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Structural Brain Imaging Techniques: Cerebral Angiography

- an enhanced X-ray that uses dyes to make up for the relatively poor soft-tissue contrast of conventional X-rays a radio-opaque dye that absorbs X-rays better than surrounding tissue is injected into an artery that delivers blood to the brain - this substance heightens the contrast between the cerebral circulatory system and surrounding brain tissue during an X-ray the most prominent aspect of the central nervous system imaged in a cerebral angiogram is the brain vasculature - angiograms can show vasculature and indicate the presence of a tumor or aneurysm

Functional Brain-Imaging Techniques: Positron Emission Tomography (PET)

- an invasive, diagnostic imaging technique for measuring the metabolic activity of cells in the human body - developed in the mid 1970s; the first scanning method to give functional information about the brain activity

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Hydrogen

- the resolution of a modern MR image is far superior to a CT image, typically less than a millimeter - MRI utilizes the magnetic properties of hydrogen protons, as they are highly abundant in the fluids and organic compounds of the brain and body - the main function of an MRI scanner is to artificially excite these hydrogen protons and then measure their relaxation properties over time

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Radiofrequency Pulses - Switched Off

- after the RF pulse is switched off, the high-energy nuclei begin to relax and realign - eventually, the longitudinal magnetization increases to its original value, while the transversal magnetization decreases to zero. - the time (in milliseconds) required for a certain percentage of the protons to realign in the longitudinal direction is termed T1 (63% recovered); the transversal relaxation time is termed T2 (63% decayed)

Functional Brain-Imaging Techniques: Optical Imaging - Resolution

- allow for spatial resolutions of 1 mm and temporal resolutions of 2-8 seconds - these technologies have been used to produce high-resolution functional maps of visual cortex in both animals and humans.

Postexperimental Data Analysis: Preparation of Figures

- almost always T1-weighted figures with color-coded brain activation data - can also use "inflated brain" in which sulci and gyri of the brain are expanded into a balloon-like shape in order to better show sulci activity (bright colors represent high differences in intensity)

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Setup

- an MRI scanner is composed of a long tube-like chamber, where a subject is placed, surrounded by electric coils hidden within the MRI apparatus - as current passes through the coils in a clockwise rotation, a magnetic field is produced longitudinal to the patient, in the direction of the feet to head - this affects the hydrogen protons in the subject's tissues

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - CT Comparison

CT scans: - are still better to see bones and calcified structures in the head - can be used for subject with pacemaker or metal objects in their body - are less expensive

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Radiofrequency Pulses - 2 Effects

applying an RF pulse that has the same frequency as the proton precession frequency causes two effects: - some protons in the parallel phase pick up energy, reverse polarity to the antiparallel phase, and therefore decrease the net longitudinal magnetization - some protons get in sync and start to precess in phase; their vectors now add up in a direction that is transverse to the external magnetic field (perpendicular to the subject's body); thus, a new transversal magnetization is established

Structural Brain Imaging Techniques: Diffusion Magnetic Resonance Imaging (dMRI) - Limitation

can provide information about which areas of the brain are connected, but it is not able to determine the direction of this connectivity (which endpoint is the source and which endpoint is the target)

Functional Brain-Imaging Techniques: Electroencephalography (EEG) - Event-Related Potentials (ERPs)

- ERPs are a measured of the brain response that directly results from a specific sensory, cognitive, or motor event - ERPs can be reliably measured using EEG that reflects thousands of simultaneously ongoing brain processes and artifacts from the environment and the subject - to see the brain's response to a stimulus, the experimenter must conduct many trials and average the results together, causing random brain activity to be averaged out and disappear

Rodent Spatial Learning/Memory Assays

- Morris water assay: the most frequently used protocol to evaluate spatial learning and memory - Barnes maze is used to evaluate the natural motivation of rodent to hide; several holes are available and only one allow it to hide - radial arm maze is used to evaluate the ability of the subject to find a reward in one arm and learn the location of this one (several days of practice are necessary)

Postexperimental Data Analysis: MNI Template

- The MNI template (Montreal Neurological Institute) is a probabilistic mapping system based on the averages of hundreds of individual brain scans and scaled to match the landmarks within the Talairach atlas then, signal intensity is compared at different time points using 2 different strategies of analyzing signal intensity in the brain: - voxelwise analysis: each voxel is analyzed for significant differences in signal intensity in time between two experimental conditions - region-of-interest (ROI) analysis: the brain is divided into a set of discrete regions assigned by the investigator and entire brain regions are compared for significant differences in signal intensity

Functional Brain-Imaging Techniques: Positron Emission Tomography (PET) - Fluorodeoxyglucose (FDG)

- a PET experiment can use a variety of positron-emitting isotopes; one of the most commonly used is fluorodeoxyglucose (FDG), a radioactive form of glucose - as metabolically active neurons require an increase in the uptake of glucose from the blood, the presence of FDG can be used as an indirect marker of neural activity

Structural Brain Imaging Techniques: Computerized Tomography (CT-scan) or Computerized Axial Tomography (CAT-scan) - Computer Algorithm

- a computer algorithm that constructs a composite picture based on the X-ray scans from all the different angles - it generates a tomogram (8-10 slices for the brain)

Functional Brain-Imaging Techniques: Magnetoencephalography (MEG)

- a non-invasive neurophysiological technique that measures the magnetic fields generated by neuronal activity of the brain the spatial distributions of the magnetic fields are analyzed to localize the sources of the activity within the brain - localization of the sources are superimposed on anatomical images (such as MRI) to provide information about both the structure and function of the brain about 50,000 neurons are required to produce a detectable signal with MEG - a number that may seem large but is actually much smaller than what is required for an EEG signal, which may require millions of neurons

Functional Brain-Imaging Techniques: Positron Emission Tomography (PET) - Positron Emitting Isotopes

- a particularly useful aspect of PET imaging is the ability to use positron emitting isotopes that can bind to specific receptors in the brain - for example, a radioactive ligand that binds to serotonin receptors can indicate the locations and binding potential of these receptors in the brain, providing information about the relative metabolism of serotonin in human subjects

Structural Brain Imaging Techniques: Computerized Tomography (CT-scan) or Computerized Axial Tomography (CAT-scan) - Setup

- a subject lies with his or her head positioned in the center of a cylinder - a narrow beam of X-rays is aimed through the person's head and hits a detector on the opposite side - the beam and detector rotate in a slow arc, taking many individual X-ray scans at the same axial plane - multiple scans taken from different angles are combined to provide information about small differences in radio-density between different brain structures.

Functional Brain-Imaging Techniques: Positron Emission Tomography (PET) - Process

- an unstable positron-emitting isotope is injected into a subject's carotid artery (a neck artery that feeds the ipsilateral cerebral hemisphere) - as the isotope decays, it emits a positron, an antimatter counterpart of an electron. - when a positron comes into contact with an electron, an annihilation event occurs, resulting in 2 gamma photons that move in opposite directions these photons pass through the body and can be measured by a gamma-detecting device that circles the subject's head - the detector identifies a pair of gamma photons that arrive at opposite sides of the subject's head at the same time, within a few nanoseconds - as the detector rotates around the subject's head, these signals can be used to derive the source of the annihilation events within the subject

Structural Brain Imaging Techniques: Diffusion Magnetic Resonance Imaging (dMRI)

- arrangements of axons form tracts of white matter between different parts of the brain - diffusion MRI gives investigators the opportunity to visualize these different white matter pathways and study the complexities of axonal architecture

Brain Imaging Techniques: X-Ray Photography

- before the 70's Technique - each of the molecules through which the beam passes absorbs some of the radiation, the unabsorbed portions of the beam reach the photographic plate - X-ray photography only characterizes the degree to which internal structures absorb X-rays Limitations - X-ray photography is useless for differentiating the substances in the brain - limited spatial resolution - they are a bit invasive because of the teratogen property of the X-rays Benefits - not as expensive as other techniques such as MRI - results as fast to get and interpret

4 General Methods of Studying the Nervous System

- case study - screens - description - manipulation

4 Structural Brain Imaging Techniques

- cerebral angiography - computerized tomography (CT) - magnetic resonance imaging (MRI) - diffusion magnetic resonance imaging (diffusion MRI)

Functional Brain-Imaging Techniques: Optical Imaging - Noninvasive Alternatives

- diffuse optical imaging (DOI) and near-infrared spectroscopy (NIRS) - noninvasive alternatives that utilize the same basic principles as invasive optical imaging but record light reflectance through the scalp the signal is much weaker than invasive optical imaging - light must pass through the superficial layers of the head to the brain, and then from the brain to optical electrodes (known as optrodes or optodes) placed on the surface of the scalp - these techniques are sensitive enough to detect large changes in neural activity and can be useful in clinical applications as an alternative to fMRI or PET because of their low cost and portability.

Functional Brain-Imaging Techniques: Magnetoencephalography (MEG) - Benefits

- direct measure of brain function, unlike functional measures such as fMRI, PET and SPECT that are secondary measures of brain function reflecting brain metabolism - completely non-invasive; it does not require the injection of isotopes or exposure to X-rays or magnetic fields; children or infants can be studied and repeated tests are possible - complementary to other modalities, the information provided by each modality adds to the full picture

Functional Brain-Imaging Techniques: Electroencephalography (EEG) - Effects of Drugs

- drugs can affect the brain and its patterns of activity - EEG is very sensitive to the action of a wide range of pharmacological substances (especially psychotropic drugs, anesthetics, and anticonvulsants); it is also affected by antihistamines and antihypertensives influence of drugs on EEG include changes in its spectral content (frequencies) and topographic characteristics. - this may be used as an indication for its potential therapeutic efficiency

Functional Brain-Imaging Techniques: Functional Magnetic Resonance Imaging (fMRI) - T2-Weighted Images

- fMRI depends on T2-weighted images because the contrast in signal intensity between deoxyhemoglobin versus oxyhemoglobin is greatest on these kinds of images - in a typical experiment, a T2-weighted image of the brain is obtained prior to the stimulus presentation - when the subject performs a task, additional T2-weighted images are obtained - active neurons cause the BOLD effect (relative increase in oxyhemoglobin), and an increase in T2-weighted signal - T2 signal prestimulus and poststimulus are compared and color coded representations are used to depict the signal intensity

Functional Brain-Imaging Techniques: Functional Magnetic Resonance Imaging (fMRI)

- fMRI produces high-resolution representations of neural activity over time - fMRI can measure the signal intensity of hemoglobin in the brain, a protein that carries oxygen to cells

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - T1/T2-Weighted Images

- for any given point in time during the relaxation phase, the T1 white matter signal is stronger than that of gray matter, and the gray matter signal is stronger than that of CSF an image of the brain formed from T1 data is referred to as a T1-weighted image - most anatomical data are presented as T1-weighted images, as these images usually show better contrast between brain structures. an image formed from T2 data is said to be T2-weighted - lesions of white matter occurring due to the rupturing of blood vessels (trauma, stroke) are more easily detectable on a T2-weighted image.

Rodent Depression Assays

- forced swim test (Porsolt test) places animal in liquid with no possibility to escape; when animal stops moving vigorously scientists consider that the animal shows behavioral despair, characteristic of depression - tail suspension assay suspends rodent by the tail until he stops moving; depressed animals give up quickly; antidepressants increase the latency - sucrose preference test is supposed to model anhedonia, the loss of desire for once an enjoyable activity; rodents usually choose sucrose on water; lack of preference indicates depression

Functional Brain-Imaging Techniques: Positron Emission Tomography (PET) - Radioactive Water

- radioactive water can also be injected into the brain's circulatory system - because there is an increase in blood flow to active areas of the brain, the PET scan will indicate the areas in which blood flow is increased during activity.

Functional Brain-Imaging Techniques: Magnetoencephalography (MEG) - Magnetic Fields

- found whenever there is a current flow, whether in a wire or a neuronal element (upper left panel) - passes unaffected through brain tissue and the skull, so it can be recorded outside the head (upper middle) - extremely small, but can be detected by sophisticated sensors that are based on superconductivity (upper right) by analyzing the spatial distributions of magnetic fields, it is possible, by using a model such as a single equivalent current dipole (lower middle), to estimate the intracranial localization of the generator source and superimpose it on an MRI (lower right) - but this requires to solve the inverse problem, so to choose the "best" solution.

General Methods of Studying the Nervous System: Case Study

- identifying interesting events that have occurred naturally and using these events to develop hypotheses that can be tested in future experiments (e.g., Phineas Gage) - circumstances are often non-repeatable in laboratory; not true experiments - however, they allow scientists to form hypotheses to test on animal models and attempt to identify the neural circuits that contribute to human behaviors

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Voxels

- in order to measure signal from individual points within the slice, two additional magnetic gradients are applied in the other two axes - each point in space will have its own unique magnetic signature; each point has a specific volume and is termed a voxel, a three-dimensional version of a pixel that represents a cubic volume of brain space the resolution of each voxel is determined by the values of the gradients applied to the subject - with greater magnetic field strengths, more dramatic gradients can be established - spatial resolution of the MRI scanner is function of the value of the gradients bigger/smaller - the bigger the voxel, the more blurry is the picture - the smaller the voxel, the clearer is the picture; the more time it takes to get it

Functional Brain-Imaging Techniques: Single-Proton Emission Computerized Tomography (SPECT)

- it is very similar to PET imaging, producing functional images of neural activity but no structural data - a radioactive probe is injected (or inhaled) into the circulatory system and binds red blood cells to be carried throughout the body - because blood flow is increased in active brain structures, the radioactive signal is used to assess an increase in neural metabolism - very useful to follow cancer, because it is cheaper (no need to get cyclotron on site); however, it presents the same disadvantages as PET

Rodent Motor Assays - Locomotor Activity

- locomotion assays are used to determine the net motor activity of an animal over a given time period - running wheel is very simple but efficient for some animals - homecage activity uses infrared system or cameras to detect when the subject moves - open field locomotion test is used to measure the movements and exploration behaviors in an isolated environment

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - 3 Valuable Characteristics

- noninvasive (sometimes with contrast agents used to increase visibility of water-rich regions); no X-ray radiation are necessary - slices of the brain can be obtained in any angle (≠CT dependent on the axis of rotation of the X-ray emitter and detectors in the apparatus) - by varying gradient and RF pulse parameters, MRI scanners can generate contrast between different kinds of neural tissue

Rodent Nonspatial Learning/Memory Assays

- novel object recognition assesses an animal's innate ability to distinguish an old from a new object; normal rodents remember the old object and spend relatively more time exploring the new object. delayed match to sample/nonmatch to sample can be used to train an animal to make a response (i.e. poking its nose into a hole or pressing a lever for a reward in response to a stimulus, often a light appearing above the lever) - match to sample task, a light appears above one lever, and the animal must choose to press the lever beneath that light - nonmatch to sample task, a light appears, and the animal must choose to press the opposite lever - can be used to deal with timing and delay

Rodent Anxiety Assays

- open-field test is also used to evaluate anxiety; anxious animal spend less time in open area - elevated plus maze: normal animals avoid open arms - defensive marble burying uses rodents tendency to bury objects, particularly when anxious - Geller-seifter conflict test uses classical conditioning; scientist trains animals to press levers to get reward and add electric shocks; anxious animals press lever less than others

Functional Brain-Imaging Techniques: Electroencephalography (EEG) - Seizures

- patients with epilepsy present very specific patterns - partial seizures show very specific large amplitude components in few electrodes - generalized seizures show modification on all electrodes during the episode

Structural Brain Imaging Techniques: Diffusion Magnetic Resonance Imaging (dMRI) - Combining Other Techniques

- possible to combine diffusion MRI with functional MRI - the combination of these methods may reveal information about functional connectivity between brain structures

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Radiofrequency Pulses

- prior to the beginning of an imaging session, there is a net magnetic field vector in the parallel direction, longitudinal to the subject's body (A) - in order to collect data for an MR image, the subject is briefly exposed to pulses of electromagnetic energy (radiofrequency (RF) pulses)

Functional Brain-Imaging Techniques: Optical Imaging - Process

- produce images of neural activity by measuring changes in blood flow and metabolism from the surface of the brain - light is shined on an exposed portion of the brain and is reflected off the surface, detected by a sensitive camera and recorded by a computer when neurons are more active, changes in the blood volume, blood oxygenation, and the light-scattering properties of neural tissue (resulting from ion and chemical movements) all cause small (0.1 - 3.0%) changes in the reflectance of light from the brain's surface - changes in light reflectance can be associated to the presentation of a stimulus

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Protons

- protons are like miniature magnets. they spin around an axis and their spinning positive charge induces a tiny magnetic field (A) - normally, the magnetic fields of individual protons orient in random directions (B) - when a subject is placed inside the strong magnetic field of an MRI machine, the magnetic fields of individual protons align in the axis of the field (C & D)

Functional Brain-Imaging Techniques: Functional Magnetic Resonance Imaging (fMRI) - Limitations - False Positives

- random noise and large scale statistical comparison increase the chance to see false positives (seeing voxels wrongly, showing significantly different activities between conditions) - serious use of statistical comparisons is crucial in fMRI studies and reproducibility of the results is even more important to ensure the validity of the discoveries - corrections for multiple comparisons need to be used in order to avoid false positives - old published results have to be scrutinized to determine their validity

Rodent Social Assays

- resident-intruder assay measures territorial behavior in males, aggressive behaviors, attacks as well as time spent investigating each other - social approach/avoidance presents choice between animal and inanimate object; animals tend to choose the other similar animal; can evaluate social avoidance

Rodent Motor Coordination Assays - Motor, Coordination, and Balance

- rotarod is used to test balance of animals suspended above a padded base - footprint pattern assay is used to follow the animal's paws in a certain space; scientists dip their paws in ink; useful for studying deficits in muscular coordination - hanging wire assay is used to evaluate neuromuscular deficits; rodents placed on a shaking grid progressively put upside-down to evaluate their ability to maintain the grip (up to 60 seconds) and avoid falling - vertical pole test is lifted vertically and angled until the animal falls

General Methods of Studying the Nervous System: Screens

- searching for anatomical structures, neurons, proteins, or genes that could play a role in a subject of interest - they are not necessarily driven by hypotheses, but help identifying candidates that can form the basis for future hypothesis-driven research screens can be performed at different levels: - neuroscientists can observe brain activities as the present certain types of visual stimuli performing a screen of the different brain regions - genetics can examine thousands of genes to identify which genes are necessary for a behavior to occur.

Rodent Nociception Assays

- tail flick assay is composed of a high intensity beam of light producing painful heat sensation causing withdrawal reflexes - Hargreaves assay is similar but focused on the hind paw - hot plate assay is used to maintain animals in a tube directly on contact with a hot surface calibrated to make the subject react in 10 seconds; researchers measure the latency of reaction (liking, jumping, vocalizing) - Von Frey assay is used to examine the sensitivity to pinch and mechanical stimuli - formalin assay is used to evaluate sensitivity to noxious chemical stimuli

General Methods of Studying the Nervous System: Manipulation

- testing hypotheses by determining the effects of an independent variable on a dependent variable 2 most common types: - loss of function ("necessity"): a part of a system is diminished or removed in an attempt to determine if it is necessary for a certain process to occur; IV is the loss of the structure; DV is the effect on another aspect of the nervous system. - gain-of-function ("sufficiency"): an aspect of the nervous system is increased relative to normal (e.g., electrical stimulation of the visual system influences visual perception)

Functional Brain-Imaging Techniques: Electroencephalography (EEG) - Event-Related Potentials (ERPs) - P300

- the P300 is a very studied ERP component - elicited in the process of decision making and considered to be an endogenous potential, as its occurrence links not to the physical attributes of a stimulus, but to a person's reaction to it - thought to reflect processes involved in stimulus evaluation or categorization - elicited using the oddball paradigm, in which low-probability target items are mixed with high-probability non-target (or "standard") items

Functional Brain-Imaging Techniques: Functional Magnetic Resonance Imaging (fMRI) - Four-Dimensional Data

- the amount of T2-weighted signal is compared between the prestimulus and poststimulus time points and color coded to depict the signal intensity - this data is typically superimposed over a T1-weighted image that more clearly depicts the underlying anatomy of the brain - the end result is a colorful statistical representation of neural activity superimposed on an anatomical image of the brain; a depiction of the BOLD response over time - fMRI data represent four-dimensional data: the x, y, z coordinate planes for each voxel in space, as well as the fourth dimension of time (the "before and after" time points during which the stimulus is presented)

Considerations for Choosing/Performing a Behavioral Assay: Choosing an Appropriate Behavioral Paradigm

- the assay must be quantifiable, with the ability to measure discrete, easily observable variables (e.g. drinking behavior in rodents) variability in individuals: - genetics predispositions - environmental influences

Brain Imaging Techniques: Structural Imaging Technologies

- the contrast between gray and white matter is often structurally very informative so, structural imaging technologies differentiate between: - proteins and carbohydrates (cell bodies) - fat (axon tracts) - salt water (CSF) to reveal the brain architecture

Postexperimental Data Analysis: Talairach Space

- the most widely used coordinate system for normalizing fMRI data - used to define the location of all the structures in the brain in postmortem observations

Levels of Investigation

- the nervous system is extremely complicated and can be examined at multiple levels - macroscopic structures seem to support different functions on their own - these structure are organized in networks supporting more refined functions (e.g., language) - neurons (~86 billion) are the most basic component of these structure and take part to the networks with the synapses they develop (~100 trillion) - the specialized functions supported by the different types of neurons are possible because of their structures (soma, dendrites, and axon) - they are also possible because of the 30,000 genes providing the genetic info necessary for the production of the proteins used in each cells (neurons, glial cells, etc.)

Structural Brain Imaging Techniques: Magnetic Resonance Imaging (MRI) - Protons Precess

- the protons in a magnetic field: they do not simply stay stationary, they precess around their axis, as they are spinning the frequency with which they precess is dependent on the strength of the external magnetic field (generated by the MRI machine) - higher magnetic field strengths increase the signal-to-noise ratio and give higher contrast and spatial resolution. - in the literature, most conventional MRI machines create external magnetic fields at 1.5 - 3 Tesla; newer, more powerful MRI scanners create fields at 7 Tesla - however, these powerful magnets are also more expensive and more likely to cause physiological discomfort in subjects (i.e. nausea or dizziness)

Functional Brain-Imaging Techniques: Electroencephalography (EEG) - Scalp EEG

- the scalp EEG reflects the sum of electrical events throughout the head; it is a measure of the gross electrical activity of the brain characterized by its frequency/amplitude - not truly a brain imaging technique; however, EEG can be used to ascertain particular states of consciousness with a temporal resolution of milliseconds - these events include action potentials and postsynaptic potentials, as well as electrical signals from scalp muscles and skin - cannot determine the actual generators of the activities recorded on the scalp (inverse problem)

Structural Brain Imaging Techniques: Diffusion Magnetic Resonance Imaging (dMRI) - Water Molecules

- the term diffusion refers to the fact that water molecules, like all other molecules, randomly move through a medium over time (isotropic diffusion = all directions) - in brain tissue, water molecules tend to diffuse most rapidly along parallel bundles of fibers with coherent orientations (anisotropic diffusion). - MRI technology to analyze the magnitude and direction of the diffusion of water molecules for each voxel of tissue, thus creating a three dimensional image of fiber tracts

Functional Brain-Imaging Techniques

- they are used to measure neural activity in the CNS and determine which neural structures are active during certain mental operations - they cannot demonstrate that a brain region causes certain actions or is the specific structure that regulates a cognitive process - they can show that activity in specific brain regions is often correlated with a particular stimulus, emotional state, or behavioral task different types: - functional magnetic resonance imaging (fMRI) - positron emission tomography (PET) - single-proton emission computerized tomography (SPECT) - electroencephalography (EEG) - magnetoencephalography (MEG) - optical imaging

Functional Brain-Imaging Techniques: Electroencephalography (EEG) - Electrodes

- to produce an EEG, several disk-shaped electrodes (about half the size of a dime) are placed on the scalp in a standardized manner to allow the "descriptive localization" of the different activities and comparisons between subjects and experiments - the EEG is now generally recorded from several electrodes (32 to 256); the contact between the scalp and the electrodes uses a special gel.

Functional Brain-Imaging Techniques: Magnetoencephalography (MEG) - Limitation

- unfortunately, MEG is a very expensive technique - requires a room that can obstruct magnetic fields from outside sources; even something as small as a coffee machine in a neighboring building can be detected if the room is not adequately insulated

General Methods of Studying the Nervous System: Description

- using techniques that allow a scientist to observe the nervous system without manipulating any variables - observing properties of the nervous system without manipulation (e.g., work by Ramón y Cajal) - generally the first step for acquiring knowledge about newly discovered gene, protein, neuronal subtype, etc. - not necessarily easier than experimentation

Rodent Sensory Assays

- visual cliff assay is used to evaluate the ability of the rodent to see the drop-off at the edge of a horizontal surface - startle response assay is used to present an unexpected disruptive sensory stimulus triggering an eye blink; useful to evaluate startle reflex circuitry - taste can be evaluated using multiple bottles providing water to animals; this is useful to evaluate subject preferences and ability to detect unusual or dangerous tastes - olfaction can be evaluated by searching how long it takes for the animal to find food

Brain Imaging Techniques: 2 Categories

2 categories: - structural brain imaging techniques are used to resolve the anatomy of the brain in a living subject without physically penetrating the skull - functional brain imaging techniques are used to measure neural activity in the central nervous system without physically penetrating the skull - both can be used to correlate neural activity in specific anatomical regions with behavioral or cognitive functions

Considerations for Choosing/Performing a Behavioral Assay: Choosing an Appropriate Model Organism

2 characteristics to consider: - the natural ethological capabilities of an animal (what animals can do) - the additional experiments the scientist will use to complement behavioral experiments - it depends on what the scientists are looking for (e.g., tracking genes or neurons involved in certain behaviors)

Functional Brain-Imaging Techniques: Electroencephalography (EEG) - Patterns

EEG presents different patterns related with the levels of awareness - beta (12-24Hz): associated with focus attention or REM - alpha (8-12Hz): with light relaxation (e.g. eyes closed) - theta (4-8Hz): with light sleep - delta (0.5-4Hz): with deep sleep - gamma (24-120Hz): with high level cognitive processing (e.g., complex decision-making)

Functional Brain-Imaging Techniques: Magnetoencephalography (MEG) - Resolution

MEG offers excellent spatial resolution and temporal resolution - events with time scales on the order of milliseconds can be resolved, again differentiating MEG from fMRI, PET and SPECT, which have much longer time scales therefore, MEG can be thought of as a compromise technique: - it offers excellent temporal resolution and much better spatial resolution compared with EEG - not as good spatial resolution as other imaging techniques. - sources can be localized with millimeter precision - MEG in combination with fMRI allows for excellent temporal and spatial resolution of neural activity

Structural Brain Imaging Techniques: Computerized Tomography (CT-scan) or Computerized Axial Tomography (CAT-scan) - Modern CT Scan

modern CT scans can distinguish between: - gray matter - white matter - ventricles with a spatial resolution of millimeters they are particularly useful for: - identifying fluid boundaries, such as blood collections on the brain surface in a hematoma - detecting hard objects in soft tissue, such as a tumor or calcification - CT scanners are faster, cheaper to operate, and less prone to motion artifacts than MRI scanners; therefore, they tend to be the first tool used to diagnose a patient.

Functional Brain-Imaging Techniques: Functional Magnetic Resonance Imaging (fMRI) - BOLD Effect

on a T2-weighted image: - oxyhemoglobin signal (carrying O2) > deoxyhemoglobin (the oxygen-depleted form of hemoglobin) - this allows to examine changes in the oxygenation-state of hemoglobin over time the ability to examine changes in oxygen metabolism over time in the brain is useful because it serves as an indirect measure of neural activity. - active neurons will consume more oxygen than when they rest Blood Oxygen Level-Dependent (BOLD) effect: forms the basis of this fMRI signal - Initially, this activity decreases the levels of oxyhemoglobin and increases levels of deoxyhemoglobin - however, within seconds, the brain microvasculature responds to this local oxygen depletion by increasing the flow of oxygen-rich blood to the active area

Functional Brain-Imaging Techniques: Positron Emission Tomography (PET) - Limitations

provides a representation of neural activity but no information about brain structure - PET images are often combined with CT or MRI images to present functional data in an anatomical context - compared to fMRI, PET has about the same temporal resolution (4 - 8 seconds), a lower spatial resolution, and cannot generate anatomical data - the cost of doing PET is very expensive - most isotopes used for PET studies have extremely short half-lives (e.g., FDG 110min); positron-emitting isotopes must be synthesized on site using a cyclotron - requires the injection of radioactive substances into subjects

Functional Brain-Imaging Techniques: Functional Magnetic Resonance Imaging (fMRI) - Limitations

the actual T2 signal change for a given voxel, before and after BOLD changes, can be as low as 0.2% - this is difficult to detect, because the noise of the system can be as high as 0.3 - 0.4%! - fMRI stimuli must be repeated several times for a single subject it can take 6 - 10 seconds poststimulus for the oxygenated blood to flow to an active region - the temporal resolution (4-8 seconds) is relatively poor compared to EEG or MEG - fMRI cannot identify which neurotransmitters mediate a change in neural activity - false positives

Structural Brain Imaging Techniques: Computerized Tomography (CT-scan) or Computerized Axial Tomography (CAT-scan) - CT Scan Quality

the quality of a CT scan depends on: - the width of the X-ray beam (narrower is better) - the sensitivity of the X-ray detector - the ability of the computer to construct an image from the data

Brain Imaging Techniques: Brain Structures

they all take advantage of the different composition of distinct brain regions and use these differences to form the basis of an image - brain tissue mostly composed of cell bodies appears gray compared with other areas, and thus is referred to as "gray matter" - brain tissue mostly composed of axons and fiber tracts appears white, and thus is referred to as "white matter" - cerebrospinal fluid (CSF) in the ventricles and surrounding the brain is essentially a saline solution - neural cell bodies contain many biomolecules, including proteins and carbohydrates - axons and fiber tracts are relatively fatty due to the insulation provided by myelin.