1. Statistical Signal Processing for fMRI
Douglas N. Greve
Mark Vangel
Anastasia Yendiki

2. Overview First-Level Univariate Analysis Signal Modeling
Nuisance Modeling
Noise Modeling
Hypothesis Testing
Correction for Multiple Comparisons
Cross-Subject/Higher Level Analysis
Lab
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

3. Analysis Goals Quantify Neural Correlates in fMRI
Amplitude of Hemodynamic Response
Delay/Shape of Hemodynamic Response
Extent/Size of Activation
Localization of function
Quantify Uncertainty
Cross-subject (within group)
Cross-group – eg, Normals, Clinical Populations
Within-subject – EEG/MEG/Optical/Surgical Planning
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

4. Challenges Large Noise – thermal, physiological, motion
Small Signal – delay, dispersion
Structural/Functional Alignment – within subject
Intersubject Alignment
Copious amounts of data – eg, 20 subjects, 5 runs per subject, 100 time points per run, 64x64x30 volume = 1.2G data points
More spatial voxels than time points (multiple comparisons problem).
Model Validation
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

5. Method Correlational – synchronized stimulus and acquistion
Linear/Gaussian Assumptions
GLM – “General” Linear Model
MSE – Minimum Square Error
LMS – Least Mean Squares
“Massively Univariate”
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

6. Hemodynamic Response (BOLD)
Time-to-Peak (~6sec)
Dispersion
TR (~2sec)
Equilibrium
(~16-32sec)
Undershoot
Delay (~1-2sec)
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

7. fMRI Noise Synthetic data.
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

8. Averaging Synthetic data.
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

9. Typical Analysis Stream
Preprocessing
“Univariate” First-Level GLM Analysis
“Univariate” Higher-Level GLM Analysis
“Multivariate” Analysis
Packages:
SPM – Statistical Parametric Mapping
AFNI – Analysis of Functional NeuroImages
FSL – fMRI Software Library
FS-FAST – FreeSurfer Functional Analysis STream
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

10. Preprocessing Slice-Timing Correction (?) Motion Correction
k-Space reconstruction
Slice-Timing Correction (?)
Motion Correction
Spatial Filtering (Smoothing - FWHM)
Intensity Normalization
Temporal Filtering (or in analysis)
Per-run, within subject
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

11. Univariate First-Level Analysis
Per-voxel, per-subject
Postulate model of the observable (ie raw time course)
Signal model (eg, hemodynamic response)
Noise model (eg, autocorrelation function)
Drift (eg, mean offset, linear, quadratic)
General Linear Model (GLM)
Parameterized
Linear (superposition)
Least-mean-square estimation of parameters
Hypothesis Test = Contrast of Parameters
Assemble into a map
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

12. Univariate High-level Analysis
Per-voxel, Cross-subject
Requires intersubject registration
Dave Kennedy
Uses information from First/Lower Levels
GLM to describe relationship
Random Effects
Fixed Effects
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

13. Multivariate Statistics
Cross-voxel (within map)
Thresholding and multiple comparisons problem
Gaussian Random Fields (GRF)
Principal Component Analysis (PCA/SVD)
Independent Component Analysis
Region-of-Interest
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

14. HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

15. Hemodynamic Response Model
Time-to-Peak (~6sec)
Dispersion
TR (~2sec)
Equilibrium
(~16-32sec)
Undershoot
Delay (~1-2sec)
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

16. Visual Activation Paradigm
Flickering
Checkerboard
Visual, Auditory, Motor, Tactile, Pain, Perceptual,
Recognition, Memory, Emotion, Reward/Punishment,
Olfactory, Taste, Gastral, Gambling, Economic, Acupuncture,
Meditation, The Pepsi Challenge, …
Scientific
Clinical
Pharmaceutical
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

17. Blood Oxygen Level Dependence (BOLD)
Neurons
Deoxygenated
Hemoglobin
(ParaMagnetic)
Oxygenated
Hemoglobin
(DiaMagnetic)
Lungs
Oxygen
CO2
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

18. Functional MRI (fMRI) Sample BOLD response in 4D
Localized
Neural
Firing
Increased
Blood Flow
Stimulus
BOLD
Changes
Sample BOLD response in 4D
Space (3D) – voxels (64x64x35, 3x3x5mm^3)
Time (1D) – time points (100, 2 sec)
Time 3 …
Time 1
Time 2
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

19. } Analysis Goals Given: raw fMRI time course and
stimulus presentation times
Compute:
Hemodynamic Response (HRF) Amplitude
HRF Confidence Interval
P-Value
Noise Amplitude }
Quantify Uncertainty
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

20. Final Results: Maps Assign values to each voxel
Display as pseudo-color images
Threshold?
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

21. Final Results: Tables List of active regions Cluster Number TalX (mm)
TalY
TalZ
Volume
(mm^3)
Sig
(log10) 1
-30.5
13.2
0.2
125.6
5.7 2
4.5
9.7
-20.2
878.1
4.1 3
2.9
-18.0
17.7
400.3
3.2
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve

22. Final Results: Waveforms
Average raw data over time and space
HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve