were then given the choice between juniper- and control-flavoured food they actually preferred juniper flavoured food because of the prenatal experience they had shaping their preferences When they took offspring from mothers fed control food and gave them to mothers who had eaten the juniper berries and then those offspring were given a choice, they preferred the juniper flavoured food also and the reason for this is the influences of the post-natal environment where the offspring were exposed to the juniper flavour via the mother milk and faecal pellets she deposited in the nest, so the kits preferences are also affected by the mother's diet via the post-natal environment This is an example of maternal effects both inside and outside the womb The kit's preferences were determined by the mother's diet via the prenatal environment, milk during nursing and also via faecal pellets deposited in the nest Exposure to the juniper flavour at any point through one of these mechanisms of methods can be sufficient to lead to and induce a preference for juniper flavoured food in the young It is important to recognise this is not a genetic effect

Neuroimaging - From raw data to functional brain 'activation' maps 1) Design a task to be used in the scanner Was it a good baseline?

One that differs from the experimental condition only by the process of interest E.g., face processing - Looking at images of the human face, what would happen if in the control condition we just had nothing? Blank pictures? - If we then did a comparison between our faces vs the blank rest condition, what we would likely see is most of the brain activated because what we would be seeing there is not just activation, not just BOLD signal related to the processing of faces but BOLD signal related to the processing of all the low level visual features in the faces, you'd see the BOLD signal related to simply seeing anything because you'd see activation throughout primary and secondary visual cortex and activation in attentional regions, you would see activation throughout the brain in lots of different regions that are performing different functions With a baseline condition what is trying to be accomplished is essentially taking a lot of that irrelevant activation out of the equation and find the brain regions that are activated that are specifically related to the processing of faces Kanwisher et al (1997) Science, came up with a solution for this, in one control condition she took all these aces and simply scrambled up the features and used those scrambled faces as the control condition this maintains the same level of low visual processing between these two conditions, so these two conditions have exactly the same number of visual features between them but they're all just in a different order, in the top condition are arranged in faces and in bottom condition they are scrambled then when you do the subtraction between the two conditions you essentially subtract out any of that low level visual activation and what you're left with is ideally activation only related to processing the face or intact human face, relatively Activation in a relatively restricted area of the fusiform gyrus

The Cognitive Neuroscience of Addiction - Cannabis and Psychosis

One way of testing whether drug use causes mental illness is large scale longitudinal research which assesses the psychiatric status of youth prior to drug use, and then tests them again in adulthood after some had used cannabis The odds ratios shown for several studies below reflect the increased risk of diagnosis of psychiatric symptoms in individuals who had engaged in heavy cannabis use compared to those who had not. An odds ratio of 1 means that the groups have equal risk. However, the average odds ratio was 2.09, indicating a doubling of the risk of psychotic symptoms (such as those found in schizophrenia) given heavy cannabis use

Sex Differences - Gonadal Sexual Differentiation During embryonic development in females (the 'default' sex):

Ovary does not produce significant amounts of steroid hormones during embryonic development Each part of the body develops according to its own intrinsic programme

Hormone Structure and Action - Hormones Acting Within the Body Short-term effects

Oxytocin: milk letdown reflex - Oxytocin is a hormone with many important effects on social behaviour, but for now we will focus on milk letdown reflex - One of those complex hormonal pathways where we have a cascade of effects involving both the hypothalamus and the posterior pituitary gland - The initial stimulus for the letdown comes from the baby sucking on its mother's nipple, our receptors in the nipple sense the sucking and are stimulated to send nerve impulses to hypothalamus, and projecting from the hypothalamus to pituitary is an oxytocin neuron which stimulates the anterior pituitary gland to release oxytocin in the blood - Oxytocin stimulates the mammary glands to contract and release milk, which tends to stimulate further sucking and that is why you get positive feedback effect, release of oxytocin stimulates release of milk which stimulates more sucking which stimulates the hypothalamus which stimulates more milk production which continues until baby is satiated - Once the baby is satiated it stops sucking and crying, the stimulation stops, and the oxytocin production stops - Though the initial stimulus for this is the baby sucking, there is also a conditioned association occurring over a period of time after the baby is born which may develop between the sucking stimulation and the sound of the baby crying such that after a short amount of time even just hearing the sound of a baby crying is enough to induce the milk letdown response

Vision - P- and M- pathways from retina to VI

P- and M- pathways - P - parvocellular (small soma) - M - magnocellular (large soma) - The connections that are most important for our conscious visual experiences are routed through the LGN on the way from the retina to the cortex - These projections and the geniculate striatal pathway (striatal because the visual cortex 1 is also called the striatal area) has two pathways within it which we call parallel pathways, and which originate from the same photoreceptor in the retina - The same photoreceptor sends a signal to two functional classes of ganglion cells, the P- and M- ganglion cells which then project within the optic nerve into different layers in the LGN - Those that have two layers have neurons with larger soma and they receive input from M- ganglion cells - The other layers receive input from other ganglion cells known as P - ganglion cells and they have smaller somas - These two stream run parallel in optic nerve receiving input from the same photoreceptors, so the information diverges at the same time from one photoreceptor onto different ganglion cells - The different colours of the layers in the diagram below show that the projections come from either the left or the right eye, so all the projections are kept in a highly orderly fashion and mapped out according to the location of the photoreceptors in the retina

Synaptic Sequence - Parkinson's

Parkinson's could be seen as the opposite to schizophrenia in a way because the production of dopamine in people with Parkinson's has been reducing over time, and you get rigid movement or for example trouble initiating movement. One of the treatments for Parkinson's is to induce dopamine increasing drugs. However, medication for Parkinson's and schizophrenia push dopamine in the opposite direction and can cause each other's symptoms in high doses. Too much Parkinson's drugs = Schizophrenia symptoms Too much Schizophrenia drugs = Parkinson's symptoms Because the drugs are quite crude and don't inhibit the systems in exactly the right place within the brain, we want them to, but they do it mostly everywhere where there are dopamine receptors, causing all these different effects.

Sex Differences - Sex Differences in the Brain Connection between hemispheres

Parts of corpus callosum are bigger in right-handed than left-handed men, no such pattern for women Posterior portion (splenium) perhaps more bulbous in women than in men

Learning and Memory - Pavlov's Dog

Pavlov (1849-1936) - When a dog receives food, it starts to salivate (UR-unconditioned response) - Pavlov noticed that his experimental dogs were already salivating before being given food - Devised an experiment in which he presented a tone preceding food presentation of food and found that dogs would salivate when he heard the sound before food was even presented - Termed the sound the conditioned stimulus because the dog was conditioned to the stimulus with the presentation of food which is the unconditioned stimulus - He conditioned their response/salivation response to this stimulus and therefore called it, once the dog learned to association, the conditioned response, when the dog salivated in response to the sound Contingency = the CS predicts the occurrence of the US meaning it is contingent on the prior occurrence of the CS - CS = conditioned stimulus - US = unconditioned stimulus - CR = conditioned stimulus

Structure of the Nervous System - Central nervous system

Peripheral nervous system, rest of the nervous system outside of the brain, connects the brain to other areas, divided into somatic and autonomic nervous system somatic nervous system is nerves that take motor instructions from motor cortex to muscles autonomic nervous system does all functions happening at any given time e.g., heart rate, can be split into sympathetic (fight or flight response) and parasympathetic (reacts and tries to bring back to equilibrium) Central nervous system is spiral cord and the brain

Learning and Memory - Neural Plasticity: from behaviour to genes Memory consolidation requires protein synthesis

Pharmacological agents to dissociate different stages of encoding and (re)consolidation Drug manipulations are relatively brief, accurately timed, therefore usually reversible (within-subject control before and after treatment possible) protein-synthesis blocker has been applied in LTM studies involving the hippocampus, amygdala, prefrontal and insular cortex. Anisomycin and rapamycin are amnestic agents that affect consolidation and reconsolidation causing pronounced impairments of performance during memory retrieval

Hormones and Behaviour - Biological Rhythms

Pineal gland - Usually, unpaired structure - In birds and reptiles can sense light directly through the skull - In mammals acts via the cervical ganglia - Phasic (cf. tonic) secretion of hormones and other chemicals in cyclic patterns, hourly, diurnal, monthly, seasonally .... - Melatonin is important in regulating cyclical functions Melatonin - Released almost exclusively at night - Provides signal to track daylength and season - Controls the timing of onset of sleep (in humans) - Controls breeding condition in seasonally breeding animals

Non-Genetic Variance - Mechanisms of Social Learning 1) Local (or location) enhancement

Presence / behaviour of demonstrator draws observer's attention to specific location where behaviour is then acquired through individual learning Example: two crossbills where the green one has learnt to extract seeds from this particular pine cone and its presence or behaviour at that particular location on this particular pine cone is drawing the observer birds to that location, so when the demonstrator flies away the observer is likely to go the same location and conduct their own individual trial-and-error learning, they key part transmitted her is the drawing of attention to that specific place and behaviour itself is acquired through individual learning

Sensory Systems - Cortical encoding in form of somatotopic maps

Primary somatosensory cortex is located in the postcentral gyrus in the parietal lobe of the human brain Brodman areas 1,2 and 3a,b Adjacent regions on body are generally encoded in adjacent regions in cortex The projections are then mapped in areas that are reserved in the somatosensory cortex for each body part, such as hand, adjacent regions on the body are typically encoded in adjacent regions in the cortex and the same for facial areas

Evolution of the Brain - First 1.5 billion years of life

Prokaryotes, bacteria, includes e coli, prokaryotic simple structure where cell is enclosed by membrane which regulates contents of cell and produces energy, sensors tell what conditions are like outside cell, outside of cell has flagella which allow cells to move towards good conditions and away from bad conditions, cytoplasm contains DNA

Biology of Stress - Exhaustion Stage

Prolonged stress response depletes resources, causing stress-related illness Sugars are mobilised and energy is never stored, muscle wasting, fatigue, increased risk of diabetes Hypertension (high blood pressure) is maintained, damage to blood vessels Digestion is suppressed, peptic ulcers, irritable bowel syndrome Growth is suppressed, psychogenic dwarfism, bone decalcification Reproduction is suppressed, disrupted ovulation, impotence, loss of libido Immunity and inflammation are suppressed, long-term immunosuppression, increase disease susceptibility Cognition and sensory thresholds are altered, neurodegeneration in hippocampus and prefrontal cortex, impaired learning and memory retrieval

Biology of Stress - Alarm Reaction

Prompted by sudden, unexpected appearance of stressor Non-specific immediate behavioural response: startle Followed by specific behavioural responses (fight or flight) Accompanied by physiological changes supporting behavioural response: - Increase in blood pressure - Tachycardia (rapid heart rate) - Tachypnoea (rapid breathing) These are active coping mechanisms for controlling the threat, for immediately countering unexpected stressor and making response more effective Primarily linked to stimulation of sympatho-adrenergic system (SAS) Activates: Brainstem nuclei Vagal nerve Adrenal medulla Adrenal medulla releases adrenaline and noradrenaline into blood Noradrenaline stimulates alpha receptors in muscle; contraction redirects blood to essential organs and increases blood pressure

Hormone Structure and Action - Protein and amine hormones

Protein and amine hormones bind to specific receptors on the outside of cells They act 'rapidly' in most cases seconds to minutes Have prolonged effects Sensitivity can be altered by increasing (upregulating) or decreasing (downregulating) number of receptors on cell Stored in vesicles and secreted on demand

Human Genetic Variation - "Race" as a mechanism of discriminatory social segregation

Pseudoscientific biological concepts to cement social barriers after abolition of slavery in the 19th century: racial mixture was considered medically pathological and 'unnatural' Often asked as a radicalized question: where are you from? What are you? Race is socially constructed grouping Problems of racialised social constructions and world views: segregation, race laws, racial discrimination, microlevel of interactions and symbolisms Learning from the past: collective ideas about what their physical attributes are for individuals from different races have been used to reinforce concepts of superiority of some groups of humans over others 10% of the population in the US and UK live in interracial couples it continues to be a very common occurrence that people mix

Learning and Memory - Neural Plasticity: from behaviour to genes Hebb Synapse:

Ramon y Cajal (1893) first proposed the idea that the site of contact between neurons could play a role in memory formation Foster and Sherrington (1897) named these sites 'synapses' Hebb proposed in his book 'The Organization of Behaviour' (1949) a theory that some connection in neural networks could be strengthened if frequently activated or weakened if used less The concept of the Hebb synapse implies that the strength of synaptic transmission can increase if the presynaptic cell repeatedly and persistently activates the postsynaptic cell

Sensory Systems - Somatotopic mapping of sensory neurons

Receptive fields can be mapped for neurons in the sensory pathway Co-located receptor neurons with neighbouring receptive fields project to neighbouring areas in the somatosensory cortex To map the location of neurons that receive input from parts of the body, one can record the activity of neurons in the somatosensory cortex If the location that is touched on the skin is directly above the location of the mechanoreceptor the response will be strongest, if it moves a little away from the location of the receptors the responses will decrease, and they will be weaker the further away the stimulus is moved until it is outside of the region of the receptive field so that this receptor cannot detect this stimulus any more Adjacent areas of receptors that are neighbouring/collocated will respond to touches in different locations and because they are collocated/neighbouring on the tail they will be projected to neurons in the neighbouring areas in the somatosensory cortex as well as inside of the major areas allocated to processing signals from the tail This is another type of somatotopic mapping so one is mapping out different areas in the somatic cortex for different parts of the body, but then in the finer scale these mappings are refined by characterising different locations by maintaining the spatial characteristics of the locations relative to the boundaries of these body parts

Sensory Systems - Sensory receptors have specialised structures to detect stimuli

Receptors are either spiking or non-spiking neurons: - Input zone = where neurons collect and integrate information, either from the environment or from other cells - Integration zone = where the decision to produce a neural signal is made - Conduction zone = where information can be transmitted over great distances - Output zone = where the neuron transfers information to other cells - The transformation of the stimulus energy that the receptor neuron can interact with the help of its accessory structures is called transduction - And so, the main task of receptor neuron is to transfer dual stimulus energy into neural signals - The specific nature of accessory structures defines how the stimulus energy is filtered by the neuron receptor, a neuron cannot be sensitive for all types of energy or all strengths of signals

Synapses and Networks - Metabotropic receptors are G protein-coupled receptors (GPCRs) that are slow but influence adjacent ion channels

Receptors coupled to a G proteins (guanine nucleotide-binding protein) When activated by a conformational (shape) change of the GPCR, G proteins (i.e., its alpha-unit bound to GTP (guanosine triphosphate)) can interact directly with ion channels or control the release of another second messenger molecule inside the postsynaptic cell ((cAMP (cyclic adenosine monophosphate) or PIP2 (phosphatidylinositol 4,5-Bisphosphate) second messenger pathways)) Neurotransmitter binds G protein-coupled receptor, G protein activated, in this case activated G protein subunit moves to adjacent ion channel which causes a brief delay, channel opens, ions flow across membrane for a longer period of time

Hormones and Behaviour - Social Behaviour in Humans

Reciprocal relationship between hormones and behaviour So, hormones do appear to influence behaviour but when an animal changes its behaviour this changes the experiences it has, and this then feeds back into the levels of the hormones Meaning that if we observe naturally occurring correlations between hormones and behaviour that doesn't actually demonstrate cause and effect as we known that hormones can influence behaviour but also behaviour can influence hormones Naturally occurring hormone-behaviour correlations do not demonstrate causal effect The key methodological technique in this area is placebo-controlled double-blind experiments, important for establishing causal effect of hormone of behaviour Placebo-controlled refers to the fact that you have some control group that are given an inert placebo treatment rather than being given a dose of the hormone Double blind because the subjects and the experimenter are both blind to the treatment, the subjects are not aware what group they are in, and the experimenter at the time of observing the subject's behaviour is also unaware whether the subject is in the hormone or placebo group This allows us to establish in a rigorous way whether there is a reliable effect of the hormone on behaviour

Sensory Systems - Reflex arcs are basic neural circuits

Reflex arcs synapse in the spinal cord - Knee-jerk reflex is very fast (latency 40ms), connects the sensory (receptor) neuron directly to the motor neuron (monosynaptic = without interneurons) - The knee-jerk reflex is very fast because it has myelinated axons that project just into the spinal cord and thus the signal only has to cross a single synapse and then it very quickly travels towards the muscle eliciting the kicking response - Monosynaptic reflex arcs are where there is only one synapse between the sensory neuron and the motor neuron that in turn innervates a muscle fibre - Reflex arcs are often more complex - polysynaptic (=with several interneurons) Polysynaptic means there are several neurons that are interconnected, and the signal has to travel across several synapses, these arcs are then somewhat slower This is a di-synaptic somatic reflex arc; interneuron A might receive input also from neuron B and C which would themselves receive input from sensory neurons that connect to different areas of the skin generating more complex reflex arcs that converge on the same motor neuron Interneuron A is said to be the first-order interneuron that comes from the muscle spindle in this di-synaptic reflex arc, it's the second-order interneuron for the circuit involving interneuron B, so then interneuron B becomes the first order sensory neuron and interneuron A becomes a second-order interneuron in this somatosensory arc that involves B and A, in the last reflex interneuron arc interneuron A is said to be the third-order interneuron in the reflex arc

Vision - Who do humans (and animals) move their eyes?

Saccades (jumps) and fixations (stops) - 203 saccades per second - Alfred Yarbus (1914-1986) Russian psychologist developed the first methods to accurately measure eye movements and viewing behaviour - Direct fovea to collect information about the visual scene - We constantly move our eyes to position the fovea in different parts of the visual scene and pick up visual information with the highest acuity, however this does not mean the eye systematically scans each position in the visual field - There are sophisticated mechanisms in the brain specifically in the superior colliculus which guide the eyes and instruct the muscles where to move the eyes - They do so by jumping from one area of the visual field to the other, measured by Alfred Yarbus for the first time using his device, he found that the eye was mainly looking at very salient parts in those scenes, high contrasting parts such as on the face the eyes are highly contrasted to the rest of the face same for the mouth and a little for the nose and other features, the eye looked everywhere where there are contrast edges - These saccades and fixations are needed in order to sustain the visual image, because when you stare at a point for too long receptors stop responding, so we need to fixate in order to reduce blur and to get a clear image projected onto the fovea But then the eye has to quickly move around 2/3 times per second to any other location in order to re excite the photoreceptors, so they then start corresponding again and this way the information continuously flows to the brain The eye jumps continuously and automatically across the visual field, we don't notice that it happens, and it happens unconsciously, but it is important to keep a steady stream of information to the brain, it also directs the fovea to features that contain high contrast in the image because that where they can extract the most useful information from

Vision - The different types of eye movements

Saccades = move the eye very quickly to a new position between periods of gaze stabilisation (fixations) in order to scan the scene across the entire field of view Smooth pursuit movements = slow, keeps a moving stimulus on the fovea Optokinetic nystagmus = brings the eye back form a peripheral to a more central position after it has followed a large-scale moving stimulus (whilst head is still) Vestibulo-ocular movements = compensate for the movement of the head by moving the eye the same distance but in the opposite direction in order to maintain a constant field of view

Synaptic Sequence - Schizophrenia and Dopamine

Schizophrenia is associated with a surplus of dopamine Its symptoms include paranoia and hallucinations Neuroleptics (e.g., Haldol): anti-psychotic drugs that block the transmission of dopamine by binding to dopamine receptors without opening ion channels They are dopamine antagonists, they block the receptors, having all the dopamine but it can't do anything, so it reduces the amount of dopamine and quite successfully reduces the symptoms of schizophrenia However, again you are affecting dopamine which is something that does lots of things in the brain and so people struggle to stay on these drugs because of the large amount of side effects they experience, and once the symptoms have been gone for quite a while because you've been taking the drug and it works for you, they also become less of a powerful motivation because they are in the past whereas the side effects are experienced on a daily basis This is because you are affecting the dopamine system and you are blocking dopamine function throughout the brain

Human Genetic Variation - Scientific racism in theory and action formally denounced after WW2

Scientific racism has a deep impact on society Crimes against humanity and genocide deploy simplified wrong claims about natural selection and argue that biological "superiority" exists in particular types of humans Pseudoscience as seemingly objective justification for colonisation, slavery and social policies that control and limit life, opportunities and rights of humans considered "inferior" or in some ways not "normal" E.g., Bengal famine (1945) in the British Empire E.g., First compulsory sterilization laws (1907-1927) in the USA Nazi Germany: concentration camps, forced sterilisation, ethnic cleansing and holocaust in Nazi Germany, some eugenics programmes were funded by Rockefeller foundation USA

Learning and Memory - Neural Plasticity: from behaviour to genes Presynaptic depression

See a decrease in the neurotransmitter release in short-term memory (STM)

Learning and Memory - Neural Plasticity: from behaviour to genes Formation of long-term memory involves also changes in the number of synapses:

Sensitisation - When long-term memory is formed new synapses will be grown, this is a way to enhance synaptic transmission by creating additional synaptic sites - As in the case of sensitisation where the animal was experiencing repeated trials of sensitization that led to the formation of long-term memory, the sensory and motor neurons at the sensory and motor synapses of the gill had an increased number and density of arborisations showing that additional synaptic sites had been grown Habituation - In long-term habituation the opposite happens, the number of synapses is reduced which reduces the number of synaptic contact sites - Accordingly, the habituated lack of response will be observed for a longer time

Sensory Systems - Sensory systems: sense organs and body systems

Sensory systems are structures containing receptors and interneurons that are specialised for detecting and processing particular types of stimuli These can be sensory organs (eye, ear) or body systems (touch) The somatic sensors that perceive touch and vibration are systems with receptors all over the body (described as body systems) What happens inside sense organs? - What information do sense organs process? - How do they filter and transmit information? How sensitive is a sense organ? How do they adapt?

Sensory Systems - Skin is very sensitive to mechanical stimulation

Several somatosensory systems - Encapsulated nerve endings, long and myelinated axons - Soma are located in the dorsal root (spinal) ganglia of the spinal cord - Free nerve endings (pain, temperature), noicereceptors and sensitive to temperature - Merkel's disk (touch) - Meissner's corpuscle (touch) - Hair follicle receptor (touch) - Pacinian (or lamellated) corpuscle (vibration and pressure) - Ruffini's ending (stretch)

Hormone Structure and Action - How do hormones act within the body?

Short-term effect = e.g., oxytocin: milk letdown reflex Long-term effects = e.g., growth hormone: bone growth

Learning and Memory - Temporal Stages of Memory Formation

Shortest memories in sensory buffers (iconic memories), for example during reading when the eye performs a saccade - STM (short-term or working memory) is few seconds to maximally few minutes long - Intermediate memory is longer lasting but not as long as lTM (long-term memory)

Learning and Memory - Neural Plasticity: from behaviour to genes Hippocampal formation encodes locations in space:

Shows an experiment where the animal was released into a square open arena and the animal would explore and be provided with some food Can see that the signals cluster quite regularly across the space, these form a hexagonal pattern The grid cells instruct cells in the hippocampus which are known as place cells, and place cells fire whenever the animal is in a particular location in a space

Sensory Systems - Transmission of a sensory signal in a spiking receptor neuron

Similar to the dendrites of a postsynaptic neuron, receptors respond to stimulation with a graded potential, the receptor potential A spiking receptor neuron converts the graded receptor potential into action potentials for fast and long-distance transmission along the axon If a weak vibration is applied the response will be relatively low, only graded potential will travel to the integration zone, not enough to elicit an action potential when the stimulus is stronger the amplitude is increased however it requires an even stronger stimulus in order to get enough depolarisation to elicit an action potential that will then travel to the spinal cord

Sensory Modalities - Localising prey by sound

Some animals rely very strongly on their hearing e.g., nocturnal hunters A fox heavily relies on their hearing sense and can very accurately locate the depth and distance to its prey under the snow

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - Non-essential activations

Some brain regions may be involved in the learning of any new task, but they may not be required once the task has been learned (see multiple demand system) Some brain areas are recruited as a 'back up' in case processing requires extra resources or effort Some process an essential for the task may often co-occur with another process B that is not essential for the task For instance, reading on a computer/laptop often goes hand in hand with typing on it, so a task of reading on a computer screen may elicit activations related to typing but typing is unlikely to be causally related to reading performance

Brain Anatomy and Localisation - Is there localisation of function?

Some processes show very clear and specific localisation, and some brain regions are clearly specialised (e.g., primary sensory and motor areas) Some brain regions are clearly more essential for certain processes than other brain areas (e.g., hippocampus for memory) Higher cognition (e.g., attention, language, reasoning) may be localised, at least to a degree, but this localisation is more distributed (probably because they consist of multiple more elementary processes) and more variable The challenge is therefore to identify the more elementary constituent processes; part of the problem is also that imaging techniques/analyses may be coarse (see example with recent imaging of Broca's area) In addition to brain regions that show at least some degree of specialisation, there also seem to be some rather large multiple demand (general purpose) brain regions

Synapses and Networks - How is information coded in neural networks?

Spatial and temporal summation at the synapses determine the strength of the signal when it is passed on from one neuron to the next In feedforward circuits the signal is distributed to many neurons through divergent connections, or is determined by collecting signals from many converging neurons. Feedback loops (positive, negative) provide direct or indicted input influencing signals and thus information

The Cognitive Neuroscience of Addiction - The drugs' influence on processing of rewards (pleasure and incentives (motivation) Universal reinforcement circuit

Studies that employed electrical stimulation in rats showed that animals are prepared to work hard (e.g., pressing a lever) to receive stimulation of VTA or Nucleus Accumbens In humans, PET and fMRI studies have shown that presentation of a variety of reinforcers, such as juice, money, food, sex, alcohol, cocaine and even humour and video games, causes increased activation in the Basal Ganglia, particularly in Nucleus Accumbens Other research has shown that in rats encounters with natural reinforcers (e.g., food, sex) leads to dopamine release from VTA neurons in their synapses with Nucleus Accumbens

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal Conditioned compensatory response

Subkov and Zilov (1937) - Pavlov's colleagues - Injected dogs with adrenaline (epinephrine) on several occasions - The effect of raising blood adrenaline is to increase the heart rate - The researchers noticed that the heart rate increase following each injection was getting smaller and smaller - So, the dogs appeared to develop tolerance to adrenaline - In other words, the organism appeared to compensate for the effect of adrenaline by reducing the heart rate around the time of the injection - Keep in mind that the brain is always trying to establish and maintain equilibrium, it is its optimal point of functioning - E.g., if you have drunk lots of alcohol you may feel bad or feel lots of anxiety the next day, partly because the gaba system has been stimulated so much that the brain started reducing the amount of GABA and then when you take away the alcohol it takes a while to adjust and then you feel alcohol during that period - To explore whether this compensatory reaction actually required the drug, the researchers placed the animals in the same stand and injected them with placebo (a neutral substance that does not affect blood adrenaline) - The researchers observed a substantial decrease in heart rate following the placebo injection - Thus, the dogs were conditioned to reduce their heart rate in response to the injection-related context. Importantly, following its acquisition, this compensatory response did not require the drug itself - it was a conditioned compensatory response

Neurons - Hodgkin and Huxley (1952)

Systematically measuring the responses of the neurons in different conditions. They measure the electric signals directly by inserting sharp electrodes (type of microelectrode) into the squid's giant nerve cell. The isolated axon (approx. 2cm) was laid in a bath of seawater. A recording microelectrode was placed inside of the axon and a reference one outside. They recorded the resting potential of the neuronal membrane in the inactive neuron.

Sensory Systems - Signal Transmission in Sensory Systems

Taste receptors, photoreceptors and hair cells are non-spiking receptors, which have very short axonal endings or non-axonal endings and therefore have to synapse on a first order sensory into a neuron which will then transmit the action potentials over longer distance to other areas of the sensory pathway in the brain The receptors that are spiking have very long axons, such as olfactory receptors, here the action potentials are generated directly in the axon of these receptor cells It is important that the signals that arrive from the sensory organs are kept separate and projected to other areas in the sensory systems and in the brain using action potentials, the only way to distinguish which signal codes for which sensory stimulus is by keeping them segregated

Motor Control - Hierarchical organisation

The control of movement has a similar hierarchical structure The primary motor cortex exerts direct control over movement However, the other areas (premotor and supplementary motor) are involved in the planning of movement and integration of motor behaviour with other behaviour In addition, some subcortical structures (Basal Ganglia) and brainstem structures and groups of cells (Cerebellum; Substantia Nigra) are also involved in the fine-grained coordination and timing of movements

Brain Function and Localisation - General Principles

The control over the basic physiological processes is performed in the "old" structures of the brainstem The reason relatively little 'brain space' is dedicated to such vital functions is that they are 'hard-wired' and not subject to plasticity (e.g., learning) Higher-order cognitive functions are supported by both cortical and subcortical structures Cortical representations show hierarchical organisation, with increasingly abstract level of stimulus representation (from primary to secondary sensory areas to association areas in the sensory and motor cortices) 'Primary' sensory and motor regions tend to occupy a relatively small area of the cortex compared to secondary and association areas, probably because the more complex and flexible (task-and goal-relevant) processing is performed by secondary and association areas

Human Genetic Variation - Examples of human local adaptations in geographic clusters

- Humans within a geographical region had more frequent contact and admixture than in distant populations - Several local adaptations found in some populations besides concentration of melanin in the skin - Through continued migration and admixing spreads alleles spread across populations

Biology of Stress - Resistance Stage

- If stressor is handled successfully, body restores homeostasis and feedback loops return stress hormones to 'baseline' levels (recovery) - May see reduced impact of dressed with repeated exposures - BUT severe, uncontrollable and long-lasting aversive events may lead to sustained activation of the HPA axis leading to a chronic stress response

Sensory Systems - Stopping and suppressing sensory input

- Just as nerve cells need to be inhibited, receptors and the signals they convey also need to be "switched off" at times - It can be necessary to suppress sensory input if it is very loud or damaging or to stop processing sensory input if it is in competition with sensory input from another modality - Often suppression involves accessory organs, such structures reduce the intensity or alter the stimulus before it reaches the receptor e.g., eyelids, muscles in ear - Or it can be via top-down processes, e.g., brain stem sends messages to receptor cells in the ear to selectively dampen sounds

Biology of Stress - What tips the balance between eustress and distress?

- Quality and intensity of the stressor - Characteristic of individual challenged by the stressor - Genetic predisposition - Past history/experience - Age or stage of development - Interpretation of stimuli varies between and within individuals and may be associated with emotional state (e.g., anxiety, arousal)

Motor Control - Population vectors

- What you tend to find in neurons in the primary motor cortex is that they prefer a range of directions - This is a key finding that has led to the development of the concept of population vectors - Vector - direction of cell's preferred direction combined with information about strength of firing - Tuning of neurons is broad - neurons tend to prefer several directions - Hard to predict direction of movement from activity of a single neuron - Population vector is the sum of individual neuron vector - Population vector provides the most accurate estimate of the planned direction of movement - Direction of movement can be predicted from population vector 300 ms before initiation of movement

3 main regions the brain is divided into

Forebrain = uses current sensory input and past experiences to make and communicate decisions Midbrain = uses current sensory input to direct movement (e.g., eye movement) Hindbrain = maintains current state (e.g., temperature, energy levels) and controls mouth and various sense organs

Neurons - Neurons are in most ways typical animal cells

Each neuron has similar organelles as any other cell e.g.: - A nucleus containing the DNA (with the majority of genes) - Mitochondria (the powerhouses of the cells contain mtDNA with few genes), important for generating energy so cell can live and function - Cytoplasm - Its cell membrane however is special, it makes the neurons a special type of cell and allows it to specialise, this is possible because the body is full of water but also full of electrically charged particles, ions

Evolution of the Brain - 60 million years ago

The first primates, opposable thumbs, can turn thumb inwards to face other fingers, can grasp objects, requires greater motor control from brain, binocular vision, overlapping field of view vision from eyes, trichromatic vision can see in 3 colours, earlier mammals on see mono or di chromatically

Hormone Structure and Action - The Pituitary Gland

The gland consists of two parts which do different things: - The pituitary gland sits just below the hypothalamus and is connected to the hypothalamus via the infundibulum, and it consists of two parts that do two different things: - The anterior pituitary or adenohypophysis = synthesises and secretes hormones Posterior pituitary or neurohypophysis = stores and secretes only (no synthesis)

The Logic in Neuropsychology - Neuropsychology: strengths and limitations

The obvious advantage of neuropsychology over electrophysiology and neuroimaging is that it enables causal inference The main drawback is that lesions resulting from trauma or neurological degeneration are rarely anatomically selective, they tend to affect multiple brain regions/structures Also, brain damage is always associated with general cognitive, emotional and personality changes whose effect on cognitive performance is very considerable and difficult to separate from the effects of damage to a specific region/structure Could one disrupt the brain selectively, reversibly and safely?

The Cognitive Neuroscience of Addiction - Drug taking as self-medication in mental illness Does mental illness cause drug use?

In the context of causes of addiction, the question whether mental illness can lead to drug use as self-medication seems important

Hormones and Behaviour - Social Behaviour in Humans Generosity Zak et al (2007)

N=68 men 'One shot' economic game involving a voluntary condonation Given oxytocin vs control via nasal spray Donation were ~80% higher in oxytocin group

Brain Development and Anatomy

Nervous system begins to develop about 2 weeks Starts a little group of cells that slowly thickens It then differentiates into a forebrain, midbrain and hindbrain Then fold over itself During that the forebrain develops into cortex, the midbrain into structures like the thalamus in the centre of the brain close to the brainstem and the hindbrain develops into the cerebellum

Neuroimaging - Preprocessing Steps 1 - High pass filtering

Remove low frequency oscillations such as scanner drift that introduce noise into your data Low frequency oscillations in signal which need to be removed from the data Standard low pass filter is applied to remove this, they are approx. 120 secs, removing any kind of oscillation in the signal that occurs over around about 2 minutes This is a fairly simple step

Hormones and Behaviour - Social Behaviour

- Affiliative behaviour - Generosity - Orgasm - Trust - Parental care

Biology of Stress - Stages of the stress response:

- Alarm - Resistance - recovery/exhaustion

Non-Genetic Variance - Mechanisms of Social Learning

1. Local (or location) enhancement 2. Stimulus enhancement 3. Observational conditioning 4. Imitation 5. Goal emulation

Motor Control - The Neurobiology of Motor Control Cognitive function of basal ganglia

Around 1990s it was recognised that the basal ganglia don't only play a role in motor control but also in cognitive functions Hayes et al (1998) - Study where subjects are required to press a response according to a particular dimension of a stimulus - Could be either colour or shape and the dimensions according to which they should respond can change from one trial to another, no shift trials and shift trials with variety of different stimuli - Hayes et al got Parkinson's disease patients and control subjects to carry out this task, measured reaction times and found that Parkinson's disease patients tended to be slower overall than control subjects, but they tended to be much slower on shift trials especially than on no shift trials - Patients with Parkinson's disease have problems with the flexible control of responding in terms of cognition not just in terms of motor function

Sensory Modalities - Auditory tuning curves

Auditory interneurons - Electrophysiological recordings from six cells in the cat's auditory nerve - Arrow shows the neuron's preferred frequency Perception/Behaviour - Psychophysical experiments measuring hearing threshold - Comparisons between species show different sensitivity ranges

Neuroimaging - Block vs Event-Related Designs

BOLD signal is slow, peaks 4-5 seconds after stimulus onset and takes around 16 seconds to return to baseline All fMRI experiments originally employed block designs long periods of alternating task/baseline performance Disadvantages of block designs: - Block designs often group together in lots of trials Psychological Limitations: - Highly predictable occurrence of stimuli, subjects know what is coming and may alter strategies accordingly (not always a pro) - Inflexible for more complex tasks, impact of oddball stimuli? - Or stimuli or events that occur uncontrollably? - Ecological validity, does blocking trials change the psychological process you are interested in? - Can't separate trials by performance, e.g., to look at activation associated with correct vs incorrect response

Motor Control - Some of the brain regions involved in motor control

Basal ganglia (otherwise known as the striatum)

Biology of Stress - Feeling a little bit 'stressed' can be good

Because it increases your arousal level Yerkes-Dodson law Arousal improves performance up to an optimal point Past this point, performance begins to decrease Precise pattern is task-dependent

Learning and Memory - Memory Processes: encoding, retrieval and consolidation

Brain activation patterns differ when information is encoded (acquired) and later recalled (e.g., recognition of a visual stimulus)

Effects of Brain Damage and Brain Stimulation as a Window into the Mind - The problem of causality

Brain imaging makes it possible to examine the brain substrates of psychological processes However, neuroimaging techniques, such as MRI and PET (and any other measurement) suffer from one serious limitation The fact that some brain activity is associated with a task hypothetical psychological process does not mean that the activity causes the observed behaviour or hypothesised psychological process Just because they are associated with each other doesn't mean there is a causal link, correlation does not necessarily mean causation

Neurons - Two neural signals: graded potential and action potential

- A graded potential is hyperpolarized when the membrane potential is more negative than the resting potential - The stronger the stimulating current, the stronger is the graded potential - A graded potential is depolarized: more positive membrane potential than the resting potential - Action potential: a spike following a depolarisation that crosses the voltage threshold

Hormones and Behaviour - How do hormones influence behaviour?

- Biological rhythm - Eating and drinking behaviour - Reproductive behaviour - Social behaviour - Stress

Hormone Structure and Action - Three main types of hormone:

- Protein hormones (incl. Peptide hormones) - Amine hormones - Steroid hormones

Genes and Behaviour - What are genes?

- Sections of DNA - Located on chromosomes (DNA coiled around histones) - Located in the cell nucleus - Each chromosome contains many genes, and each gene is producing a protein

Human Genetic Variation - Early and modern humans migrated out of Africa in small and big waves Out of Africa Model

- Several events when homo sapiens left Africa Main migration and dispersal waves (in time also backwards): - 300,000 years ago: migration to Middle East and Eurasia - 60-40,000 years ago: reached Australia - 20,000 years ago: reached the Americas

Hormones and Behaviour - Endocrine system

- Signal (might be a nerve impulse or releasing hormone) - Acts on the endocrine cell - Stimulating it to release hormones into bloodstream - Travels widely around body to affect distant target cells that have the specific receptor for that hormone

Motor Control - The Neurobiology of Motor Control Effects of transcranial direct current stipulation (tDCS) on visuomotor adaptation

- Simple method involving two electrodes that are attached to part of head that deliver electrical current across scalp into the neuronal tissue underneath scalp area - tDCS increases excitability of neurons under anodal electrode - Hypothesised to improve learning

Two different approaches to data analysis:

1) Whole brain analysis = as we have just seen, examine effects on a voxel-by-voxel basis across the whole brain 2) Region of interest (ROI) analysis = restrict our analysis to a particular brain region Advantages:

Evolution of the Brain - Earth formed __________________, life started and was present by approx. ___________.

4.6. Billion years ago 3.7 billion yrs ago

Hormones and Behaviour - Parental Care (own young)

= Female rats bred for high levels of maternal behaviours have more oxytocin receptors in the central nucleus of their amygdala Female prairie voles that show more maternal behaviour have higher oxytocin receptor density in their nuclear accumbens Blocking these receptors inhibits maternal behaviour

Motor Control - Representation of movement plans

A lot of what the brain does is related to planning movements and planning motor control and learning and adapting according to new stimulus input Do neurons encode the trajectory of movement (direction, distance, force) or location of the target?

Learning and Memory - Experience-dependent Plasticity

Changes that are caused by previous experience can be observed at the level of - Behaviour (actions, emotions, knowledge) - Neurons (neural network activity) - Synapses (interactions between individual neurons) The changes in plasticity that result and are caused by different types of experiences

Sensory Modalities - Sound waves mix and impinge on the tympanum

Different to the retina, the ear cannot spatially map the locations of sound Vibrations travel from the tympanum to the middle ear where they are amplified

Motor Control - Subcortical motor structures: Basal Ganglia

Five nuclei: caudate, putamen, globus pallidus, subthalamic nucleus and substantia nigra Critical role in selection and initiation of actions Parkinson's disease, gradual loss of domaine cells in these brain regions

Sex Differences - Biological sex:

I.e., differences due to sex chromosomes (xx VS xy) and the cascade of developmental changes that follow in the vast majority of people There are exceptions: · People with other genotypes (e.g., Turner syndrome (XO), Klinefelter syndrome (XXY) · People with XX/XY genotype but atypical development, often due to mutations (e.g., androgen insensitivity syndrome, 5α-reductase deficiency) · People who have undergone medical procedures to alter sex/gender phenotype (e.g., hormone therapy, gender reassignment surgery)

Motor Control - The Neurobiology of Motor Control Role of the Basal Ganglia in Motor Control - Parkinson's Disease

Loss of dopamine neurons in the basal ganglia (striatum) Main symptoms: - Hypokinesia: reduction in voluntary movement - Bradykinesia: slow movement - Tremor

Non-Genetic Variance - Maternal Effects

Offspring's behaviour or morphology is influenced by mother's behaviour or condition Lead to a strong resemblance between what the offspring is like and what the mother is like Variation between individual is better explained by considering the mother's phenotype rather than the individual's own genotype NOT genetic transmission (but easily confused with) May act pre-birth or post birth

Human Genetic Variation - Long-lasting impact of half a century of eugenics and race science

Opposition to eugenics and race science amongst scientists and society disputing the theoretical claims, methodologies, definitions and generated disproving evidence Numbers and visibility of opponents amongst scientists started to increase after 1925 but eugenics ideas persisted widely in society e.g., included in high-school textbooks still in the 1950s Supremacy ideas persist to date, and some scientists claim to show modern evidence or confirmation of data from eugenic studies. Open database is necessary

Vision - P- and M- ganglion cells project to different layers in the LGN

P-ganglion cells (project to Parvocellular layer in LGN) - small RFs, slower conduction speed, high acuity, poor response to transient stimuli, colour sensitive M-ganglion cells (project to Magnocellular layer in LGN) - large RFs, higher conduction speed, sensitive to motion, low acuity, no colour discrimination

Motor Control - The Neurobiology of Motor Control Neuroprosthetic control of hand

Paralysed man moves arm using power of thought Reconnects his brain with his muscles Take the electrical signals representing his thoughts and using it to control stimulation of his arm and hand Bridged his spinal cord entry, thinks about moving arm and it moves

Neurons - Action potential: falling phase

Resting potential - voltage-gated channels are closed Rising phase - shooting up in the depolarization caused by the opening of voltage-gated Na+ ion channels Overshoot - the membrane potential becomes positive as more and more Na+ flow into the cell (positive feedback loop) Falling phase - Na+ ion channels become inactivated and close, while K+ channels open leading to a reduction of positive charge inside of the cell Recovery - refractory period during which all channels are closed and membrane potential returns to resting value Undershoot - K+ ion flow out of the cell through the open K+ channels

The Cognitive Neuroscience of Addiction - The drugs' influence on processing of rewards (pleasure and incentives (motivation) Dopamine and reinforcement

So, if you block the dopamine systems, the reinforcer no longer matters, it becomes the same as not getting a reinforcement or not getting your reward, and that suggests that what actually is the reinforcer is your dopamine reaction in that part of the brain to something e.g., food, that's what is really rewarding and without it becomes pointless

Hormone Structure and Action - Where are hormones produced in the body?

They are produced from endocrine glands or endocrine organs

Genes and Behaviour - Genetic Mutation Example: IQ

This kind of approach has been used to study the genetic basis of a number of aspects of our behaviour and cognition e.g., IQ

Sensory Systems - Signal Transduction in Receptor Cells

Transduction: receptor cell transforms stimulus energy into neural signal

Genes and Behaviour - Selective Breeding for Behaviour Artificial selection: rats selected for maze-running ability

Variation in how quickly rats will run through maze to find reward Selective breeding means you can gradually separate the ability of these rats to run through the maze However later studies have shown that the effects of the genotype can be masked by environmental effects, so this genetic difference is only apparent under certain environmental conditions

Learning and Memory - Neural Plasticity: from behaviour to genes Spatial Learning in Rodents

Water Maze (Morris, 2008) - escape learning task in the water maze by finding hidden platform in a fixed location, different training and testing protocols to investigate the mechanisms of learning, memory and navigation, B and C: lister-hooded rats have much better vision than white rats widely used in research, PDAPP mouse, natural mutation, by trial5 the mouse is still very slow and misses the platform, D:normal/non-transgenic mouse sitting on the submerged escape platform, dramatic decrease in time as the trials go on that it takes for mouse to find platform

Sex Differences - Sexual dimorphism

differences between sexes in anatomy, physiology, psychology and behaviour

Electrophysiological recordings of brain activity Electrophysiological approach

where you are not measuring metabolic compounds as such, but are actually measuring the electric activity directly this is done using microelectrode recordings and EEG/ERP

Human Genetic Variation - Who are we? Where are we from?

- All present population originate from one ancestral population in Africa - Genetic variation exists in every species, also in humans - Humans have migrated and mixed continuously There is no biological basis for races, race is a social construct - There is no subspecies in humans

Sensory Systems - Receptor adaptation: adjustment of thresholds over time

- A receptor neuron responds to a stimulus within a limited range of stimulus intensities - It shifts its threshold within a limited range in order to code for the prevailing range of stimulus intensities (=sensory adaptation ← →) - This maximises its coding efficiency when it is exposed to continuous, unchanging stimuli

Human Genetic Variation - Genetic variation within the same species Differences in the DNA sequences (genomes)

- Between individuals (individual variation) - Form all individuals in a community that live in the same area and interbreed (within-population variation) - Between communities in different areas that have not interbred for some period of time (between-population variation

Neurons - Major changes in the nervous system during evolution

- All animals (except sponges) have neurons - During evolution the CNS appeared in animals that had evolved more complex body plans (results from cephalisation), elaborate movements, sense and reproductive systems - Cephalisation = the formation of central ganglia and brains in one end of the animal body - Dorsal chord in the vertebrate line of the animal kingdom - Ventral chord in the invertebrate line

Hormones and Behaviour - Social Behaviour in Humans Trust, Kosfeld et al (2005)

- 2 player economic 'trust' game - One player was role of investor and the other way trustee - Both receive at start of the game 12 monetary units - The investor chooses to send 0,4,8 or 12 MU to trustee - Amount sent is triple by the experimenter - Trustee decides how much of total to send back N=194 healthy male participants - Used placebo-controlled double-blind design - They administered oxytocin via 3 puffs per nostril of a nasal spray, oxytocin vs control (double blind) 50 mins before playing the game - Those who received oxytocin made transfer on average of ~17% higher than the control group, because of the double-blind design that demonstrates a causal effect of the hormone on donation behaviour

Motor Control - Muscles

- Composed of elastic fibres that can change length and tension - Arranged in antagonistic pairs e.g., biceps and triceps

The Cognitive Neuroscience of Addiction - Effects of drug tolerance and withdrawal

- The adrenaline produces increase in heart rate, over time that is the stimulus, - The body responds by lowering it, at first the environment had nothing to do with lowering it however over time your environment is associated with lowering - This the effect of a drug can be seen as an unconditioned stimulus (US) and cues associated with its administration can be seen as conditioned stimuli (CSs)

Synaptic Sequence - agonist/antagonist

= substances that bind to receptors ad either imitate the action of the transmitter (enhancing it) or prelude it

Synaptic Sequence - Neurotransmitter inactivation and recycling

1) diffusion: the transmitter is "lost" in the inter-cellular space 2) enzymatic degradation: enzymes break down the transmitter 3) re-uptake (uptake): the transmitter is recycled either in the pre-synaptic or the post-synaptic neuron. This is the most economical way to inactivate the transmitter: saves synthesis resources

Hormones and Behaviour - Oxytocin

= a mammalian peptide hormone that acts on the central nervous system - generally associated with uterine muscle contraction at birth and milk letdown - also governs a suite of prosocial behaviours (as do analogues (e.g., isotocin) in other taxonomic groups)

Neurons - Microelectrode recordings of membrane potentials

A microelectrode is either placed inside the neuron (intracellular recordings) and outside (extracellular recordings), two ways we can directly measure the signals of neurons Neuronal signals are measured as differences in potentials between wired electrodes (units-millivolt) by creating an electrical circuit that connects the electrodes with the intra- or extracellular fluids. The strength of the small currents can also be measured (units - milliampere)

Human Genetic Variation - Measuring correlations between traits prior to the genomic age Measuring the human body

Anthropometry: measuring variations in body, head (cranium) and face Correlation with racial categories, intelligence, behavioural (e.g., criminal acts) and psychological traits Francis Galton (1888) correlated head size vs degree results in 1000 male undergraduates at Cambridge University claiming a strong relationship and proposing later the concept of generalized mental ability (GMA, "g" factor). Pearson (1906: just r=0.11), later on Pearson found that the correlation within this data was actually not very strong

Synaptic Sequence - Methamphetamine ('Speed') and Amphetamine derivatives (e.g., Ecstasy)

As cocaine, these substances reduce the transport of monoamine neurotransmitters (dopamine, noradrenaline, serotonin) In addition, they also attach to enzymes that break down these neurotransmitters, speed, cocaine and ecstasy etc act on the enzymes that break down these neurotransmitters (noradrenaline, serotonin, dopamine) and they also prevent reuptake of these neurotransmitters which boost those nerve transmitter levels The overall effect is a boost in neurotransmitter transmission, this can cause you to begin feeling really high in mood because you have increased your serotonin levels and dopamine levels quite drastically This is very rewarding and keeps you awake so that creates all those sensations related to taking these drugs

Learning and Memory - Episodic-like Memories in Non-humans

Definition of human episodic memory: recall of unique experiences explicitly located in the past ('mental time traveller') as a conscious experience, language-based reports - Has been claimed for a long time that episodic memories are unique to humans and it is something that differentiates them from animals - In animals the ability to form and recall memories for events they personally experience in the past are tight to a specific context - Novelty and familiarity judgements, e.g., delayed non-matching to sample - Retrieval of when-where-what memories (Nick Clayton & Tony DIckinson 1998): learning of context-dependent tasks in scrub jays, had to learn where they stashed a mealworm or a seed, studies showed during tests jays were able to tell whether they stashed mealworm a long time ago or recently to make sure the mealworm was fresh

Learning and Memory - Appetitive Association

Degree of coincidence of CS and US determine learning outcome Temporal contiguity: reinforcement is most effective if reward coincides or follows the CS shortly after (forward pairing of CS and US) Furthermore, the US should be unexpected or surprising prior to conditioning, and the animal needs to attend to the CS

Evolution of the Brain - 65 million years ago

Dinosaurs wiped out, mammals flourish and diversity

Genes and Behaviour - Genotype and Phenotype

Genotype = the entire set of genes an individual possesses Phenotype = the observable characteristics of an individual, influenced by genes and environment

Human Genetic Variation - Human body height: classical example of quantitative genetics

Human body height is highly heritable but also a highly polygenic trait Studied for over a century, now genomic studies reveal the high complexity of genetic interactions and role of biologically relevant genes and non-coding DNA Hundreds of variants of many genes and non-coding DNA at more than 180 genomic loci determine how tall a person grows in a given environment (Allen et al, 2010, Nature, 467, 832-838 Locus - physical location of a gene or other DNA sequence on a chromosome

Genes and Behaviour - Gene products: proteins

Large, complex molecules that do most of the work in cells Proteins are large complex molecules doing most of the work in cells, they have a number of structures including primary, secondary, tertiary and quaternary structures There are a variety of types of proteins: - Antibodies - Enzymes - Messengers e.g., hormones - Structural components e.g., membrane channels, actin in muscles - Transport/storage of substances

Sensory Systems - Receptors that transmit signals from skin to spinal cord

Pacinian corpuscle (in skin, muscles - detecting vibration and pressure) is a unipolar cell that extends one branch of its axon to skin and other to spinal cord Afferent projection forms the dorsal root (spinal) nerve, and the cell bodies are part of the dorsal root (spinal) ganglion

Genes and Behaviour - To what extent is behaviour transmitted by genes? Traits are determined by genes and the environment in conjunction which often leads to continuous variation in traits

Quantitative traits can be: - Morphological - Physiological - Behavioural Norm of reaction = pattern of phenotypic expression of a single genotype across a range of environments

Vision - Most Mammals have Dichromatic Colour Vision

S-cones (short wavelength sensitive receptor) M-cones (medium wavelength sensitive receptor) L-cones (long-wavelength sensitive receptor) - Most mammals are dichromats and lack the M-cone - Trichromats (humans, few old-world primates) discriminate more colours than dichromats - Marine mammals (whales, seals) do not see colours (only L-cone)

Sensory Systems - Small and large receptive field of neurons

Small receptive fields in touch-sensitive receptors: free nerve endings, Merkel's disc and Meissner's corpuscle sense innervate the surface of the skin and are sensitive to stimuli in small areas of the skin, therefore it is said that they have small receptive field, they respond to touch only in this very small area of the skin Wide or large receptive fields: Pacinian corpuscles and Ruffini's endings innervate deeper layers of the skin and are sensitive to stimuli over a larger area of the skin, have wide or large receptive fields

Non-Genetic Variance - Social Learning Difference pervasive form of non-genetic inheritance Example:

Spread of milk-bottle opening by tits in the UK - Fisher & Hinde (1949) suggested to be responsible for the spread of milk-bottle opening behaviour by blue tits and other tit species across the UK in the last century Milk delivered to doorstep and tits learned to peck through top caps to get access to the milk and cream underneath The experimenters documented the locations in the UK where this behaviour could be found Prior to 1935, there were only a few isolated locations where this was found By 1947, it was much more widespread and the speed of the spread of this behaviour means it is likely to be happening too fast to be explained by genetic transmission

Brain Anatomy and Localisation: Perception - Hierarchical Organisation

The cortical areas where the sensory information arrives (via relay nuclei in the brainstem, particularly via the Thalamus) are referred to as primary visual/auditory/sensory-motor areas This perceptual information then gets passed to the secondary sensory areas, where more sophisticated processing takes place From the secondary sensory areas, the processing moves to the association areas where information from different modalities and of different types is integrated Higher order processing occurring, other part of the brain no longer directly related to perception want to do something with objects, brain is set of neurons allowing you to process environmental information Thalamic nuclei relays for sensory information, different elements do different things, processing of information into what we know as a meaningful experience

Synapses and Networks - Signal weakens the longer it travels

The longer the distance the stronger the attenuation There need to be many voltage-gated ion channels along the whole axon - Solutions to reduce costs of signal transmission: - Long neurons have thick axons (squid, invertebrates) - Myelinisation of axons in spiking neurons (mostly vertebrates), white matter - Neurologia cells: Assist the signal propagation (Schwann cells, oligodendrocytes) Provide nutrients to neurons (astrocytes) Clear debris and mediate immune response (microglia)

Motor Control - The _______ is our motor control e.g., moving hands and feet

The output is our motor control e.g., moving hands and feet

Hormone Structure and Action - Pituitary hormones and their targets

The pituitary gland is a really important endocrine gland because it's involved in the production and regulation of so many important hormones in our bodies The pituitary gland is richly vascularised, there is a proliferation of blood vessels and projecting down from the hypothalamus there are neuroendocrine cells which produces releasing hormone which travels around the network and stimulates the production of various other hormones by the pituitary gland that have a variety of effects on the body There then may be negative feedback effects on both the pituitary gland and the hypothalamus to inhibit further production of those particular hormones

Electrophysiological recordings of brain activity - What information can one extract from an EEG? One can examine how rapidly the EEG signal oscillates:

This is referred as frequency or spectral analysis The frequency and shape of EEG can be used to inform us on sleep behaviour or detect pathologies (e.g., epilepsy) Segments of the EEG associated with particular stimuli can be analysed separately: Event-Related Potentials (ERPs)

Neuroimaging - Preprocessing Steps 5 - Normalization

When we're doing an fMRI experiment, as with other experiments, what we are interested in is not the activation of any particular subject, but we are interested in scanning a whole group of subjects and trying to make some claims that we can then apply to the whole population To do that we need to be able to compare activations across different subjects Different subjects have different brains, and they have different shaped brains, more substantially in some situations then in others Every brain is different however ultimately, we want to bring all of those brains into alignment, so what we do is we warp each brain into what we call a standardised space using an international standard. Standardised space - Montreal Neurological Institute (MNI) space Combination of 352 MRI scans on normal controls Why normalise? So that we can compare activation across subjects and do group analyses What we do with normalisation is we take each individual brain, and we warp it so that it fits into that standardised brain This is quite a complex step and there are a number of complex algorithms involved which change the brain

Hormones and Behaviour - Biological Rhythms Melatonin controls breeding condition in seasonally breeding animals

e.g., hamsters - as animal moves into autumn, it senses longer autumn nights using pineal gland - pineal gland prolongs nocturnal secretion of melatonin which makes hypothalamus more sensitive to -ve feedback effects of gonadal steroids - so, less GnRH is released, and less gonadotropin is released to gonads atrophy - when spring returns the animal sense shorter spring night, pineal gland reduced nocturnal secretion of melatonin - the hypothalamus becomes less sensitive to -ve feedback effects of gonadal steroids and more GnRH is released - so, more gonadotropin is released, and the gonads swell, and the animal prepares to breed - so, it's these changes in day length across the year that caused the pineal gland to change its release of melatonin that has these knock-on effects on condition of gonads

Sex Differences - Sex Differences in the Brain Brain masculinisation

- Female guinea pigs treated with testosterone when pregnant produce defeminised, masculinised daughters with male-typical behaviour - Female rhesus macaques given testosterone as new-borns show male-typical behaviour as adults: - Pursuit and mounting of other females Pelvic thrusting - Post-ejaculatory behaviours - Preference for female partners Can see a causal effect of testosterone levels on these sex differences in behaviour

Genes and Behaviour - To what extent is behaviour transmitted by genes? Maternal behaviour in mice

A more complex example Maternal behaviour in mice and maternal behaviour involves a range of different activity E.g., creating a nest, nursing etc ... A single fosB mutation in mice causes disruption of maternal behaviour: creating a nest, cleaning the pups, retrieving them to the nest, crouching over them for warmth and nursing The mouse with this fosB mutation can be seen ignoring her pups and not showing the characteristic maternal behaviour Though we have a complex behaviour a single gene can determine phenotypic expression of complex behaviour fosB gene products widely expressed in brain, but mainly in preoptic area of hypothalamus (critical for nurturing behaviour) fosB-deficient mice have normal motor behaviour, normal levels of reproductive hormones and enact glands (i.e., mutation has specific effect)

Human Genetic Variation - Over ten years of GWAS in psychiatry

Candidate genes studied for several decades but studies often underpowered, with small sample sizes. First GWAS study in psychiatry in 2007 funded by the Welcome Trust By March 2017 there were 2,430 studies, 1,818 phenotypes and 28,462 associated SNPs reported in the GWAS catalogue. Psychology-related: 472 studies on 198 phenotypes and 6,632 SNPs SNP-Phenotype Network - Red: significant association (p≤2x10 ^-8) with psychological/psychiatric phenotypes (yellow) and at least one other phenotype - Blue: non-psychological phenotype Shows that a number of psychological traits, e.g., Alzheimer's disease, can be correlated in these snip phenotype networks, we know quite a lot about a few candidate genes and again the location of these genes I known so these snips can be analysed in relationship to non-gene functions even though a lot of snips are located in non-coding DN

Sensory Systems - Connectivity in the brain

Connectivity is identified anatomically or functionally Descriptions of anatomical connections give very limited insight into functional hierarchies and information flow: 1) serial connections Bottom-up processing (e.g., sensory organ to primary cortex) Top-down control (e.g., modulation, inhibition, synchronisation) 2) parallel streams (e.g., signals diverge into different networks) 3) cross-connections (e.g., modulation, inhibition, synchronisation) Diagram of the connectivity in the primate visual system (Felleman & Van Essen, 1991, Cereb. Cortex) - This kind of connectivity is identified either functionally or anatomically, there are many functional interactions between brain areas that also rely on the knowledge of the anatomical connectivity and functional significance that could be established - The anatomical connection itself is quite limited in terms of how these hierarchies are organised, what their particular functions are, what happens at each step of that permit and how information is flowing - Information can flow in both directions from the sensory organ diverging into different areas (bottom-up processing), but also different areas can exert control on other layers and if the information typically travels through those layers first and these areas connect back to those layers it could be mentioned in terms of top-down control - The cross connections help to modulate the activity of neural network, inhibit networks or synchronise networks

Electrophysiological recordings of brain activity ERPs: averaging segments

Different types of stimuli are separately averaged and then compared - E.g., famous faces versus non-famous faces - Cut out the bits of the EEG that follow each particular stimulus and then you average all them together for each of the stimuli - The reason you do that is because at any given moment in the EEG lots of different things are happening, so it makes it particularly related to the stimulus - You often take a small section of the pre-stimulus period and then a slightly arbitrary amount of time depending on the time interval, after the stimulus you are interested in also, you take that and you do x100 trials and you average it using a signal averaging computer and you get instead of a picture showing all activation, a waveform showing the event-related potential of the particular stimulus

Human Genetic Variation - Mystery of shrinking body heights

Discovery of previously unknown cyclic changes in human body height in Europe and North America during the Industrial revolution Shrinking body sizes in soldiers and workers despite growing economies Intensification of labour spared economic interest in understanding the biological causes and the impact of nutrition and health in early age in body conditions

Biology of Stress - Coping and Cognitive Appraisal Lazarus's transactional theory (Lazarus (1966), Lazarus & Folkman (1984)

Dynamic relationship between: - Environmental demands (stressors) - Individual's psychological resources for dealing with them (coping ability) 'Negative stress' (≈distress) results from a perceived imbalance between these demands and resources Beginnings of modern research on stress: combars stress in WWII veterans (Lazarus & Folkman, 1984) Why did some soldiers cope with the horror when their comrades did not?

Genes and Behaviour - Genetic Mutation

Estimates of genetic and environmental effects from twin studies Genetic mutation occurs spontaneously in organism in their natural environments but there are certain things that can increase the mutation rate above the normal spontaneous levels Mutagens and radiation increase mutation rate above the spontaneous level

Neurons - Hodgkin-Huxley Model: Action potentials are mediated by Na+ and K+ voltage-gated channels

Hodgkin-Huxley Model: Action potentials are mediated by Na+ and K+ voltage-gated channels Resting potential - voltage-gated Na+ and K+ channels are closed They postulated that these two types of channels, the voltage-gated potassium and sodium channels are the main ones that contribute to the generation of the action potential When they added a depolarising current, they measured a depolarizing graded potential that quickly turned into a spike, reaches a maximum value called the rising phase Rising phase - depolarization caused by the opening of voltage-gated Na+ ion channels Showed that the rising phase is mediated by sodium ions that flow into the cell Overshoot - the membrane potential becomes positive as more and more Na+ flows into the cell (positive feedback loop)

Hormone Structure and Action - What controls hormone production?

Hormone production needs to be constantly managed Feedback loops play a key role Usually this involves negative feedback: high levels of hormone inhibit production of hormone → maintains homeostasis, maintains systems relatively steady state Sometimes do involve positive feedback, example is oxytocin secretion in milk letdown reflex Key pathways of hormonal production and regulation: - Autocrine feedback - Target cell feedback - Brain regulation - Brain and pituitary regulation

Learning and Memory - Neural Plasticity: from behaviour to genes Structural changes in the hippocampus are associated with extensive spatial learning and route following

How adaptable and changeable is the brain? - Response to environmental stimulation under natural conditions - London Taxi Drivers have large hippocampi (Maguire et al. 2000 PNAS) - Compared to bus drivers have greater grey matter volume in mid-posterior hippocampi and less volume in anterior hippocampi (Maguire et al 2006 Hippocampus)

Evolution of the Brain - Last 2 million years of evolution

Humans, in last 1.5 million years rapid expansion of brain size in homoerectus particularly, debate about why such a massive expansion in brain volume in that period, changes in hands and teeth tended to happen before rapid expansion of brain size, perhaps associated with use of tools, use of tools allows you to obtain more energy which enables you to build a bigger brain

Human Genetic Variation - GWAS: potential for personalised treatments

Importantly in a population, these genome-wide associations generate a genetic profile at the population level that differ in different population which help to estimate predisposition and risks to different health related conditions in a population to establish individual risk profiles and from those it is possible to derive individual risk profiles which can help to develop personalised treatments to prevent and treat disorders more effectively Increasing amounts of data become available from hospitals New for new diagnostic tools, drugs and therapies that prevent or treat diseases more effectively and with less side effects

Sensory Modalities - Tonotopic mapping in the inferior colliculus and A1

In all layers including the cortex and the inferior colliculus there are tonotopic mappings

Neurons - Chemical Concentration Gradients

In any situation where ions can move, they will try to distribute themselves evenly, they constantly move Diffusion, if particles are poured in one end then over time they will distribute and the whole body of water will have the same concentration everywhere, particles move from areas of high concentration to areas of low concentration, they move down their concentration gradient

Sensory Systems - Sensory receptors and interneurons project to segregated areas

In the cortex, the primary sensory cortices are all located in different areas

Motor Control - The Neurobiology of Motor Control Visuomotor Adaptation, Seidler et al (2006)

Inaccurate visual feedback while subject performs task Early trials show adjustment or late adjustment when they realise what is going on Movement trajectories for final trials are much more adapted and better accurate If you do this kind of experiment with an fMRI you can see a range of different brain regions including frontal cortex and basal ganglia, in early trials you can see an increase in activation across many different brain regions but using fMRI means it's not clear what different regions are doing, only activation is shown Increased activations across motor regions with visuomotor adaptation, but what do these increases mean? - Formation and storage of new motor patterns - Prediction error? - Increased attention? Patients with lesions in the cerebellum, prefrontal cortex and parietal cortex have deficits in learning to move in novel environment What are the different contributions of these brain regions to sensorimotor adaptation?

Vision - Neurons of the M- and P- pathway project to different layers in VI

M-cells project to layer 4ca P-cells project to layer 4c and 2,3b (interblob) The projection that originates from the P- and M- ganglion cells via the magnocellular and parvocellular layers in the LGN so there is a key separation between the pathways even though they receive the same information at the same time from the same receptors that send their signals parallel through these two pathways

Learning and Memory - Optogenetics: precise temporary inactivation of neurons

More precise and also reversible Light-sensitive molecules are inserted in membrane using genetic tools and genetic engineering, animals are selectively bred to generate transgenic lines to investigate specific circuits in the brain, genetically tractable models: mainly mice, Drosophila flies, zebrafish larvae ChR2 channel-rhodopsin (blue light sensitive) and NpHR halo-rhodopsin (yellow light sensitive), the genes that code for these rhodopsins are inherited through transgenic lines and expressed in each individual that is bred, functional control of targeted cell types using light of a specific wavelength, microstimulations during behavioural tests with high spatial and temporal precision, reversible, temporary manipulation allowing within-subject comparisons

Synapses and Networks - Conduction velocity increases with increase of diameter and with myelinisation of axons

Myelinated neurons with thin axons can reach similar conduction velocities as those with unmyelinated thick axons, Hill et al (2008) Animal Physiology

Learning and Memory - Neural Plasticity: from behaviour to genes NMDA Receptors Act as Coincidence Detectors

NMDA receptors open when both conditions are met: 1) binding of glutamate 2) membrane depolarizes above threshold expelling the Mg2+ plug This leads to an influx of Ca2+ ions into the postsynaptic cell, which also contributes to the EPSP

The Logic in Neuropsychology - A suitable control condition

Need to control for somatosensory and auditory effects of TMS No TMS is not enough as a control, because at least some of the effect of TMS is due to the noise and sensation it elicits Sham TMS-noise but no stimulation: does not control for somatosensory component (the sensation on the scalp, muscle twitches, discomfort) Better control site (over area that is unlikely to be involved in task) Sometimes it is difficult to ensure that control site has equivalent somatosensory and auditory effects to test site

Two main ways brain sends messages to rest of body:

Nervous system, electrical signals = quick and costly, network structure determines which cells receive the messages, messages travel to target cells at tips of neurons Vascular system (blood system), hormones (chemical communication) = slow and cheap, typically takes a second to reach target, not very energetically expensive, smaller infrastructure costs, membrane receptors determine which cells receive the message

Sex Differences - Types of Hormone Action

Organisational effects = effects on tissue differentiation and development, these are permanent, fundamentally changing development of tissues in permanent way Activational effects = effects of hormones that occur in a fully developed organism; may depend on prior exposure to organisational effects of hormones, transient effect, it does not persist indefinitely Sexual differentiation in mammals depends on organisational effects of hormones during development

Genes and Behaviour - Genetic Mutation E.g., social amnesia is related to mutation in single gene

Related to the hormone oxytocin Mice carry a particular mutation that knocks out oxytocin gene, can't produce it, males having this mutation show a drastic change in their social behaviour If they are presented with an unfamiliar female, then over time the normal mouse after successive presentation with that same female would investigate less and less Whereas a male with this oxytocin mutation has social amnesia and treats the female as if they are unfamiliar every time The lack of oxytocin production means that they don't recognise that female that they have encountered previously

Neuroimaging - Brain imaging techniques

Structural: taking images in the brain at a single point in time (e.g., CT, MRI) Functional: enables us to take images of the brain at different points in time whilst the brain is active (e.g., PET and fMRI)

The Cognitive Neuroscience of Addiction - What drugs do people get addicted to?

The more compatible it is with daily life the more likely it is you will get addicted to it Ideas around the length of use, shorter trips are more addictive because they are compatible with daily life Drugs associated with addiction - Nicotine - Alcohol - Amphetamine - Caffeine - Heroin - cocaine/crack - (Cannabis) - (prescription drugs, such as painkillers and Benzo's) Drugs less associated with addiction - MDMA - Psychedelics - Behaviours associated with addiction - Gambling - Gaming? - Sex addiction?

Neuroimaging - Preprocessing Steps 6 - Spatial Smoothing Effect of Smoothing on Activation Maps

The unsmoothed data can see is kind of speckly and pixelated with random spots of activation which are fairly unconnected The on the data after it has been smoothed everything goes more blurry on the scan, what is happening if you are getting rid of the sharp transitions between voxels and you are smoothing them out so the voxels have a more smooth transition from one to the next This leads to clusters of activation, you can begin to see patterns where neighbouring clusters become activated, this is a very important step in being able to identify clusters of co-activated voxels

Hormone Structure and Action - Action of protein and amine hormones

There is a particular receptor in the cell membrane (see diagram) that is specific to a particular hormone type And when these protein hormones arrive at this target cell because this particular target cell has specificity for this protein hormone then that protein hormone can bind to that receptor, which changes the shape of the receptor This induces the release of substances within the cell, which initiates a series of processes, so these substances released within the cell are referred to a secondary messenger which then alter the function of the cell and they can have a range of biological effects Example: if you consider the effects of the amine hormone adrenaline and noradrenaline which have a wide range of physiological effects such as increased heart rate

Human Genetic Variation - Measuring correlations between traits prior to the genomic age Broad population surveys and case studies

Trace differences in mental, emotional, personality and behavioural traits (e.g., alcoholism, "feeblemindedness") through IQ tests, genealogy or statistical surveys of mental ("madness") and other illnesses (e.g., Tuskegee study of syphilis in African Americans)