Gamma network topology and pathological changes in drug-resistant temporal lobe epilepsy with cognitive deficits

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy, frequently accompanied with cognitive deficits. The present study aims to investigate functional network alterations affected by cognitive impairments in drug-resistant TLE. Patients with drug-resistant TLE were divided into normal cognition (NC) and abnormal cognition (AC) groups based on their primary medical history and completed the Wechsler intelligence scale. Thirty-one patients in the NC group and 30 in the AC group had mean intelligence quotients (IQ) of 107 (96-137) and 71 (60-85), respectively. Eighteen controls were enrolled in the study. Graph theory analysis showed decreased alpha small world index (SWI) in the AC group compared to that in the NC group and controls. Increased SWI in the fast rhythm was observed in both TLE groups compared with controls. But the gamma SWI in the AC group declined and was significantly lower than in the NC group at 50–70 Hz. A lower IQ is associated with a decreased SWI in alpha and 50-70Hz. Spectral analysis revealed reduced alpha power and increased delta power in the TLE groups compared to the controls. Immunofluorescence analysis revealed more severe amyloid-β (Aβ) and phosphorylated Tau (p-Tau) loads in the resected hippocampus of the AC group than that of NC group. Cognitive deficits in drug-resistant TLE are associated with general EEG activity slowing, loss of efficiency in gamma connectivity, and increased Aβ and p-Tau expression. These alterations are potential markers and intervention targets for concomitant cognitive decline in drug-resistant epilepsy.