Methods in Cognitive Neuroscience. Methods for studying the brain. Single Cell Recording

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1 Methods in Cognitive Neuroscience Dr. Sukhvinder Obhi Department of Psychology & Centre for Cognitive Neuroscience 1 Methods for studying the brain Single Cell Recording Lesion Method Human Psychophysiology EEG & ERPs Magnetoencephalography (MEG) Magnetic Resonance Imaging Transcranial Magnetic Stimulation 2 Single Cell Recording A thin electrode is inserted into an animals brain Tip of electrode usually sits outside the neuron makes this an extracellular method Depending on the type of electrode - picks up activity of a single neuron (single unit recording) or a small set of neurons (multiple unit recording) Computer algorithms can differentiate pooled activity into contributions from individual neurons 3 1

2 Single Cell Recording Record from a series of cells A single cell does not respond to all stimuli -Cell 1 colour not shape -Cell 2 shape not colour Visually sensitive cells only respond to stimuli in a limited region of space cell s receptive field 4 For example, some neurons will respond only when the stimulus appears in the upper right part of the visual field 5 Pros and Cons of single cell recording Usually restricted to small sample of cells Might be more important to consider the responses of different groups of cells rather than a single cell New techniques are emerging to enable multiple single cell recording This could bring about the next revolution in neurophysiology 6 2

3 Lesion Method Gets round the restrictive issue in single cell recording looks at larger regions Logic - If a region contributes to a task, lesioning region should impair task performance Ethical concerns prevent this technique being used on humans 7 Example of the Lesion Method Normal 5 months after SMA lesion Brinkman,1984 SMA is involved in coordinating the hands in a goaldirected fashion 8 Neuropsychological case studies Brain damaged patients provide another powerful line of evidence Temporal lobe damage (Visual Agnosia) Intact action, impaired perception single dissociation spared on task A, impaired on Task B) 9 3

4 Neuropsychological Cases Parietal Lobe lesion Optic Ataxia Intact perception, impaired action Single dissociation 10 Double Dissociation Two single dissociations with opposite and complimentary pattern of results: Performance (arbitrary units) Perception Task Action Task Temporal Damage leading to VA Parietal Damage leading to OA 11 Not real data, schematic for explanatory purpose only Limitations of the lesion method Damage to area X impairs behaviour Y - tells us that X is necessary for Y but not sufficient Eg: A radio has many parts (speakers, tuner, power switch) damage to any one of these impairs the playing of music but can t claim one of these specific parts (alone) is responsible for playing the music! Critical that lesions in different parts of the network are examined before conclusions drawn (with caution) Human patients: reorganisation can be a problem when drawing conclusions 12 4

5 Potential problem Lesions are studied to infer computational role of a particular region of the brain Long after injury, brain may have reorganized (plasticity) and we might not know exactly how Thus, it may be difficult to relate deficits to normal brain function because we are measuring performance of a reorganized system! 13 Example the changing brain Typically, we ascribe visual processing to areas of visual cortex However, in some early blind people, visual cortex is found to underlie tactile discrimination Termed cross-modal plasticity see TMS study in readings 14 Animal testing issues 15 5

6 Animal testing issues 16 Psychophysiology in Humans: EEG Scalp electroencephalography (EEG) represents the sum of electrical events throughout the head Some EEG waveforms are associated with particular states of consciousness For example alpha waves have a frequency of 8-13Hz and are associated with relaxed wakefulness 17 EEG electrode placement: system 18 6

7 Individual electrodes 19 EEG electrode Cap 20 Typical EEG waveforms & psychological correlates 21 7

8 Event related potentials (ERPs) Sometimes we are interested in electrical brain responses to certain events rather than the general background activity Evoked responses occur in response to certain events Eg., sensory evoked potential is the change in the cortical EEG signal that is elicited by the presentation of a sensory stimulus (VEPs, SEPs etc) 22 Evoked Potentials 23 EEG & Movement Preparation Precedes voluntary motor act; 2 components Early component: occurs from ~ s prior to a voluntary act Late component: occurs from~0.5 s-0 s prior to movement Thought to reflect voluntary motor preparation 24 8

9 Pros and Cons of ERPs Pros: Excellent temporal resolution (1 ms timescale) Relatively cheap Can detect activity in gyri and sulci Cons: Poor spatial resolution This is due to the inverse problem 25 Inverse Problem Given a pattern of electrical activity picked up at the scalp there are numerous possible distributions of sources in the cortex Electric activity is also subject to distortion as it moves through brain (does not move uniformly through the brain) 26 Dipole modelling Can use sophisticated computer algorithms to model placement of generators in the brain that would lead to observed pattern of scalp EEG Not an extremely accurate technique more than one pattern of generators could fit pattern of scalp activity For precise spatial information better off using different technique 27 9

10 Magnetoencephalography (MEG) Active neurons produce small magnetic fields MEG has the same excellent temporal resolution as EEG but it has an advantage in that sources of the magnetic activity can be better localized (2-3 mm) A limitation is that MEG can only detect fields due to current flow oriented parallel to the surface of the skull (i.e., in sulci) Magnetic fields also drop off quicker than electrical activity so MEG better at surface activity detection Also, very expensive, over $1 million for a whole head system 28 MEG 29 Magnetic Resonance Imaging (MRI) 30 10

11 MRI basics Hydrogen atoms contained in brain tissue are magnetic and randomly aligned They align when an external magnetic field is applied When a radio wave is applied, they are perturbed at the resonant frequency As relax, radio signal that varies as a function of the position of the atoms in the magnetic field Can therefore localize where in the brain the emitted radio signal was generated Density of hydrogen in different tissue varies making it possible to identify specific structures31 The hardware 4T magnet RF Coil gradient coil (inside) 32 Credit: Jody Culham s website, UWO Structural MR Images 33 11

12 MRI vs. fmri MRI studies brain anatomy. Functional MRI (fmri) studies brain function. Credit: Jody Culham s fmri for Dummies 34 Functional MRI Basic Idea The behavioural tasks that we perform in everyday life are driven by underlying neural activity This neural activity is in turn fuelled by oxygen Oxygen is carried to the site of neural activity by hemoglobin fmri can determine increases in the flow of oxygenated hemoglobin to the brain area of interest This measurement is called the Blood-Oxygenation- Level-Dependent effect or BOLD 35 Timescale of BOLD effect Neural events occur on a millisecond time scale The BOLD response occurs on a timescale of 2-10 seconds Therefore, when a neural area becomes active, there is an initial drop in the level of oxygen in the area due to the increase in metabolic activity This drop is compensated for after a few seconds by the arrival of freshly oxygenated hemoglobin 36 12

13 Timescale of the BOLD effect 37 Data from cat visual cortex using a 4.7T scanner Benefits of fmri Spatial resolution (volume elements or voxels ) ~ 3-5mm Potential to get even better as higher field magnets are developed Temporal resolution from several hundred milliseconds to a few seconds Non-invasive so can test same subject multiple times allows a complete statistical analysis of results Techniques exist for locking the fmri signal to a specific event event-related-fmri enables brain activity to be examined as a function of an experimental manipulation 38 Overview of Experimental Designs Brain always spontaneously busy If we just measured brain activation in one task (say moving the right finger in response to a beep) which aspect of activation reflects the movement? Need to look at differences between conditions 39 13

14 Analysis basics Several stages to fmri data analysis Data comes from different brains so need to normalize fit into a standard template Enables you to make meaningful comparisons Other procedures to clean up the data smoothing Then apply statistical test to each voxel and see whether there is a significant difference in activation between conditions of interest 40 Cognitive Subtraction Hypothetical activation pattern beep Move finger Condition 1 beep Condition 2 41 What activation relates to finger movement? Subtract the beep from the beep + finger movement result: Beep + Movement condition Beep Only condition Finger movement specific activation 42 14

15 Potential Problem Assumes that adding a component to the task leaves the other component unchanged Does not take account of potential changes due to task change (called interactions in Ward book) Perhaps, processes underlying hearing a beep and pressing a button are actually different from just hearing a beep? (termed assumption of pure insertion ) 43 Potential solution To maximize chances that process of interest is isolated, have multiple conditions all involving that process Then perform multiple subtractions. If region really does underlie particular component, should be good agreement across multiple subtractions Care needs to be taken in choosing/designing conditions 44 Simple example Add extra conditions + perform extra subtractions: Condition 3 Visual stimulus Move finger Condition 4 Visual stimulus Condition 5 Nothing rest condition 45 15

16 To isolate activity related to response Compare activations in following subtractions: (Beep + move condition) (beep condition) = movement related activation (Visual stimulus + move condition) (visual stimulus condition) = movement related activation (Move condition) (rest condition)= movement related activation Reduces the chances that interactions between processes could contaminate results if only one subtraction performed Essentially conjunctions can help confirm a particular activation that is thought to underlie a certain function 46 Some limitations of fmri Not a direct measure of neural activity it is a measure of metabolic change as a result of neural activity Temporal resolution is not great due to blood response lagging neural response by seconds Scanning environment can be claustrophobic for some participants Excess movement can cause problems with the fmri signal so limited ability to study large movements 47 Functional Images 48 16

17 Transcranial Magnetic Stimulation An electromagnetic technique that can be used to interfere with ongoing neural activity This makes the area being stimulated less capable of performing task related processing Can be used online or as repetitive trains offline Limited to investigations of cortical areas (can t go too deep beneath the cortical surface) Similar idea to the lesion technique, but lesions are temporary and safely induced 49 TMS - application 50 A Typical rtms Experiment Self Other discrimination experiment Previous fmri research suggested that right inferior parietal lobule involved in self processing (e.g., own body perception) However, conclusions limited by correlational nature of fmri 51 17

18 Uddin et al, 2007 The experiment Engaged subjects in a self-other discrimination task using morphed images Could be morphed to be 0%, 20%, 40%, 60%, 80% or 100% self or other Other face was a familiar friend or family member 52 The Protocol Block of trials 20 mins 1 Hz 100% rmt to either right IPL, or left IPL (control separate day) Block of trials Compare performance 53 NB:Response hand switched half way through, and order of starting hand and stimulation site counterbalanced across subjects Results Results indicated impaired self-other discrimination only for right IPL stimulation No effect of left IPL stimulation Therefore, right IPL concluded to play causal role in self-other discrimination 54 18

19 Technique Space & Triangulation 55 A couple of specific examples A blocked fmri experiment An event related fmri experiment A single pulse TMS experiment A repetitive TMS experiment 56 19

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