1: Methods
• Chris Rorden
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What is neuropsychology?
Tools
Methods
Pathology
• www.mricro.com
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What is neuropsychology?
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Patient WW
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History of hypertension
Massive Right Hemisphere Stroke
Poor emotional control and judgment.
Anosognosia: unaware of illness.
Partially paralyzed on left side.
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Stroke
Stroke ruined WW’s life and career.
 Stroke is the leading cause of disability.
 3rd leading cause of death
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In USA alone
 500,000
people suffer stroke per year
 150,000 people die of stroke per year
 4 million living with stroke
 $30 billion in health care costs
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True cost to society greater still
What was the cost of WW’s stroke?
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President Woodrow Wilson
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28th US President
Stroke on October 1919:
remained in office until 1921.
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Cabinet, Vice President, public
unaware
Unable to continue supporting
League of Nations
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Senate rejected the League’s
Treaty of Versailles
Wanted to run for president for
another 4 years despite handicap.
Edith Wilson controlled access to
president.
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No new policy
Major defeat for Wilson’s party in
1920 elections.
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What is neuropsychology?
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Examine consequences of brain injury.
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Identify problems experienced by patient,
e.g. movement, vision, memory, etc.
Identify brain regions injured.
Infer that impaired functions require
damaged brain regions.
Allows us to understand brain function.
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Neuropsychology: Defined
Psychology attempts to understand
behavior
 1860-1980’s: Neuropsychology =
science relating anatomy to behavior.
 Today: ‘cognitive neuroscience’ = science
relating anatomy to behavior.
 Today: ‘neuropsychology’ = branch of
cognitive neuroscience that examines
neurological patients.
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Neuropsychology: Branches
Clinical: Assessment and Rehabilitation
 Experimental: Gain theoretical
understanding of the brain and
developing new treatments.
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Basic method
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Explore patients with brain damage.
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Common logical tools
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Infer impaired behaviour dealt with by damaged regions.
Infer that damaged regions are not required by skills that are
preserved.
Association: similar symptoms
Dissociations: specific deficits
Double dissociations: two anatomically and behaviourally
distinct groups.
Group vs. Single subject designs
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Lesions tremendously variable: makes group designs difficult
as patients have hetergenous pathology.
Group designs better for making generalizations regarding
anatomy.
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Behavioural testing
Goal: relate brain anatomy to behaviour
 Requires
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technique for assessing anatomy (e.g. CT)
behavioural tasks.
Tasks should tell us about the patient’s
deficits:
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What functions are compromised?
What functions are spared?
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Behavioural testing
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Common test batteries allow us to compare
different studies, e.g.
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General intelligence (WISC/WAIS) with subtests
revealing verbal or reasoning deficits.
Common tests for vision, memory, motor control,
language, etc
To test specific hypotheses, we also often
employ custom designed experiments
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Designed to get a pure measure of deficit than
general test batteries.
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Associations
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Damage to one region of the brain often leads
to a series of deficits.
Example: Balint’s syndrome:
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Simultanagnosia (only perceive one item at a time)
Optic ataxia (failure to make eye movements)
Optic apraxia (inability to reach to seen target)
Damage to region X leads to deficits in A,B,C
Inference: Tasks A,B,C require same neural
circuit.
Alternative: A,B,C may be processed by
separate functional regions that are anatomical
neighbors.
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Dissociations
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Patient is impaired in one task but fine in a
different task.
Example: Blindsight
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Loss of perception: patient reports being blind
Motion detection fine
Dissociations suggest that tasks rely on
separate networks.
Problem: perhaps impaired task is simply more
difficult. Performance on the ‘unimpaired’ task
is at ceiling.
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Double dissociation
Two patient groups with complementary
dissociations:
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Group 1: good at task A, impaired on task B
Group 2: impaired on task A, good at task B
Suggests distinct processing for the two tasks.
Patient groups have distinct behaviour and
anatomy.
performance
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TaskA TaskB
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Double Dissociation (Goodale et al. [1994] Curr Biol. 4:604610)
When shown two
shapes (left), DF was
poor at saying if the
shapes were same or
different, RV was
good at this task.
chance
0%
DF RV
Control
25%
DF
RV
Frequency
When asked to grasp
an object, DF
grasped near the
centre (like healthy
people), RV was
poor at this task.
100%
0%
0
15 0
15 0
15
30
Distance from centre (mm)
Strokes
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Strokes
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Ischemic: Blood supply occluded 80%
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Haemorrhagic: Blood bleeding 20%
Some ischemic strokes are temporary: transitory
ischemic attacks (TIA).
‘Infarct’: Dead tissue following stroke.
Stroke-buster drugs (Thrombolytic agents) can
dissolve clots, saving the brain if given early after
onset.
– Contraindicated if haemorrhagic.
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Embolic
Thrombotic
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Ischemic Strokes
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Thrombosis: growth in artery prevents bloodflow
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If narrowing (stenosis) is detected early, operation can
prevent stroke.
Embolism: particle in blood flow lodged in artery
Major Arteries
 Carotid
 Anterior Cerebral
 Middle Cerebral
Posterior Cerebral
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Middle cerebral artery (MCA)
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MCA occlusion
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Most common: embolism travels
up carotid artery
MCA supplies lateral bank of
cortex (image from strokecenter.org)
Damages regions near superior
temporal sulcus (sylvian fissure).
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Lower figure shows regions
damaged in 24 MCA patients, Mort
et al. 2003.
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Haemorrhages
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20% of strokes are bleeds
Typically, due to ruptured aneurysm
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CT of recent haemorrhage
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An aneurysm is a sac-like protrusion of an artery caused
by a weakened area within the vessel wall.
Introspectively, the worst headache of your life.
http://www.microvent.com/
Surgery to clip aneurysm can save patients life.
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Impact injuries (RTA)
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Regardless of direction of
impact, frontal and
temporal poles
vulnerable
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Coup injury
Contre coup
White matter damage
common
Swelling of brain or
bleeding can be fatal
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Visualising brain injury
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Neuropsychology – correlate
brain injury with brain function
Requires accurate measures of
brain injury.
Historically: autopsy.
Today: brain imaging.
Warning: symmetry makes
mirror-mistakes easy.
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Radiological convention: left
shown on right side.
Neurological convention: left
shown on left.
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L
Visualising brain injury
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Anatomical methods: show appearance
of brain
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X-rays
CT/CAT scans
MRI/MRA (magnetic resonance)
Measures of brain function
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Blood flow (PET/SPECT/fMRI).
Neuron’s electrical responses (EEG/EEG)
Neuron’s magnetic responses (MEG)
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Plain Film X-rays
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X-ray tube projects through head
Detector plate measures transmission of X-rays
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Bone relatively opaque to X-rays
Soft tissue relatively transparent
Useful for Angiography, looking for broken bones
Poor for questions about grey vs white matter
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CT scans (aka CAT scans)
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A series of X-rays are taken at different
angles
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X-ray tube and detector spin around axis,
hence ‘computerized axial tomography’
(CAT scan)
Computer reconstructs 2D slices
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CT scans
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Neurological uses
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Stroke - Cerebrovascular Accident
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blockage or bleed Haemorrhagic CVA from Ischemic CVA
Brain tumors (larger than 2-4 mm)
Enhanced with contrast material
Hydrocephalus
Subdural Hematoma
Evaluation of traumatic Head Injury
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XRays
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Plain film vs computerized tomography (CT)
Contrast
No Contrast
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Plain film
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CT
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Rendered CT
MRI
Magnetic resonance imaging
 Does not expose individual to X-rays
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MRI
Powerful magnetic field (often 1.5Tesla,
e.g. 30,000 times Earth’s magnetic field).
 Atoms align with field.
 Radio pulses ‘flip’ hydrogen atoms.
 Different tissues
have different
times to realign.
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MRI compass analogy
Compass needle points North
 Briefly put magnet on right side:
needle points East
 After magnet is removed, needle
points North again (lower energy
state)
 Needles in different fluids will
take different time to return to
North
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N
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MRI compass analogy
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Spin of H atoms aligns with static
magnetic field
Briefly apply radiofrequency pulse:
spin tipped
After RF pulse, H atoms realign to
field (‘relaxation’, lower energy
state)
Relaxation releases energy in the
form of a radio signal.
Atoms in different tissues (fat,
muscle, etc) require different time
to realign (relax).
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Traditional MRI protocols
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Different types of MRI scan
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T1
T1 (anatomical): fast to acquire, excellent
structural detail (e.g. white and gray matter).
T2 (pathological): slower to acquire,
therefore usually lower resolution than T1.
Excellent for finding lesions.
T2
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MRI scans
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3 T1-weighted MRI scans:
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Left image: Healthy individual
Right image: MCA infarct: note lesioned tissue and
enlarged ventricles.
Middle: Healthy individual, despite large ventricles and
wide sulci. Large skull: perhaps hydrocephalus early in
development.
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MRI clinical uses for neurology
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Arteriovenous malformation
Hydrocephalus
Subacute subtle hemorrhagic CVA
Ischemic CVA with 48 hours of symptom onset
Cerebral Contusion
Shearing injury
Dementia
Brain tumor
Cerebral atrophy
Multiple Sclerosis
Pituitary disease (Amenorrhea or Galactorrhea)
Congenital anomalies
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from www.fpnotebook.com
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Clinical MRI
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68 year old male
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Right MCA infarction
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T1-weighted scan
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Husain & Rorden (2003)
MRI problems
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Problems with MRI
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T1/T2/PD images not sensitive to stroke < 24
hours old.
Noisy, confined space
Bone better imaged by CT than most MRI scans
Image intensity relative, not comparable across
patients.
CT and conventional MRI show damaged areas,
but structurally intact areas are not necessarily
functioning correctly!
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MRI problems: Metal and MRI
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Ferromagnetic materials (e.g. most steel alloys) can
cause problems
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Heating or movement
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Many haemorrhagic stroke patients treated with metal
‘aneurysm clips’
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Ensure clip is MRI-friendly metal
hoover >
< welding tank
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Different scans
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Scan type (CT, MRI) influences lesion appearance.
Lesions appear different with time.
acute
+3days
Example of stroke:
CT
writes,
but can’t read, “alexia
without agraphia”
Lesion
invisible in acute scans
T2 MRI
For more examples, www.med.harvard.edu/AANLIB/
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Imaging Infarcts
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MRI
MRA (Magnetic Resonance Angiography): sometimes
with contrast agent (Gadolinium)
Xray’s with contrast agent in blood
MRA
stroke MRA
Xray
Future MRI protocols
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Diffusion-weighted imaging
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Perfusion-weighted imaging
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Strokes show up immediately.
Shows permanent white-matter damage.
Some DWI techniques are calibrated values.
Strokes show up immediately.
Indicates amount of blood supply and latency
Images courtesy Paul Morgan (Nottingham)
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Measuring brain activity
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MRI/CT can show us damaged regions
Major problem: Are anatomically intact regions
functioning normally?
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Impossible to tell with anatomical scans
Our goal: relate behaviour to anatomy
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Requires accurate measure of damaged anatomy.
Measures of brain activity
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help us determine anatomical consequence of brain
damage.
Identify lesions immediately after onset, when they
are invisible to standard CT/MRI.
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PET/SPECT
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Positron Emission Tomography and Single Photon
Emission Computerized Tomography
(SPET/SPECT) are a type of CT scan.
–Standard
CTs: transmission of Xrays
Measure
Xray transparency of material
between xray tube and detector
–PET/SPECT
looks at emission of
radioactive material.
E.G.
Radioactive oxygen isotope injected
into blood
Brain
regions that use oxygen emit more
positrons
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fMRI
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Functional MRI offers indirect measure for brain
activity.
May help show whether patient will recover.
Example: Stroke patient unable to move left hand.
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Forced left hand movement (curling fingers)
Below: statistical map from fMRI (red) on top of T1 MRI
scan (gray).
Note: appropriate regions respond: perhaps spared.
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Diaschisis
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Destroyed regions of the brain stop firing.
Consequence: connected regions also stop
functioning normally.
‘Crossed Cerebellar Diaschisis’: damage to one
hemisphere temporarily stuns other side.
Stroke:
Reduced
blood flow
Diaschisis:
intact region
is not
functioning
normally
Diaschisis
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Diaschisis poses a major problem for
neuropsychology
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Immediately after lesion, many regions will be
disabled.
 Difficult
to assess which regions are really
inoperative.
 Impossible to see what single region does if many
are knocked out.
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If we wait to test patients, their brains may
reorganize.
 Difficult
to infer healthy function of damaged region
if intact regions have changed their function.
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Measuring electrical activity
When neurons fire, they create
electical dipoles.
 Neurons aligned perpendicular to
cortical surface.
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EEG
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With EEG we measure rhythms of the brain:
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Alpha 7-13 Hz: mostly posterior. It is brought out by closing the
eyes and by relaxation, and abolished by thinking. It is the major
rhythm seen in normal relaxed adults
Beta >13 Hz: most evident frontally. It is accentuated by sedatives.
It is the dominant rhythm in people who are alert or anxious or who
have their eyes open
Theta 3.5-7.5 Hz and is classed as "slow" activity. It is abnormal in
awake adults but is perfectly normal in children upto 13 years and
in sleep
Delta <3 Hz. It tends to be the highest in amplitude. It is quite
normal and is the dominant rhythm in infants up to one year and in
stages 3 and 4 of sleep
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Useful for measuring sleep
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http://www.brown.edu/Departments/Clinical_Neurosciences/louis/eegfreq.html
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Event related potentials
ERPs are a type of EEG
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Continuously collect EEGs
Present many trials of stimuli (e.g. brief sound)
Compute average brain response to stimuli
Spatial resolution poor,
(use MRI to localize
damage)
Good temporal
resolution (when is
activity happening).
Signal V
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0
100 200
300
Time (ms)
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Magnetoencephalography [MEG]
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MEG is the measurement of the
magnetic fields naturally present
outside the head due to electrical
activity in the brain. Sensors make
no contact with scalp
Better spatial resolution than
EEG/ERP
Expensive
Requires very low noise
environment (e.g. no lorries driving
by)
www.aston.ac.uk/psychology/meg/
Problems with neuropsychology
“George Miller coined the term ‘cognitive
neuroscience’…we already knew that
neuropsychology was not what we had in
mind…the bankruptcy and intellectual
impoverishment of that idea seemed self
evident.”
-Michael S. Gazzaniga, 2000
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Problems with Neuropsychology
What are weaknesses of this technique?
 This course examines findings from
neuropsychology
 Be critical of science: particularly of
frontier
 Understand the limitations of every
technique
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1.) Modularity assumption
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Modularity assumption:
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We assume that when one region is
damaged, other regions do not adapt their
function.
In reality, brain reorganizes quickly. Intact
regions change their behaviour, so difficult to
infer function of damaged region.
aka ‘Locality Assumption’, see Farah’s
Behav Brain Sciences article.
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2.) Lesions extensive and varied
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Small lesions (e.g. lacunar infarts) often have
no behavioural consequence.
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Brain redundant, robust to partial damage of system
Most work done with patients who have large
lesions.
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Lesions often damage several functional centers, so
few ‘pure’ patients
Lesion size and location variable, so hard to find
group of similar patients. Inferences from single
patients weak.
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3.) Lesion anatomy inaccurate
Anatomical scans show us regions that
are destroyed.
 But anatomically intact regions may not
be functioning (e.g. perhaps
disconnected, or diaschisis).
 Poor anatomy will weaken our level of
inference.
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4.) Variability of functional anatomy
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We assume that an anatomical region of
the brain does the same function in all
individuals.
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Clearly not always correct: e.g. Wada test
indicates left hemisphere required for
language in MOST but not all individuals.
Variability of function across individuals
reduces power of group studies.
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5.) Poor temporal resolution
Even if neuropsychology establishes
which regions are required for task, it is
hard to infer the stages of processing.
 For example, V1 damage causes visual
deficits. But how long after the onset of a
visual stimuli does V1 become active?
 Other cognitive neuroscience techniques
offer converging evidence.
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Do we despair?
Neuropsychology has major limitations
 Every tool used in cognitive neuroscience
has major limitations.
 Convergent evidence required:
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Do different techniques give the same
answer?
This is why cog neuro is exciting! We have
to think critically about the implications of
each result.
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Reflection, questions
New tools offer new insight into brain
function
 Golden age for neuroscience: like
explorers in age of Columbus
 Q: What are weaknesses for other
techniques used by cognitive
neuroscience?
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