Year: 2024
Type: preprint
Abstract: There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory. Using computational modeling, we linked this observation to transient saturation block as a precursor to seizure invasion, as supported by multiple lines of evidence in the patient data. We propose that transient blocking of inhibitory firing due to selective fast-spiking interneuron saturation—resulting from intense excitatory synaptic drive—is a novel mechanism that contributes to inhibitory failure, allowing seizure propagation.
Source: medRxiv
Authors: Edward M. Merricks, Sarita S. Deshpande, Alexander H. Agopyan-Miu, Elliot H. Smith, Emily D. Schlafly, Guy M. McKhann, Robert R. Goodman, Sameer A. Sheth, Bradley Greger, Paul A. House, Emad N. Eskandar, Joseph R. Madsen, Sydney S. Cash, Andrew J. Trevelyan, Wim van Drongelen, Catherine A. Schevon
Institutions: Columbia University Irving Medical Center, University of Chicago, University of Utah, Boston University, Hackensack Meridian School of Medicine, Baylor College of Medicine, Arizona State University, Intermountain Healthcare, Intermountain Medical Center, Montefiore Medical Center, Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, Newcastle University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4391246498