1. Introduction: fMRI for Newbies

2. MRI vs. fMRI Functional MRI (fMRI) studies brain function.
MRI studies brain anatomy.

3. Brain Imaging: Anatomy
CAT
Photography
PET
MRI
Source: modified from Posner & Raichle, Images of Mind

4.  neural activity   blood oxygen   fMRI signal
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

5. The First “Brain Imaging Experiment”
… and probably the cheapest one too!
E = mc2
???
Angelo Mosso
Italian physiologist
( )
“[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)

6. The Rise of fMRI Number of papers (PubMed) Year of Publication
800
700
600
500
Number of papers (PubMed)
400
300
200
100
1990
1995
2000
Year of Publication
Slide modified from Mel Goodale

7. fMRI Activation Flickering Checkerboard Brain Activity Time 
OFF (60 s) - ON (60 s) -OFF (60 s) - ON (60 s) - OFF (60 s)
Brain
Activity
Time 
Source: Kwong et al., 1992

8. PET and fMRI Activation
Source: Posner & Raichle, Images of Mind

9. fMRI Setup

10. Category-Specific Visual Areas
objects
faces
Malach, 2002, TICS
Parahippocampal Place Area (PPA)
place-selective
places > (objects and faces)
places > scrambled images
places
Fusiform Face Area (FFA) or pFs
face-selective
faces > (objects & scenes)
faces > scrambled images
~ posterior fusiform sulcus (pFs)
Lateral Occipital (LO)
object-selective
objects > (faces & scenes)
objects > scrambled images

11. 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)

12. 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
Note: That’s one g, two t’s
In this example, these are the functional slices we want: 12 slices x 6 mm

13. 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

14. Slice Terminology VOXEL (Volumetric Pixel) IN-PLANE SLICE
Slice Thickness
e.g., 6 mm
Number of Slices
e.g., 10
SAGITTAL SLICE
VOXEL
(Volumetric Pixel)
3 mm
6 mm
Matrix Size
e.g., 64 x 64
In-plane resolution
e.g., 192 mm / 64
= 3 mm
IN-PLANE SLICE
Field of View (FOV)
e.g., 19.2 cm

15. 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 = 4:32)
4D data: 3 spatial, 1 temporal …

16. Anatomic Slices Corresponding to Functional Slices

17. Time Courses
Arbitrary signal varies from voxel to voxel, day to day, subject to subject
(ARBITRARY UNITS)
MR SIGNAL
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 %.
MR SIGNAL
(% Change)

18. Activation Statistics
Functional images
Time
fMRI
Signal
(% change)
ROI Time Course
Condition
~2s
Region of interest (ROI)
Condition 1
Statistical Map
superimposed on anatomical MRI image
Condition 2
Time
...
~ 5 min

19. Statistical Maps & Time Courses
Use stat maps to pick regions
Then extract the time course

20. 2D  3D

21. 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
condition: one set of stimuli or one task
4 stimulus conditions
+ 1 baseline condition (fixation)
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).
A session consists of one or more experiments.
Each experiment consists of several (e.g., 1-8) runs
More 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)

22. Design Jargon: Paradigm
paradigm (or protocol): the set of conditions and their order used in a particular run
volume #1
(time = 0)
volume #105
(time = 105 vol x 2 sec/vol = 210 sec = 3:30)
run
epoch: one instance of a condition
first “objects right” epoch
second “objects right” epoch
epoch
8 vol x 2 sec/vol = 16 sec
Time

23. fMRI Equipment Magnet (4T) Gradient Coil Head Coil Surface Coil
RF Coil
gradient coil
(inside)
Head Coil
Surface Coil
Source: Joe Gati, photos

24. What Does fMRI Measure? Big magnetic field RF (radio frequency) coil
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)

25. BOLD signal Blood Oxygen Level Dependent signal
neural activity   blood flow   oxyhemoglobin   T2*   MR signal
Source: fMRIB Brief Introduction to fMRI

26. JODY – THE FOLLOWING SLIDES ARE FROM THE NORWAY PAGE

27. Statistical Maps & Time Courses
Use stat maps to pick regions
Then extract the time course

28. Percent Signal Change
505 1%
500
205
200
Slide from Duke course

29. Stats on Anatomical

30. 2D  3D

31. 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
condition: one set of stimuli or one task
2 stimulus conditions
+ 1 baseline condition (fixation)
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).
A session consists of one or more experiments.
Each experiment consists of several (e.g., 1-8) runs
More 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)

32. Design Jargon: Paradigm
paradigm (or protocol): the set of conditions and their order used in a particular run
epoch: one instance of a condition
epoch
8 vol x 2 sec/vol = 16 sec
volume #1
(time = 0)
volume #136
(time = 136 vol x 2 sec/vol = 272 sec = 4:32)
run
first “intact objects” epoch
first “scrambled objects” epoch
second “intact objects” epoch
Time

33. 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 [ 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

34. Necessary Equipment Magnet Gradient Coil RF Coil 4T magnet RF Coil
(inside)
Magnet
Gradient Coil
RF Coil
Source for Photos: Joe Gati

35. Susceptibility Artifacts
T1-weighted image
T2*-weighted image
sinuses
ear
canals
-artifacts occur near junctions between air and tissue
sinuses, ear canals

36. The Benefit of Susceptibility
Susceptibility variations can also be seen around blood vessels where deoxyhemoglobin affects T2* in nearby tissue
Aha!
Modified from: Robert Cox’s web slides

37. 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

38. Comparing Electrophysiolgy and BOLD
Data Source: Disbrow et al., 2000, PNAS
Figure Source, Huettel, Song & McCarthy, Functional Magnetic Resonance Imaging

39. 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
Verb generation
Verb generation after 15 min practice
Ideas from: Scannell & Young, 1999,
Proc Biol Sci
Raichle & Posner, Images of Mind cover image

40. 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

41. Don’t Trust Sinus Activity
You will sometimes see bogus “activity” in the sagittal sinus

42. 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

43. 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)