Network alterations in temporal lobe epilepsy during non-rapid eye movement sleep and wakefulness

Objective Investigate sleep and temporal lobe epilepsy (TLE) effects on EEG-derived brain networks. Methods High-density EEG was recorded during non-REM sleep (N2) and wakefulness in 23 patients and healthy controls (HC). Epochs without epileptic discharges were source-reconstructed in 72 brain regions and connectivity was estimated. Network integration (Efficiency, E) and segregation (Clustering Coefficient, CC) at global and hemispheric level (GE, avgCC, HE, HCC) were calculated. These were compared between groups across frequency bands and correlated with the individual proportion of wakefulness-or sleep-related seizures. Results Patients had higher delta GE, delta avgCC and theta avgCC than controls, irrespective of the vigilance state (TLE > HC, p<.01). During wakefulness, theta GE of patients was higher than controls (p<.001) and, for patients, theta GE during wakefulness was higher than during N2 (p<.05). Wake-to-sleep differences in TLE were notable only in the ipsilateral hemisphere (HE and HCC, p<.05). Only measures from wakefulness recordings correlated with the proportion of wakefulness-or sleep-related seizures. Conclusions TLE network alterations are more prominent during wakefulness and at lower frequencies. Increased integration and segregation suggest a pathological ‘small world’ configuration with a possible inhibitory role. Significance Network alterations in TLE occur and are easier to detect during wakefulness. ### Competing Interest Statement MS has shares in Epilog and received speaker fees from UCB. SV has shares in Epilog. ### Funding Statement This work was funded by the German Research Foundation (grant DFG 422589384 to BJV), the Swiss National Science Foundation (SNSF) (grant no. 192749 and CRSII5_209470 to SV; grant no. CRS115-180365 to MS; grant no. 155120 to LP), the NIH/NCCAM P01AT004952 (to GT), NIH/NIMH 5P20MH077967 (to GT), and Tiny Blue Dot Inc. grant MSN196438/AAC1335 (to GT). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethic committee of the canton of Geneva (Commission cantonale d'ethique de la recherche CCER) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All patients agreed to data reuse for research purposes, but not all agreed to data sharing. Therefore, the EEG data used in this study cannot be shared on a public platform.