Identification of Pre-Spike Network in Patients with Mesial Temporal Lobe Epilepsy

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.

Interictal epileptiform discharges in focal epilepsy are preceded by a gradual increase in low-frequency oscillations

“…Previous studies have shown that changes in synchronization of oscillatory brain activity occurs prior to IED onset (Keller et al, 2010;Faizo et al, 2014;Bourel-Ponchel et al, 2017). However, it has not been clear whether these pre-IED oscillations exhibit a dynamical evolution, with increasing synchronization in the irritative zone.…”

“…In support of this view, several computational and animal models have demonstrated that IEDs and their cellular correlate, the paroxysmal depolarizing shift, can be triggered to occur momentously by increasing the excitation/inhibition ratio (Ayala et al, 1970;Schwartzkroin and Prince, 1979;Voskuyl and Albus, 1985;Mccormick and Contreras, 2001). However, analysis of human IED generation demonstrate that that there are additional changes in the brain state prior to IED onset, indicating that the context surrounding IED events develop over a longer time scale (Keller et al, 2010;Faizo et al, 2014;Bourel-Ponchel et al, 2017). Hemodynamical activation, for instance, peak one second before IEDs occur (Hawco et al, 2007;Jacobs et al, 2009;Rathakrishnan et al, 2010).…”

“…Hemodynamical activation, for instance, peak one second before IEDs occur (Hawco et al, 2007;Jacobs et al, 2009;Rathakrishnan et al, 2010). Such changes are seen not only in the region generating IEDs -the so-called irritative zone (Jehi, 2018) -but also at distant regions, accompanied by altered connectivity patterns (Kobayashi et al, 2006;Faizo et al, 2014).…”

The Role of EEG-fMRI in Studying Cognitive Network Alterations in Epilepsy

“…However, the effects of IEDs on cognitive networks were not often explored until recently. Following pioneering work relating IED-correlated decreases in Default Mode Network activity in temporal lobe epilepsy (84) and generalized epilepsy (85), recent works have shown the possible impact of interictal activity on several ICNs in focal epilepsy in adults (33, 36, 45), focal epilepsy in children (22), children with idiopathic focal epilepsy [Benign Epilepsy with Centro-temporal Spikes (BECTS)] (53, 55, 86), epileptic encephalopathy (56–59), as well as generalized epilepsies (61, 64), including Childhood Absence Epilepsy (CAE) (87), and even reflex epilepsies (60). The majority of recent EEG-fMRI studies who evaluate the interaction between interictal discharges, ICNs, and their relationship to neuropsychological outcome have been in BECTS patients; these studies found a negative correlation between cognitive functioning and Functional Connectivity (FC).…”

Interictal Epileptiform Discharges Might Be More Likely During Particular Phases of Brain Activity

“…Independently of Lopes et al, Faizo et al recently studied functional connectivity between hippocampi immediately prior to IEDs in a group of 15 mesial TLE patients ( 20 ). They observed functional connectivity decrease prior to the IED onset.…”