A simple introduction to fMRI study design for social science and other researchers outside the field who might want to design a study using fMRI brain scanning technology

1. fMRI
Study
Design
The basic framework
Russell James, J.D., Ph.D.
Texas Tech University

2. Goals of fMRI Study Design
1. Create a 2. Detect brain
desired signals
cognitive associated
state with that state
(standard (fMRI-specific
experimental experimental
design issues) design issues)

3. We want to estimate the likelihood
that a voxel, or group of voxels, is
responding to the stimulus

4. But, fMRI data is not like this
Activation

5. fMRI data is like this
Activation

6. The signal change is small.
The signal is noisy.
Activation

7. The
signal
change is
small
½% to 3%
change in
intensity with
a 1.5 T scanner

8. The signal
is noisy
1. The brain
is noisy
2. The scanner
is noisy

9. The brain is noisy
The brain is
constantly active,
constantly firing,
constantly receiving
input, constantly
sending instructions

10. The brain is noisy
Even conscious
thought is scattered.
Did you think about
something other
than fMRI in the
last 3 minutes?

11. How do
we
design
for noisy
brains?
1. Contrasts 2. Repetition

12. Think in contrasts

13. A single image A contrast can
contains much subtract out
unrelated brain the noise
activations
Task A-
Task A Task B Task B

14. Think of study design in terms of
contrasts
Image Image of
Image task A-
of task of task
A Image of
B task B

15. The comparison task can be “rest”
Image Image of
Image task A-
of task of task
A Image of
B task B

16. We can use a
“cognitive subtraction”
comparison to isolate an activity
- =

17. Cognitive subtraction:
the comparison task is
identical, except for one
variation of interest

18. Cognitive subtraction: View famous
faces v. non-famous faces

19. How might you improve cognitive
subtraction in this picture selection?
Match gender? Color pallet?
Expressions? Clothing choice?

20. Levels of cognitive subtraction
• Basic cognitive subtraction:
Stronger Results
Rational argument of validity
• Cognitive conjunction:
Two cognitive subtraction
designs show same activation
difference
• Parametric design:
Increasing levels of a factor
correspond with increasing
levels of activation

21. Cognitive conjunction
Memorizing
letters
v.
Memorizing v. Reading
numbers numbers

22. Parametric design
Increasing activation
Memorize 9 numbers ● ●
Memorize 6 numbers
● ●
Memorize 3 numbers
● ●
Memorize 1 number

23. Design for BIG contrasts
fMRI is too
noisy to be
good at
subtle Contrast extreme
cognitive differences first
differences

24. How do
we
design
for noisy
brains?
1. Contrasts 2. Repetition

25. Design for
repeated
activations

26. In social sciences we may get
1,000 people to make one
decision on a survey
In fMRI we get 25
people to do a task 40 times
for 1,000 activations

27. Two common design types
Event
Related
Block Design
Design

28. Block Design
Time

29. Stacking the HRFs
Within a certain
range, repeating
a stimulus will
cause the HRF
to stack linearly.
This causes
large total signal
change in block
designs.

30. Event Related Design

31. Block design advantages
• Easiest way to
detect differences
among two
comparison states
• Largest HRF
activation
• More robust to
unexpected HRF
shapes

32. BOLD response in
block v. event related (slow)

33. Event related design advantages
Block designs may not work
• Modeling incorrect
responses (can’t
know in advance)
• Habituation may
prevent activations
Can precisely observe
the actual HRF
Permits self-paced
trials

34. Barriers to repeating the activation

35. Barriers to repeating the activation
• Repetitions can
get boring or
predictable,
reducing activation
• Emotional states
may not be induced
or changed quickly
• Some decisions are
difficult to repeat
• Some biases can
be added once, but
not removed

36. Repetitions can get boring or
predictable, reducing activation
+ + +
+ + +
+ + +

37. Emotional states may
not be induced or
changed quickly
Think of the happiest
moment of your life
for 12 seconds
Think of the most painful
moment for 12 seconds
Think of the 2nd happiest
moment for 12 seconds
Think of the 2nd most
painful moment for 12 seconds

38. Some decisions are difficult to
repeat
“If you died today
what percentage of
your estate would you
want to leave to your
children?”
Are you sure?
Any second thoughts?
Want to think about
it some more?

39. Some biases are not easily removed
1. How much of a $100
extra payment will you
give to the United Way?
2. The United Way CEO
made $1,037,140 last
year.
3. How much of a $100
extra payment will you
give to the United Way?
1st comparison works great,
but can you repeat this?

40. The signal
is noisy
1. The brain
is noisy
2. The scanner
is noisy

41. Designing for a noisy scanner
Physical
issues
Timing
issues

42. Physical issues of a
noisy scanner
Machine Metal Movement

43. Machine
Optimizing
machine, setting
parameters,
region of
interest, speed v.
resolution, etc.

44. Metal: Limit any ferrous content to
avoid disturbances in magnetic field

45. Movement
Keep the subject still during runs
• Motivated
subjects
• Foam packing
Statistical
adjustments (but,
may not help task-
related movement)

46. Designing for a noisy scanner
Physical
issues
Timing
issues

47. Timing
issues
of a
noisy
scanner
signal

48. Scanner Drift
Over longer periods of time (2-10
minutes), the magnetic field of the
scanner can slowly rise and fall.

49. Scanner Drift
Comparison across long (>2min)
periods should be avoided.
Condition A Condition A
Condition B Condition B
A–B shows magnetic differences but not from HRF

50. What is wrong with this?
30 sec block of task A (version 1)
30 sec block of task A (version 2)
30 sec block of task A (version 3)
30 sec block of task A (version 4)
30 sec block of task B (version 1)
30 sec block of task B (version 2)
30 sec block of task B (version 3)
30 sec block of task B (version 4)
30 sec block of task C (version 1)
30 sec block of task C (version 2)
30 sec block of task C (version 3)
30 sec block of task C (version 4)

51. What is wrong with this?
30 sec block of task A (version 1)
30 sec block of task A (version 2)
30 sec block of task A (version 3) Comparing
30 sec block of task A (version 4) A to C
spans well
30 sec block of task B (version 1)
over 120
30 sec block of task B (version 2) seconds so
30 sec block of task B (version 3) we can’t
30 sec block of task B (version 4) distinguish
30 sec block of task C (version 1) from
30 sec block of task C (version 2) scanner
30 sec block of task C (version 3) drift
30 sec block of task C (version 4)

52. Block Design Timing Issues
Ideal timing 15-20 seconds on then
15-20 seconds off (or A then B)
• Long enough for HRF
to relax in between
presentations
• Short enough for
many comparison
blocks within short
time

53. Slow Event-Related Timing Issues
Waiting 12+ seconds in
between each event to
allow HRF to calm
down
Boring and inefficient

54. Rapid Event-
Related
Design
Timing
Issues
Jitter spacing to record different
parts of the HRF and to avoid
correlation with other functions like
heartbeat and breathing

55. Rapid Event-
Related
Design
Timing
Issues
Gap spacing >4 seconds, else
• HRF blurring: Not enough time
for noticeable HRF changes
• Non-linearity: HRFs don’t stack
linearly forever
Optimum jittering estimation
programs (e.g., OptSeq - Doug Greves; Genetic Algorithm - Tor Wager)

56. Session Timing
Typically, studies
include groups of
tasks of 4-10 min.
with intervening 2
min. breaks.
Also need high
resolution (T1) scan
~5 min.; Locater
scans (~30 sec.); T2
axial scan for
radiologist (~2 min.)

57. In a 48 minute 10 min. subject in and out
session, you may Locator – 20 seconds
get about 24-28 Short Break
minutes of actual T2 axial: 2 min
stimulus Break
presentation
T1 high resolution: 5 min
Break - wake up
Block 1: 8 minutes
Break/Instructions: 2 min
Block 2: 8 minutes
Break/Instructions: 2 min
Block 3: 8 minutes

58. $650/hour scanner time
~$1300/hour stimulus time
~$20+ per minute
~$1+ every 3 seconds
Add 12 sec. to 25 subjects = $100+

59. With so many, many design
issues to think about, what is
the best way to
design your
first study?

60. Stand on some
shoulders!

61. Find a good prior study, copy the
technical elements, but change your
item of interest

62. fMRI
Study
Design
The basic framework
Russell James, J.D., Ph.D.
Texas Tech University