Issues in Experimental Design

1. Issues in Experimental Design fMRI Graduate Course October 30, 2002

2. What is Experimental Design? • Controlling the timing and quality of presented stimuli to influence resulting brain processes • What can we control? • Experimental comparisons (what is to be measured?) • Stimulus properties (what is presented?) • Stimulus timing (when is it presented?) • Subject instructions (what do subjects do with it?)

3. Goals of Experimental Design • To maximize the ability to test hypotheses • To facilitate generation of new hypotheses

4. Detection vs. Estimation • Detection: What is active? • Estimation: How does its activity change over time?

5. Detection • Detection power defined by SNR • Depends greatly on hemodynamic response shape SNR = aM/ M = hemodynamic changes (unit) a = measured amplitude  = noise standard deviation

6. Estimation • Ability to determine the shape of fMRI response • Accurate estimation relies on minimization of variance in estimate of HDR at each time point • Efficiency of estimation is generally independent of HDR form

7. Optimal Experimental Design • Maximizing both Detection and Estimation • Maximal variance in stimulus timing (increases estimation) • Maximal variance in measured signal (increases detection) • Limitations • Refractory effects • Signal saturation

8. fMRI Design Types • Blocked Designs • Event-Related Designs • Periodic Single Trial • Jittered Single Trial • Staggered Single Trial • Mixed Designs • Combination blocked/event-related • Variable stimulus probability

9. 1. Blocked Designs

10. 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

11. 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

12. 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 allow for more transitions • Task-related variability increases (relative to non-task) with increasing numbers of transitions • 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

13. What baseline should you choose? • Task A vs. Task B • 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 • Example: Squeezing Right Hand vs. Rest • Shows you activity associated with task • May introduce unwanted results

14. From Shulman et al., 1997 (PET data) From Binder et al., 1999

15. From Huettel et al., 2002 (Baseline > Target Detection) From Huettel et al., 2001 (Change Detection)

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 • Emotional processes • Gathering/evaluation about the world around you • Awareness (of self) • Online monitoring of sensory information • Daydreaming

17. Power in Blocked Designs • Summation of responses results in large variance Single, unit amplitude HDR, convolved by 1, 2, 4 ,8, 12, or 16 events (1s apart).

18. HDR Estimation: Blocked Designs

19. Power in Blocked Designs 2. Transitions between blocks Simulation of single run with either 2 or 10 blocks.

20. Power in Blocked Designs 2. Transitions between blocks Addition of linear drift within run.

21. Power in Blocked Designs 2. Transitions between blocks Addition of noise (SNR = 0.67)

22. Limitations of Blocked Designs • Very sensitive to signal drift • Sensitive to head motion, especially when only a few blocks are used. • Poor choice of baseline may preclude meaningful conclusions • Many tasks cannot be conducted repeatedly • Difficult to estimate the HDR

23. 2. Event-Related Designs

24. What are Event-Related Designs? • Event-related designs associate brain processes with discrete events, which may occur at any point in the scanning session.

25. Why use event-related designs? • Some experimental tasks are naturally event-related • Allows studying of trial effects • Simple analyses • Selective averaging • No assumptions of linearity required

26. 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

27. 12sec 8sec 4sec Trial Spacing Effects: Periodic Designs 20sec

28. ISI: Interstimulus Interval SD: Stimulus Duration From Bandettini and Cox, 2000

29. 2b. Jittered Single Trial Designs • Varying the timing of trials within a run

30. Effects of Jittering on Stimulus Variance

31. Effects of ISI on Power Birn et al, 2002

32. 2c. Staggered Single Trial • By presenting stimuli at different timings, relative to a TR, you can achieve sub-TR resolution • Significant cost in number of trials presented • Resulting loss in experimental power • Very sensitive to scanner drift and other sources of variability

33. +0s Two HDR epochs sampled at a 3s TR. +1s Each row is sampled at a different phase. +2s

34. +0s Two of the phases are normal. +1s But, one has a change in one trial (e.g., head motion) +2s

35. Post-Hoc Sorting of Trials Data from old/new episodic memory test. From Konishi, et al., 2000

36. Limitations of Event-Related Designs • Differential effects of interstimulus interval • Long intervals do not optimally increase stimulus variance • Short intervals may result in refractory effects • Detection ability dependent on form of HDR • Length of “event” may not be known

37. 3. Mixed Designs

38. 3a. Combination Blocked/Event • Both blocked and event-related design aspects are used (for different purposes) • Blocked design is used to evaluate state-dependent effects • Event-related design is used to evaluate item-related effects • Analyses are conducted largely independently between the two measures • Cognitive processes are assumed to be independent

39. … … Target-related Activity (Phasic) Blocked-related Activity (Tonic) Task-Initiation Activity (Tonic) Task-Offset Activity (Tonic) Mixed Blocked/Event-related Design

40. 3b. Variable Stimulus Probability • Stimulus probability is varied in a blocked fashion • Appears similar to the combination design • Mixed design used to maximize experimental power for single design • Assumes that processes of interest do not vary as a function of stimulus timing • Cognitive processing • Refractory effects

41. Random and Semi-Random Designs From Liu et al., 2001

42. 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