Functional Magnetic Resonance Imaging ;
What is it and what can it do?
Heather Rupp
Common Themes in Reproductive Diversity
Kinsey Institute
Indiana University
Note- Most slides were taken from Jody Culham’s fMRI for Dummies web site
New York Times
September 26, 2006
Is Hysteria Real? Brain Images Say Yes
By ERIKA KINETZ
Hysteria is a 4,000-year-old diagnosis that has been applied to no mean parade of witches, saints and, of course, Anna O.
But over the last 50 years, the word has been spoken less and less. The disappearance of hysteria has been heralded at least since the 1960’s. What had been a
Victorian catch-all splintered into many different diagnoses. Hysteria seemed to be a vanished 19th-century extravagance useful for literary analysis but surely
out of place in the serious reaches of contemporary science. …
New York Times
September 10, 2006, Sunday
The Basics; An Image of Consciousness Creates a Stir
By BENEDICT CAREY (NYT)
ABSTRACT - Neuroscientists were anxious as well as exuberant over the report last week that doctors in England had found clearsigns of awareness in a braindamaged woman who was in a vegetative state. They insisted that the breathtaking finding -- that a brain thought to be all but dark flared with ...
MSNBC.com
May 8, 2006
Research finds differences in lesbian brains
p.m. ET May 8, 2006
WASHINGTON - Lesbians’ brains react differently to sex hormones than those of heterosexual women.
An earlier study of gay men also showed their brain response was different from straight men — an even stronger difference than has
now been found in lesbians…..
Today’s Goals
I. What does brain imaging actually measure?
MRI
fMRI
II. Experimental Design
Basics
Some Considerations
III. Data
Units of measurement
Basic Analysis
Measuring Brain Function
• Phrenology
• Lesions
• EEG/ERP
• Electrophysiology
• Need to balance considerations of spatial resolution, temporal
resolution, and invasiveness.
Magnetic Resonance Imaging
(MRI)
History of NMR
NMR = nuclear magnetic resonance
Felix Block and Edward Purcell
1946: atomic nuclei absorb and reemit radio frequency energy
1952: Nobel prize in physics
nuclear: properties of nuclei of atoms
magnetic: magnetic field required
resonance: interaction between
magnetic field and radio frequency
Bloch
NMR  MRI: Why the name change?
most likely explanation:
nuclear has bad connotations
Purcell
How do you take a ‘picture’ of a
brain?
• Take advantage of the high (and variable) water composition of
human tissue.
• Hydrogen protons align with magnetic field.
• Disrupt field and measure return (T1)- different brain regions
vary.
The Big Magnet
Very strong
1 Tesla (T) = 10,000 Gauss
Earth’s magnetic field = 0.5 Gauss
4 Tesla = 4 x 10,000  0.5 = 80,000X Earth’s magnetic field
Continuously on
Main field = B0
Robarts Research Institute 4T
x 80,000 =
Source: www.spacedaily.com
B0
Outside magnetic field
Protons align with field
• randomly oriented
Inside magnetic field
M
• spins tend to align parallel or anti-parallel
to B0
• net magnetization (M) along B0
• spins precess with random phase
• no net magnetization in transverse plane
• only 0.0003% of protons/T align with field
longitudinal
axis
Longitudinal
magnetization
transverse
plane
M=0
Source: Mark Cohen’s web slides
Source: Robert Cox’s web slides
RF Excitation
Excite Radio Frequency (RF) field
• transmission coil: apply magnetic field along B1
(perpendicular to B0) for ~3 ms
• oscillating field at Larmor frequency
• frequencies in range of radio transmissions
• B1 is small: ~1/10,000 T
• tips M to transverse plane – spirals down
• analogies: guitar string (Noll), swing (Cox)
• final angle between B0 and B1 is the flip angle
Transverse
magnetization
B0
B1
Source: Robert Cox’s web slides
T1 and TR
T1 = recovery of longitudinal (B0) magnetization
• used in anatomical images
• ~500-1000 msec (longer with bigger B0)
TR (repetition time) = time to wait after excitation before sampling T1
Source: Mark Cohen’s web slides
T2 and TE
T2 = decay of transverse magnetization
TE (time to echo) = time to wait to measure T2 or T2* (after refocusing
with spin echo or gradient echo)
Source: Mark Cohen’s web slides
T1
T2
How do you take a ‘picture’ of a
brain?
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: Mark Cohen’s web slides
How do you take a ‘picture’ of
the body?
MRI vs. fMRI
MRI studies brain anatomy.
Functional MRI (fMRI)
studies brain function.
Source: Jody Culham’s fMRI for Dummies web site
Functional Magnetic Resonance
Imaging (fMRI)
History of fMRI
fMRI
-1990: Ogawa observes BOLD effect with T2*
blood vessels became more visible as blood oxygen decreased
-1991: Belliveau observes first functional images using a contrast
agent
-1992: Ogawa et al. and Kwong et al. publish first functional images
using BOLD signal
Ogawa
First Functional Images
Flickering Checkerboard
OFF (60 s) - ON (60 s) -OFF (60 s) - ON (60 s) - OFF (60 s)
Source: Kwong et al., 1992
How do you make a ‘movie’
brain function?
1) Don’t look at T1 (recovery to magnetic field orientation), look at
relaxation away from field T2, T2*
2) Relaxation differs locally and with changes in blood flow
BOLD signal
Blood Oxygen Level Dependent signal
neural activity   blood flow   oxyhemoglobin   T2*   MR signal
Source: fMRIB Brief Introduction to fMRI
Hemodynamic Response Function
% signal change
= (point – baseline)/baseline
usually 0.5-3%
time to rise
signal begins to rise soon after stimulus begins
time to peak
initial dip
signal peaks 4-6 sec after stimulus begins
-more focal and potentially a better
measure
post stimulus undershoot
-somewhat elusive so far, not
signal suppressed after stimulation ends
everyone can find it
Summary:
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 (fMRI)
high resolution
(1 mm)
MRI
Summary:
MRI vs. fMRI
fMRI
low resolution
(~3 mm but can be better)
one image
fMRI
Blood Oxygenation Level Dependent (BOLD) signal
indirect measure of neural activity
 neural activity
…
many images
(e.g., every 2 sec for 5 mins)
  blood oxygen   fMRI signal
Source: Jody Culham’s fMRI for Dummies web site
Today’s Goals
I. What does brain imaging actually measure?
MRI
fMRI
II. Experimental Design
Basics
Some Considerations
III. Data
Units of measurement
Basic Analysis
fMRI Experiment Stages: Prep
1) Prepare subject
•
Consent form
•
•
Safety screening
Instructions
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
Note: That’s one g, two t’s
Take images along the midline to use to plan slices
Source: Jody Culham’s fMRI for Dummies web site
fMRI Experiment Stages: Anatomicals
4) Take anatomical (T1) images
•
high-resolution images (e.g., 1x1x2.5 mm)
•
•
3D data: 3 spatial dimensions, sampled at one point in time
64 anatomical slices takes ~5 minutes
Source: Jody Culham’s fMRI for Dummies web site
fMRI Experiment Stages: Functionals
5) Take functional (T2*) images
•
images are indirectly related to neural activity
•
•
•
•
usually low resolution images (3x3x5 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 150
volumes = 300 sec = 5 minutes)
4D data: 3 spatial, 1 temporal
…
first volume
(2 sec to acquire)
Source: Jody Culham’s fMRI for Dummies web site
Subtraction Logic
Cognitive subtraction originated with reaction time experiments
(F. C. Donders, a Dutch physiologist).
Measure the time for a process to occur by comparing two reaction
times, one which has the same components as the other + the
process of interest.
Example:
T1: Hit a button when you see a light
T2: Hit a button when the light is green but not red
T3: Hit the left button when the light is green and the right button when
the light is red
T2 – T1 = time to make discrimination between light color
T3 – T2 = time to make a decision
Assumption of pure insertion: You can insert a component process into a
task without disrupting the other components.
Widely criticized
You Must Have a Baseline!
Change only one thing between
conditions!
Two paired conditions should differ by the inclusion/exclusion of a single mental
process
How do we control the mental operations that subjects carry out in the scanner?
i)
ii)
Manipulate the stimulus
•
works best for automatic mental processes
Manipulate the task
•
works best for controlled mental processes
DON’T DO BOTH AT ONCE!!!
Source: Nancy Kanwisher
Dealing with Attentional
Confounds
fMRI data seem highly susceptible to the amount of attention drawn to the stimulus
or devoted to the task.
How can you ensure that activation is not simply due to an attentional confound?
Add an attentional requirement to all stimuli or tasks.
Add a “one back” task
• subject must hit a button whenever a
stimulus repeats
• the repetition detection is much harder for
the scrambled shapes
• any activation for the intact shapes cannot
be due only to attention
Time
Other common confounds that
reviewers love to hate:
• eye movements
• motor movements
Blocked Design
Block Designs
= trial of one type
(e.g., face image)
= trial of another type
(e.g., place image)
Assumption: Because the hemodynamic response
delays and blurs the response to activation, the
temporal resolution of fMRI is limited.
WRONG!!!!!
Blocked vs. Event-related
Source: Buckner 1998
Some Considerations
PHYSIOLOGICAL FACTORS
SOLUTION & TRADEOFF
Cardiac and respiratory noise
Monitor and compensate
– hassle
Head (and body) motion
Use experienced or well-warned subjects
– limits useable subjects
Use head-restraint system
– possible subject discomfort
Post-processing correction
– often incompletely effective
– 2nd order effects
– can introduce other artifacts
Single trials to avoid body motion
Low frequency noise
Use smart design
Perform post-processing filtering
BOLD noise (neural and vascular fluctuations)
Use many trials to average out variability
Behavioral variations
Use well-controlled paradigm
Use many trials to average out variability
Source: Doug Noll’s online tutorial
Some Considerations
Average cost of performing an fMRI experiment in 1998:
Average cost of performing a thought experiment:
Your Salary
CONCLUSION: Unless you are Bill Gates or Michael Jordan, a thought experiment is
much more efficient!
Magnet Safety
The whopping strength of the magnet makes safety essential.
Things fly – Even big things!
Source: www.howstuffworks.com
Source: http://www.simplyphysics.com/
flying_objects.html
Source: Jody Culham’s fMRI for Dummies web site
Subject Safety
Anyone going near the magnet – subjects, staff and visitors – must be
thoroughly screened:
Subjects must have no metal in their bodies:
• pacemaker
• aneurysm clips
• metal implants (e.g., cochlear implants)
• interuterine devices (IUDs)
• some dental work (fillings okay)
This subject was wearing a hair band with a ~2 mm
Subjects must remove metal from their bodies
copper clamp. Left: with hair band. Right: without.
• jewellery, watch, piercings
Source: Jorge Jovicich
• coins, etc.
• wallet
• any metal that may distort the field (e.g., underwire bra)
Subjects must be given ear plugs (acoustic noise can reach 120 dB)
Source: Jody Culham’s fMRI for Dummies web site
Thought Experiments
• What do you hope to find?
• What would that tell you about the cognitive process involved?
• Would it add anything to what is already known from other
techniques?
• Could the same question be asked more easily & cheaply with other
techniques?
• Would fMRI add enough to justify the immense expense and effort?
• What would be the alternative outcomes (and/or null hypothesis)?
• Or is there not really any plausible alternative (in which case the
experiment may not be worth doing)?
• If the alternative outcome occurred, would the study still be
interesting?
• If the alternative outcome is not interesting, is the hoped-for
outcome likely enough to justify the attempt?
• What would the headline be if it worked?
• What are the possible confounds?
• Can you control for those confounds?
• Has the experiment already been done?
Today’s Goals
I. What does brain imaging actually measure?
MRI
fMRI
II. Experimental Design
Basics
Some Considerations
III. Data
Units of measurement
Basic Analysis
The Data Unit
VOXEL
(Volumetric Pixel)
Slice Thickness
e.g., 6 mm
In-plane resolution
e.g., 192 mm / 64
= 3 mm
3 mm
6 mm
SAGITTAL SLICE
IN-PLANE SLICE
Number of Slices
e.g., 10
Matrix Size
e.g., 64 x 64
Field of View (FOV)
e.g., 19.2 cm
Source: Jody Culham’s fMRI for Dummies web site
3 mm
Data Unit
Functional images
~2s
ROI Time
Course
fMRI
Signal
(% change)
Time
Condition
Statistical Map
superimposed on
anatomical MRI image
Time
Region of interest (ROI)
~ 5 min
Source: Jody Culham’s fMRI for Dummies web site
Averaged Over Trials
Single trials
Average of all trials from 2 runs
Activation is Averaged
Source: Posner & Raichle, Images of Mind
Brain Averaging
Individual brains are different shapes and sizes…
How can we compare or average brains?
Talairach & Tournoux, 1988
• squish or stretch brain into “shoe box”
• extract 3D coordinate (x, y, z) for each
activation focus
Note: That’s TalAIRach, not TAILarach!
Source: Brain Voyager course slides
What do the pretty pictures mean?
Source: Jody Culham’s fMRI for Dummies web site
Careful!
1. "Brain Area X is activated by Task A."
Compared to what? Activations are differences!
2. "Baseline".
Huh?! There's a role for this, but be careful.
3. Inferring: Because Region X responded significantly more strongly in Task A than
control, but didn't respond significantly more strongly in Task B than control, it is
selectively activated by Task A.
A difference in significances is not necessarily a significant difference.
4. Imputing a specific function to a region of cortex from a difference in only two
conditions.
Data always underdetermines theory, but reasonable hypotheses about function
require multiple tests applied to the same region of cortex.
5. "Gyrus X was active in my comparison of tasks B and C, and in Joe Shmo's
comparison of tasks D and E, so the same area must be involved in both tasks B
and D."
Gyri can be very big places; need within-subject data.
Source: Nancy Kanwisher
Next Time
• Meet in Room 130 Psychology
• Volunteers?
• http://www.indiana.edu/~imaging/index.html
Top Ten Things Sex and Brain
Imaging Have in Common
10. It's not how big the region is, it's what you do with it.
9. Both involve heavy PETting.
8. It's important to select regions of interest.
7. Experts agree that timing is critical.
6. Both require correction for motion.
5. Experimentation is everything.
4. You often can't get access when you need it.
3. You always hope for multiple activations.
2. Both make a lot of noise.
1. Both are better when the assumption of pure insertion is met.
Source: students in the Dartmouth McPew Summer Institute