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Issues in Experimental Design . fMRI Graduate Course October 30, 2002. 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?)
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Issues in Experimental Design fMRI Graduate Course October 30, 2002
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?)
Goals of Experimental Design • To maximize the ability to test hypotheses • To facilitate generation of new hypotheses
Detection vs. Estimation • Detection: What is active? • Estimation: How does its activity change over time?
Detection • Detection power defined by SNR • Depends greatly on hemodynamic response shape SNR = aM/ M = hemodynamic changes (unit) a = measured amplitude = noise standard deviation
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
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
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
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
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
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
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
From Shulman et al., 1997 (PET data) From Binder et al., 1999
From Huettel et al., 2002 (Baseline > Target Detection) From Huettel et al., 2001 (Change Detection)
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
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).
Power in Blocked Designs 2. Transitions between blocks Simulation of single run with either 2 or 10 blocks.
Power in Blocked Designs 2. Transitions between blocks Addition of linear drift within run.
Power in Blocked Designs 2. Transitions between blocks Addition of noise (SNR = 0.67)
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
What are Event-Related Designs? • Event-related designs associate brain processes with discrete events, which may occur at any point in the scanning session.
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
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
12sec 8sec 4sec Trial Spacing Effects: Periodic Designs 20sec
ISI: Interstimulus Interval SD: Stimulus Duration From Bandettini and Cox, 2000
2b. Jittered Single Trial Designs • Varying the timing of trials within a run
Effects of ISI on Power Birn et al, 2002
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
+0s Two HDR epochs sampled at a 3s TR. +1s Each row is sampled at a different phase. +2s
+0s Two of the phases are normal. +1s But, one has a change in one trial (e.g., head motion) +2s
Post-Hoc Sorting of Trials Data from old/new episodic memory test. From Konishi, et al., 2000
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
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
… … Target-related Activity (Phasic) Blocked-related Activity (Tonic) Task-Initiation Activity (Tonic) Task-Offset Activity (Tonic) Mixed Blocked/Event-related Design
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
Random and Semi-Random Designs From Liu et al., 2001
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