1. Experimental Design FMRI Graduate Course (NBIO 381, PSY 362)
Dr. Scott Huettel, Course Director
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

2. Experimental Design: Terminology
Variables
Independent vs. Dependent
Categorical vs. Continuous
Contrasts
Experimental vs. Control
Parametric vs. subtractive
Comparisons of subjects
Between- vs. Within-subjects
Confounding factors
Randomization, counterbalancing
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

3. What is fMRI Experimental Design?
Controlling the timing and quality of cognitive operations (IVs) to influence brain activation (DVs)
What can we control?
Stimulus properties (what is presented?)
Stimulus timing (when is it presented?)
Subject instructions (what do subjects do with it?)
What are the goals of experimental design?
To test specific hypotheses (i.e., hypothesis-driven)
To generate new hypotheses (i.e., data-driven)
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

4. What types of hypotheses are possible for fMRI data?
fmri-fig jpg
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

5. Optimal Experimental Design
Maximizing both Detection and Estimation
Maximal variance in signal (incr. detect.)
Maximal variance in stimulus timing (incr. est.)
Limitations on Optimal Design
Refractory effects
Signal saturation
Subject’s predictability
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

6. fMRI Design Types Blocked Designs Event-Related Designs Mixed Designs
Periodic Single Trial
Jittered Single Trial
Mixed Designs
- Combination blocked/event-related
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

7. 1. Blocked Designs
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

8. What are Blocked Designs?
Blocked designs segregate different cognitive processes into distinct time periods
Task A
Task B
Task A
Task B
Task A
Task B
Task A
Task B
Task A
REST
Task B
REST
Task A
REST
Task B
REST
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

9. PET Designs Measurements done following injection of radioactive bolus
Uses total activity throughout task interval (~30s)
Blocked designs necessary
Task 1 = Injection 1
Task 2 = Injection 2
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

10. Choosing Length of Blocks
Longer block lengths allow for stability of extended responses
Hemodynamic response saturates following extended stimulation
After about 10s, activation reaches max
Many tasks require extended intervals
Processing may differ throughout the task period
Shorter block lengths move your signal to higher frequencies
Away from low-frequency noise: scanner drift, etc.
Periodic blocks may result in aliasing of other variance in the data
Example: if the person breathes at a regular rate of 1 breath/5sec, and the blocks occur every 10s
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

11. fmri-fig jpg
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

12. fmri-fig jpg
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

13. Types of Blocked Design
Task A vs. Task B (… vs. Task C…)
Example: Squeezing Right Hand vs. Left Hand
Allows you to distinguish differential activation between conditions
Does not allow identification of activity common to both tasks
Can control for uninteresting activity
Task A vs. No-task (… vs. Task C…)
Example: Squeezing Right Hand vs. Rest
Shows you activity associated with task
May introduce unwanted results
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

14. fmri-fig-11-12-0.jpg Adapted from Gusnard & Raichle (2001)
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

15. Cerebral Metabolic Rate of O2 Oxygen Extraction Fraction
Any true baseline?
Cerebral Blood Flow
Cerebral Metabolic Rate of O2
Oxygen Extraction Fraction
fmri-fig jpg
Adapted from Gusnard & Raichle (2001)
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

16. Non-Task Processing
In many experiments, activation is greater in baseline conditions than in task conditions!
Requires interpretations of significant activation
Suggests the idea of baseline/resting mental processes
Gathering/evaluation about the world around you
Awareness (of self)
Online monitoring of sensory information
Daydreaming
This collection of processes is often called the “Default Mode”
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

17. Vision. Default Mode! Memory.
Damoiseaux 2006 analyzed separate 10-subject resting-state data sets, using Independent Components analysis.
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

18. Power in Blocked Designs
Summation of responses results in large variance
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

19. HDR Estimation: Blocked Designs
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

20. Deeper concept…
We want the changes evoked by the task to be at different parts of the frequency spectrum than non-task-evoked changes.
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

21. Limitations of Blocked Designs
Very sensitive to signal drift
Poor choice of conditions/baseline may preclude meaningful conclusions
Many tasks cannot be conducted repeatedly
Difficult to estimate the Hemodynamic Response
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

22. 2. Event-Related Designs
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

23. What are Event-Related Designs?
Event-related designs associate brain processes with discrete events, which may occur at any point in the scanning session.
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

24. Why use event-related designs?
Some experimental tasks are naturally event-related
Allows studying of trial effects
Improves relation to behavioral factors
Simple analyses
Selective averaging
General linear models
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

25. 2a. Periodic Single Trial Designs
Stimulus events presented infrequently with long interstimulus intervals
500 ms
500 ms
500 ms
500 ms
18 s
18 s
18 s
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

26. fmri-fig-11-16-2.jpg McCarthy et al., (1997)
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

27. Trial Spacing Effects: Periodic Designs
12sec
20sec
8sec
4sec
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

28. Why not short, periodic designs?
ISI: Interstimulus Interval
SD: Stimulus Duration
From Bandettini and Cox, 2000
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

29. 2b. Jittered Single Trial Designs
Varying the timing of trials within a run
Varying the timing of events within a trial
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

30. Effects of Jittering on Stimulus Variance
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

31. How rapidly can we present stimuli?
fmri-fig jpg
Dale and Buckner (1997)
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

32. Effects of ISI on Power Birn et al, 2002
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

33. Efficient Experimental Design
Maximal
Relative Efficiency
None
Mean Interval between Stimuli (sec)
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

34. Post-Hoc Sorting of Trials
Using information about fMRI activation at memory encoding to predict behavioral performance at memory retrieval.
From Kim and Cabeza, 2007
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

35. Limitations of Event-Related Designs
None, really, at least with design itself.
The key issues are:
Can my subjects perform the task as designed?
Are the processes of interest independent from each other (in time, amplitude, etc.)?
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

36. You can model a block with events…
Blocked (solid)
Event-related model reaches peak sooner…
Event-Related (dashed)
… and returns to baseline more slowly.
In this study, some language-related regions were better modeled by event-related.
From Mechelli, et al., 2003
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

37. 3. Mixed Designs
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

38. 3a. Mixed: Combination Blocked/Event
Both blocked and event-related design aspects are used (for different purposes)
Blocked design: state-dependent effects
Event-related design: item-related effects
Analyses can model these as separate phenomena, if cognitive processes are independent.
“Memory load effects” vs. “Item retrieval effects”
Or, interactions can be modeled.
Effects of memory load on item retrieval activation.
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

39. fmri-fig jpg
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

40. FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

41. How do we identify efficient designs?
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

42. Issues in Design Efficiency
Not all random designs are equally efficient!
Design efficiency is defined in relation to some contrast
Efficiency may interact with predictability & expectation
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

43. Iterative (Genetic) Algorithms
Select the most efficient designs
Eliminate inefficient designs A B C A B C
Designs A B C
Designs A B C
Retest modifications of efficient designs A B C
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

44. Summary of Experiment Design
Main Issues to Consider
What design constraints are induced by my task?
What am I trying to measure?
What sorts of non-task-related variability do I want to avoid?
Rules of thumb
Blocked Designs:
Powerful for detecting activation
Useful for examining state changes
Event-Related Designs:
Powerful for estimating time course of activity
Allows determination of baseline activity
Best for post hoc trial sorting
Mixed Designs
Best combination of detection and estimation
Much more complicated analyses
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University