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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Hemodynamic Response Model TR (~2sec) Time-to-Peak (~6sec) Dispersion Undershoot Equilibrium (~16-32sec) Delay (~1-2sec)

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

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HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve Blood Oxygen Level Dependence (BOLD) Neurons Lungs OxygenCO2 Oxygenated Hemoglobin (DiaMagnetic) Deoxygenated Hemoglobin (ParaMagnetic)

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

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

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

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HST583: Statistical Signal Processing for fMRI -- Douglas N. Greve Final Results: Tables List of active regions Cluster Number TalX (mm) TalY (mm) TalZ (mm) Volume (mm^3) Sig (log10) 1-30.513.20.2125.65.7 24.59.7-20.2878.14.1 32.9-18.017.7400.33.2

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

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