Basics of Experimental Design for fMRI: Block Designs http://www.fmri4newbies.com/ Last Update: February 4, 2013 Last Course: Psychology 9223, W2013, Western University Jody Culham Brain and Mind Institute Department of Psychology University of Western Ontario
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Basics of Experimental Design for fMRI: Block Designs Last Update: February 4, 2013 Last Course: Psychology 9223, W2013, Western.
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Basics of Experimental Designfor fMRI:
Block Designs
http://www.fmri4newbies.com/
Last Update: February 4, 2013Last Course: Psychology 9223, W2013, Western University
Jody CulhamBrain and Mind Institute
Department of PsychologyUniversity of Western Ontario
“Attending a poster session at a recent meeting, I was reminded of the old adage ‘To the man who has only a hammer, the whole world looks like a nail.’ In this case, however, instead of a hammer we had a magnetic resonance imaging (MRI) machine and instead of nails we had a study. Many of the studies summarized in the posters did not seem to be designed to answer questions about the functioning of the brain; neither did they seem to bear on specific questions about the roles of particular brain regions. Rather, they could best be described as ‘exploratory’. People were asked to engage in some task while the activity in their brains was monitored, and this activity was then interpreted post hoc.”
-- Stephen M. Kosslyn (1999). If neuroimaging is the answer, what is the question? Phil Trans R Soc Lond B, 354, 1283-1294.
"...the single most critical piece of equipment is still the researcher's own brain. All the equipment in the world will not help us if we do not know how to use it properly, which requires more than just knowing how to operate it. Aristotle would not necessarily have been more profound had he owned a laptop and known how to program. What is badly needed now, with all these scanners whirring away, is an understanding of exactly what we are observing, and seeing, and measuring, and wondering about."
-- Endel Tulving, interview in Cognitive Neuroscience (2002, Gazzaniga , Ivry & Mangun, Eds., NY: Norton, p. 323)
“The Romney amygdala activation might indicate anxiety, or any number of other feelings that are associated with the amygdala -- anger, happiness or even sexual excitement”
• It’s the most expensive approach• If you’re interested in behavior, study behavior• EEG/ERP/MEG have better temporal resolution• TMS and neuropsychology speak more directly to causality
– fMRI activation may be epiphenomonal
• neurophysiology/eCoG give more direct access to neural processing
What Can fMRI Add?• explicit testing of models derived from other approaches• inform and constrain theories of cognition• whole brain coverage that can constrain or direct data from
other approaches (neurophysiology, ERPs, ECoG) • investigation of neural mechanisms of elaborated human
functions (language, math, tool use)• correlations between brain and behavior• help to understand clinical disorders or development• look at coding and connections between brain regions
Thought Experiments• What do you hope to find? • What would that tell you about the cognitive process involved? • Would it add anything to what is already known from other techniques? • Could the same question be asked more easily, more cheaply or better with other techniques?
• What would be the alternative outcomes (and/or null hypothesis)? • Or is there not really any plausible alternative (in which case the experiment may not be worth doing)? • If the alternative outcome occurred, would the study still be interesting? • If the alternative outcome is not interesting, is the hoped-for outcome likely enough to justify the attempt? • What would the “headline” be if it worked? Is it sexy enough to warrant the time, funding and effort? • “Ideas are cheap.” -- Jody’s former supervisor, Jane Raymond
• Good experimenters generate many ideas and ensure that only the fittest survive
• What are the possible confounds?• Can you control for those confounds?
• Has the experiment already been done? “A year of research can save you an hour on PubMed!”
Three Stages of an ExperimentSledgehammer Approach• brute force experiment• powerful stimulus• don’t try to control for everything• run a couple of subjects -- see if it looks promising• if it doesn’t look great, tweak the stimulus or task• try to be a subject yourself so you can notice any problems with stimuli or subject strategies
Real Experiment• at some point, you have to stop changing things and collect enough subjects run with the same conditions to publish it• incorporate appropriate control conditions• random effects analysis requires at least 10 subjects• can run all subjects in one or two days
• pro: minimize setup and variability• con: “bad magnet day” means a lot of wasted time
Whipped Cream• after the real experiment works, then think about a “whipped cream” version• going straight to whipped cream is a huge endeavor, especially if you’re new to imaging• mixed metaphor: “never sacrifice the meat & potatoes to get the gravy” (“never sacrifice the hot chocolate to get the whipped cream” doesn’t have quite the same punch)
• fMRI is the art of the barely possible• neuropsychology is the art of the barely possible
• combining fMRI and neuropsychology can be very valuable
• BUT it’s (art of the barely possible)2
• If you want to test a paradigm in patients or special groups (either single cases or group studies), I recommend developing a robust paradigm in control subjects first
• It’s generally a bad idea to use patients for pilot testing
Dealing with Attentional ConfoundsfMRI data seem highly susceptible to the amount of attention drawn to the stimulus or devoted to the task.
Add an attentional requirement to all stimuli or tasks.
How can you ensure that activation is not simply due to an attentional confound?
Time
Example: Add a “one back” task• subject must hit a button whenever a stimulus repeats• the repetition detection is much harder for the scrambled shapes • any activation for the intact shapes cannot be due only to attention
Other common confounds that reviewers love to hate:• eye movements• motor movements
Is concurrent behavioral data necessary?“Ideally, a concurrent, observable and measureable behavioral response, such as a yes or no bar-press response, measuring accuracy or reaction time, should verify task performance.”-- Mark Cohen & Susan Bookheimer, TINS, 1994
“I wonder whether PET research so far has taken the methods of experimental psychology too seriously. In standard psychology we need to have the subject do some task with an externalizable yes-or-no answer so that we have some reaction times and error rates to analyze – those are our only data. But with neuroimaging you’re looking at the brain directly so you literally don’t need the button press… I wonder whether we can be more clever in figuring out how to get subjects to think certain kinds of thoughts silently, without forcing them to do some arbitrary classification task as well. I suspect that when you have people do some artificial task and look at their brains, the strongest activity you’ll see is in the parts of the brain that are responsible for doing artificial tasks.-- Steve Pinker, interview in the Journal of Cognitive Neuroscience, 1994
You decide:• number of slices• slice orientation• slice thickness• in-plane resolution (field of view and matrix size)• volume acquisition time (usually = TR)• length of a run• number of runs• duration and sequence of epochs within each run• counterbalancing within or between subjects
Your physicist can help you decide:• pulse sequence (e.g., gradient echo vs. spin echo)• k-space sampling (e.g., echo-planar vs. spiral imaging)• TR, TE, flip angle, etc.
Number of slices vs. volume acquisition time• the more slices you take, the longer you need to acquire them• e.g., 30 slices in 2 sec vs. 45 slices in 3 sec
“fMRI is like trying to assemble a ship in a bottle – every which way you try to move, you encounter a constraint” -- Mel Goodale
Number of slices vs. in-plane resolution• the higher your in-plane resolution, the fewer slices you can acquire in a constant volume acquisition time• e.g., in 2 sec, 7 slices at 1.5 x 1.5 mm resolution (128 x 128 matrix) vs. 28 slices at 3 mm x 3 mm resolution (64 x 64 matrix)
More Power to Ya!Statistical Power• the probability of rejecting the null hypothesis when it is actually false• “if there’s an effect, how likely are you to find it”?
Effect size• bigger effects, more power
• e.g., LO localizer (intact vs. scrambled objects) -- 1 run is usually enough• looking for activation during imagery of objects might require many more runs
Sample size• larger n, more power
• more subjects• longer runs• more runs per subject
Why?• subjects get drowsy and bored• magnet may have different amounts of noise from one run to another (e.g., spike)• some stats (e.g., z-normalization) may affect stats differently between runs
By this logic, there is higher activation for Places than Faces in the data to the left.Do you agree?
Bottom line: If you want to compare A vs. B, compare A vs. B! Simple, eh?
As far as possible, put the two conditions you want to compare within the same run.
Common flawed logic: Run1: A – baseline Run2: B – baseline
“A – 0 was significant, B – 0 was not, Area X is activated by A more than B”
How long should a run be?• Short enough that the subject can remain comfortable without moving or swallowing• Long enough that you’re not wasting a lot of time restarting the scanner• My ideal is ~6 ± 2 minutes
Options for Block Design SequencesThat design was only one of many possibilities. Let’s consider some of the other options and the pros and cons of each.
Let’s assume we want to have an LO localizerWe need at least two conditions:
but we could consider including a third condition
Let’s assume that in all cases we need 2 sec/volume to cover the range of slices we require
Let’s also assume a total run duration of 136 volumes (x 2 sec = 272 sec = 4 min, 16 sec
Alternation every 4 sec (2 volumes)• signal amplitude is weakened by HRF because signal doesn’t have enough time to return to baseline• not to far from range of breathing frequency (every 4-10 sec) could lead to respiratory artifacts• if design is a task manipulation, subject is constantly changing tasks, gets confused
4 sec stimuli (2 volumes) with 8 sec (4 volumes) baseline• we’ve gained back most of the HRF-based amplitude loss but the other problems still remain• now we’re spending most of our time sampling the baseline
Alternation Every 68 sec (34 volumes)• more noise at low frequencies• linear trend confound• subject will get bored• very few repetitions – hard to do eyeball test of significance
Every 16 sec (8 volumes)• allows enough time for signal to oscillate fully• not near artifact frequencies• enough repetitions to see cycles by eye• a reasonable time for subjects to keep doing the same thing
• If you start and end with a baseline condition, you’re less likely to lose information with linear trend removal and you can use the last epoch in an event related average
But I have 4 conditions to compare!Here are a couple of options.
A. Orderly progressionPro: SimpleCon: May be some confounds (e.g., linear trend if you predict green&blue > pink&yellow)
B. Random order in each runPro: order effects should average outCon: pain to make various protocols, no possibility to average all data into one time course, many frequencies involved
C. Kanwisher lab clustered design• sets of four main condition epochs separated by baseline epochs• each main condition appears at each location in sequence of four• two counterbalanced orders (1st half of first order same as 2nd half of second order and vice versa) – can even rearrange data from 2nd order to allow averaging with 1st order
Pro: spends most of your n on key conditions, provides more repetitionsCon: not great for event-related averaging because orders are not balanced (e.g., in top order, blue is preceded by the baseline 1X, by green 2X, by yellow 1X and by pink 0X.
As you can imagine, the more conditions you try to shove in a run, the thornier ordering issues are and the fewer n you have for each condition.
Prepare Well: Experiments• test all equipment in advance• test software under realistic circumstances (same computer, timing and
duration as fMRI experiments)
• make sure you know all of the parameters the technician will want (e.g., pulse sequence, timing, slices and orientation)
• at RRI, prepare a spreadsheet with mouseclicks and stopwatch times• check the timing as you go, especially at the beginning of an experiment
• keep accurate log notes as you go• check with the technician regularly to ensure that your log notes record
the same run number as the scanner• attach your timing spreadsheet to the log notes for that subject• write down any problems that arose (e.g., “subject missed second last
trial”; “subject drowsy through first ~third of run”)
• move data to secure location as soon as possible• save one backup in the rawest form possible
– if advances in reconstruction occur, you will need unprocessed data to use them
• save other backups at natural points (e.g., backup and delete 2D data once you’ve made 3D data)– have redundancy– don’t put all backups on the same CD/DVD or you’re toast if one is
damaged (CDs aren’t forever like we once thought)
• save full projects to one DVD (or HD partition) once you’re done so you can reload an entire project if you need to reanalyze
• ask a stupid question– e.g., “I wonder what lights up for nose picking vs. rest”
• compare poorly-defined conditions that differ in many respects• use a paradigm from another technique (e.g., cognitive psychology)
without optimizing any of the timing for fMRI, e.g., 1 minute epochs• be naively optimistic
– go straight for the “whipped cream” experiment without starting with a “sledgehammer” experiment
• never look at raw data, time courses or individual data, just plunk it all into one big stat model and look at what comes out
• publish a long list of activated foci in every possible comparison• don’t use any statistical corrections• write a long discussion on why your task activates the subcortico-