Experimental Design FMRI Undergraduate Course (PSY 181F) FMRI Graduate Course (NBIO 381, PSY 362) Dr. Scott Huettel, Course Director FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

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

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

What types of hypotheses are possible for fMRI data? fmri-fig-11-03-0.jpg FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

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

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

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

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

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

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

fmri-fig-11-10-1.jpg FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

fmri-fig-11-10-2.jpg FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

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

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

Cerebral Metabolic Rate of O2 Oxygen Extraction Fraction Any true baseline? Cerebral Blood Flow Cerebral Metabolic Rate of O2 Oxygen Extraction Fraction fmri-fig-11-13-0.jpg Adapted from Gusnard & Raichle (2001) FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

How rapidly can we present stimuli? fmri-fig-11-17-0.jpg Dale and Buckner (1997) FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

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

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

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

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

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

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

fmri-fig-11-21-0.jpg FMRI – Week 8 – Experimental Design Scott Huettel, Duke University

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

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