Introduction to Functional MRI

1
Introduction to Functional MRI
Jody Culham Department of Psychology University
of Western Ontario
http//www.fmri4newbies.com/
Last Update November 29, 2008 fMRI Course,
Louvain, Belgium
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MRI vs. fMRI
Functional MRI (fMRI) studies brain function.
MRI studies brain anatomy.
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Brain Imaging Anatomy
CAT
PET
Photography
MRI
Source modified from Posner Raichle, Images of
Mind
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MRI vs. fMRI
MRI
fMRI
high resolution (1 mm)
low resolution (3 mm but can be better)
one image

fMRI Blood Oxygenation Level Dependent (BOLD)
signal indirect measure of neural activity
many images (e.g., every 2 sec for 5 mins)
? neural activity ? ? blood oxygen ? ?
fMRI signal
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The First Brain Imaging Experiment
and probably the cheapest one too!
Angelo Mosso Italian physiologist (1846-1910)
In Mossos experiments the subject to be
observed lay on a delicately balanced table which
could tip downward either at the head or at the
foot if the weight of either end were increased.
The moment emotional or intellectual activity
began in the subject, down went the balance at
the head-end, in consequence of the
redistribution of blood in his system. --
William James, Principles of Psychology (1890)
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The Rise of fMRI
800
700
600
500
Number of papers (PubMed)
400
300
200
100
0
1990
1995
2000
Year of Publication
Slide modified from Mel Goodale
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fMRI Activation
Flickering Checkerboard OFF (60 s) - ON (60 s)
-OFF (60 s) - ON (60 s) - OFF (60 s)
Brain Activity
Time ?
Source Kwong et al., 1992
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PET and fMRI Activation
Source Posner Raichle, Images of Mind
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fMRI Setup
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Category-Specific Visual Areas
objects
faces
Malach, 2002, TICS

• Parahippocampal Place Area (PPA)
• place-selective
• places gt (objects and faces)
• places gt scrambled images

places

• Fusiform Face Area (FFA) or pFs
• face-selective
• faces gt (objects scenes)
• faces gt scrambled images
• posterior fusiform sulcus (pFs)

• Lateral Occipital (LO)
• object-selective
• objects gt (faces scenes)
• objects gt scrambled images

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A Simple Experiment LO Localizer

• Lateral Occipital Complex
• responds when subject views objects

Blank Screen
Intact Objects
Scrambled Objects
TIME
One volume (12 slices) every 2 seconds for 272
seconds (4 minutes, 32 seconds) Condition
changes every 16 seconds (8 volumes)
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fMRI Experiment Stages Prep

• 1) Prepare subject
• Consent form
• Safety screening
• Instructions and practice trials if appropriate
• 2) Shimming
• putting body in magnetic field makes it
  non-uniform
• adjust 3 orthogonal weak magnets to make
  magnetic field as homogenous as possible
• 3) Sagittals
• Take images along the midline to use to plan
  slices

Perhaps the most frequently misspelled word in
fMRI Should have one g, two ts
In this example, these are the functional slices
we want 12 slices x 6 mm
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fMRI Experiment Stages Anatomicals

• 4) Take anatomical (T1) images
• high-resolution images (e.g., 0.75 x 0.75 x 3.0
  mm)
• 3D data 3 spatial dimensions, sampled at one
  point in time
• 64 anatomical slices takes 4 minutes

64 slices x 3 mm
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Slice Terminology
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fMRI Experiment Stages Functionals

• 5) Take functional (T2) images
• images are indirectly related to neural activity
• usually low resolution images (3 x 3 x 6 mm)
• all slices at one time a volume (sometimes
  also called an image)
• sample many volumes (time points) (e.g., 1
  volume every 2 seconds for 136 volumes 272 sec
  432)
• 4D data 3 spatial, 1 temporal

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Anatomic Slices Corresponding to Functional Slices
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Time Courses
Arbitrary signal varies from coil to coil, voxel
to voxel, day to day, subject to subject
MR SIGNAL (ARBITRARY UNITS)
TIME
To make the y-axis more meaningful, we usually
convert the signal into units of
change 100(x - baseline)/baseline Changes are
typically in the order of 0.5-4 .
MR SIGNAL ( Change)
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Activation Statistics
Functional images
Time
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Statistical Maps Time Courses
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Stats on Anatomical
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2D ? 3D
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Design Jargon Runs
session all of the scans collected from one
subject in one day
run (or scan) one continuous period of fMRI
scanning (5-7 min)
experiment a set of conditions you want to
compare to each other
Note Terminology can vary from one fMRI site to
another (e.g., some places use scan to refer to
what weve called a volume).
A session consists of one or more
experiments. Each experiment consists of several
(e.g., 1-8) runs More runs/expt are needed when
signalnoise is low or the effect is weak. Thus
each session consists of numerous (e.g., 5-20)
runs (e.g., 0.5 3 hours)
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Design Jargon Paradigm
paradigm (or protocol) the set of conditions and
their order used in a particular run
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Recipe for MRI

• 1) Put subject in big magnetic field (leave him
  there)
• 2) Transmit radio waves into subject about 3
  ms
• 3) Turn off radio wave transmitter
• 4) Receive radio waves re-transmitted by subject
• Manipulate re-transmission with magnetic fields
  during this readout interval 10-100 ms MRI
  is not a snapshot
• 5) Store measured radio wave data vs. time
• Now go back to 2) to get some more data
• 6) Process raw data to reconstruct images
• 7) Allow subject to leave scanner (this is
  optional)

Source Robert Coxs web slides
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Necessary Equipment
4T magnet
RF Coil
gradient coil (inside)
Magnet
Gradient Coil
RF Coil
Source for Photos Joe Gati
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The Big Magnet
Very strong 1 Tesla (T) 10,000 Gauss Earths
magnetic field 0.5 Gauss 4 Tesla 4 x 10,000 ?
0.5 80,000X Earths magnetic field Continuously
on Main field B0
Robarts Research Institute 4T
x 80,000
Source www.spacedaily.com
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Susceptibility Artifacts
T1-weighted image
T2-weighted image
sinuses
ear canals

• -T2 artifacts occur near junctions between air
  and tissue
• sinuses, ear canals

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The Benefit of Susceptibility
Susceptibility variations can also be seen around
blood vessels where deoxyhemoglobin affects T2
in nearby tissue
Modified from Robert Coxs web slides
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Deoxygenated Blood ? Signal Loss

• Oxygenated blood?
• No signal loss

Deoxygenated blood? Signal loss!!!
Images from Huettel, Song McCarthy, 2004,
Functional Magnetic Resonance Imaging
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Hemoglobin
Figure Source, Huettel, Song McCarthy, 2004,
Functional Magnetic Resonance Imaging
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BOLD Time Course
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Stimulus to BOLD
Source Arthurs Boniface, 2002, Trends in
Neurosciences
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Neural Networks
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Post-Synaptic Potentials

• The inputs to a neuron (post-synaptic potentials)
  increase (excitatory PSPs) or decrease
  (inhibitory PSPs) the membrane voltage
• If the summed PSPs at the axon hillock push the
  voltage above the threshold, the neuron will fire
  an action potential

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Even Simple Circuits Arent Simple
gray matter(dendrites, cell bodies synapses)
Lower tier area (e.g., thalamus)
white matter (axons)

• Will BOLD activation from the blue voxel reflect
  
• output of the black neuron (action potentials)?
• excitatory input (green synapses)?
• inhibitory input (red synapses)?
• inputs from the same layer (which constitute
  80 of synapses)?
• feedforward projections (from lower-tier areas)?
• feedback projections (from higher-tier areas)?

Middle tier area (e.g., V1, primary visual
cortex)
Higher tier area (e.g., V2, secondary visual
cortex)

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BOLD Correlations

• Local Field Potentials (LFP)
• reflect post-synaptic potentials
• similar to what EEG (ERPs) and MEG measure
• Multi-Unit Activity (MUA)
• reflects action potentials
• similar to what most electrophysiology measures
• Logothetis et al. (2001)
• combined BOLD fMRI and electrophysiological
  recordings
• found that BOLD activity is more closely related
  to LFPs than MUA

Source Logothetis et al., 2001, Nature
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Comparing Electrophysiolgy and BOLD
Data Source Disbrow et al., 2000, PNAS Figure
Source, Huettel, Song McCarthy, Functional
Magnetic Resonance Imaging
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fMRI Measures the Population Activity

• population activity depends on
• how active the neurons are
• how many neurons are active
• manipulations that change the activity of many
  neurons a little have a show bigger activation
  differences than manipulations that change the
  activation of a few neurons a lot
• attention
• ? activity
• learning
• ? activity
• fMRI may not
• match single neuron
• physiology results

Raichle Posner, Images of Mind cover image
Ideas from Scannell Young, 1999, Proc Biol Sci
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Vasculature
Source Menon Kim, TICS
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Macro- vs. micro- vasculature

• Macrovasculaturevessels gt 25 ?m
  radius(cortical and pial veins)? linear and
  oriented? cause both magnitude and phase changes
• Microvasculaturevessels lt 25 ?m
  radius(venuoles and capillaries) ? randomly
  oriented? cause only magnitude changes

Capillary beds within the cortex.
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Why are vessels a problem?

• large vessels produce BOLD activation further
  from the true site of activation than small
  vessels (especially problematic for
  high-resolution fMRI)
• large vessels line the sulci and make it hard to
  tell which bank of a sulcus the activity arises
  from
• the signal change in large vessels can be
  considerably higher than in small vessels (e.g.,
  10 vs. 2)
• activation in large vessels occurs later than in
  small ones
• vessel artifacts are worse with gradient echo
  sequences (compared to asymmetric spin echo for
  example) and low field strengths

Source Ono et al., 1990, Atlas of the Cerebral
Sulci
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Dont Trust Sinus Activity

• You will sometimes see bogus activity in the
  sagittal sinus

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More Caveats

• brain vs. vein debate
• source of signal affects spatial resolution
• scientists havent agreed on a single theory to
  explain the relationship between oxygen, glucose
  metabolism and blood flow
• no one really understands how neurons trigger
  increased blood flow
• neural synchrony may be a factor

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The Concise Summary
We sort of understand this (e.g., psychophysics,
neurophysiology)
We sort of understand this (MR Physics)
Were _at_ clueless here!
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Bottom Line

• Despite all the caveats, questions and concerns,
  BOLD imaging is well-correlated with results from
  other methods
• BOLD imaging can resolve activation at a fairly
  small scale (e.g., retinotopic mapping)
• PSPs and action potentials are correlated so
  either way, its getting at something meaningful
• even if BOLD activation doesnt correlate
  completely with electrophysiology, that doesnt
  mean its wrong
• may be picking up other processing info (e.g.,
  PSPs, synchrony)