Transcript An Introduction to Functional MRI
Experimental Design
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 – 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
1) Blocked Designs 2) Event-Related Designs a) Periodic Single Trial b) Jittered Single Trial 3) Mixed Designs - Combination blocked/event-related
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University
FMRI – Week 8 – Experimental Design
1. Blocked Designs
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 – Week 8 – Experimental Design Scott Huettel, Duke University
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
Adapted from Gusnard & Raichle (2001) FMRI – Week 8 – Experimental Design Scott Huettel, Duke University
Cerebral Blood Flow Cerebral Metabolic Rate of O 2 Oxygen Extraction Fraction Adapted from Gusnard & Raichle (2001) FMRI – Week 8 – Experimental Design
Any true baseline?
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
1. 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
McCarthy et al., (1997) FMRI – Week 8 – Experimental Design Scott Huettel, Duke University
Trial Spacing Effects: Periodic Designs
20sec 12sec 4sec 8sec
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
Scott Huettel, Duke University FMRI – Week 8 – Experimental Design
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?
Dale and Buckner (1997) FMRI – Week 8 – Experimental Design Scott Huettel, Duke University
Effects of ISI on Power
FMRI – Week 8 – Experimental Design
Birn et al, 2002
Scott Huettel, Duke University
Efficient Experimental Design
Maximal None
Mean Interval between Stimuli (sec)
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University
Post-Hoc Sorting of Trials
From Kim and Cabeza, 2007
FMRI – Week 8 – Experimental Design
Using information about fMRI activation at memory
encoding
to predict behavioral performance at memory
retrieval
.
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 (dashed) FMRI – Week 8 – Experimental Design Event-related model reaches peak sooner… … and returns to baseline more slowly.
In this study, some language-related regions were better modeled by event-related.
From Mechelli, et al., 2003
Scott Huettel, Duke University
FMRI – Week 8 – Experimental Design
3. Mixed Designs
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 – Week 8 – Experimental Design Scott Huettel, Duke University
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University
How do we identify efficient designs?
FMRI – Week 8 – Experimental Design Scott Huettel, Duke University
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
Iterative (Genetic) Algorithms
Select the most efficient designs A B C A B C A B C
Designs
A B C
Designs
Retest modifications of efficient designs FMRI – Week 8 – Experimental Design Eliminate inefficient designs A B C 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