Localization of ictal fear and related brain network

Ictal fear (IF) is a common psychiatric manifestation in focal epilepsy, yet its electrophysiological mechanisms and associated brain networks remain poorly understood. Existing models are largely extrapolated from canonical fear-processing frameworks rather than direct intracranial evidence.

We retrospectively analyzed stereo-electroencephalography (SEEG) recordings from patients with drug-resistant epilepsy who exhibited clinically and electrophysiologically confirmed IF. Epileptogenicity Index (EI) analysis was used to classify brain regions into epileptogenic, propagation, and non-involved zones. Functional connectivity was quantified using a nonlinear regression coefficient (h²) across full frequency band and frequency-specific signals, aligned to IF onset.

6 patients met the inclusion criteria, contributing a total of 44 seizures, including 24 IF(+) and 20 IF(-) events. IF(+) seizures consistently involved the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and hippocampus, despite heterogeneous epileptogenic origins. Compared with IF(-) seizures, IF(+) seizures exhibited significantly increased functional connectivity within a distributed brain network. The most prominent between-group differences were observed in theta/alpha bands, particularly characterized by enhanced hippocampus-anterior cingulate and related interactions. In contrast, connectivity differences in gamma band were predominantly confined to frontal networks.

These findings delineate the regional and network-level electrophysiological features associated with IF. IF is not attributable to a single anatomical substrate but is instead linked to abnormal engagement of distributed limbic-prefrontal networks, with a core connectivity pattern centered on hippocampus-anterior cingulate interactions. Adopting a network-based perspective may facilitate individualized clinical interpretation of IF and provide broader insights into pathological fear states beyond epilepsy.