introduction: fmri for newbies. mri studies brain anatomy. functional mri (fmri) studies brain...
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MRI studies brain anatomy.Functional MRI (fMRI) studies brain function.
MRI vs. fMRI
Brain Imaging: Anatomy
Photography
CAT
PET
MRI
Source: modified from Posner & Raichle, Images of Mind
MRI vs. fMRI
neural activity blood oxygen fMRI signal
MRI fMRI
one image
many images (e.g., every 2 sec for 5 mins)
high resolution(1 mm)
low resolution(~3 mm but can be better)
fMRI Blood Oxygenation Level Dependent (BOLD) signal
indirect measure of neural activity
…
E = mc2
???
The First “Brain Imaging Experiment”
“[In Mosso’s 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)
Angelo MossoItalian physiologist
(1846-1910)
… and probably the cheapest one too!
100
200
300
400
500
600
700
800
0
Num
ber
of p
aper
s (P
ubM
ed)
1990 1995 2000
746 papers (2001)
Year of Publication Slide modified from Mel Goodale
The Rise of fMRI
fMRI Activation
Time
BrainActivity
Source: Kwong et al., 1992
Flickering CheckerboardOFF (60 s) - ON (60 s) -OFF (60 s) - ON (60 s) - OFF (60 s)
Category-Specific Visual Areas
• Lateral Occipital (LO)– object-selective– objects > (faces & scenes)– objects > scrambled images
faces
places
objects
Malach, 2002, TICS
• Fusiform Face Area (FFA) or pFs– face-selective– faces > (objects & scenes)– faces > scrambled images– ~ posterior fusiform sulcus (pFs)
• Parahippocampal Place Area (PPA)– place-selective– places > (objects and faces)– places > scrambled images
A Simple Experiment: LO Localizer
IntactObjects
ScrambledObjects
BlankScreen
TIME
One volume (12 slices) every 2 seconds for 272 seconds (4 minutes, 32 seconds)
Condition changes every 16 seconds (8 volumes)
Lateral Occipital Complex• responds when subject views objects
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) SagittalsTake images along the midline to use to plan slices
Note: That’s one g, two t’s
In this example, these are the functional slices we want: 12 slices x 6 mm
fMRI Experiment Stages: Anatomicals4) 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
Slice Thicknesse.g., 6 mm
Number of Slicese.g., 10
SAGITTAL SLICE IN-PLANE SLICE
Field of View (FOV)e.g., 19.2 cm
VOXEL(Volumetric Pixel)
3 mm
3 mm6 mm
Slice Terminology
Matrix Sizee.g., 64 x 64
In-plane resolutione.g., 192 mm / 64
= 3 mm
fMRI Experiment Stages: Functionals5) 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 = 4:32)• 4D data: 3 spatial, 1 temporal
…
Time Courses
TIME
MR
SIG
NA
L(A
RB
ITR
AR
Y U
NIT
S)
MR
SIG
NA
L(%
Cha
nge)
Arbitrary signal varies from voxel to voxel, day to day, subject to subject
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 %.
Statistical Mapsuperimposed on
anatomical MRI image
~2s
Functional images
Time
Condition 1
Condition 2 ...
~ 5 min
Time
fMRISignal
(% change)
ROI Time Course
Condition
Activation Statistics
Region of interest (ROI)
Statistical Maps & Time Courses
Use stat maps to pick regions
Then extract the time course
Design Jargon: Runs
run (or scan): one continuous period of fMRI scanning (~5-7 min) session: all of the scans collected from one subject in one day
experiment: a set of conditions you want to compare to each othercondition: one set of stimuli or one task
4 stimulus conditions+ 1 baseline condition (fixation)
A session consists of one or more experiments.Each experiment consists of several (e.g., 1-8) runsMore runs/expt are needed when signal:noise is low or the effect is weak.Thus each session consists of numerous (e.g., 5-20) runs (e.g., 0.5 – 3 hours)
Note: Terminology can vary from one fMRI site to another (e.g., some places use “scan” to refer to what we’ve called a volume).
Design Jargon: Paradigm
paradigm (or protocol): the set of conditions and their order used in a particular run
Time
volume #1(time = 0)
volume #105(time = 105 vol x 2 sec/vol = 210 sec = 3:30)
runepoch: one instance of a condition
first “objects right” epochsecond “objects right” epoch
epoch 8 vol x 2 sec/vol = 16 sec
fMRI Equipment
Magnet (4T)
Head Coil
Source: Joe Gati, photos
RF Coil
4T magnet
gradient coil(inside)
Surface Coil
Gradient Coil
What Does fMRI Measure?
• Big magnetic field– protons (hydrogen molecules) in body become aligned to field
• RF (radio frequency) coil– radio frequency pulse– knocks protons over– as protons realign with field, they emit energy that coil receives
(like an antenna)
• Gradient coils– make it possible to encode spatial information
• MR signal differs depending on– concentration of hydrogen in an area (anatomical MRI)– amount of oxy- vs. deoxyhemoglobin in an area (functional MRI)
BOLD signal
Source: fMRIB Brief Introduction to fMRI
neural activity blood flow oxyhemoglobin T2* MR signal
Blood Oxygen Level Dependent signal
Statistical Maps & Time Courses
Use stat maps to pick regions
Then extract the time course
Design Jargon: Runs
run (or scan): one continuous period of fMRI scanning (~5-7 min) session: all of the scans collected from one subject in one day
experiment: a set of conditions you want to compare to each othercondition: one set of stimuli or one task
2 stimulus conditions+ 1 baseline condition (fixation)
A session consists of one or more experiments.Each experiment consists of several (e.g., 1-8) runsMore runs/expt are needed when signal:noise is low or the effect is weak.Thus each session consists of numerous (e.g., 5-20) runs (e.g., 0.5 – 3 hours)
Note: Terminology can vary from one fMRI site to another (e.g., some places use “scan” to refer to what we’ve called a volume).
Design Jargon: Paradigm
paradigm (or protocol): the set of conditions and their order used in a particular run
Time
volume #1(time = 0)
volume #136(time = 136 vol x 2 sec/vol = 272 sec = 4:32)
run
first “intact objects” epoch
second “intact objects” epoch
epoch: one instance of a condition
epoch 8 vol x 2 sec/vol = 16 sec
first “scrambled objects” epoch
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 Cox’s web slides
Necessary Equipment
Magnet Gradient Coil RF Coil
Source for Photos: Joe Gati
RF Coil
4T magnet
gradient coil(inside)
Susceptibility Artifacts
-artifacts occur near junctions between air and tissue• sinuses, ear canals
sinuses
earcanals
T1-weighted image T2*-weighted image
The Benefit of Susceptibility
Modified from: Robert Cox’s web slides
Susceptibility variations can also be seen around blood vessels where deoxyhemoglobin affects T2* in nearby tissue
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
Comparing Electrophysiolgy and BOLD
Data Source: Disbrow et al., 2000, PNASFigure Source, Huettel, Song & McCarthy, Functional Magnetic Resonance Imaging
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 notmatch single neuronphysiology results
Verb generation Verb generation after 15 min practice
Raichle & Posner, Images of Mind cover imageIdeas from: Scannell & Young, 1999, Proc Biol Sci
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
Don’t Trust Sinus Activity
• You will sometimes see bogus “activity” in the sagittal sinus
More Caveats
• “brain vs. vein” debate – source of signal affects spatial resolution
• scientists haven’t 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
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, it’s getting at something meaningful
• even if BOLD activation doesn’t correlate completely with electrophysiology, that doesn’t mean it’s wrong– may be picking up other processing info (e.g., PSPs, synchrony)
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