Abstracts

Rationale: Mesial temporal lobe epilepsy (mTLE) is the most common surgical epilepsy syndrome. Noninvasively lateralizing mTLE preoperatively may be challenging, given frequency of rapid contralateral seizure spread. Resting-state fMRI has been used to identify connectivity abnormalities in mTLE, involving mesial temporal structures and networks like default mode network (DMN). It is unclear if directed/nondirected connectivity between mesial temporal structures and resting-state networks may aid mTLE lateralization. Also, it is unknown if directionality of hippocampal connectivity abnormalities using fMRI resemble those using stereo-SEEG (SEEG) in mTLE patients.

Methods: We acquired 20 minutes of resting-state fMRI in 52 mTLE patients and 52 age/gender matched controls. In patients vs controls, we evaluated fMRI functional connectivity of bilateral hippocampi, amygdalae, and select resting-state networks (default mode, central executive, salience, visual) using non-directed Pearson correlation (Z-scored), network-based statistic (NBS), and directed dynamic causal modeling (DCM). We also acquired 2 minutes of resting-state SEEG in 17 unilateral mTLE. With SEEG, we measured hippocampal vs extrahippocampal inward partial directed coherence (PDC) strength.

Results: Right mTLE patients demonstrated reduced undirected functional connectivity (Z) between right hippocampus and DMN vs left mTLE and controls (p< 0.001,corrected,ANOVA). Similar alterations were not seen between hippocampus and other resting-state networks. In DMN, largest alterations of right hippocampal connectivity in right mTLE patients were in medial orbitofrontal, inferior parietal, and precuneus regions (p< 0.001,each,corrected,ANOVA). With mesial temporal and DMN nodes, NBS analysis (Fig.1) demonstrated the network that distinguished right vs left mTLE patients included right hippocampus/amygdala, bilateral inferior parietal, precuneus, and medial orbitofrontal, and right lateral orbitofrontal regions (9 of 14 nodes,p=0.006,corrected). With model exceedance probabilities, DCM analysis identified directed connectivity models explaining differences between right and left mTLE, revealed cross-hemispheric connectivity between hippocampi/amygdalae was inward to epileptogenic side mostly (Fig.2). This fMRI finding resembled SEEG finding, where inward connectivity was significantly higher in epileptogenic hippocampi vs other regions in right/left mTLE (p< 0.05,t-tests,corrected).