Introduction to fMRI experimental design
OR: How to plan a good study
Christiane Thiel
Biological Psychology Lab
Department of Psychology
Carl von Ossietzky Universität Oldenburg
A Reminder on Temporal and Spatial Resolution
CT
MRI
PET
fMRI
EEG
ERP
MEG
TMS
Magentic Resonance Imaging (MRI)
MRI: Brain Structure
fMRI: Brain Function
From neuronal activity to “blobs”
Neuronal activity
Stimulus
„Fancy Pictures“
From neuronal activity to “blobs”
Neuronal activity
Stimulus
Neurovascular
coupling
Hemodynamic
response
Detection by
MRI scanner
„Fancy Pictures“
Statistical
Analysis
Overview: How to plan a good study
• Different Design Types
– Categorical, factorial, parametric designs
– Blocked vs. event-related designs
• Optimizing the Design
– How many stimuli, ordering etc.
• Design and Scanning
– Timing issues
– Special case of sparse sampling
Main Message
A good design is THE most important thing
in fMRI studies
The comparison condition
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• brain has constant supply of blood and oxygen, i.e. is
always active
• In order to infer functional specialization, one needs to
compare RELATIVE differences in brain activity between
two or more conditions
•  Logic of cognitive subtraction
Cognitive Subtraction requires a pure insertion
assumption
„Motherlove“
Face processing
unkown child
Familiarity
Familiarity
Face processing
Face processing
familiar child
own child
Different Design Types
• Categorical
• Factorial designs
• Parametric designs
Analysis: Where is brain activity bigger when processing
faces as compared to houses [F-H]
Different Design Types
Factor Stimulus
uF
uH
fF
fH
Factor Familiarity
• Categorical
• Factorial designs
• Parametric designs
Analysis:
1. Factor Stimulus: e.g. where is brain activity bigger when
processing faces as compared to houses [uF+fF]-[uH+fH]
2. Factor Familiarity: e.g. where is brain activity bigger when
procesing familiar as compared to unfamiliar stimuli? [fF+fH][uF+uH]
3. Interaction: e.g. brain regions with higher activity for familiarity
only for faces [fF-uF]-[fH-uH]
Different Design Types
• Categorical
• Factorial designs
• Parametric designs
Analysis:
1. Where in thes brain does activity increase with increasing
emotionality?
Nature. 1996 Oct 31;383(6603):812-5.
A differential neural response in the human amygdala to fearful and happy facial expressions
Presentation of Stimuli
• Block Design
• Event-related Design
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Similar stimuli are grouped together
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Presentation of Stimuli
• Block Design
• Event-related Design
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Stimuli are presented randomly
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Advantages of Block and Event-related Designs
Block Design
Event-related Design
Higher statistical power
Prevents building of
expectations/cognitive sets
Better when different conditions
involve performing different
tasks
Post hoc classification of trials
possible
Enables using paradigms where
events can only be indicated by
subjects (e.g. perceptual
changes)
Enables using paradigms where
trials cannot be blocked (e.g.
oddballs)
Optimising the Design
Block Design Issues
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How long should a block be?
How many blocks do I need?
Do I need a fixation baseline?
In what order should blocks be presented?
Do subjects need breaks during scanning?
See also http://imaging.mrc-cbu.cam.ac.uk/imaging/DesignEfficiency
A frequent answer: “It depends”
How long should a block be?
The hemodynamic response function
acts as low pass filter
 Experimental variance must be
present at sufficient low frequencies to
pass
1/f power structure of noise
 Experimental variance must be
present at sufficient high frequencies to
avoid noise and the high pass filter used
in the analysis
Optimal block length: 14-20 sec, i.e. 0.036-0.025 Hz
Aguirre, GK, D'Esposito, M. in Moonen and Bandettini, "Functional MRI" Springer, 1999
How long should a block be?
How many blocks do I need?
• The more the better
! but long scanning sessions induce more motion artefacts and
fatigue in subjects!
• There is no general recommendation since it depends
very much on your experiment
• Unless you know that your effect size is high, I would not
go for less than six per condition and limit the number of
conditions
Do I need a fixation baseline?
• If you are interested in a differential contrast: NO
• If you are interested in a main effect: YES
• If you are interested in common activations: YES
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In what order should blocks be presented?
fixed
random
A-B-C-A-B-C…
C-A-B-C-B-C-C-B-A-….
Bad from a psychological point of view
Good from a psychological point of
view
Good from a view of statistical power
Bad from a view of statistical power:
distributes the variance of task
paradigm over multiple frequencies,
including low frequencies which may
be removed by high pass filter
•A compromise might be to randomize for each subject the first blocks (e.g. first
ten) and then keep this randomized order
•Think before on what blocks you would like to contrast – those which you whish
to contrast should not be presented far apart in time
Do subjects need breaks during scanning?
• Only stop scanner if this is strictly necessary (i.e.
children, older subjects who need a rest)
• Breaks
– Disrupt equilibrium (extra dummy scans)
– Reduce efficiency of temporal filtering (since the data
no longer constitutes a single time series)
– Increases movements in between sessions
Optimising the Design
Event-related Design
• How many events do I need?
• How close together should events be presented?
• Do I need a fixation baseline?
How many events do I need?
• The more the better
! but long scanning sessions induce more motion artefacts and
fatigue in subjects!
• There is no general recommendation since it depends
very much on your experiment
• I would not go for less than 20 events per condition
unless you know that your effect size is high
How close together should events be presented?
• Early event-related designs:
long Stimulus Onset
Asynchrony (SOA) to allow
BOLD response to return to
baseline  boring to subject,
long scanning times
• if the BOLD response is explicitly
modelled, overlap between successive
responses at short SOAs can be
accommodated… … particularly if
responses are assumed to superpose
linearly
• Short SOAs can be very efficient
Buckner, Human Brain Mapping 1998
How close together should events be presented?
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With randomised designs, optimal SOA for
differential effect (e.g. face-house) is
minimal SOA
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Due to nonlinearity SOA should not be less
than 2 sec.
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optimal SOA for main effect (face+house)
is 16-20s.
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Inclusion of null events (i.e. baseline)
increases efficiency for main effect with
small SOAs
Josephs and Henson 1999
2 sec
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Optimizing the Design
Design Issues: General
• How long should I scan?
• Should subjects do a task?
• How many subjects should I scan?
Optimizing the Design
How long should I scan?
The longer the better , but:
!
but long scanning sessions induce more motion artefacts and
fatigue in subjects
For healthy volunteers I would not recommend scanning sessions
longer than 30-40 minutes
For special groups (children, patients etc.) even 15 minutes can be
a challenge!
Optimizing the Design
Should subjects do a task?
General Rule: Keep subjects as busy as possible
But task requirements should be comparable across
conditions
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Bad example for a task: Press a button whenever a face is presented
Optimizing the Design
How many subjects should I scan?
reproducability
The more the better …
Depends on whether high
interindividual variability
Nowadays most cognitive
experiments aim for at least
around 20 subjects
sensitivity
Thirion et al 2007
Design and Scanning: Timing Issues
Scans
TR=4s
Stimulus (synchronous) SOA=8s
Scans
TR=4s
Stimulus (aynchronous)
SOA=6s
Sampling rate=4s
Sampling rate=2s
See also Miezin et al 2002
Design and Scanning: Sparse Sampling
TR=e.g. 10s
Scans
TA=e.g. 2s
Auditory Stimulus
For different designs see Gaab et al 2007
Indicated for auditory studies if:
-stimuli cannot be well perceived in
the presence of scanner noise
-interested mainly in neural activity in
primary auditory cortex
Krumbholz in Funktionelle MRT … Fink und Schneider 2006
Some Scanning Terminology
3 mm
3 mm
3 mm
voxel
Structural Scan/T1 Image
Area covered during fMRI measurements
25 slices, 3 mm thick, 0.75 mm gap,
In plane resolution: 3x3 mm
ascending aquisition
Some Scanning Terminology
Functional images /EPI *images
This is one volume/scan
consisting of 25 slices, it took 2
seconds to aqcuire, this is
called the TR (time of
repetition, in SPM: interscan
interval)
fMRI experiments consist of many
scans, this is called the time series,
our time series consisted of 415
scans
* Echo planar imaging – fast MR imaging sequence
How NOT to do an imaging experiment
• ask a stupid question
– e.g., “I wonder what lights up for motherlove”
• Start the experiment without any hypothesis
• compare poorly-defined conditions that differ in many respects
• use a paradigm from another area (e.g., neuropsychology, EEG) without
optimizing any of the timing for fMRI
• 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 subcorticooccipito-parieto-temporo-frontal network