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Cognitive Neuroscience Methods

Henk J. Haarmann, Ph.D

Structural brain imaging:
Computerized Tomography (CT, also known as CAT)
Structural Magnetic Resonance Imaging (MRI)
Functional brain imaging: PET, fMRI
Neuro-electrical recording/stimulation:
Electrode recording/stimulation (single-, multiple-electrode)
Electro-encephalography (EEG)
Event-related brain potentials (ERP, form of EEG)
Magnetic Encephalography (MEG)
Transcranial magnetic stimulation (TMS)
Cognitive testing
Double dissociation method
Psychological experiment
Computer modeling/simulation
Neural network modeling
Why measure brain activation?
Localization of brain function
Critical and participating areas
Determining timing of function
controlled vs. automatic
syntactic vs. semantic
immediate processing vs short-term retention,
normal vs. delayed activation / reduced amplitude)
Determining spatial-temporal cooperation of
regions in network
Determining re-organization of function, after
brain damage, spontaneous recovery, Tx
Determining normal and delayed development of
Structural Magnetic Resonance
Imaging (structural MRI)
Transverse/Axial Coronal Sagital
Nuclear Physics of structural MRI
Hydrogen atoms in tissue
have a random orientation
become aligned in magnetic field
emit energy when perturbed by
a radio wave and wobbling back
have a different density in gray
versus white matter
Functional neuroimaging
Measure increases/decreases in regional
blood flow during information processing
tasks and while at rest
Active brain regions receive more blood,
since blood caries oxygen & glucose used
by neurons
Overview PET
measurement principles
nuclear physics
Positron Emission Tomography
A PET SCANNER: injection of
radioactive tracer into blood stream
PET measurement principles
Radio-active tracer O
Half life of about 2 minutes
injected into blood flow
greatest concentration in active brain areas
consume oxygen and glucose in blood flow
location and concentration measurable
During decay positron emitted spontaneously
collision with electron
gamma ray released
picked up by gamma ray detector
Nuclear physics of PET scanning
Radioactive tracer,
e.g. H
Advantages & disadvantages PET
Relatively good spatial resolution (5-10mm), better
ERP/MEG, worse fMRI (1-3mm)
Tracing of different biochemical processes
Invasive (injection of radio-active tracer)
Limited testing (due to decay of tracer 40 sec)
Need to block stimuli by condition
Poor temporal resolution
Overview fMRI
same as scanner used for structural MRI
measurement principles
description of brain activation
Identification of participating voxels
Correlation method
Subtraction method
Describing regions of interest (ROIs)
Brodman areas
Advantages versus disadvantages & limitations
fMRI measurement principles
Contrast agent hemoglobin (HB)
naturally present in blood flow
carried by oxygen
paramagnetic in its deoxygenated state
greatest concentration in active brain areas
due to blood flow oxygenation response
location and concentration measurable
decrease in ratio of deoxygenated/oxygenated HB
decrease in magnetic field signal of deoxygenated HB
decrease in energy release of magnetically aligned and
perturbed HB atoms.
fMRI image superimposed on
structural MRI image
* | +
The star is above the plus
Description of brain activation
Small brain area showing increased regional blood
flow, in an experimental condition relative to a control
condition (e.g., rest)
Size depends on spatial resolution
Precision of measurement in space
E.g., 3mm x 3mm x 3mm
Degree of brain activation
Number of voxels
Intensity of activation of a voxel
Region of interest (ROI)
Larger brain area observed in study (e.g., Wernickes
Functional neuroimaging of adult males with dyslexia
(Eden et al, 1996, Nature)
Motion detection area
Active in controls
Inactive in dyslexics
Identifying participating voxels I
Identifying participating voxels II
Subtraction method
Brain activation Experimental condition
Brain activation Control condition
Brain activation Unique to Experimental Condition
Example of the subtraction
Subtraction method
Brain activation sentence verification
Brain activation consonant strings
Brain activation unique to sentence verification
Another example of the
subtraction method
Subtraction method
Brain activation moving dots
Brain activation stationary dots
Brain activation unique to moving dots
1) Molecular
2) External granular (A)
3) External pyramidal (A)
4) Internal granular (S)
5) Internal pyramidal (M)
6) Fusiform
A = association
S = sensory input
M= motor output
Layers of neo-cortex
Regions of interest: Brodman areas
Brodman areas (lateral view)
Regions of interest: Brodman areas
Advantages fMRI
Non-invasive (versus PET)
Best spatial resolution of non-invasive
Electrode recording (< 1mm) > fMRI (1-3mm)
> PET (5-10mm) > MEG > ERP
Shows all participating areas, not just
critical ones
Single-subject studies are possible
Disadvantages & limitations fMRI
Poor temporal resolution
Precision of measurement in real time
Electrode recording > ERP/MEG > fMRI/PET
No differentiation between neuro-electrical excitation and
Difficult to use with subjects and to obtain good measurements
Sensitivity to head motion
Contra indicators
Pregnancy, Obesity, Metal parts (pacemakers, shrapnel, glasses)
Relatively weak signal increases (1-3%)
Very expensive to acquire, use & maintain
Personnel intensive: Neuro-radiologist, Nurse, Physicist, Statistician,
Computer Scientist, Cognitive Psychologists, Research SLP
Overview single/multiple electrode recording
/ stimulation
Single electrode recording
Encoding of information through firing rate
Binding of information through synchronization
Mapping of somato-sensory & primary motor
Multiple electrode recording in epilepsy
Advantages vs. disadvantages & limitations
Single-electrode recording in
Encoding of information thru neural firing rate
For example, detection orientation visual bar
Encoding of information thru neural firing rate.
For example, detection of movement direction
Encoding of information thru synchronous firing
For example, visual binding
Electrical stimulation
Multi-electrode recording &
stimulation in epilepsy patients
Example of single electrode recording: a neuron in
the hippocampus responds selectively to sad faces
Fried, I., MacDonald, K.A., Wilson, C.L. (1997). Single neuron activity in
human hippocampus and amygdala during recognition of faces and objects.
Neuron, 18, 753-65
Advantages versus disadvantages of single /
multiple electrode recording / stimulation
Only in patients who have to undergo surgery and give their
informed consent for additional research
Not necessarily typical of normal brain
Possible danger of damaging artery/vein & causing
Best possible spatial & temporal resolution
Differentiation between excitation & inhibition
Study of activation dynamics of neural network
Overview: Electro-encephalography (EEG)
Scalp-attached electrodes
Positioning of electrodes
What aspect of brain activity does EEG measure?
Need for signal amplification and averaging
EEG frequency bands & states of consciousness
Event-related brain potentials (ERPs)
Measures EEG time-locked to presentation of a stimulus event
Example of peripheral ERP component (auditory evoked potential)
Example of central ERP component (N400 to semantic violations)
Inverse problem (explaining in part poor spatial resolution)
Advantages versus disadvantages & limitations
Scalp-attached electrodes
Checking impedances of scalp electrodes
International 10-20 system: ensures electrodes are
placed over specific cerebral locations
C=central, O=occipital, F= frontal, P= parietal, T=Temporal
Subscript: odd (1,3,5,7) left, even (2,4,6,8) right hemisphere, z=midline
Nasion=point between forehead and nose, Inion=bump at back of skull
EEG and brain activity
EEG & Brain activity
EEG measures post-synaptic currents (PSPs) in large
numbers of neurons, especially on apical dendrites
of pyramidal cells (70% of cells in neocortex)
Necessary conditions for measuring this signal
Aligned orientation of dendrites (not random, but e.g.
Synchronous activation of few hundred thousand neurons
Signal amplification & averaging
EEG Frequency bands
DELTA: <4 hz (deep sleep, coma)
THETA: 4-8 hz (hippocampal and limbic activity: memory, emotion)
ALPHA: 8-12 hz (alert, but not actively processing information, most
prominent over occipital and frontal lobe, e.g., when eyes closed)
BETA: 13-30hz (alert and actively processing information)
GAMMA: >30-35 hz (Related to stream of consciousness? Binding of
information from different brain modulates into coherent percept,
sustained by re-entrant, positive feedback loops of neuronal cell-
assemblies onto themselves).
Note. Hz = number oscillations per second (e.g., 3 Hz below)
0ms 1000ms (1sec)
EEG profiles & consciousness
The auditory evoked potential:
example of an event related potential
Example of a central ERP component: N400
to semantic violations
(Kutas & Hilyard, 1980)
Changes in EEG coherence during cognitive
tasks (Haarmann, Cameron, & Ruchkin, submitted)
Inverse problem in EEG/MEG
how many sources?
location of sources?
Source localization
ERP & eye movement artifacts
Eye movements & blinks produce fluctuating electrical fields in
same frequency range as neurons
Eyeball generates dipole field with positive and negative charge between
which current flows
Propagated back across scalp (brain acts as volume conductor)
Eye movements & blinks therefore contaminate ERP recording
1) instruction to subject: fixate & do not move eyes
2) after experiment discard trials on which eye blink occurs
3) estimate & remove part of signal due to eye movement & blinks
(e.g., Haarmann, Cameron, Ruchkin, Cognitive Brain Research, in press)
Advantages & Disadvantages of
Excellent temporal resolution
Multi-modal measure
amplitude, polarity, continuous in time, frequency-specific,
Relatively low cost: ERP < MEG < fMRI, PET
Many peripheral and central ERP components are known
Poor spatial resolution (inverse problem)
Many trials needed for averaging
Sensitive to eye movement artifacts (but can be filtered out)
Time consuming attachment of electrodes
Overview MEG
MEG scanner
Squid technology
Examples of MEG measurements
MEG scanner
MEG scanner consists of SQUIDs
Superconducting Quantum Interference Device
Detects magnetic flux
Between 100-300 squids in whole-head MEG
connected to sensor coils that lie in a configuration
that roughly follows the curvature of the head
Placed in magnetically shielded room
1000 fold attenuation of environmental magnetic noise
Traffic, elevators, jumping on floor, turning of chair
Cooled by liquid helium
Subject is shielded from cold temperature
Examples of MEG measurements
Scalp plot
Topographic map
MEG trace
Anatomical overlay of MEG
Advantages MEG
Fully non-invasive
no need for injection of radioactive tracer, ionizing
radiation such as X-rays, exposure to magnetic
field, or attachment electrodes
Excellent temporal resolution (same as ERP)
Multi-modal measure (same as ERP)
amplitude, continuous in time, frequency-specific,
Medium cost: ERP < MEG < fMRI, PET
Disadvantages MEG
Poor spatial resolution (due to inverse problem),
but better than ERP
In-homogeneities at scalp/skull affect conduction of
electrical but not magnetic field
Sensitive to tangential but not radial component of
brain activity
Tangential = perpendicular to banks of sulci
Radial = perpendicular to crowns of gyri (& scalp)
Many trials needed for averaging (same as ERP)
Sensitive to eye movement artifacts (same as
ERP), but can be filtered out
Overview of Transcranial Magnetic
Stimulation (TMS)
Stimulating coil inducing TMS
Operating principles of TMS
Effects of TMS
Uses of TMS
Advantages & disadvantages of TMS
TMS stimulating coil
TMS stimulating coil
TMS operation principles
Stimulating coil
Coil has round shape or figure 8 shape
Produces clicking sound
Brief current pulses of several kiloamperes
Causes time-varying magnetic field, about 2
Tesla strong, perpendicular to direction of
current (right hand rule), 100-200 microseconds
Induces current flow in opposition direction in
neural tissue
without known damage
FDA approved pulse sequences
at thumb-twitch intensity
Electrode-less electrical stimulation of brain
Effects of TMS
Sensation of scalp being drawn up
Muscle twitches
Interference with sensation
e.g., flashes & blind spots in vision
No reports of evoked memories or smells
Short-lasting effects
Single-burst stimulation
Long-lasting effects
Repeated stimulation
Effects can last Up to few minutes to hours
Low-frequency stimulation (<1Hz) causes depression of activity
e.g., when over auditory cortex of Schizophrenics, reduced auditory
High-frequency stimulation (>1Hz) causes enhanced activity
(possibly mediated by raising of baseline activity of neurons)
Faster picture naming with temporal lobe stimulation
Faster problem solving with PFC stimulation (Grafman, Neurology)
Uses of TMS
Mapping of brain regions
Motor mapping
TMS causes muscle twitching, especially, as coil is over the
cortical area that controls a particular muscle
Electrodes attached to muscle measure its response
Visual suppression mapping
TMS causes transient blind spot (e.g., subject cannot report a
letters identity)
What does visual cortex of congenitally blind person do?
Possible Treatment of neuropsychiatric /
neuropsychological impairments, such as
Depression & Parkinsons
20-30min/day, 2-4 weeks, over left PFC
TMS used in motor mapping (Leventon, MIT)
Index finger Forearm Biceps Jaw
TMS used to suppress vision in left (red) and
right (blue) visual field (Leventon, MIT)
Advantages/disadvantages of TMS
Fairly non-invasive stimulation of brain
No intra-cranial electrode implantation
More focal than electrode stimulation (as in ECT), since skull
does not interfere with magnetic field
No anesthesia or analgesics are required
Artificial lesions
What areas are critical for a function (versus fMRI what areas are
participating in function)
No need for patients to study brain operation
Treatment effects, not merely passive measurement
occasional mild headache
Depth of stimulation limited to 2cm below surface of skull
Due to attenuation of magnetic field with log of distance
Double dissociation method
Neural Network
Neural network model (Haarmann & Usher, 2001;
see also Haarmann, Just, & Carpenter, 1997)