Methods Flashcards
Perturbation Approaches
Alter brain in someway and observe how behavior changes.
Assumption: changes in performance reflect specific processing within the perturbed region.
Approaches include: Natural lesions in humans Induced lesions in animal models Electrical stimulation Pharmacological lesion Transcranial magnetic stimulation
Natural lesions in humans
A regions of the brain that has been damaged or destroyed due to stroke or injury.
Examine behavioral and cognitive deficits and infer from them what that part of the brain is doing.
In humans we look at naturally occurring lesions.
Particularly popular during and following second world war.
Several famous examples including Phineas Gage, Henry Molaison and D.F.
Limitations of Natural Lesions in Humans
Cannot control size or location of lesion.
Not localized to single functional or anatomical region.
Time since injury may be important.
Brain networks may vary across individual.
What imaging tool is typically used to study natural lesions?
MRI
Advantages of experimental lesions over natural lesions
More control over the location and extent of the lesions
Better test of hypothesis concerning specific regions and groups of regions.
Safer alternatives to experimental lesions
Temporarily deactivate specific regions of the brain by cooling or injecting drug to anesthetize.
Downsides to experimental lesions
Difficult and time consuming to train animals
Some ethical concerns over producing lesions.
Reversible lesions
Limitations of assumptions of mapping
Avoid naïve mapping of complex psychological process onto discrete brain regions.
Transcranial Magnetic Stimulation (TMS)
Technique to stimulate the brain from outside of the head
Pass a very strong electrical current through a coil.
Generates a magnetic field that enters the head that
induces current in the brain, interacting with the activity of neurons.
Single Pulse TMS
Transiently influences neurons.
Effect are very brief.
Effective for mapping perceptual and motor areas and evaluating cortical excitability.
Understanding temporal relationships
Repetitive TMS (rTMS)
Results in longer term increase or decrease in cortical excitability.
Useful for understanding how brain areas interact during cognition.
Can be used as a form of temporary lesion.
What is the point of the figure 8 coil?
Figure 8 coil used to improve spatial specificity.
Current travels around coil.
Induces magnetic field that sums along the coil midline.
Results in more focused magnetic field and electric field.
Advantages of TMS
Non-invasive
Effects are temporary
Can infer causality
Disadvantages of TMS
Similar to that of lesions.
Used to alter activity in cortex but not deep structures.
Can indirectly activate large areas of cortex.
Don’t always know where you are stimulating
Has risks associated with it – e.g. seizure.
TMS assessment of Visual Cortex
Subjects must identify letters presented on a computer screen.
TMS is applied over visual cortex at various delays with respect to stimulus onset.
Acts to disrupt normal processing.
TMS selectively affects performance between 70 and 150 ms after stimulus onset.
Conclude that affected area is critical for letter identification and that it is processing information at about 100 ms after stimulus onset
Single and Multi Unit Studies
Using fine wire electrodes (1/1000 mm) to measure neural activity from a single or multiple neurons.
Measure relationship between firing rate of neuron and an external stimulus or task.
Used to understand receptive fields, response properties, cellular basis of learning and memory
, plasticity in the nervous system
Disadvantages of single and multi unit studies
Record from only a very small number of neurons whereas cognition is mediated by huge numbers of neurons distributed over many areas.
The activity in one cell may not be representative of what an entire area is doing.
Difficult to get monkey to perform complex cognitive tasks and to report on their experience.
Cannot study reasoning, social interaction and language…
MEG
Magnetic fields generated by the brain measured from outside the head.
Neural Basis of EEG
Pyramidal neurons of the cortex.
Extracellular current flow related to dendritic currents.
Requires large number of synchronous neurons.
Highly sensitive to conductivity of the head (skull, skin, fluid, brain, etc)
Event Related Potentials (ERP)
Electrical brain response related to mental operations or cognition.
Time locked to an external stimulus or internal cognitive event.
Small signal that requires averaging of data over multiple trials.
Responses named according to polarity and latency (N100, P200), or order (N1, P2).
Useful for investigating timing of functional brain activity.
Inverse Problem
The distribution of activity measured at the scalp can, in theory, be produced by one of an infinite number of possible sources in the brain.
MEG
Measures magnetic fields generate by electrical currents in the brain.
Magnetic fields are related to electrical current according to the “right hand rule”
Activity in neurons generates a magnetic field.
MEG can detect those fields as they exit or enter the scalp.
Advantages of PET
Brain based method of activity.
Can image deep structures.
New isotopes are being generated to allow for imaging of different compounds: Glucose / Dopamine
Many clinical uses
Disadvantages of PET
Secondary measure of neural activity.
Injection of radioactive tracer makes it invasive - limits number of exposures.
Has very poor temporal resolution.
Provides only moderate spatial resolution.
tractography
Connecting ellipses based on orientation allows for the tracking of specific white matter tracts in the brain
Computer Modeling
Using computer programs to model and simulate neural system to test hypothesis about how they process information
Simulations are usually of a very specific system or process (no whole brain yet!).
Advantages of computer modeling
Require all assumptions to be made explicit.
Explicit tests of hypothesis concerning specific computations and how they are implemented.
Quickly and easily test a very large number of experimental situations.
Makes detailed predictions that may not be intuitive.
Disadvantages of computer modeling
Computer models are inevitably over simplifications of the system under investigation.
Usually apply to only a very specific problem or set of problems.
Can explain one experimental finding!
Require Specialized knowledge and skills to use
Simple modeling stages
1) Include relevant information - How much detail is needed? What factors are important?
2) Recreating observations - Does the model do what people do?
3) Making predictions – What new information does the model provide?
4) Update the model or design real experiment
5) Repeat!!!
What happens metabolically in the brain when areas in the brain have increased activity? (MRI and blood)
The amount of oxygen being delivered to the local area increases
The amount of oxygen removed from blood stream decreases
Oxygen rich blood is less magnetic and results in larger (~2%) BOLD signal.
Timescale of BOLD
Response to brief stimulus is both delayed and extended in time.
With respect to the stimulus the response.
Begins at about 2 seconds.
Peaks at about 5 seconds.
Returns to baseline at about 11 seconds.
Better temporal resolution than PET but still much less then EEG/MEG
Single Dissociation
Logic used to determine whether component processes are mediated by separate brain areas.
Requires at least two groups and two tasks.
Group 1: Lesion in area “A”
Group 2: No lesion – control
Tasks: X & Y
Compared to no lesion, damage to area “A” interrupts function X but not function Y.
Area “A” is related to function X but not Y.
Shows a level of independence between X & Y.
Double dissociation
Similar in logic to single dissociation
More powerful because it overcomes limitations of single dissociation
Can establish whether two tasks are independent.
Group 1
Lesion in region “A” (not “B”)
Impaired on function X but not function Y
Group 2
Lesions in region “B” (not “A”)
Impaired on function Y but not function X.
Establishes the independence of the tasks and their separate neural representation.
