Frequency-specific network changes in mesial temporal lobe epilepsy: Analysis of chronic and transient dysfunctions in the temporo-amygdala-orbitofrontal network using magnetoencephalography

Objective: Mesial temporal lobe epilepsy (MTLE) is associated with disruptions in the temporo-amygdala-orbitofrontal (TAO) network, a key component of the limbic system. We aimed to investigate TAO network alterations in patients with MTLE using magnetoencephalography (MEG), which overcomes susceptibility artifacts that limit functional MRI analysis of the orbitofrontal cortex. Methods: Nine seizure-free patients with MTLE post-temporal lobectomy and nine age- and sex-matched healthy controls were recruited. Preoperative MEG data were collected and segmented into frequency bands ranging from delta to ripple to assess functional connectivity (FC) between the bilateral hippocampi and TAO network. Results: Patients with MTLE exhibited increased FC between the affected hippocampus and amygdala across all frequency bands. Additionally, FC between the affected hippocampus and the medial prefrontal cortex (mPFC), orbitofrontal gyrus (OFG), and amygdala was elevated in the gamma and ripple bands compared with healthy controls. Conversely, FC between the healthy hippocampus and mPFC decreased in the alpha and beta bands. Furthermore, FC within the TAO network fluctuated before and after epileptic spikes; there was a decrease in the delta band between the bilateral hippocampi and the amygdala, OFG, and thalamus, whereas FC between the hippocampus and mPFC increased in the alpha, beta, and ripple bands. Significance: These findings suggest the formation of an abnormal network involving the affected hippocampus and the TAO network, particularly in the gamma-ripple bands, indicating epilepsy-induced network disruptions. Reduced FC in the healthy hippocampus and the TAO network may reflect frontal lobe dysfunction related to emotion and cognition. Additionally, both chronic and transient FC changes observed via MEG may contribute to the cognitive and psychiatric impairments experienced by patients with MTLE. This study highlights the significance of frequency-specific network alterations in understanding MTLE's pathophysiology and its impact on limbic system functions. Plain language summary: In mesial temporal lobe epilepsy, there may be abnormal connectivity between the hippocampus and the limbic system, which is involved in memory, cognition, and emotion. The changes in connectivity observed using magnetoencephalography may be implicated in cognitive and psychiatric problems experienced by patients with mesial temporal lobe epilepsy. Examining disruptions in the connectivity across brain regions in relation to epileptic activity could further the understanding of the pathophysiology of this debilitating condition and its impact on behavioral and emotional functions, among others.