Fundamentals of Neuroscience Neuroimaging in Cognitive Neuroscience

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Fundamentals of NeuroscienceNeuroimaging in
Cognitive Neuroscience
James Danckert PAS 4040 jdancker_at_watarts.ca
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Functional Neuroimaging

• Electrical activity
• Event-related potentials (ERP), visual evoked
  potentials (VEP) all derivative from EEG
• Stimulation
• Trans-cranial magnetic stimulation single vs.
  rapid pulse TMS
• Metabolism
• Positron Emission Tomography (PET) and Blood
  Oxygenated Level Dependent (BOLD) functional MRI
  (fMRI)

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EEG

• Large populations of neurons firing produce
  electrical potentials that can be measured at the
  scalp
• Signals are passively conducted through the skull
  and scalp and can be amplified and measured
• Difference between reference (ground) and
  recording electrodes are measured to give the
  electrical potential electroencephalogram (EEG)

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ERPs and VEPs

• EEG tends to record global brain activity
• ERPs (and VEPs) are a special case of EEG
• average EEG trace from a large number of trials
• align signal to onset of a stimulus or response
  hence event-related potential (ERP)

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Pros and cons of ERPs.
Pros

• Good temporal resolution
• Linked to specific physiological markers (e.g.,
  N1, P3 etc. which in turn can be linked to known
  cognitive processes)

Cons

• Poor spatial resolution
• Difficult to get at some brain regions (OFC,
  temporal cortex)

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Transcranial Magnetic Stimulation (TMS)

• Thompson (1910) placed head between two coils
  and stimulated at 42 Hz
• saw flashing lights magnetophosphenes
• was probably stimulating the retina and not the
  visual cortex

Cowey and Walsh, 2001
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TMS

• TMS applies a magnetic pulse to a certain brain
  region to temporarily modulate the function of
  that region

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TMS
circular coil
induced current

• the induced current in the tissue is in the
  opposite direction to that of the coil
• the intensity of the signal drops off towards
  the centre and outside of the coil

Cowey and Walsh, 2001
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TMS
little or no change
maximum hyperpolarization
maximum depolarization

• the flow of the current must cross the axon to
  cause stimulation or interruption of function (N3
  will not be stimulated)

Cowey and Walsh, 2001
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TMS
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Spatial extent of TMS

• spatial extent of induced electric field
• drops 75 within 10 mm
• affects 600 mm2 of neural tissue

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Rapid vs. Single Pulse TMS

• for single pulse TMS duration of stimulation 1
  msec, but affects motor cortex for up to 100 msec
• for rapid or repetitive pulse TMS stimuli are
  delivered in trains with frequencies from 1 to 25
  Hz (1 25 times per second)
• duration of after-effects for rapid pulse TMS
  anywhere from msec to several seconds

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Transcranial magnetic stimulation (TMS / rTMS)

• excitatory or inhibitory reversible effects
  depending on site and parameters of stimulation
  (e.g. frequency of pulses)
• -gt facilitates or slows down cognitive
  process/behavior
• when inhibitory, referred to as virtual lesion
  technique
• can give precise timing information (msec
  level) due to transient nature of effects
• rTMS is beginning to be used as a treatment for
  depression (focus is on DLPFC)

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TMS

• Poor spatial localisation how focal is the
  stimulation?
• Cant stimulate certain areas (e.g., temporal
  lobe) and can only stimulate cortical surface
• Good temporal resolution
• Can presumably disrupt individual processes
  within a task.
• Distance effects changed interactions due to
  stimulation
• Can induce seizures (particularly rTMS)

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Frameless stereotaxy and fMRI

• areas can be identified functionally and then
  used to position the coil in a TMS study using
  the frameless stereotaxy method
• Paus is attempting to directly combine fMRI and
  TMS with TMS pulses delivered in between fMRI
  runs

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Metabolic Imaging

• Two main techniques positron emission
  tomography (PET) and functional MRI (fMRI)
• Activity in cells requires energy (oxygen and
  glucose)
• Increased neural activity will lead to changes in
  cerebral blood volume (CBV), cerebral blood flow
  (CBF) and the rate of metabolism of glucose and
  oxygen (CRMGl and CRMO)
• These changes in blood flow and metabolism can be
  measured using PET and fMRI

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Positron Emission Tomography (PET)

• Measures local changes in cerebral blood flow
  (CBF) or volume and can also be used to trace
  certain neurotransmitters (but can only do one of
  these at a time)
• Radioactive isotopes are used as tracers
• The isotopes rapidly decay emitting positrons
• When the positrons collide with electrons two
  photons (or gamma rays) are emitted
• The two photons travel in opposite directions
  allowing the location of the collision to be
  determined

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Positron Emission Tomography (PET)
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PET and subtraction

• Run two conditions stimulation (e.g., look at
  visual images) vs. control (e.g., look at blank
  screen)
• Measure the difference in activation between the
  two images (i.e., subtract control from
  stimulation)
• This provides a picture of regional cerebral
  blood flow relative to visual stimulation.

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Motion vs. colour.

• Subject views coloured screen (left) vs. moving
  random black and white dots (right)
• Both task activate early visual areas (V1 and V2)
• Subtracting the two images reveals different
  brain areas for colour (V4) vs. motion (V5)
  processing

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PET vs. fMRI

• PET allows you to track multiple metabolic
  processes so long as the emitted photon can be
  detected allows imaging of some
  neurotransmitters
• PET is invasive radioactive isotopes can only
  be administered (at experimental levels) every 4
  5 years
• fMRI has much greater spatial resolution ( mms)
• fMRI has greater temporal resolution can detect
  activation to stimuli appearing for less than a
  second (PET is limited by the half life of the
  isotope used)

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fMRI
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Magnet safety

• very strong magnetic fields even large and
  heavy objects can fly into the magnet bore

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Cerebral blood supply.

• Capillaries
• Y80 at rest.
• Y90 during activation.
• 8 mm diameter.
• 40 blood volume of cortical tissue.
• Primary site of O2 exchange with tissue.

• Arterioles
• Y95 at rest.
• Y100 during activation.
• 25 mm diameter.
• lt15 blood volume of cortical tissue.
• Venules
• Y60 at rest.
• Y90 during activation.
• 25-50 mm diameter.
• 40 blood volume of cortical tissue.
• Red blood cell
• 6 mm wide and 1-2 mm thick.
• Delivers O2 in form of oxyhemoglobin.

Transit Time 2-3 s
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Cerebral blood supply.
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fMRI

• Deoxyhaemoglobin is paramagnetic
• When neural activity increases more oxygenated
  blood than is needed is delivered to the site
• This leads to an imbalance in oxyhaemoglobin and
  deoxyhaemoglobin more oxy than deoxy
• fMRI is able to measure this difference due to
  the different magnetic properties of oxy and
  deoxyhaemoglobin

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fMRI and BOLD

• blood oxygenated level dependent (BOLD) signal is
  actually a complex combination of
• rate of glucose and oxygen metabolism
• CBV
• CBF
• same subtraction logic used in PET is used in fMRI

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fMRI block design

• fMRI (like PET) began examining brain activity
  using block designs

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fMRI event-related design

• allows randomization of stimuli (not possible in
  PET)

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fMRI event-related design

• BOLD response has a predictable form
• In rapid event-related designs the signal to a
  given trial type is deconvolved using models of
  the BOLD response

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Linearity of BOLD response
Dale Buckner, 1997
Linearity Do things really add up?
Not quite linear but good enough !
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Fixed vs. Random Intervals
If trials are jittered, ? ITI ? ?power
Source Burock et al., 1998
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fMRI spatial resolution

• images can be co-registered to the subjects own
  brain (not an average brain as in PET)

PET
fMRI
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fMRI and topologies

• Using fMRI to map different brain functions

Penfields maps
Servos et al., 1998 red wrist orange shoulder
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Retintopy

• 8 Hz flicker (checks reverse contrast 8X/sec)
• good stimulus for driving visual areas
• subjects must maintain fixation (on red dot)

Source Jody Culham
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EXPECTED RESPONSE PROFILE OF AREA RESPONDING TO
STIMULUS
To analyze retinotopic data Analyze the data
with a set of functions with the same profile but
different phase offsets. For any voxels that
show a significant response to any of the
functions, color code the activation by the phase
offset that yielded maximum activation (e.g.,
maximum response to foveal stimulus red,
maximum response to peripheral stimulus pink)
time 0
time 20 sec
time 40 sec
0
20
40
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STIMULUS
time 60 sec
Source Jody Culham
TIME ?
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Retintopy Eccentricity
calcarine sulcus
left occipital lobe
right occipital lobe

• foveal area represented at occipital pole
• peripheral regions represented more anteriorly

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Retinotopy
Source Sereno et al., 1995
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Other Sensory -topies
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Saccadotopy

• delayed saccades
• move saccadic target systematically around the
  clock

Source Sereno et al., 2001
http//kamares.ucsd.edu/sereno/LIP/both-closeups
tim.mpg Marty Serenos web page
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Break
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Finding the human homologue of monkey area X!

• recent research has used monkey neurophys to
  guide fMRI in humans

Dukelow et al. 2001
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Problems with the search for homologues

• Absence of activation doesnt mean the absence of
  function
• Presence of activation doesnt imply sole locus
  of function
• But our brains are different!
• Confirmatory hypotheses

Dukelow et al. 2001
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fMRI and diagnosis

• fMRI is starting to be used in patients with
  epilepsy
• one goal is to use this as a tool to localise
  language, memory etc. prior to surgery
• another goal would be to use fMRI to study the
  propogation of seizures
• in stroke patients fMRI can be used to chart
  recovery of function

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Patient SP congenital porencephalic cyst
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SP - motor strip
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SP somatosensory strip
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images
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fMRI and cognition

• What not to do poorly designed tasks!
• What is the right inferior parietal lobes
  contribution to movement control?
• spatial component of movements
• compare imagined movements with only a spatial
  component vs. movements with a sequential
  component

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Supplementary Motor Area (SMA)
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Bilateral superior parietal
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Design Problems

• What could the right vs. left parietal difference
  be due to?

• Attention? possibly!
• Differences in eye movements? maybe!

• Were the tasks really different in the intended
  way?

• Perhaps both tasks were spatial in nature and
  both tasks had a sequential component, so

• So did you just test task difficulty?

• Maybe, what of it?

• Why is right parietal more active for less
  difficult tasks then?

• I dont know and I dont care, piss off! Im
  gonna start again!

• Boy, you must be rich then!!!

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Confirming modularity

• Nancy Kanwisher and the parahippocampal recliner
  region!

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Is that all there is to it?

• Alex Martin and co. suggest that the FFA responds
  to other kinds of objects too
• Isabelle Gauthier and co. suggest that it is
  expertise with faces which drives the activation

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Exploring behaviours

• Prism adaptation ameliorates neglect how?
• First, explore the direct effects of prism
  adaptation in the healthy brain.
• Clower et al 1996 used PET to do this but
  reversed the direction of prismatic shift every 5
  trials.

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Prism Adaptation Rossetti and colleagues

• prisms shift world further to the right (into the
  patients good field)
• patients movements compensate for the prismatic
  shift in the opposite direction
• after effects lead to better processing of
  previously neglected stimuli

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Setup.
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Protocol I.
2 sec
2 sec
0.5 sec
11.5 sec
2 sec
5 runs with prisms (50 trials) 5 runs without
prisms (50)
2 sec
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Protocol II.
2 sec volumes so 2 sec for critical stimulus
(the target) and 12 sec for post stimulus return
to baseline (a la Bandettini).
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Protocol III.
4T scanner at Robarts 17 pseudo-axial slices 5
mm thick TR 2 sec 2-shot EPI
sequence Co-registered to 128 slice anatomical
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Adapting in the magnet.
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Finding ROIs.
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Modeling the peak activation across trials.
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Left and right superior parietal cortices.
Left Superior Parietal
Right Superior Parietal
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Cerebellar ROIs.
Medial Cerebellum
Right Lateral Cerebellum
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SMA.
transverse
sagittal
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Bottom line?

• Difficult to image the direct effects of
  adaptation in normals.
• Image good adaptors OR change protocol to look
  at after effects of adaptation with all its
  problems

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Conclusions?

• fMRI should be used for good and not evil!

I wonder if fMRI could be used to cure cancer?
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Acknowledgements

• fMRI of epilepsy patient
• Stacey Danckert
• Seyed Mirsitari
• David Carey
• Mel Goodale
• Ravi Menon
• Jody Culham

• fMRI of prism adaptation
• Susanne Ferber
• Stacey Danckert
• Mel Goodale
• Yves Rossetti

• fMRI of imagined movements
• it was all my fault!

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End of Lecture