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http://www.sph.umich.edu/~nichols
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Outline
• Data Modeling
– General Linear Model
– Linear Model Predictors
– Temporal Autocorrelation
– Random Effects Models
• Statistical Inference
– Statistic Images & Hypothesis Testing
– Multiple Testing Problem
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Basic fMRI Example
• Data at one
voxel
– Rest vs.
passive
word
listening
• Is there an
effect?
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A Linear Model
• “Linear” in
parameters
β1 & β2
error
Time
= β1 + β2 +
Intensity x1 x2 ε
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Linear model, in image form…
= β1 + β2 +
Y = β1 x1 + β 2 x2 + ε 6
Linear model, in image form…
Estimated
= β̂1 + β̂ 2 +
Y = βˆ1 x1 + ˆ
β 2 x2 + εˆ 7
… in image matrix form…
βˆ1
= × ˆ +
β 2
Y = X × β̂ + εˆ 8
… in matrix form.
1 p 1 1
Y = Xβ + ε
β
p
Y = X + ε
N N N
N: Number of scans, p: Number of regressors 9
Linear Model Predictors
• Signal Predictors
– Block designs
– Event-related responses
• Nuisance Predictors
– Drift
– Regression parameters
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Signal Predictors
• Linear Time-Invariant system
Blocks
• LTI specified solely by
– Stimulus function of Events
experiment
– Hemodynamic Response
Function (HRF)
• Response to instantaneous
impulse 11
Convolution Block Design Event-Related
Examples
Experimental
Stimulus
Function
Hemodynamic
Response
Function
Predicted
Response
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HRF Models
• Canonical HRF
– Most sensitive
if it is correct
– If wrong, leads to
bias and/or poor fit
• E.g. True response
may be faster/slower
SPM’s HRF
• E.g. True response
may have smaller/
bigger undershoot
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HRF Models
• Smooth Basis HRFs
– More flexible
– Less interpretable
• No one parameter Gamma Basis
explains the response
– Less sensitive relative
to canonical (only
if canonical is correct)
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Fourier Basis
HRF Models
• Deconvolution
– Most flexible
• Allows any shape
• Even bizarre,
non-sensical ones
– Least sensitive relative
to canonical (again, if
canonical is correct) Deconvolution Basis
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Drift Models
• Drift
– Slowly varying
– Nuisance variability
• Models
– Linear, quadratic
– Discrete Cosine Transform
Discrete Cosine 16
Transform Basis
General Linear Model
Recap
• Fits data Y as linear combination of
predictor columns of X
Y = Xβ + ε
• Very “General”
– Correlation, ANOVA, ANCOVA, …
• Only as good as your X matrix
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Temporal Autocorrelation
• Standard statistical methods assume
independent errors
– Error εi tells you nothing about εj i ≠ j
• fMRI errors not independent
– Autocorrelation due to
– Physiological effects
– Scanner instability
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Temporal Autocorrelation
In Brief
• Independence
• Precoloring
• Prewhitening
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Autocorrelation:
Independence Model
• Ignore autocorrelation
• Leads to
– Under-estimation of variance
– Over-estimation of significance
– Too many false positives
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Autocorrelation:
Precoloring
• Temporally blur, smooth your data
– This induces more dependence!
– But we exactly know the form of the
dependence induced
– Assume that intrinsic autocorrelation is
negligible relative to smoothing
• Then we know autocorrelation exactly
• Correct GLM inferences based on “known”
autocorrelation
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[Friston, et al., “To smooth or not to smooth…” NI 12:196-208 2000]
Autocorrelation:
Prewhitening
• Statistically optimal solution
• If know true autocorrelation exactly, can
undo the dependence
– De-correlate your data, your model
– Then proceed as with independent data
• Problem is obtaining accurate estimates of
autocorrelation
– Some sort of regularization is required
• Spatial smoothing of some sort 22
Autocorrelation Redux
Advantage Disadvantage Software
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Building Statistic Images
Predictor of interest
β1
β2
β3
= β4
+
β5
β6
β7
β8
Y = X × ββ + ε
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Building Statistic Images
c’ = 1 0 0 0 0 0 0 0
• Contrast
– A linear combination
b1 b2 b3 b4 b5 ....
of parameters
– c’β
contrast of
estimated
parameters
c’b
T= T=
variance
estimate s2c’(X’X)+c
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Hypothesis Test
• So now have a value T for our statistic
• How big is big
– Is T=2 big? T=20?
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Hypothesis Testing
• Assume Null Hypothesis of no signal
T
• Given that there is no
signal, how likely
is our measured T?
• P-value measures this P-val
– Probability of obtaining T
as large or larger
∀ α level
– Acceptable false positive rate 29
Random Effects Models
• GLM has only one source of randomness
Y = Xβ + ε
– Residual error
• But people are another source of error
– Everyone activates somewhat differently…
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Distribution of
Fixed vs. each subject’s
Random effect
Effects Subj. 1
Subj. 2
• Fixed Effects
– Intra-subject Subj. 3
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Multiple Testing Problem
• Inference on statistic images
– Fit GLM at each voxel
– Create statistic images of effect
• Which of 100,000 voxels are significant?
α=0.05 ⇒ 5,000 false positives!
t > 0.5 t > 1.5 t > 2.5 t > 3.5 t > 4.5 t > 5.5 t > 6.5
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MCP Solutions:
Measuring False Positives
• Familywise Error Rate (FWER)
– Familywise Error
• Existence of one or more false positives
– FWER is probability of familywise error
• False Discovery Rate (FDR)
– R voxels declared active, V falsely so
• Observed false discovery rate: V/R
– FDR = E(V/R)
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FWER MCP Solutions
• Bonferroni
• Maximum Distribution Methods
– Random Field Theory
– Permutation
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FWER MCP Solutions
• Bonferroni
• Maximum Distribution Methods
– Random Field Theory
– Permutation
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FWER MCP Solutions:
Controlling FWER w/ Max
• FWER & distribution of maximum
FWER = P(FWE)
= P(One or more voxels ≥ u | Ho)
= P(Max voxel ≥ u | Ho)
• 100(1-α)%ile of max distn controls FWER
FWER = P(Max voxel ≥ uα | Ho) ≤ α
α 38
uα
FWER MCP Solutions:
Random Field Theory
• Euler Characteristic χu
– Topological Measure
• #blobs - #holes
Threshold
– At high thresholds, Random Field
Signal
Signal+Noise
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Control of Per Comparison Rate at 10%
11.3% 11.3% 12.5% 10.8% 11.5% 10.0% 10.7% 11.2% 10.2% 9.5%
Percentage of Null Pixels that are False Positives
FWE
Occurrence of Familywise Error
6.7% 10.4% 14.9% 9.3% 16.2% 13.8% 14.0% 10.5% 12.2% 8.7%
Percentage of Activated Pixels that are False Positives 43
Controlling FDR:
Benjamini & Hochberg
• Select desired limit q on E(FDR)
• Order p-values, p(1) ≤ p(2) ≤ ... ≤ p(V)
• Let r be largest i such that
1
p(i) ≤ i/V × q
p(i)
p-value
• Reject all hypotheses
corresponding to
p(1), ... , p(r).
i/V × q
0
0 1
i/V
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Conclusions
• Analyzing fMRI Data
– Need linear regression basics
– Lots of disk space, and time
– Watch for MTP (no fishing!)
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Thanks
• Slide help
– Stefan Keibel, Rik Henson, JB Poline, Andrew
Holmes
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