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Issues in Experimental Design

Issues in Experimental Design. fMRI Graduate Course October 19, 2004. Terminology. Independent vs. Dependent variables Categorical vs. Continuous variables Between- vs. Within-subjects manipulations Experimental vs. Control conditions Confounding factors Randomization, counterbalancing

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Issues in Experimental Design

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  1. Issues in Experimental Design fMRI Graduate Course October 19, 2004

  2. Terminology • Independent vs. Dependent variables • Categorical vs. Continuous variables • Between- vs. Within-subjects manipulations • Experimental vs. Control conditions • Confounding factors • Randomization, counterbalancing • Parametric vs. subtractive designs

  3. What is fMRI Experimental Design? • Controlling the timing and quality of cognitive operations (IVs) to influence resulting brain processes (DVs) • 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?)

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

  5. What types of hypotheses are possible for fMRI data?

  6. Epiphenomena?

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

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

  9. 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

  10. 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

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

  12. 1. Blocked Designs

  13. 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

  14. 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

  15. 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

  16. 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

  17. Adapted from Gusnard & Raichle (2001)

  18. Adapted from Gusnard & Raichle (2001)

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

  20. From Huettel et al., 2004 (Baseline > Target Detection) From Huettel et al., 2001 (Change Detection)

  21. 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

  22. 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).

  23. HDR Estimation: Blocked Designs

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

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

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

  27. Deeper concept… We want the changes evoked by the task to be at different parts of the frequency spectrum than non-task-evoked changes.

  28. 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

  29. 2. Event-Related Designs

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

  31. 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

  32. Word-stem completion task. Blocked design: 30s on/off. Event-related design: 15s ISI. Buckner et al., (1996)

  33. Buckner et al., (1996)

  34. McCarthy et al., (1997)

  35. McCarthy et al., (1997)

  36. Dale and Buckner (1997)

  37. 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

  38. 12sec 8sec 4sec Trial Spacing Effects: Periodic Designs 20sec

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

  40. 2b. Jittered Single Trial Designs • Varying the timing of trials within a run • Varying the timing of events within a trial

  41. Effects of Jittering on Stimulus Variance

  42. From Hopfinger et al., 2000

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

  44. 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 • Also called Interleaved Stimulus Presentation

  45. +0s Two of the phases are normal. +1s But, one has a change in one trial (e.g., head motion) +2s

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