Local structural connectivity directs seizure spread in focal epilepsy

How does the human brain9s structural scaffold give rise to its intricate functional dynamics? This is a central challenge in translational neuroscience, particularly in epilepsy, a disorder that affects over 50 million people worldwide. Treatment for medication-resistant focal epilepsy is often structural - through surgery, devices or focal laser ablation - but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG (iEEG). Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and iEEG, across preictal and ictal periods in 45 seizures from 9 patients with unilateral drug-resistant focal epilepsy. We use High Angular Resolution Diffusion Imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered iEEG. Across all frequency bands, we find significant increases in structure-function coupling from preictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are stereotyped, and a function of each patient9s individual anatomy. These results suggest that seizures harness the underlying structural connectome as they propagate. Our findings suggest that the relationship between structural and functional connectivity in epilepsy may inform current and new therapies to map and alter seizure spread, and pave the way for better-targeted, patient-specific interventions.