Psyc 301 - Exam 2

Genetics and MS

- Even if there is a little genetics, its not very high - Very high external factor that is causing this

What would happen if damage to ventral pathway?

Trouble with meaningfulness of words Might be able to say syllables back to someone But don't understand that they form a word Trouble with morpheme Wernicke's aphasia

Primary Motor Cortex

Aka precentral gyrus, M1 Somatotopic organization: homunculus (Penfield) - map built in Receives feedback from muscle and joints Neurons code for preferred direction Damage is not as disruptive as you might think - independent movement - astereognosia - reduced speed/accuracy/force Plan goes here to make movements happen Large lesions don't have that much of an effect - loss of functional segregation - loss of moving limbs independently, but can still use it Astereognosia: loss of ability to recognize items by touch

What would happen if there is damage to dorsal pathway?

Won't be able to speak, trouble producing speech at all Comprehension still pretty good Utter a few words Ex. "Tan, Broca's aphasia

Grandmother Cell Argument

Brain must code things in a certain way (must be distributed) - if your grandmother cell got destroyed, you would not know your grandmother

Dopamine's Role in Movement

D1 receptors more in direct pathway D2 receptors more in indirect pathway When dopamine is released from substantia nigra, you are to have a stronger go pathway and a weaker stop pathway - dopamine encourages movement Dopamine D1-family receptors have a positive modulatory role Dopamine D2-family receptors have a negative modulatory role SNc releases dopamine onto striatum D1R activity increases transmission in the direct/GO pathway D2R activity decreases transmission in the indirect/STOP pathway Net result: more go, less stop -> Movement

Case Study: Patient G.O.

Damage to somatosensory nerves of his arms Numerous problems with movement Could no longer feel touch, vibration Had problems with doing tasks Wasn't getting any feedback so he couldn't adjust for changes He could still use his hand Difficult time maintaining the right amount of force Had to look at his hand to keep holding something

Episodic Memory

How you felt The story you remember

Brain and Memory

Inflexibility might be more important than flexibility - if your brain changes too much, you'll lose your memories and the things that make you you

Fluent Aphasia

Intact vocal mechanisms, can speak, real words, words don't make sense altogether - ex. Wernicke's aphasia - often accompanied with troubles with speech comprehension Impairment in input or reception of language, but not production 1. Wernicke's aphasia, or Sensory Aphasia - deficits in classifying sounds or comprehending words - word salad: intelligible words strung together randomly - patient confuses phonetic characteristics - Cannot write because cannot discern phonemic characteristics - can grasp little segments that make sense, but as a whole doesn't make sense - can't comprehend his own words 2. Conduction Aphasia - can speak, name objects, and understand speech but cannot repeat words - problem is a disconnection between the "perceptual word image" and the motor systems producing the words - cannot repeat words - can't do rote tasks, like counting 3. Anomic Aphasia or Amnesic Aphasia - can comprehend speech, produce meaningful speech, and can repeat speech - great difficulty naming objects - ex. a patient who sees a picture of a ship anchor.. "I know what it does , you use it to anchor a ship" - although patient is able to use word as a verb they are unable to access it as a noun

Broca's Area

Is at the front 2 parts of Broca's area - anterior/ventral = involve in semantic processing (meaning of the words) - posterior/dorsal = sounds themselves (phonological processing) - production, phonemes themselves Archiar faliculus

Contemporary Theory: Dual Language Pathway

Language moving in multiple directions Area 6 (motor cortex) and 47 (semantics?) are often the targets of flow of info Bottom-up/Dorsal Language Pathway - language production pathway - only pathway used when someone is asked to repeat nonsense words - related to short-term/working memory - take semantics and put it to action - hold it in working memory - phonetics Top-down/Ventral Language Pathway - has to do with semantics, meaning of the language - also important for separating homonyms - interacts with our long-term memory (e.g., our vocabularly) - what is the meaning of sound - knowledge you have (vocab, things in your long-term memory, semantics( and sending it to the most basic processes - semantics - long-term memory

Damage to the Cerebellum - Possible Effects

Loss of ability to precisely control the direction, force, velocity, and amplitude of movements Loss of ability to adapt patterns of motor output to changing conditions Difficulties in maintaining steady postures (e.g., standing) Disturbances in balance, gait, and the control of eye movement Impairments on measures of attention and executive control, procedural memory, working memory, language and visual-spatial processing Impairments in the learning of new motor sequences May have trouble keeping a beat Only 10% of brain, but 50% of neurons See loss of coordination when alcohol is consumed Could remove it from a brain and they would live Loss of ability to adapt patterns - correcting

Parkinson's Disease

Loss of dopamine (90% of substantia nigra neurons have died by the time symptoms emerge) If you lose this dopaminergic activity - less activity in GO pathway, more activity in STOP pathway Resting tremor, losing the inhibition of a tremor that we all have - probably from the cerebellum, when you lose these dopamine receptors is when you see it In PD, most of the dopaminergic neurons of the SNc die As such, dopamine is not released onto the striatum This decreases transmission in the GO pathway This also increases transmission in the STOP pathway Net result: less go, more stop = diminished movement Treatment? - L-Dopa - Deep brain stimulation of the STN

Guest Lecture - Traumatic Brain Injury

Luge accident GCS score was 4 and 24 hours later was 4 - best score was 15 Her initial crash gave her a grade 2 concussion, then this second accident really topped it off Subdural hematoma (volume of a tennis ball) - in right frontal lobe - skull fracture on the left - brain was swollen Woke up 10 days after incident Lost ability to walk/talk Within the next week in neuro unit, she made huge progress - swelling went down and cognitive performance came back Started being able to walk well Sodium chloride deficient for 6 months - had to have extra salt Had troubles with balance because the hematoma was pressing on cerebellum Only had 1 - 3 month follow up Wasn't going to school, exhibiting signs of depression Wouldn't sleep more than 15 minutes per night in hospital - insomnia has stayed with her Crashed in January, first day back to school was in March, and only went back for 2hrs/day and added on By the end of the year, she wrote her finals Had issues with short-term memory and balance Had a 10 year follow up - called in for research purposes - scar tissue in brain - dead tissue in areas that didn't have bleeding - memorization takes a lot extra effort - balance is still an issue - anxiety levels increase Had a concussion since, but recovered fine

Chronic vs. Acute Dysfunction

Massive tumour, little impairment vs. Sudden stroke with associated damage (of a comparable size), functionally devastated When you have slow growth, you have reorganization occurring at the same time

Planning Out Movements

More than one way to carry out a movement Ex. signing your name with your toe Motor Equivalence = when you can do the same thing with different motor groups - ex. writing your name with your hand and then your foot - motor programs are coded independent of the group of muscles

Two Pathways of the Basal Ganglia

1. "Go" Pathway - encourages activity to happen - excites - direct pathway 2. "Stop" Pathway - discourages activity - inhibits - indirect pathway Motor/premotor areas in frontal cortex are normally tonically inhibited - result = no movement To activate motor cortex, we need to inhibit the inhibition: this is called disinhibition - result = movement Direct/"Go" Pathway: facilitates disinhibition of frontal cortex Indirect/"Stop" Pathway: facilitates inhibition of frontal cortex Whether or not movement occurs depends on balance of activity in these 2 pathways Motor output depends on a ratio of indirect pathway activity vs. direct pathway activity Different from hierarchy discussed earlier, this is happening outside of the motor hierarchy - problems with basal ganglia can result in a lot of problems with actions

Language Disorders

1. Aphasia - most broad - inability or difficulty producing coherent speech - many cases they can speak, but doesn't mean they are conveying meaningful sentences - 2 types: fluent and non-fluent 2. Alexia - inability to read 3. Dyslexia - difficulties reading 4. Agraphia - inability to write

Posterior Parietal Cortex Damage

1. Apraxia (inability to perform movements on command) - occurs when posterior parietal association cortex is lesioned - associated with left hemisphere damage - symptoms are bilateral - left posterior parietal damage -apraxia is seen on both sides, even though damage is on left - inability to perform a movement when asked to - evident on nonsensical gestures, and using tools, problems with mimicking gestures 2. Contralateral Neglect (fail to respond to visual, auditory, or somatosensory stimuli) - produced by very large right parietal lesions - individuals only attend to right side of body or items in environment - individuals are capable of unconsciously perceiving objects on the left - cant attend to their left, egocentric, if they turn they could see what they previously couldn't - no problem with their perception

Hierarchal Control of Movement

1. Association Cortex 2. Secondary Motor Cortex 3. Primary Motor Cortex - elicits the movements 4. Brain Stem Motor Nuclei 5. Spinal Motor Circuits Advantage of this design: - as you learn, lower levels of hierarchy can take care of a lot of tasks, higher levels can focus on more complex tasks But, basal ganglia and cerebellum are often left out of this model, but they are involved in movement

The Old Theory: Wernicke-Geschwind Model of Language

1. Comprehension is extracted from sounds in Wernicke's area 2. And passed over the arcuate fasciculus pathway 3. To Broca's area to be articulated as speech Word sounds are sent to the Primary Auditory Cortex Word meaning is represented in Wernicke's area Word meaning is sent to Broca's area via the arcuate fasciculus Broca's area sends instructions for speech articulation to the motor cortex To read, visual areas send information to the angular gyrus and to Wernicke's or Broca's area Shortcomings to this model: - doesn't take into account many other brain regions involved - overly simplistic when it comes to "regions" of Broca's area, Wernicke's area, and directionality of flow - relied mostly on diffuse loss-of-function studies - unilateral directionality, which realistically doesn't work - we should be going in both directions

Types of Memory - Based on Level of Awareness

1. Explicit Memory - conscious access to it - ex. going to school for the first time 2. Implicit Memory - don't have access to it, not explicitly accessible - ex. how to ride a bike

Movement: more than motor neurons

1. Intention/decision/goal: ex. "I want to chop an onion" 2. Motor Plan - pick up onion, pick up knife, etc. - motor patterns and need the right sequence 3. Motor Signal - deliver individual components of motor plan 4. Movement 5. Sensory Information - proprioception: ex. if you close your eyes, you still know where your body is; your awareness/perception of self in the world -sensory feedback (ex. how successfully did we chop the onion) - visual, auditory, etc. information - use as feedback to adjust and fine tune motor signals

Why is studying neural basis of language complex?

1. Most of the brain takes part in language in one way or another 2. Most patients who add information to studies of language have had strokes, usually of the middle cerebral artery 3. Immediately following stroke, symptoms are generally severe but improve considerably as time passes 4. Aphasia syndromes described as nonfluent (Broca's) or fluent (Wernicke's) have many varied symptoms, each of which may have different neural basis

Language in non-human animals

1. Raised a chimp as much like a human by trying to teach it language - "Nim Chimpsky" - failure to learn language - using ASL would say things like "banana eat me" - no syntax 2. "Yerkish" Computer learning - chimps passed their vocabulary on to their offspring - but again, missed the syntax 3. Alex the parrot - can look at objects and answer questions about them - shows he can understand - amazing vocabulary - can speak back to you - was able to discriminate between blue blocks - hard cognitive task to differentiate, had a concept of zero - was able to generate words that he had never heard before - ex. first time he was presented with apple he made up a word "banerry" because he had had banana and strawberry before - but even he couldn't understand syntax - researcher got a pet store owner to choose a parrot at random, to prove she could train an average parrot

Types of Amnesia

1. Retrograde Amnesia - loss of memories you already had, but can form new memories 2. Anterograde Amnesia - the events that happened right before may be a bit lost - long-term past memories are maintained - but can't form new memories

Central Sensorimotor Program Theory

1. The lower levels of the sensorimotor system hierarchy possess "sensorimotor programs", and those programs represent particular patterns of activity 2. A particular movement is produced by activating the appropriate combination of these sensorimotor programs 3. Once a particular level of the sensorimotor hierarchy is activated, it is capable of operating on the basis of sensory feedback without direct control by the higher levels Higher things are designed from higher sensorimotor programs Lower levels are handling the stuff that we don't need to think about (automatic) Don't need cortex to keep helping you

Viral Infections - 2 types

1. Those that have a particular affinity for neural tissue 2. Those that attack all tissues indiscriminately - including nervous tissue

Different Causes of Movement

1. Top-down: guided by thoughts, self, your deliberate focused attention - intentional, voluntary - ex. you choosing to look for your keys - frontal eye field/supplementary eye field - for voluntary eye movements 2. Bottom-up - ex. fly goes past frog, tongue snatches it - superior colliculus - what makes you look at bright lights - or hearing a loud noise - automatic, driven by environmental stimuli process

Sensorimotor Association Cortex

2 main sections: 1. Dorsolateral prefrontal association cortex 2. Posterior parietal cortex Multimodal - get input from a lot of sensory systems - info is quite abstract

Bacterium

A unicellular organism Has a plasnomembrane Self-sustaining Large in comparison to virus

Describe Ramachandran's theory of anosognosia that incorporates hemispheric specialization

Ansognosia only seems to appear when damage is on the right hemisphere - gives you the clue for why this happens lies in the hemispheric specialization You ignore something that doesn't fit with your belief system, so you don't have to completely rewrite your belief system Minor discrepancy it makes sense to deny something Large discrepancy, you need a mechanism to say you need to rewrite the entire script - that is what your right hemisphere does - so if it is damaged, the left hemisphere allows you to deny things and the right hemisphere does not stop it

"Go" Pathway

At rest, your GPi is constantly telling your motor cortex to not do an action - tonic inhibition You inhibit the inhibition, which frees it to perform the behaviour = disinhibition 1. Cortex excites striatum 2. Striatum increases the inhibition of the GPi 3. Makes the connection weaker from the GPi - can't inhibit anymore More D1 receptors

Speech Zones Mapped by Brain-Imaging Techniques

Binder and colleagues (1997) - speech zones are widespread throughout the brain

Aphasia and Regional Function

Broca's Area, "Tan" - Tan had a stroke, only word he could say was "Tan" - could no longer generate any language - when he died, they found he had damage to prefrontal cortex, "Broca's area" - had quite diffuse damage though Wernicke's area, "word salad" - can speak, but makes no sense - can't comprehend what they are saying or what other's are saying - on the edge of the temporal lobe, straddling parietal lobe - area that is processing sound is right next to it

Lexicon

Collection of all words in a given language

Language

Comes from the word for "tongue" The combination of sounds for communication Sign language is perfectly sufficient as a language Uniquely human?

Non-Fluent Aphasia

Comprehension is intact, but trouble producing words - utterances could be slow or broken - ex. Broca's aphasia 1. Broca's Aphasia, or expressive aphasia - can understand speech - labors hard to produce speech - can be mild or severe - cognitively intact, can comprehend, troubles generating words or longer phrases 2. Global Aphasia - labored speech, poor comprehension - damage to both dorsal and ventral streams

Bacterial Infections: Syphilis

Dormancy stage is so long (15-20 years) Detectable - run antibiotics and get rid of it Later stages: general paresis (loss of touch with reality)

Secondary Motor Cortex

Eight areas of secondary motor cortex: - 2 areas of premotor cortex - 3 supplemental motor areas - 3 cingulate motor areas Projects to primary motor cortex, each other, and brainstem Produce complex movements (before and during voluntary movements) Exact role of these areas is unclear Premotor areas encode spatial relations and program movements Feeding into primary motor cortex Where complex motor planning occurs Mirror neurons located here Put plan together

"Stop" Pathway

Encouraging the inhibition 2 parts: 1. Cortex excites striatum, which inhibits GPe, which means inhibitory signal to GPi is weaker, GPi is stronger in inhibiting the thalamus 2. Cortex excites striatum, inhibits GPe, inhibits STN, which excites GPi, making GPi's inhibiting signal even stronger to thalamus More D2 receptors

Phonemes

Fundamental language sounds that form a word Most basic things

Right-Hemisphere Contributions to Language

Good auditory comprehension of language Hemispherectomy (removal of a hemisphere) - if left hemisphere is removed early, the right hemisphere can acquire language - if left hemisphere removed in adults, severe deficits in speech but still good auditory comprehension - removal of the right hemisphere produces subtle changes in language comprehension Involved in tone of voice, comprehension of language, melody, visual meaning

Case of Clive Wearing

Got meningitis, then lost ability to remember anything new (anterograde amnesia) He could remember things before meningitis (not retrograde amnesia) No short-term memory

Huntington's Disease

HD affects neurons across the brain, but especially the striatum In particular, the striatal neurons that project to GPe die (i.e., neurons in the indirect pathway) This decreases transmission in indirect/STOP pathway Net result= no stop = excessive movement No treatment Problem with hungtin protein is preferentially killing cells in the indirect pathway, in striatum that projects to GPe GO pathway has less competition More GO pathway, less STOP pathway

Patient H.M.

Had severe epilepsy Had a bilateral medial temporal lobectomy - removed part of the temporal lobes on both sides (includes hippocampus) His seizures went away, but was unable to form new memories (anterograde amnesia) But he was unable to communicate for a bit - got into 4 different types of memory Some retrograde amnesia Digit span test - healthy human can remember around 7 digits - same for H.M. Had problems putting things into long-term memory H.M. was unable to consolidate - he could encode sensory information to working memory - he was unable to perform retrieval

Could H.M. still form long-term memories?

He couldn't recall (weren't explicit) - but he could still remember things, just wouldn't tell you he could because he didn't know/think he could Mirror-drawing test - H.M. got better at the task, everytime he would need the directions explained and he had no recollection of doing the task before - basal ganglia was intact and was bringing it on more Pavlovian conditioning - different patient had hesitation to shake a man's hand after being shocked by them previously Priming - long list of words that they read, then show word completion tasks and they are quicker to use words from the study sheets than other words All of these were intact in H.M.

Semantic Memory

Memory for facts

All Memory Types

Memory: 1. Working Memory - digit span, mental manipulation, visual/audio loop, prefrontal cortex, work space, a lot of cortex, remembering a phone number 2. Long-term Memory (2 types): 1. Explicit Memory (2 types): 1. Semantic Memory 2. Episodic Memory 2. Implicit Memory - procedural, priming, conditioning, learning habits

Basal Ganglia

Modulates motor output (classical view) Critical to habit formation Many cognitive roles Promotes skill learning Caudate nucleus + putamen = striatum Globus palidus (external and internal) Subthalamic nucleus (right below thalamus) Substantia nigra Contribute to a circuit - doesn't go down the spine, stays in the system Habit formation "Volume knob" - changing force , dynamics to which you did the behaviour Reward circuits Procedural memory, habits, learning things in an automatic way

Neurotoxins: Heavy Metals

Mercury can accumulate in the brain and permanently damage it - producing a toxic psychosis "Mad Hatter" - hatters would use mercury in their felts, in it's liquid form it can evaporate easily and it's the gas form that leads to toxic psychosis Mercury can be used as preservative for vaccines - but no evidence to suggest harmful neurological effects

Fasano and Lazano (2015) - What do the authors identify as being some of the future directions for DBS?

Need reliable methods to predict the surgical outcome The future of DBS technology will probably see an integration of different emerging tools that will allow for safer and more accurate placement of electrodes and subsequently optimized therapeutic benefit in a growing number of clinical indivations, possibly to be performed on an outpatient basis

Language in the Brain

No reason to believe there is a one-to-one ration for a region and each part of language

Brain Areas Activated by Language Tasks

Nouns for Tools - premotor cortex and temporal cortex are active with nouns for tools Selecting words - looks like Broca's areas - premotor cortex is active in a task requiring matching a noun to one of four target words Generating Nouns - you activate different areas along the temporal lobe - comes together as a multisensory system - fMRI studies don't show us all the important parts

Fasano and Lazano (2015) - Describe the long-term outcomes of DBS treatment in Parkinson's disease. What is the 'long-term DBS syndrome'?

Patients have consistently shown an enduring beneficial effect of surgery on motor fluctuations, dyskinesias and the appendicular cardinal signs STN DBS may improve patients' survival STN DBS does not appear to halt Parkinson's disease progression and the phenotype of the 'long-term DBS syndrome' emerges over the years - The clinical picture of these patients is dominated by axial motor problems (dysarthria, freezing of gait and postural instability)

In what patient population is anosognosia most common?

Patients with damage to right parietal lobe or right hemisphere Often after a stroke

Practice Makes Chunk-fect

Practice can create and/or modify sensorimotor programs Most theories talk of two sorts of processes that influence the learning of sensorimotor programs: - response chunking - shifting control to lower levels We can take discreet bits of info and chunk them together - ex. phone numbers, put chunks of 3 together - what you use to learn to read - happens in basal ganglia

Posterior Parietal Cortex

Provides information on where body parts are in relation to the external world Receives input from visual, auditory, and somatosensory systems Output goes to secondary motor cortex Stimulation of this area makes the subject feel they are performing an action Has to do with proprioception Helps you know where you are in the world, how your balance is Stimulating at low currents = people will feel the intention of performing an action -ex. "I am going to take my hat off Stimulating at higher currents = feel like they actually performed the action - ex. "I took my hat off"

Cerebellum

Receives inputs from: - primary and secondary motor cortex - information about descending motor signals from the brain stem nuclei - feedback from motor responses via the somatosensory and vestibular systems In other words, it compares our intended movements to our actual movements, and then corrects our motor behaviour It is also critical for timing and sequence (both motor and cognitive) Quick, adjusting system - adjusts 7x/second System is perfectly situated to compare the plan you thought you'd make and what actually happened - take this information to adjust to be closer to what you wanted - feedback system for intention and reality

Dorsolateral Prefrontal Cortex

Receives projections from posterior parietal cortex - getting projections from all over the board Projects to secondary motor cortex, primary cortex, and frontal eye field Involved in assessments of external stimuli May work with posterior parietal cortex in decisions regarding voluntary response initiation dlPFC fires first in motor chain Decision making, voluntary movement But also critically involved in so many other functions (e.g., problem solving, math, working memory, learning) As such, damage here affects a number of sophisticated cognitive functions Plans, decisions, actions are being decided upon The you that acts in the world begins here Earliest in initiating an action Switching strategies becomes very difficult if you have damage here

Korsakoff's Syndrome

See in alcohol abusers Attributable to the brain damage that results from thiamine (vitamin B1) deficiency; thiamine deficiency often accompanies prolonged heavy alcohol consumption 2 main mechanisms: 1. Alcohol decreases ability to absorb thiamine properly 2. Heavy drinkers - alcohol is calories/sugar, so they eat a lot less food, get caloric requirements from alcohol, not getting thiamine in diet - malnutrition When it results from prolonged heavy alcohol consumption, the full syndrome involves severe anterograde and retrograde amnesia, sensory and motor problems, extreme confusion, and personality changes When it results purely from thiamine deficiency, it involves severe anterograde and mild retrograde amnesia - lose themselves, become irritable The amnesic syndrome is considered a medical diencephalic amnesia - defined like that because you see diffuse damage across the brain but most profound damage in diencephalon, thalamus and hypothalamus - when you damage medial thalamus, you lose the access to long-term memories or the memories themselves If you catch it early, a thiamine-rich diet can help somewhat, but if the damage is done, the damage is done Beriberi = early stages of Korsakoff's syndrome, pretty much - but from diet - ex. documentary where a guy ate a thiamine-deficient diet while in hospital for something else and got Korsakoff's syndrom - has to relive same feelings over and over Alcohol is a GABA agonist and glutamate antagonist

Types of Memory - Duration

Short-term (aka Working) memory - can use digit span test - where you hold onto memory and play around with it Long-term memory consolidation - taking short-term memories and putting them into long-term Retrieval when you pull long-term memory back to working memory Rehearsal - when you keep something in short-term memory

Stigma Around Epilepsy

Someone was having convulsions, and people just left them because they didn't now what to do - results in major depressive disorder and higher suicide rates (especially high when intractable epilepsy -nothing works to help it)

Morphemes

Smallest meaningful units of words Aren't quite words for some of them Ex. anti-

Localization of Lesions in Aphasia

Speaking takes a lot of us Predominantly left hemisphere Having a stroke along mid-cerebral artery can produce diffuse damage for both ventral and dorsal streams

Parts of the Two Pathways of the Basal Ganglia

Striatum - has a lot of dopamine receptors - D1 enhance function; positive modulates behaviour - D2 inhibits function; negatively modulates behaviour Globus palladus - 2 regions Substantia nigra - dopamine comes from here - all this activity goes to the thalamus (key regulator of conscious awareness) Lots of info coming from cortex to basal ganglia, then goes out through thalamus to cortex - helps regulate behaviours Glutamate = excitatory projections/green GABA = inhibitory = red

Discourse

Stringing sentences together to form a meaningful narrative

Parasites: Neurocysticercosis

Tape worm in the brain At a certain stage of their life cycle, it can cross the blood-brain barrier - non-specific - can attack anywhere - usually from eating undercooked pork

Viral Infections: Rabies

The rabies virus has an affinity for the nervous system Specifically damaging areas that make the individual angry Only 15% of those with bites get rabies Requires a very specific means of entry - crucial event when the animal bites, the virus has to get into your motor neurons and travel in a retrograde mechanism to your brain - takes about a month before it gets in your brain - real aversion to water, trouble swallowing - final periods: mania, or lethargic for time - early stages: fever, fog over consciousness - death usually occurs from problems with breathing

General Paresis

The syndrome of psychosis/dementia that results from a syphilitic infection of the brain Loss of touch with reality

Is that all there is? Motor Hierarchy

The theoretical association -> secondary -> primary -> brain stem -> spinal cord Hierarchy cannot account for many notable motor disorders Also damage to cerebellum displays motor damage and that isn't accounted for Parkinson's disease - dopamine enriched areas of substantia nigra die off - tremor at rest - inability to initiate or maintain voluntary movement = akinesia - bradykinesia = movements that you do have are slowed down - poverty of movement - problems with cessation of movement Huntington's disease = excessive movement - non-stop, constant movement - makes sleep very difficult - lose a lot of weight, because they're moving all the time - gene called Huntington, if parent has it you have a 50/50 chance of having it - can't be easily explained by the model because damage is often in the basal ganglia Stereotypy and impulsivity in psychostimulant addiction - low levels = goal-direct behaviour - higher doses = excessive itching, grinding teeth, impulsivity (cognitive and motor) = species-specific behaviours result

Ballistic Movements

Trading off accuracy for speed These are just quick Not adjusted on the fly, no correcting Cerebellum doesn't have any role in this

Fluent (and non-fluent) Aphasia

Transcortical Aphasia, or isolation syndrome - can repeat (echolalia) words - cannot speak spontaneously - often poor comprehension

Cortical Language Components: Nonfluent

Usually to Broca's area, presumably dorsal pathways - speech production - ventral pathway left reasonably intact - was able to use procedural memory to count Dronkers and colleagues (1999): Symptoms of nonfluent aphasia - apraxia of speech (damage to the insula) - deficits in sentence comprehension (damage to the superior temporal gyrus) - repetition of speech (damage to arcuate fasciculus) - working memory and articulation impairment (Broca's area damage)

Cortical Language Components: Fluent

Usually to Wernicke's area, presumably ventral pathway Dronkers and colleagues (1999): Symptoms of fluent aphasia: -lack of speech comprehension and other core difficulties with language - damage to the medial temporal lobe and underlying white matter - damage to temporal cortex contributes to deficits in holding sentences in memory until can be repeated - many other areas involved

Increasing Dopamine Transmission/Dopamine and Reward

Ventral tegmental area = tuned to reward more than substantia nigra All drugs that are addictive are increasing dopamine function - less STOP pathway, more GO pathway Common thing you see with drug users - at lower levels, greater increase in motivational behaviour - often find, people are more impulsive and motor impulsive At high levels, species-specific repetitive behaviours - ex. in rats, grooming with licking - ex. in humans, picking at skin Treatment: gets complicated while mixing motor and cognitive - all tangled up - basal ganglia is just one region involved in brain motor and cognitive things All drugs of addiction directly or indirectly increase dopamine transmission from SNc and the other main dopaminergic region, VTA While the pathways before are normally thought for movement, they apply somewhat (and are analagous to other pathways) for reward and motivation, learning, habit formation THus, drugs like cocaine or amphetamines increase goal-directed behaviours, impulsivity, and (at higher doses) repetitive behaviours In general, basal ganglia is involved in habits and things you have done for a while and can do well - ex. driving - as you get better, you don't need to use cortex (higher level) to perform the action, rather than the lower level: basal ganglia

Prosody

Vocal intonations Tone of voice Something that is happy might be in a higher tone

Anatomical Studies: Speech Zones Mapped by Brain Stimulation and Surgical Lesions

Wilder Penfield - identified and mapped neocortical language zones during surgery Effects of Cortical Stimulation: - total arrest of speech (almost before he realizes what has happened) - hesitation and slurring of speech - speech distortion and repetition of speech - number confusion while counting - naming difficulties - misnaming and perseveration - these apply to modern stimulation (e.g. TMS)

Types of Generalized Seizures

1. Absence Seizure (aka petit mal) - no significant convulsion - the primary symptoms are: loss of consciousness, cessation of ongoing behaviour, vacant look, fluttering eyelids - no convulsions, but consciousness seems to disappear - lost look in eyes - danger to it, ex. if you were driving - 3-per-second ichtal patterns - bilaterally symmetrical 3-per-second spike-and-wave discharge - really common in children, often resolves itself 2. Tonic-Clonic Seizures (aka Grand Mal) - loss of consciousness, loss of equilibrium, violent tonic-clonic convulsion - tongue-biting, urination, and cyanosis are also common - what most people think of when they think of epilepsy - may be breathing, but creates a hypoxic state - hypoxia = lack of oxygen - can be a secondary problem to the seizure - don't restrain, keep on side, pillow under head - if over 4 minutes = status epileptus - doesn't go away as quickly as normal - have muscle rigidity (tonic) and tremors (clonic)

Treatments of Epilepsy

1. Anticonvulsants - get rid of seizures, but not epilepsy - lessen frequency and severity of seizures - 1/3 to 1/2 of patients are not satisfied with the drugs - when they try another drug, even less of a chance that the medication works - if we increase functionality in GABA system, should reduce convulsions = how anticonvulsants work 2. Vagus Nerve Stimulation - put a pacemaker in and stimulates vagus nerve at some sort of level - only moderately effective 3. Ketogenic Diet - high fat, low carbs - liver converts fat to ketones - ketones are beneficial to systems 4. Cannabidiol - found in marijuana - supposed to have epileptic benefits, calms convulsions - indirect effects of feeling better - targeting endocannabanoid system but only weakly binds to endocannabinoid receptors 5. Surgical Procedures - for severe intractable epilepsy - "no brain is better than bad brain" - take more brain out than too little - take a little more than the focus point - prior to surgery, electrodes are sometimes inserted into/onto the cortex to find the epileptic focus - subdermal grids - drop grid in - touches cortex, records EEG, gets a much stronger signal than EEG cause it is directly touching brain - if it is a deeper brain region (ex. hippocampus) you need to stick an electrode in

Fasano and Lazano (2015) - Know the key points listed in the box on page 424

1. Deep brain stimulation has become widely accepted as a treatment for Parkinson's disease, dystonia, and tremor and as an off-label treatment for many other movement disorders 2. DBS field is expanding exponentially along two not mutually exclusive directions: clinical and technological 3. Clinically, we have achieved a deeper understanding of outcomes, thus facilitating the process of target and patient's selection 4. The recent technological advantages of neuromodulation have opened new avenues toward new targets and indications

Types of Seizures

1. Focal Seizures - start in a single brain area and stays - ex. motor cortex seizure 2. Generalized Seizure - across brain - secondary generalization: often starts focally, but spreads elsewhere

What are the three phases of TTM?

1. Induction - when treating patients who have experienced cardiac arrest, induction to target temperature should be as rapid as possible to minimize ongoing, irreversible ischaemic neuronal injury - application of ice packs and infusion of cold IV fluids 2. Maintenance - once induction has begun, a device is applied to complete the cooling and begin the maintenance phase - advanced cooling technology can maintain core body temperature with only minor fluctuations - fever no longer occurs 3. Rewarming - the most dangerous phase, particularly in patients with intracranial mass effect who are at risk of elevated ICP - a rapid increase in body temperature can cause systemic vasodilation and hypotension, which can in turn trigger cerebral vasodilation and ICP plateau waves - in most cases, a rewarming rate of .25 degrees celcius per hour is recommended, and rewarming should always be performed in a controlled manner to avoid overshoot and hyperthermia

Common Misconceptions About Brain Dysfunction

1. Many people believe that recovery from brain dysfunction depends in large part on the injured person's efforts - a lot of brain injuries result in loss of effort, increase in fatigue 2. Many people believe that a person with even severe brain dysfunction can recover completely (apart from some persistent problems with memory) - limitation on how much recovery you can sustain 3. Many people misattribute a behaviour (e.g., fatigue, aggression) that is the result of brain dysfunction to the person's personality or life stage - impulsivity and attention can be a common issue with a brain injury 4. Social psychologists have shown that people are more forgiving of a person's behaviour if they have a bandage on their head or a visible scar on their head - way we apply empathy depends on if we believe them/can see them 5. Many people believe that emotional problems after brain injury are usually not related to brain dysfunction - how much agency and autonomy bring us happiness 6. Many people believe that a second brain injury can restore lost memories in individuals with amnesia 7. Many people believe that people with amnesia are totally normal in every other respect 8. Many people believe that people with amnesia have no trouble learning new information (i.e., they believe their amnesia is entirely retrograde - loss of memory for events prior to the brain injury) - can also have anterograde amnesia

Theories of Pathogenesis of MS

1. Primarily an autoimmune disease ("outside-in" theory) - you lose myelin, then have problems with neuron firing - neuroinflammation causing cell damage - not an attack of the immune system - would expect it to be the other way around in outside in theory - if it was an immune function disorder you wouldn't have a primary progressive form of the disease - immune modulator should be effective for all types of it, if it was an immune disorder to stop or slow it down from attacking itself 2. Primarily a neurodegenerative disease with inflammation in some patients ("inside-out" theory) - neurodegeneration first that causes inflammation of myelin - problems with neuron firing, then problems with myelin - evidence is more compelling for this theory - the problem is first that the cells are dying and the immune response is your body trying to clean it up and deal with the degeneration

Types of Focal Seizures

1. Simple Partial Seizures: symptoms are primarily sensory or motor or both - typically no loss of consciousness - Jacksonian seizure - stays contained within an area or type of behaviour 2. Complex Partial Seizures - patients engage in compulsive, repetitive, simple behaviours (automatisms) and more complex behaviours that can appear perfectly normal - disruption and/or alteration of consciousness is common - larger scope - familiar behaviour (learned behaviour is often shown and is done almost as an automatism - reflex) - usually have the same behaviour everytime For both focal seizures - more of a focus on behaviour

Multiple Sclerosis Treatments

1. Vitamin D supplements (maybe) 2. Corticosteroids - reduces neuroinflammation 3. Immune system modulators - seems to come with large side effects 4. Cannabis - issue of spasticity which feels terrible, tight muscles, smoking cannabis has some anti inflammatory qualities and can help with some spasticity - is alright 5. Physical therapy - seems to help with tense muscles 6. Muscle relaxants 7. "Liberation treatment" of the veins (NO) - theory of inadequate vein system of removing blood from brain, couple of years of hope for this, but no evidence supports 8. Hopefully more/better soon

Anosognosia

A brain dysfunctional patient does not appear to be aware of impaired neurological or neuropsychological functioning which is obvious to the clinician Unaware they have a problem Denial Stroke affecting right frontal parietal lobe commonly causes paralysis on the left, but a certain percentage of these patients don't think they are paralyzed Patient believes the paralyzed limb doesn't belong to them Why does this denial happen? - the kind of denial they use involves a lot of tricks to avoid moving that limb (ex. "im too tired to touch your nose") Freudian rationalization - repression, denial After a week or 2, most patients eventually believe or acknowledge that they are paralyzed Hemiplegia - paralysis on one side Confabulation - "rewriting the script" - make a story that matches the situation Somatoparaphrenia - identify paralyzed limb as not your own Defense mechanisms - some evidence for denial, but not all defence mechanisms

Secondary Effects: Diaschisis

A brain legion can cause dysfunction in an area remote to it because of its strong connections with that area Thus, recovery can occur because of a spontaneous reduction of diaschisis (metabolic depression in cerebral areas remote to the lesion) Changes in blood flow across other regions - areas remote to it - its axons are no longer innervating other regions, decreased blood flow Some recovery you see is from diaschisis going away

Compensatory Strategies

A mainstay of rehabilitation of patients with brain dysfunction So recovery may not represent true restitution of function, but substitution of a new behaviour So, a patient learns strategies to adapt to his or her new motor, sensory, or cognitive impairments When patients go in for rehab, goal is to find strategies to work around functional deficit Ex. study of rats (bilateral injuries in motor areas) - beam walking test - initially animals are much worse - after edema and main stitches have healed, animals are just as good at walking across beam - see that the lesioned rats have a strange pattern of gait (haven't recovered fully, but found compensatory strategies)

Rosenbaum et al. (2005) - explain what is meant by the 'single memory, single locus' concept of amnesia

Amnesia came to be seen as a severe impairment of a single kind of memory ("declarative memory") attributable to the pathology of a single brain region (hippocampus or MTL) 1-1 ratio?

Bacterial Infections

Bacteria often attack the meninges, producing an inflammation known as meningitis Infections of the brain - invasion by a microorganism Can get into the brain (encephalitis) or meninges (meningitis) When bacteria attack the brain Blood-brain barrier might get outsmarted by them Viral meninges - bad, but resolves Bacterial meningitis - really bad, kills 1/4 - starts with headaches, fevers, irritability

Convulsions

Behavioural manifestations -what we normally call the seizure

Progression: Relapsing-Remitting Form of Multiple Sclerosis

CIS: clinically isolated syndrome - Often see an initial symptomatic time period (i.e. One problem - vision numbness, etc.) - Clinically isolated syndrome - first event you see - Think it was just a weird time in life, but sometime starts showing up again RRMS: relapsing remitting MS - You have it, flare up, rigidity with muscles - Take muscle relaxants - About once a year you will go through these periods and starts to get faster - Can reliably measure immune system dysfunction/over using immune system SPMS: secondary progressive - See a combination of cellular degeneration and immune response - Just happens because immune system is so overworked and degenerated - Relatively little immune system - Immune drugs don't seem to help as much - Overtime still get degeneration, there is a period where there is an immune response but then it gets smaller and smaller - Cellular degeneration has progressed so far that a doctor would call them MS symptoms - Don't have good/bad days - Just gets progressively worse and worse MS - Once degeneration is gone its gone, - In Peripheral nervous system there can be regrowth and regeneration - Cant get it in the CNS

Describe the 'virtual reality box' that Ramachandran and colleagues used to rule out contralateral neglect as a potential mechanism of anosognosia.

Cardboard box with an arrangement of mirrors and gloves called the Nielsen box - put gloves on two hands and look at your hand - move hand to the sound of the metronome - see your hand moving - then you have your assistant under the table wearing a glove - participant closes eyes and during that period a mirror flips down and the assistant puts their hand into the box - student looks inside box and is looking at assistants hand, but thinks they are looking at their hand - told to move hand, but seeing the assistants hand (thinking its theirs) not moving the hand Tried on a patient with anosognosia - on their good hand, sees it is not moving - they don't register surprise, they say they see it is moving - still denying that his right hand is not moving (denying artificial paralysis) Shows that it is not contralateral neglect causing anosognosia, but that the patient is not able to tolerate any discrepancy

Epilepsy

Characterized by recurrent unprovoked seizures - due to atypical, excessive or synchronous neuronal activity in the brain Best understood as a collection of individual disorders that share an abnormal tendency to cause epileptic seizures, consisting of dozens of epilepsy syndromes Diagnosis relies heavily on EEG Cells are firing all at once (large amplitude spikes) - smaller waves means they are not firing altogether Some things are more likely to promote a seizure (ex. too much caffeine, alcohol, fatigue) - but we consider them to be unprovoked Prevalence 1% Way in which it manifests looks different Relatively small number actually have the convulsions Seizure and convulsions are not the same

Fasano and Lazano (2015) - What form(s) of DBS is/are effective for the treatment of dystonia?

DBS is generally less effective in nonisolated dystonias due to the progressive nature of these degenerative disorders The effect of DBS appears to be less predictable in patients with DYT6 Better outcome in late timing of surgery Better outcome in ablation vs. neuromodulation type of surgery Better outcome when low amount of energy was delivered

Fasano and Lazano (2015) - What form of DBS is effective for the treatment of essential tremor?

DBS of the ventro-intermedius nucleus (Vim) of the thalamus is an effective treatment for essential tremor especially beyond 8 years Although a loss of benefit is sometimes observed over time Thus, it is not yet clear whether this represents tolerance to stimulation or disease progression

Comorbidities of Epilepsy

Diabetes Major depressive disorder Anxiety disorders Migraine headaches Stroke Heart disease - relationship between cardiovascular heath and neurological function Asthma Arthritis Suicide

Risk Factors for Early vs. Late Seizures

Early: - focal neurological signs - any neurological signs - subarachnoid hemorrhage - injury before 5 years - lineal skull fracture Late: - early seizures, especially when delayed - at least one nonreactive pupil - dural penetration - injury after 16 years of age - Glasgow Coma Scale score of 3-8 - time to following commands of a week or more - parietal lesion on CT Both: - intracranial hematoma - post-traumatic amnesia >24 hours - depressed skull fracture If certain factors are in both, we really don't know the mechanisms behind it - Glasgow of 3 - basically gone - greatly diminished conscious state - if in a coma for a while, more likely to develop epilepsy later on

Environmental Factors in Recovery

Environmental factors may affect the amount of functional recovery following brain injury -ex. animal models, enriched environments - rats in enriched environments (lots of things to do): have better functional recovery Monkeys with focal strokes to the motor cortex that were retrained in skilled hand use - monkeys do regular hand training, region that accounts for hand goes into other regions - enlargement of cortical space

Understand the difference between epileptic and psychogenic nonepileptic seizures, and describe an example of a psychogenic nonepileptic seizure.

Epilepsy is classified as an organic disease Psychogenic nonepileptic seizure as a functional disorder because no physical site of injury can be dound The neurologist who suspects PNES must become a medical detective, relying on a clue from her patient, such as a seizure triggered by some powerful emotional event - then again, there are epileptic patients who can seize after a shock or a strong emotional experience too Some epileptic also have PNES

Effect of Age on Brain Recovery

Ex. Jodie had a surgery called hemispherectomy where they removed half her brain - surgery occurred at the age of 3, and she is totally fine now Injury at younger ages leads to better recovery If there is damage at a younger age, you can have rewiring - shifts to other hemisphere Less plastic as you age - but these synaptic connections are what makes you you, so you don't want them to be too plastic for that reason Removal of an infant monkey's primary motor cortex results in a less dramatic impairment than in an adult monkey Brain injury resulting in aphasia before age 1 is associated with the best recovery; recovery diminishes as age increases Prefrontal lesions before 16 months may be associated with an inability to learn social and moral rules later in life

Flu May Impact Brain Health

Female mice infected with 2 different strains of the flu exhibit changes to the structure and function of the hippocampus that persist for one month after infection H3N2 and H7N7 caused memory impairments that were associated with structural changes to neurons in the hippocampus The infections also activated the brain's immune cells in this region for an extended period and altered the expression of genes implicated in disorders including depression, autism, and schizophrenia

What are the mechanisms underlying the beneficial effects of TTM?

For many years, hypothermia was thought to act primarily by lowering brain metabolism: for every 1 degree celcius reduction in brain temperature, a 6% reduction in cerebral metabolic rate is observed By limiting the consumption of oxygen and glucose by the brain, hypothermia reduces the risk of energy failure, thereby preventing the failure of sodium pumps and calcium influx, and decreasing the risk of cell death The response to hypothermia causes reductions in excitotoxic neurotransmitter release, free radical formation and sustained electrical depolarizations, and inhibition of proinflammatory and apoptotic pathways These mechanisms stabalize the blood-brain barrier, decrease oedema and reduce ICP The most robust clinical manifestation is the reduction in ICP when body temperature is reduced to 35.5 degrees celcius or lower - the mechanism of pressure decrease is multifactorial, but the effect seems to be exerted mainly through reductions in inflammation, vasogenic oedema, and cerebral blood volume

Early vs. Late Seizures

Immediate Seizures = occurring within 24 hours after injury Early Seizures = occur less than 1 week after injury Late Seizures = occur more than 1 week after injury Latent Period = time between injury and onset of late seizures - 15% will develop like 20 years after - what might be driving the latent period

Fasano and Lazano (2015) - Explain when deep brain stimulation (DBS) should be offered as a treatment for Parkinson's disease

In the past, DBS was only offered in the late phase of the disease, a number of considerations have now moved the time for surgery earlier: 1. DBS produces motor improvement of signs responding to dopaminergic drugs, whereas unresponsive features often predominate in the late stages of the disease 2. Older patients are more likely to develop axial motor functions 3. Performing DBS at advanced stages of illness can alleviate certain aspects of motor dysfunction without addressing the ongoing difficulties in well-being and social relations with themselves, spouses, families, and socio-professional environment Others have proposed STN DBS in patients without motor fluctuation, but this approach is less compelling as it exposes patients to potentially dangerous side-effects without improving the motor function and quality of life and an unclear impact over the long term

What forms of acute brain injury is TTM useful for (or potentially useful for)?

Increased ICP Ischaemic Stroke Unknown: - intracerebral haemorrhage - subarchnoid haemorrhage

The epileptic focus is much more likely to be found in the frontal or temporal lobes than other parts of the cortex. Why?

LTP: you change overall baseline activity at a synapse - increases sensitivity - areas that are more sensitive to this are more likely to have an epileptic focus

Neurotoxins: Lead

Lead can also lead to toxic psychosis "Crackpots" Houses built before 1960 there is a chance there is lead in the paint Lead can lead to toxic psychosis due to like sandpapering the walls and inhaling it Crackpots, pots that cracked in the middle and were lined with lead 1980, most interior paint was all gone but maybe still outside by 1992 no lead inside or outside the house the reason lead was there in the first place is it causes paint to dry better and has a better appearance mostly gone now, not a worry there are still places that use lead paint, mostly in children's toys made somewhere else and imported here

Traumatic Brain Injury and Epilepsy Paper

Leading cause of epilepsy This population-based study suggests that the risk of epileptic seizures is increased twofold after mild and ninefold after severe traumatic brain injury Although the risk after an isolated intracranial hemorrhage or brain contusion is increased 5- to 6fold, a combination of these diagnoses leads to a 43 times increased risk During the first 6 months after a severe TBI, the risk for epileptic seizures is increased almost 50 times The risk for developing epileptic seizures is still increased >10 years after the trauma 8

Effects of Anosognosia

Linked to various forms of dysfunction: - movement disorders - contralateral neglect - memory disorders - dysexecutive syndrome ('frontal lobe syndrome'): Disinhibition, aggression, impulsiveness, and disruptions in planning and certain types of memory (i.e., working memory) Not a permanent or long term thing - predicts long term recovery

Geography of MS

MS is most common in Canada More common in individuals who spent their childhood/teenage years in a cold climate Even looking specifically in countries there is a north south gradient, with southern areas having a lower incidence Rare in certain groups - Ancestries with links to Africa/Asia but no reason why yet

Wilder Penfield

Mapped cortex of brain (somatosensory system) A lot of work with epileptic patients - stimulated parts of brain (depolarized) - wanted to find the area that the patient acknowledged before a seizure - he wanted to find the focus, to help treat

Semantics

Meaning of words and sentences that correspond to all lexical items

Summarize the methods and results of the Mahler et al. study in 2-3sentences.

Methods: used the Stockholm Incidence Registry on Epilepsy to carry out a population-based case-control study - 15000 matched controls - relative risks (RRs) for unprovoked seizures were estimated after various TBI diagnoses, and influences of TBI diagnoses, and influences of TBI severity and time since trauma were studied in detail Results: After hospitalization for mild TBI, the RR was 2.0 - the RR was higher after brain contusion, whereas a combination of both diagnoses led to a further sevenfold increase in RR - the risk was greatest during the first 6 months after severe TBI

Rosenbaum et al. (2005) - Describe K.C.'s brain pathology (see section 5) and its functional implications (see 5.4)

Mild diffuse cortical atrophy - reflects thinning of the cortical rims and underlying white matter in all lobes and coincides with bilateral ventricular enlargement - left hemisphere is affected to a greater extent Focal signal abnormalities are observed predominantly in the left hemisphere - posterior lesion in the occipital-temporal cortex and underlying white matter softening of the brain tissue is seen in the lingual gyrus, fusiform gyrus, cuneus, precuneus, and parts of superior, middle, and inferior occipital gyri The left anterior hypointensity may reflect sequelae of the subdural hematoma that was diagnosed and removed in hospital immediately following his head trauma Pronounced bilateral signal abnormalities in the hippocampal formation and notable atrophy in neighboring parahippocampal gyrus Functional implications: - damage to occipotemporal structures, largely in the left hemisphere, from cuneus and through lingual and parahippocampal gyri, is consistent with difficulties in perception of colour and face matching under degraded conditions; importantly, other aspects of his perception and recognition are preserved, including tasks requiring basic visual feature analysis such as line orientation and form discrimination, as well as more complex processes such as reading and face recognitions - possible that damage to posterior neocortical areas contributed to his autobiographical episodic memory loss by affecting his visual imagery - damage to regions of frontal cortex is limited to dorsolateral and pre-motor areas, performance on tests of phonemic, but not semantic, fluency is impaired - the extent of damage to K.C.'s medial temporal lobes, particularly to his hippocampus and parahippocampus, and associatied diencephalic and basal forebrain structures, is in line with his profound impairment on all explicit tests of new learning and memory - additional damage to his amygdala may account for his blunted affect and personality changes

Therapy Dose

More therapy time, more recovery (even when controlling for time post-injury)

What shortcomings in the literature motivated the study done by Mahler et al.?

Most previous reports are cohort studies of selected TBI patients from trauma centers, making it difficult to generalize from these results - included only patients younger than 26 years

Describe the typical natural course of anosognosia. Is this condition always permanent?

No, it typically lasts only 2-3 weeks at most

Fasano and Lazano (2015) - What other movement disorders has DBS been used to treat?

Other movement disorders that had positive results were: - Lubag disease - Wilson's disease - PKAN - Neuro-acantocytosis - senataxin mutation-related dystonia - paroxysmal nonkinesigenic dyskinesia - stereotypies in autism spectrum disorder

Progression: Primary Progressive Form of MS

PPMS = primary progressive MS - Looks very similar to secondary progressive, its just that in SS you have relapsing and remitting first GRAPH - If underneath the bar regular symptoms, if above it is clinically significant - Cells are degenerating for one reason or another, not an immune system problem, but body starts responding

Language Structure

Phonemes - fundamental language sounds that form a word - most basic Morphemes - smallest meaningful units of words - aren't quite words for some of them - ex "anti-" Lexicon - all the words in a language - collection of all words in a given language Syntax - rules of grammar - no other species can keep up here - ex. ability to differentiate "Jay hit son" or Jay's son hit Jay" carry very different meaning Semantics - meaning of all words and sentences that correspond to all lexical items Prosody - vocal intonations - tone of voice - something that is happy, might be in a higher tone Discourse - stringing sentences together to form a meaningful narrative

Summarize the relationship between TBI severity and the occurrence of posttraumatic epilepsy. What did Mahler et al. contribute to this field of study?

Previous research showed that brain contusion and subdural hematoma were identified as the strongest risk factors for PTE, whereas other factors like skull fractures, older age, and prolonged loss of consciousness were weaker, but significant factors Seems to be a relation between amount of focal tissue destruction and development of PTE Mahler et al. confirmed the association between TBI severity and risk for developing unprovoked seizures As AF is comparable for mild and severe TBI, both diagnoses roughly contribute equally to the disease burden of epilepsy in society due to the higher prevalence of mild TBI The risk for unprovoked epileptic seizures was highest within the first 6 months after mild and severe TBI Patients with a combination of cerebral contusion and ICH are at very high risk for unprovoked seizures and PTE, which calls for closer monitoring and special precautions in particular during the first years after the trauma

Anosognosia Impairs Functional Recovery

Prigatano and Wong (1999) - when prediction improves, the likelihood of achieving rehabilitation goals improve - the better you are at assessing your abilities, the better your recovery Jehkonen et al. (2000) - those with initial anosognosia had poorer functional outcomes - but in all patients, anosognosia was gone after 3 months Gialanella et al. (2005) - rehabilitation progress not as strong when anosognosia is present - half patients had contralateral neglect - half had neglect and anosognosia - results: rehabilitation progress wasn't as strong if anosognosia was present early on Cheng and Man (2006) - "Awareness Intervention Program" - build awareness in anosognosia - decrease anosognosia you should have better recovery - ran AIP with stroke patients - showed improved self-awareness but not a better recover - Intervention program: education about what was going on, constant reminders that parts of their body weren't functioning as normal, predictive -AIP group showed improved self-awareness but was not associated with improved functional outcome

Multiple Sclerosis

Progressive disorder that primarily attacks the myelin of axons in the CNS, but there is also cell loss Common symptoms in advanced cases: visual disturbances, muscular weakness, numbness, tremor, and loss of motor coordination The immune system appears to attack the CNS myelin as if it were a foreign substance Transmission cant continue all the way down the axon without this myelin - MAIN ISSUE Ebstine Bar virus: MONO - Mono leads to a stronger likelihood to develop MS later in life - Makes it seem more of an external element, heavily driven by environment, rather than genetic - Women more than men :3 to 2 or 3 to 1 women to men Typically the problems (i.e. vision) seems to be heavily determined upon where the brain is damaged, can have damage in many different areas, can be all over cortex, symptoms are a result of where the damage is Doesn't always start in the same spot Used to think: Must be some dysfunction in the immune system and that's why its attacking - but FALSE

Virus

Protein Chunk of RNA/DNA inside Is it even a living thing? - self-replicating - but relies on other organisms - sneaks its genetic code into you and uses your DNA

Critique the psychogenic vs. organic dichotomy.

Psychogenic is said to be without any organic basis, non-organic? - does that mean that psychogenic seizures are unreal, ungrounded, and immaterial?

Syntax

Rules of grammar No other species can keep up here Ex. ability to differentiate between "Jay hit son" or "son hit Jay" - carries very different meaning

The Halle Berry Neuron

Science has benefitted greatly from research with epileptic patients Found the "Halle Berry Neuron" Electrode was stuck in near hippocampus and rhinocortex - researchers showed patients pictures of people/things - on this electrode looked to see if it was showing preference to certain things, and it did find that one neuron fired strangly for Halle Berry - the cell fired to any picture of Halle Berry with any hairstyle, outfit, sunglasses on or off - didn't respond to people who looked similar or other actors/actresses - part of brain that represents specific categories - you need to know who Halle Berry is

Seizure

Spontaneous activity that isn't (can be) provoked - typically unprovoked Need to have 2+ seizures on two separate days with 24 hours separating them to have the diagnosis of epilepsy The activity that is going on in the brain (measure with EEG) During the seizure you get interichtal spikes, set space between them - usually pre-ichtal before seizure - post-ichtal after seizure Looking for bursts of high-amplitude spikes

Vitamin D and MS

Strong link with Vitamin D - Specifically you see lower levels of vitamin D in individuals who are living in these colder countries, not getting the vitamin D from the sun - Vitamin D promotes calcium absorption in the gut but nor direct link why that leads to cellular degeneration - If you give MS patients vitamin D supplements, some studies say it helps, some do not - Existing vitamin D levels are predictors of MS later on, risk factor

Secondary Effects: Edema

Swelling (edema) after stroke may mask or distort functions in essentially intact regions of the brain Dissipation of these effects may account for substantial early recovery May look like recovery, but that tissue was never damaged, the swelling just went away - secondary effects have just cleared

Why does philosophy matter in 'brain matters'?

The argument over mind-body still exists today and can be harmful for certain diagnoses

Fasano and Lazano (2015) - Explain the current state of the research on whether it is better to administer DBS to the subthalamic nucleus or the globus pallidus when treating Parkinson's disease

The motor benefits can be similar with each target, but the pendulum is swinging towards favouring STN for greater benefit in the severity of off symptoms and cost-efficacy, whereas dyskinesias suppression and long-term effects on stability and cognitive favour GPi

What is targeted temperature management (TTM)?

Therapeutic cooling of the human body Potentially the most powerful neuroprotective agent available for the treatment of acute brain injury

Effect of Lesion Size and Location

There is a direct relationship between the size of a brain lesion and the extent of recovery Larger lesions generally result in more functional impairments In addition, patients with bilateral lesions show less recovery than patients with unilateral lesions - ex., bilateral hippocampal lesions result in profound anterograde amnesia while unilateral lesions result in less severe impairments Bigger lesions = more dramatic impairments Bilateral vs. unilateral lesiosn - if one half is damaged (unilateral) nearby regions or the other half can pick up some of the slack - bilateral lesions result in more severe outcomes

Discuss the degree to which Cartesian dualism still haunts modern medicine and neuroscience.

There is no consensual theoretical model for the brain-mind The terms neural correlates, underpinnings, and representations do not close the psyche/soma gap, they expose it The course of research rests on paradigms - primary assumptions that lie beneath all scientific investigation, and sometimes those paradigms shift Paradigms such as "functional or organic", "mental or physical" are not only wrong, but lead to bad habits of thinking because they lead to static and obsolete ideas and do not allow for modern pluralistic and dynamic ideas of matter and structure xf

What does the paper indicate is the relationship between time-since-stroke and benefits of increases in therapy time?

There was a significant positive effect of time scheduled for therapy on outcomes even when controlling for time after stroke No interaction between time after stroke and time scheduled for therapy - therapy is beneficial no matter what point after stroke

Briefly describe the key points of the study, as listed on page 1439.

This population-based study suggests that the risk of epileptic seizures is increased twofold after mild and ninefold after severe traumatic brain injury Although the risk after an isolated intracranial hemorrhage or brain contusion is increased 5- to 6fold, a combination of these diagnoses leads to a 43 times increased risk During the first 6 months after a severe TBI, the risk for epileptic seizures is increased almost 50 times The risk for developing epileptic seizures is still increased >10 years after the trauma 8

Does the dose-response relationship hold for all types of therapies?

Time in therapy is a robust predictor of recovery across different types of therapy

Tonic-Clonic Seizures

Tonus = rigidity, tightness of the muscles Clonus = tremor

Mechanisms Following TBI - Epilepsy

Too much excitation (glutamate) results in damage Difference in how the cell responds - more sensitive Lots of glutamate release - signal cascades can cause more receptors to move to the membrane - cause more receptors to be made At unhealthy levels - increase the likelihood of having an AP - if you do this all over, you get a higher chance of spontaneous activity

Parasites : Toxoplasma gondii:

Toxoplasma gondii: eukaryotic parasite - cats are considered the true host - have to have some of their stages of life outside the cat and then get back to the cat Sapolski found that this parasite will infect rats, show they have a loss of fear of cats (not other animals) - amygdala; fear circuit is diminished and mating signal circuit is increased - rats approach the smell of the cat and parasite returns to the cat Toxoplasmosis - when it manifests as a symptomatic illness - differences on personality, more obsessive over something

General Risk Factors for Epilepsy

Traumatic brain injury - but doesn't mean you will develop epilepsy if you get one Infections at a young age affecting CNS Strokes Vascular Congenital Tumor Degenerative 65% cryptogenic/idiopathic types of epilepsy = we don't know why/where it came from

What is the dose-response relationship for rehabilitative therapy following stroke?

Treatment groups receiving more therapy improved beyond control groups that received less Increased time scheduled for therapy was a significant predictor of increased improvement by itself Positive relationship

Describe Ramachandran's theory as to why typical persons engage in denial and give an example of such denial. According to Ramachandran, do evolutionary explanations of denial hold up under scrutiny

Typical persons - reason you can deceive yourself is that when you tell someone else, you already believe it, so they won't know you are lying - this is why it evolved Evolutionary explanations - seems maladaptive - but it defeats the whole purpose of lying, because you don't have access to the truth anymore His theory = disorder of belief

Epileptic Aura

Visual, another sensory, a feeling, smell, sense of dread, anxiety anger all can come on before a seizure Important for 2 reasons: 1. The nature of the aura is predictive of the epileptic focus - epileptic focus = part of "bad brain" where you see the EEG spikes starts and spreads at -part of brain we want to target with threatment 2. They warn the epileptic of an impending seizure

Relationship between vaccines and autism?

Wakefield - 12 kids who had autism, also had vaccine No control group, small sample, and correlation does not equal causation If you had a control group, they probably would have all had the vaccine too Wakefield was trying to sell his own vaccine

Reflex Epilepsy

When a certain activity happens it triggers a seizure - ex. everytime they brush their teeth, have an orgasm

Rosenbaum et al. (2005) - Describe the case of K.C. (i.e., the events that led to his brain dysfunction and his pattern of deficits as described in section 4. How are the cases of K.C. and H.M. the same and how are they different?

When he was 16, a bale of hay fell on his head and he lost consciousness Another incident occurred when his homemade dune buggy collided with a much larger vehicle, resulting in a fractured mandible but no loss of consciousness - no apparent change to his cognitive functioning Age of 30, he got into a motorcycle accident, leaving him densely amnesic Most of K.C.'s intellectual and cognitive function outside the domain of episodic memory are largely, although not completely, preserved Deficits: - Visual impairments in colour perception - impairments were also present on a more complex face-matching task that requires the synthesis of multiple visual features - working memory was normal - severe anterograde memory impairment (unable to retain any information over delays as short as 20 or 30 minutes on the same tasks - during testing he could not produce a single episode from his past that was distinct in time and place

Describe what happens when someone with a paralyzed left arm with anosognosia is given the choice of unscrewing a light bulb for $5 or untying their shoe for $10. How does that compare to what happens when you give the same two choices to someone with a paralyzed left arm without anosognosia?

With anosognosia: - patient goes straight for the shoe - starts playing with the laces for 10 minutes - no sign of frustration - continue to choose this option every attempt; meaning they repressed their own failed attempts Someone with a paralyzed left arm without anosognosia: - they immediately go for the light bulg - it is very difficult to tie shoelaces with one hand

Rosenbaum et al. (2005) - What did the case of H.M. tell us about memory?

Work with H.M. produced clear distinctions between memory and other intellectual functions - it showed that severe anterograde amnesia for material encountered post-injury could occur despite relatively preserved intelligence, language, and reasoning ability - it drew a sharp distinction between long-term and short-term memory: dense amnesia for ongoing happenings could occur despite normal ability to hold in mind and make use of information involved in ongoing activity - showed that not all expressions of long-term memory were impaired: H.M. was capable of learning skills and acquiring perceptual information, even in situations in which he was not aware that he had learned anything - together with the observations reported by other experimentally minded neuropsychological students of memory disorders, these findings helped pave the way to the widely accepted idea of multiple memory systems