Distinct Theta-gamma network reorganization differentiates hippocampal sclerosis and MRI-negative mesial temporal lobe epilepsy.

INTRODUCTION Temporal lobe epilepsy (TLE), particularly mesial temporal lobe epilepsy (MTLE), often presents with visual working memory (VWM) impairments, with potential heterogeneity between hippocampal sclerosis (HS) and MRI-negative subtypes. However, task-related electrophysiological (EEG) evidence regarding brain network alterations during VWM processing in MTLE remains limited. This study aims to identify shared brain network alterations and their behavioral correlates in patients with MTLE and to further characterize subtype-specific differences between HS-MTLE and MRI negative-MTLE.

Methods

We recruited 60 right-handed participants, including 30 patients with MTLE (12 HS-MTLE, 18 MRI negative-MTLE) and 30 healthy controls (HCs). All participants completed the Chinese version of the Wechsler Memory Scale-Revised (WMS-RC) and performed a VWM task during simultaneous EEG recording. Graph theory analysis was used to assess the in-degree and out-degree of directed functional networks in the theta and gamma frequency bands; the results were correlated with clinical and cognitive behavioral indicators.

Results

Behaviorally, patients with MTLE showed significant VWM impairments compared with HCs, with no significant difference between HS and MRI-negative subtypes. Common network alterations in patients with MTLE included decreased theta-band connectivity from occipital to temporal regions, with this theta-band connectivity significantly associated with slower task responses and reduced accuracy. In subgroup analysis, the HS-MTLE group showed reduced theta outflow and abnormally enhanced gamma activity in posterior occipital regions. Conversely, the MRI negative-MTLE group showed more widespread increases in gamma-band in-degree and out-degree across anterior regions, including prefrontal, frontocentral, and temporal areas.

Conclusion

Patients with MTLE share a common alteration in occipital-to-temporal information transfer during VWM. Exploratory analyses suggest distinct network alterations between HS-MTLE and MRI negative-MTLE, presenting with abnormalities in posterior and anterior networks, respectively. These hypothesis-generating findings provide electrophysiological evidence to support precise subtyping of MTLE and targeted cognitive intervention development.