HST 583 fMRI DATA ANALYSIS AND ACQUISITION Neural Signal Processing for Functional Neuroimaging Neuroscience Statistics Research Laboratory Massachusetts General Hospital Harvard Medical School/MIT Division of Health, Sciences and Technology HST.583: Functional Magnetic Resonance Imaging: Data Acquisition and Analysis Harvard-MIT Division of Health Sciences and Technology Dr. Emery Brown Outline • Spatial Temporal Scales of Neurophysiologic Measurements • Neural Signal Processing for fMRI • Signal Processing for EEG in the fMRI Scanner • Combined EEG/fMRI • Conclusion THE STATISTICAL PARADIGM (Box, Tukey) Question Preliminary Data (Exploration Data Analysis) Models Experiment (Confirmatory Analysis) Model Fit Goodness-of-fit not satisfactory Assessment Satisfactory Make an Inference Make a Decision Spatio-Temporal Scales EEG + fMRI Neurons Kandel, Schwartz & Jessell Action Potentials (Spike Trains) Neuron Stimuli 2. SIGNAL PROCESSING for fMRI DATA ANALYSIS Question: Can we construct an accurate statistical model to describe the spatial temporal patterns of activation in fMRI images from visual and motor cortices during combined motor and visual tasks? (Purdon et al., 2001; Solo et al., 2001) What Makes Up An fMRI Signal? Hemodynamic Response/MR Physics i) stimulus paradigm a) event-related b) block ii) blood flow iii) blood volume iv) hemoglobin and deoxy hemoglobin content Noise Stochastic i) physiologic ii) scanner noise Systematic i) motion artifact ii) drift iii) [distortion] iv) [registration], [susceptibility] Physiologic Response Model: Block Design Physiologic Model: Event-Related Design Physiologic Response: Flow,Volume and Interaction Models Volume Term Flow Term 1 1 0.5 0.5 0 0 20 40 60 80 100 120 0 0 fa=1 Interaction Term 120 100 80 60 40 20 fb=-0.5 1 Modeled BOLD Signal fc=0.2 0.5 0.6 0.4 0 0 20 40 60 80 100 120 0.2 0 -0.2 0 20 40 60 80 100 120 Scanner and Physiologic Noise Models fMRI Time Series Model Baseline Activation Drift AR(1)+White xP (t ) = mP + bPt + sP (t ) + vP (t ) Activation Model t = time, P = spatial location sP ( t - Dp ) = (baseO2 +Blood O2IR ∗stimulus) × (basevol +Blood volumeIR ∗stimulus) Correlated Noise Model Pixelwise Activation Confidence Intervals for the Slice β − 2σ β β β + 2σ β Signal Processing for EEG in the fMRI Scanner How can we remove the artefacts from EEG signals recorded simultaneously with fMRI measurements? (Bonmassar et al. 2002) Ballistocardiogram Noise Outside Magnet 150 EEG signal (uV) 100 50 0 -50 -100 -150 0 1 2 3 4 5 Time (sec) 6 7 8 9 10 4 5 Time (sec) 6 7 8 9 10 Inside Magnet 150 EEG Signal (uV) 100 50 0 -50 -100 -150 0 1 2 3 Faraday’s Induced Noise ∂φ v B ε=N— ∂t • A Fundamental Physical Problem w/ EEG/fMRI: – Motion of the EEG electrodes and leads generates noise currents! • Machine Motion – helium pump, vibration of table, ventilation system • Physiological Motion – heart beat (ballistocardiogram), breathing, subject motion Noise vs. Signal... The Noise: • Ballistocardiogram: >150 µV @ 1.5T in many cases • Motion: > 200 µV @ 1.5T The Signal: • ERPs: < 10 µV, reject epochs if > 50 µV • Alpha waves: < 100 µV Adaptive Filtering • Use a motion sensor to measure the ballistocardiogram and head motion – Place near temporal artery to pick up ballistocardiogram • Use motion signal to remove induced noise Adaptive Filter Algorithm • Observed signal y (t ) = s (t ) + n(t ) Induced noise True underlying EEG • Linear time-varying FIR model for induced noise N −1 n(t ) = ∑ w (k )m(t − k ) t k =0 FIR kernel Motion sensor signal Data • 5 subjects • Alpha waves – 10 seconds eyes open, 20 seconds eyes closed over 3 minutes • Visual Evoked Potentials (VEPs) • Motion – Head-nod once per 7-10 seconds for 5 minutes – Added simulated epileptic spikes Results: Alpha Waves Results: Alpha Waves Outside Magnet Results: Alpha Waves 35 35 30 30 25 25 Frequency (Hz) Frequency (Hz) Eyes Closed Eyes Open 20 15 20 15 10 10 5 5 0 0 20 40 Time (sec) 60 80 Before Adaptive Filtering 0 0 20 40 Time (sec) 60 80 After Adaptive Filtering COMBINED EEG/fMRI What are the advantages to combining EEG and fMRI?( Liu, Belliveau and Dale 1998) Combined EEG/fMRI • Combines high temporal resolution of EEG with high spatial resolution of fMRI • Applications – – – – Event related potentials EEG-Triggered fMRI of Epilepsy Sleep Anesthesia EEG trigger fMRI trigger Stimulus Presentation The Sequence used in Simultaneous EEG/fMRI 15 sec of 4-8 Hz Checkerboard Reversal 15 sec of fixation 15 sec of 4-8 Hz Checkerboard Reversal EEG/VEP Window 30 sec fMRI Window 30 sec 100 msec 15 sec of fixation TO RT Time Combining EEG and fMRI • (A) fMRI regions of activation for 2 subjects. The fMRI activity was consistently localized to the posterior portion of the calcarine sulcus. • (B) Anatomically constrained EEG (aEEG). The cortical activity was localized along the entire length of the calcarine sulcus. • (C) Combined EEG/fMRI (fEEG). The localizations are similar to the fMRI results and considerably more focal than the unconstrained EEG localizations Spatiotemporal Dynamics of Brain Activity following visual stimulation Cortical activations changes over time • Seven snapshots of the cortical activity movie, without and with fMRI constraint. • The peaks of activity occur at the same time for both the EEG (alone) localization and the fMRI constrained localization. • Spatial extent of the fMRI constrained EEG localization is more focal than the results based on EEG measurements alone. Conclusion • Well Poised Question • Careful Experimental Design/Measurement Techniques • Signal Processing Analysis Is An Important Feature of Experimental Design, Data Acquisition and Analysis. • Data Analysis Should Be Carried Out Within the Statistical Paradigm.