Thalamic connectivity mirrors spatial maps of network dysfunction in nonlesional focal epilepsy

Focal epilepsy is increasingly conceptualized as a network disorder, yet the extent to which network dysfunction reflects a shared phenotype remains unknown. Spatially conserved patterns of network dysfunction may implicate a centralized mechanism underlying widespread impairment. Here, we investigate whether network connectivity disruptions are spatially similar across temporal lobe and extra-temporal lobe epilepsy cohorts and whether shared dysfunction aligns with thalamic connectivity profiles.

We retrospectively analyzed resting-state magnetoencephalographic imaging from 71 individuals with nonlesional, drug-resistant focal epilepsy (n = 45 temporal, n = 26 extratemporal), collected between 2014 and 2023, and healthy controls (n = 18). Source reconstructed time series were bandpass filtered, and long-range functional connectivity was quantified using imaginary coherence. Network disturbance maps were computed as T-score maps, comparing functional connectivity in epilepsy cohorts to controls, across topographical parcels and frequency bands. Spatial similarity of temporal and extratemporal network dysfunction maps were assessed using Pearson correlations. To infer thalamic involvement, shared network dysfunction maps were correlated with normative functional magnetic resonance imaging-derived thalamocortical connectivity profiles.

Extra-temporal lobe epilepsy demonstrated reduced global network connectivity relative to controls in the delta (p = .012), alpha (p = .034), and gamma (p < .001) frequency bands. Across all frequencies, the spatial patterns of network disturbances between temporal and extratemporal cohorts were significantly correlated (r = .287-.717, all p < .001), indicating a shared network dysfunction. Shared spatial maps of network dysfunction correlated with normative thalamocortical connectivity profiles, with significant correlations in the anterior, pulvinar, and dorsomedial thalamus.

Nonlesional focal epilepsy exhibits a common, frequency-dependent pattern of cortical network dysfunction that is spatially aligned with thalamic connectivity, supporting a thalamic hub contribution to widespread network impairment.