Spectrally-resolved transfer entropy in resting-state SEEG reveals epileptogenic and non-epileptogenic communication in adults and children with refractory epilepsy

Abstract

Objective. To characterise directed, frequency-resolved communication between seizure onset zone (SOZ) and non-involved zone (NIZ) regions in resting-state stereo-electroencephalography (SEEG) from adults and children with drug-resistant epilepsy (DRE). Approach. We analysed retrospective SEEG from 21 adults and 18 paediatric patients who underwent focal resective surgery. Channels were grouped into four link classes (SOZ → SOZ, NIZ → SOZ, SOZ → NIZ, NIZ → NIZ). Signals were decomposed into delta, theta, alpha, beta, gamma, and broadband bands, and transfer entropy (TE) was estimated with a Gaussian estimator. For each source–target channel pair, an optimal temporal delay was selected by scanning delays from 2–200 ms and choosing the delay that maximised broadband TE. Significance testing used 100 phase-randomised surrogates per source and per target; Benjamini–Hochberg false discovery rate correction (α = 0.05) was applied within each band-to-band TE grid (separately for source- and target-surrogate p-values). Main results. In NIZ → SOZ links median communication delays were longer in adults than children (median 87.9 ms vs 68.0 ms; Mann–Whitney p < 1 × 10−10; Kolmogorov–Smirnov p < 1 × 10−10). Across most link classes, dominant source frequencies were broadband, delta, and theta. A distinct SOZ → SOZ pattern emerged: adults showed broadband, alpha, and beta source dominance with prominent broadband → gamma transfer, whereas children showed broadband, delta, and theta dominance while retaining broadband → gamma contribution. Cross-link-class source and target frequency distributions differed significantly in both cohorts (p < 0.05). While intra-regional SOZ–SOZ communication revealed unique multiplex signatures, inter-regional NIZ → SOZ interactions did not show a distinct spectral profile from non-involved connectivity. Significance. Resting-state SEEG communication in DRE exhibits multiplex, cross-frequency directed interactions. Spectrally resolved TE reveals conserved and cohort-specific shifts in SOZ-NIZ communication motifs. While these differences are confounded by pathology and site variations, they provide a frequency-specific characterization of the epileptogenic network that may support grounded interpretation of resting-state dynamics.