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. 2025 Jun;66(6):1945-1958.
doi: 10.1111/epi.18317. Epub 2025 Feb 18.

Differential functional connectivity of amygdala in drug-resistant temporal lobe epilepsy

Thandar Aung  1 , Lilly W Tang  1   2 , Jonathan Ho  1   2 , Luke C Henry  2 , Naoki Ikegaya  2   3 , Michel Modo  4   5 , Jorge Gonzalez Martinez  2
Affiliations

Differential functional connectivity of amygdala in drug-resistant temporal lobe epilepsy

Thandar Aung et al. Epilepsia. 2025 Jun.

Abstract

Objective: Recent studies highlight the amygdala's crucial role in temporal lobe epilepsy (TLE), particularly in magnetic resonance imaging-negative cases and new TLE subtypes with structural amygdala changes. This study aims to investigate the electrophysiological properties and connectivity patterns of the amygdaloid complex in TLE patients using stereoelectroencephalography (SEEG).

Methods: From March 2020 to December 2023, we collected data from nine patients with drug-resistant TLE who underwent SEEG with dual amygdala trajectories: dorsal amygdala (DA) targeting medial and central nuclei, and ventral amygdala (VA) targeting basal and lateral nuclei. We analyzed interictal and ictal activities, focusing on power spectral density, interictal epileptiform discharges (IEDs), and coherence between DA and VA regions and ipsilateral regions of the temporal-limbic network, including the hippocampus, superior temporal gyrus, entorhinal cortex, fusiform gyrus, orbitofrontal cortex, temporal pole, and ventral insula.

Results: IEDs were significantly higher in the DA, particularly in patients with epileptogenic zones involving the amygdala. We identified frequency-dependent connectivity patterns between DA and VA with ipsilateral cortical areas of interest during ictal activity. The VA exhibited higher connectivity with the limbic network in a greater number of seizures, particularly with the hippocampal head, entorhinal cortex, fusiform gyrus, and temporal pole in delta and theta frequencies. In contrast, DA connectivity was mainly confined to the hippocampus in theta and high-gamma frequency ranges.

Significance: Our findings reveal distinct functional connectivity patterns and potentially divergent roles of DA and VA in TLE. These insights could refine intracranial sampling protocols of the amygdaloid complex, guiding more precise strategies for resection and neuromodulation in TLE patients.

Keywords: amygdala; coherence; connectivity; epilepsy surgery; temporal lobe epilepsy; time–frequency analysis.

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