Basics of Experimental Design for fMRI Last Update: November 2008.
Issues in Experimental Design fMRI Graduate Course October 26, 2005.
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Transcript of Issues in Experimental Design fMRI Graduate Course October 26, 2005.
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Issues in Experimental Design
fMRI Graduate Course
October 26, 2005
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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
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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?)
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Goals of Experimental Design
• To maximize the ability to test hypotheses
• To facilitate generation of new hypotheses
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What types of hypotheses are possible for fMRI data?
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Epiphenomena?
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• Detection: What is active?
• Estimation: How does activity change over time?
Detection vs. Estimation
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Detection
• Detection power defined by SNR
• Depends greatly on hemodynamic response shape
SNR = aM/M = hemodynamic changes (unit)
a = measured amplitude
= noise standard deviation
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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
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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
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fMRI Design Types
1) Blocked Designs
2) Event-Related Designsa) Periodic Single Trial
b) Jittered Single Trial
c) Staggered or Interleaved Single Trial
3) Mixed Designsa) Combination blocked/event-related
b) Variable stimulus probability
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1. Blocked Designs
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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 Task BREST REST Task A Task BREST REST
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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
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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
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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
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Adapted from Gusnard & Raichle (2001)
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Adapted from Gusnard & Raichle (2001)
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From Shulman et al., 1997 (PET data)
From Binder et al., 1999
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From Huettel et al., 2001 (Change Detection)
From Huettel et al., 2004 (Baseline > Target Detection)
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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
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Power in Blocked Designs
1. Summation of responses results in large variance
Single, unit amplitude HDR, convolved by 1, 2, 4 ,8, 12, or 16 events (1s apart).
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HDR Estimation: Blocked Designs
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Power in Blocked Designs
2. Transitions between blocks
Simulation of single run with either 2 or 10 blocks.
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Power in Blocked Designs
2. Transitions between blocks
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Addition of linear drift within run.
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Power in Blocked Designs
2. Transitions between blocks
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Addition of noise (SNR = 0.67)
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Deeper concept…
We want the changes evoked by the task to be at different parts of the frequency spectrum than non-task-evoked changes.
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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
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2. Event-Related Designs
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What are Event-Related Designs?
• Event-related designs associate brain processes with discrete events, which may occur at any point in the scanning session.
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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
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Buckner et al., (1996)
Word-stem completion task. Blocked design: 30s on/off. Event-related design: 15s ISI.
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Buckner et al., (1996)
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McCarthy et al., (1997)
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McCarthy et al., (1997)
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Dale and Buckner (1997)
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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
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Trial Spacing Effects: Periodic Designs
20sec
8sec 4sec
12sec
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From Bandettini and Cox, 2000
ISI: Interstimulus Interval
SD: Stimulus Duration
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2b. Jittered Single Trial Designs
• Varying the timing of trials within a run
• Varying the timing of events within a trial
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Effects of Jittering on Stimulus Variance
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From Hopfinger et al., 2000
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Effects of ISI on Power
Birn et al, 2002
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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
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Two of the phases are normal.
But, one has a change in one trial (e.g., head motion)
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Post-Hoc Sorting of Trials
From Konishi, et al., 2000
Data from old/new episodic memory test.
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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
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3. Mixed Designs
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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
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… …
Mixed Blocked/Event-related Design
Target-related Activity (Phasic)
Blocked-related Activity (Tonic)
Task-Initiation Activity (Tonic)
Task-Offset Activity (Tonic)
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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
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Random and Semi-Random Designs
From Liu et al., 2001
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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