Advantages and disadvantages of a fast fMRI sequence in the context of EEG–fMRI investigation of epilepsy patients: A realistic simulation study

Abstract

EEG–fMRI is an established technique to allow mapping BOLD changes in response to interictal discharges recorded in the EEG of epilepsy patients. Traditional fMRI experiments rely on an echo planar imaging (EPI) sequence with a time resolution given by its time-to-repetition (TR) of ~2s. Recently, multiple fast fMRI sequences have been developed to get around the limited temporal resolution of the EPI sequence, and achieved a TR in the 100ms range or lower. One such sequence is called Magnetic Resonance EncephaloGraphy (MREG). Its high temporal resolution should offer increased detection sensitivity and statistical power in the context of epilepsy studies and in fMRI experiments in general. The aim of this work was to investigate the advantages and disadvantages offered by MREG. This was done by superimposing artificial event-related BOLD responses on EPI and MREG background signals, from 5 epileptic patients, that were free of epileptic discharges (spikes) on simultaneously recorded EEG. These functional datasets simulated different spiking rates and hemodynamic response amplitudes, and were analyzed with the commonly used General Linear Model (GLM) with the canonical hemodynamic response function (HRF) as a fixed model of the response. Robustness to violation of the assumptions of the GLM was additionally assessed with similar simulations using variable spike-to-spike response amplitudes and 8 non-canonical HRFs. Consistent with previous work, MREG yields higher maximum statistical t-values than EPI, but our simulations showed these statistics to be inflated, as the false positive rate at a standard threshold was high. At thresholds set to appropriately control specificity, EPI showed better true positive rate and larger cluster size than MREG. However, the lack of an appropriate calibration of the amplitude of the responses across the sequences precludes definitive judgment on their relative sensitivity. In addition, we show that a mismatch between the assumed and actual HRF impairs more MREG detection performance, but that EPI is more affected by non-modeled spike-to-spike variations of response amplitude. Filtering-out physiological noise, which is not aliased at the fast sampling rate of MREG, and the modeling of temporal autocorrelation are advantageous in increasing the detection power of MREG. This simulation study 1) warrants care when interpreting statistical t-values from fast fMRI sequences, 2) proposes thresholds for valid inferences and processing methods for maximal sensitivities, and 3) demonstrates the relative robustness/susceptibility of MREG and EPI to violation of the GLM's assumptions.