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Pathological hippocampal-cortical hypersynchronization disrupts memory in temporal lobe epilepsy: A multimodal intracranial electroencephalographic-functional magnetic resonance imaging study.

Ruxue Gong Xiaolong Peng Rebecca W. Roth Haris Rashid William Yun Daniel L. Drane Leonardo Bonilha Lisa M McTeague E. Gleichgerrcht
Aug 2026 · Epilepsia · 0 citations · 46 references
Medicine

TL;DR

The multimodal findings suggest that increased hippocampal connectivity in the epileptogenic hemisphere may reflect pathological hypersynchronization that disrupts efficient memory network coordination in TLE and highlight hippocampal connectivity as a promising candidate biomarker for characterizing individual memory outcomes.

Abstract

Objective

Memory impairment is a common comorbidity in temporal lobe epilepsy (TLE) and is thought to arise from hippocampal dysfunction and disrupted interactions within a distributed memory network involving medial temporal, frontal, and parietal cortical regions. However, the network-level mechanisms underlying memory impairment in TLE remain poorly understood. Leveraging complementary intracranial electroencephalography (iEEG) and resting-state functional magnetic resonance imaging (rsfMRI), this study aimed to investigate hippocampal network alterations associated with memory dysfunction in TLE and characterize hippocampal-cortical connectivity patterns linked to individual differences in memory performance.

Methods

This retrospective study included 29 patients with TLE who underwent structural MRI and rsfMRI, 13 of whom also underwent interictal iEEG. For each participant, 94 subject-specific regions of interest (ROIs) were generated, including 92 cortical ROIs from individualized rsfMRI parcellation and bilateral hippocampal ROIs defined using FreeSurfer subcortical segmentation. iEEG signals were projected onto these ROIs for cross-modal alignment. Hippocampal-cortical connectivity was estimated using rsfMRI functional connectivity and iEEG imaginary coherence, with hemispheres standardized relative to the epileptogenic side. Memory-related connectivity within the hippocampal network was then identified through behavioral-connectivity correlation analysis followed by Elastic Net regularization.

Results

Increased ipsilesional hippocampal-cortical alpha-band (8-12 Hz) connectivity derived from interictal iEEG was significantly correlated with worse Logical Memory performance. Consistently, rsfMRI analyses revealed a significant epileptogenic side (ipsilesional vs. contralesional) and connection type (within- vs. between-hemisphere) interaction, with stronger within-hemispheric hippocampal-cortical connectivity in the ipsilesional hemisphere. Behavioral-connectivity analyses indicate that immediate and delayed recall shared a core episodic memory architecture, but delayed recall relied more on large-scale network coordination supporting retrieval after a delay.

Significance

Our multimodal findings suggest that increased hippocampal connectivity in the epileptogenic hemisphere may reflect pathological hypersynchronization that disrupts efficient memory network coordination in TLE and highlight hippocampal connectivity as a promising candidate biomarker for characterizing individual memory outcomes.

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