Integrating polyspikes and excitability markers for epileptic network identification

Epilepsy is increasingly recognized as a disorder of distributed brain networks rather than a disease arising from a single seizure focus. Although clinical practice remains centered on localization of the seizure onset zone (SOZ), persistent seizures following apparently successful resection suggest that epileptogenic activity is often supported by broader networks of interconnected regions. A major challenge for both surgical and neuromodulatory treatment is identifying not only where seizures occur, but also which connected brain structures are components of a network that may underlie the generation of seizures. Here, we propose network excitability mapping as a translational framework for characterizing epileptic networks. In this view, epileptic networks can be described along two complementary dimensions: 1) local excitability and 2) network recruitment. We highlight evidence that the aperiodic (1/f) slope of field-potential recordings provides a mechanistically grounded measure of local excitability, while polyspike structure can reflect the degree to which epileptiform activity recruits distributed network nodes. Recent studies, and preliminary data presented here, combining electrophysiology, calcium imaging, and computational modeling suggest that these measures capture distinct but related aspects of epileptic network function. Together, these approaches support a shift from SOZ-based paradigms toward functional mapping of epileptic networks. We argue that combining measures of excitability and recruitment may enable construction of individualized excitability maps capable of informing surgical planning, optimizing neurostimulation, and improving seizure control. Establishing translational biomarkers of network engagement will be critical for advancing precision therapies in epilepsy.