Abstract

Background: Seizures and interictal spikes in mesial temporal lobe epilepsy (MTLE) affect a network of brain regions rather than a single epileptic focus. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have demonstrated a functional network in which hemodynamic changes are time-locked to spikes. However, whether this reflects the propagation of neuronal activity from a focus, or conversely the activation of a network linked to spike generation remains unknown. The functional connectivity (FC) changes prior to spikes may provide information about the connectivity changes that lead to the generation of spikes. We used EEG-fMRI to investigate FC changes immediately prior to the appearance of interictal spikes on EEG in patients with MTLE.Methods/principal findings: Fifteen patients with MTLE underwent continuous EEG-fMRI during rest. Spikes were identified on EEG and three 10 s epochs were defined relative to spike onset: spike (0–10 s), pre-spike (−10 to 0 s), and rest (−20 to −10 s, with no previous spikes in the preceding 45s). Significant spike-related activation in the hippocampus ipsilateral to the seizure focus was found compared to the pre-spike and rest epochs. The peak voxel within the hippocampus ipsilateral to the seizure focus was used as a seed region for FC analysis in the three conditions. A significant change in FC patterns was observed before the appearance of electrographic spikes. Specifically, there was significant loss of coherence between both hippocampi during the pre-spike period compared to spike and rest states.Conclusion/significance: In keeping with previous findings of abnormal inter-hemispheric hippocampal connectivity in MTLE, our findings specifically link reduced connectivity to the period immediately before spikes. This brief decoupling is consistent with a deficit in mutual (inter-hemispheric) hippocampal inhibition that may predispose to spike generation.

Highlights

  • Mesial temporal lobe epilepsy (MTLE) is the most common symptomatic focal epilepsy and is frequently associated with hippocampal sclerosis (HS), i.e., neuronal cell loss and gliosis of the hippocampus [1, 2]

  • Epileptogenic networks have been explored via single photon emission computed tomography (SPECT) [6], positron emission tomography (PET) [7], and simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (EEG-fMRI) [8]

  • FUNCTIONAL CONNECTIVITY ANALYSIS During the rest epoch, the ipsilateral hippocampus was functionally connected with the contralateral hippocampus, and the parahippocampal gyri, fusiform gyri, amygdala, and cerebellar cortex bilaterally (Figures 3Aa1,Bb1; Table 3)

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Summary

Introduction

Mesial temporal lobe epilepsy (MTLE) is the most common symptomatic focal epilepsy and is frequently associated with hippocampal sclerosis (HS), i.e., neuronal cell loss and gliosis of the hippocampus [1, 2]. EEG-fMRI studies in patients with MTLE have demonstrated widespread activation and deactivation in temporal lobe structures, in the hippocampus ipsilateral to scalp recorded interictal spikes, as well as in extra-temporal regions [9, 10]. EEG-fMRI findings have demonstrated hemodynamic alterations that occur immediately prior to interictal spikes [11, 12]. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have demonstrated a functional network in which hemodynamic changes are time-locked to spikes. Whether this reflects the propagation of neuronal activity from a focus, or the activation of a network linked to spike generation remains unknown.

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