Thalamocortical network dynamics in focal epilepsy: SEEG investigation

Abstract

Thalamic neuromodulation is clinically effective in drug{-}resistant epilepsy, suggesting critical contributions of the thalamus to the epileptogenic process. However, the underlying electrophysiologic mechanisms remain poorly characterized. Converging evidence implicates the thalamus in shaping large{-}scale functional interactions across the cortex. We hypothesized that ictal changes in thalamic activity track cortical network dynamics associated with seizure propagation. We analyzed stereo{-}electroencephalography recordings from 16 patients with focal epilepsy (255 seizures) with simultaneous sampling of the thalamus (anterior nucleus, N=14; pulvinar, N=11) and cortex. Cortical regions of interest included the seizure onset zone (SOZ), surrounding cortices (near{-}SOZ), and control regions from the contralateral hemisphere. We characterized seizure dynamics across spatial scales, from local activity within each region to network{-}level, inter{-}regional interactions. Local activity was decomposed into its periodic (oscillatory) and aperiodic components. Network interactions were characterized by directed functional connectivity computed with a multivariate method. Seizures were associated with increased broadband power (a proxy for neuronal population firing rates) and low{-}frequency rhythmic activity across the thalamocortical network relative to interictal baseline levels. In contrast, consistent changes in aperiodic slope (a putative marker of excitation{-}inhibition balance) were specific to the thalamus, which showed an early and sustained steepening (i.e., more negative slope). While local rhythms were heterogeneous across the canonical frequency bands, inter{-}regional interactions predominantly involved the beta band (13{-}30 Hz). Shortly after onset, both forward outflow from SOZ to near{-}SOZ and feedback inflow in the reverse direction were increased. These bidirectional effects were expressed via both a direct cortico{-}cortical pathway and an indirect transthalamic route, operating in parallel. These dynamics were further stratified based on seizure subtypes, leveraging the fact that there was minimal propagation of ictal activity to the near{-}SOZ in subclinical seizures. The ictal drop in thalamic aperiodic slope was primarily observed in clinical seizures. At the network level, whereas SOZ[->]near{-}SOZ outflow was present across seizure types, reverse feedback was particularly enhanced in clinical seizures. Multivariable regression showed that the degree of thalamic slope steepening uniquely tracked seizure{-}to{-}seizure fluctuations in the strength of near{-} SOZ[->]SOZ feedback, and further predicted seizure durations. Together these findings highlight thalamic aperiodic slope as an index of cortical network dynamics linked to seizure propagation, with potential clinical utility for further development of physiology{-}informed precision neuromodulation.