Thalamocortical connectivity and nucleus-specific thalamic dysfunction in temporal lobe epilepsy: an integrative review.

Abstract

Temporal lobe epilepsy (TLE) is increasingly recognized as a distributed network disorder extending beyond mesial temporal structures. Among the brain regions implicated in epileptic network organization, the thalamus has emerged as a key hub due to its extensive structural and functional connections with cortical, limbic, and subcortical systems.This integrative review aimed to synthesize current evidence regarding nucleus-specific thalamic abnormalities and thalamocortical connectivity alterations in TLE.A literature search was conducted following PRISMA guidelines using PubMed and Google Scholar databases. Twenty-eight studies were included in the qualitative synthesis, with nineteen studies providing detailed nucleus-specific structural, functional, or electrophysiological characterization of thalamic involvement.Across structural MRI, diffusion imaging, resting-state functional MRI, magnetoencephalography, and stereo-electroencephalography studies, convergent evidence indicated preferential involvement of the anterior thalamic nucleus (ANT), mediodorsal nucleus (MD), pulvinar, and intralaminar nuclei. TLE with mesial temporal sclerosis generally exhibited more extensive thalamic atrophy and thalamotemporal disconnection, whereas MRI-negative TLE showed more heterogeneous functional and network-level abnormalities. Electrophysiological studies demonstrated dynamic thalamic participation in seizure propagation and network synchronization, supporting an active role of thalamic nuclei in epileptic processes. Emerging longitudinal evidence further suggests that thalamocortical networks may undergo postoperative reorganization following successful epilepsy surgery.Overall, the available evidence supports a transition from a predominantly hippocampocentric framework toward a distributed thalamocortical network model of TLE. Nucleus-specific thalamic dysfunction appears to contribute to seizure propagation, cognitive impairment, and large-scale network dysregulation, highlighting the importance of multimodal approaches for understanding epileptic network organization.