White matter signals reflect information transmission between brain regions during seizures

The brain’s white matter is a dynamic and active tissue which coordinates brain function through the transmission and modulation of information between regions via action potentials. While scientific and clinical interest in studying white matter via diffusion imaging has grown rapidly, an electrophysiologic understanding of white matter in healthy and disease states remains elusive. And although human white matter recordings are acquired in intracranial EEG studies in epilepsy, clinical evaluation typically focuses on gray matter structures to understand seizure generation and plan surgical intervention despite the role of white matter in coordinating and propagating epileptic activity. Here, we study white matter recordings in 29 patients with drug-resistant epilepsy who underwent stereo EEG for surgical evaluation. We elucidate properties of both electrical activity and network connectivity within white matter and its relationship to cortical connectivity. We further integrate tractography and stereo EEG recordings to demonstrate that our observed white matter dynamics reflect underlying structural connectivity patterns between gray matter structures, emphasizing white matter’s role in information transmission during seizures. Finally, we find that increased white matter connectivity to the presumed seizure onset zone is associated with poor surgical outcome after epilepsy surgery. Our findings support the ‘The Distributed Epileptic Network Hypothesis’, which states that the true seizure onset zone is not a single focal anatomical location per se (in some cases), but rather a distributed epileptic network where many brain regions interact together, allowing a patient to enter a seizure state. Therefore, we propose that white matter electrophysiology and connectivity may represent information on the spatial distribution of epilepsy and thus its amenability to intervention, whether through focal ablation or modulation through devices. Overall, white matter functional recordings may provide a wealth of currently untapped knowledge about the neurobiology of disease and could guide clinical decision making in treating drug-resistant epilepsy patients.