Interictal waking and sleep electrophysiological properties of the thalamus in focal epilepsies

Introduction Addressing drug-resistant epilepsy poses a significant clinical hurdle, particularly when conventional resective surgery is not feasible. Deep brain stimulation (DBS) emerges as a potential therapeutic avenue for such cases. To shed light on the thalamo-cortical epileptogenic networks and refine prognostic indicators and treatments, we conducted an exhaustive examination of interictal data from thalamic stereoelectroencephalography (SEEG) recordings in a substantial patient cohort (n=121). Our investigation delved into thalamo-cortical connectivity, interictal hyperexcitability biomarkers, and their associations with clinical parameters during both rest and non-rapid eye movement (NREM) sleep states. Methodology We conducted an observational study retrospectively gathering data from patients who underwent stereotactic-EEG with thalamic implantation as part of pre-surgical evaluation. Interictal recordings during rest and NREM sleep were analyzed to detect spikes and fast ripples automatically. Functional connectivity between the thalamus and other brain regions (involved or non-involved in the epileptogenic network) was examined using linear regression analysis (R2), while statistical evaluations assessed relationships between these measures, patient outcomes, and clinical variables. Results Elevated rates of thalamic spikes and fast ripples during sleep were linked to unfavorable surgical outcomes (Engel class III/IV) compared to favorable outcomes (Engel class I/II). Thalamo-cortical functional connectivity analysis revealed heightened thalamic strength, particularly in the beta and gamma bands during sleep, among patients with poor surgical outcomes, especially with non-involved networks. Conversely, during rest, lower spike and fast ripple rates were observed in patients with longer epilepsy durations. Furthermore, thalamic strength values during resting state were diminished in patients with prolonged epilepsy durations and older age. Discussion Our study uncovered heightened thalamic interictal activity and thalamo-cortical functional connectivity during sleep in patients with unfavorable surgical outcomes, within the largest cohort of patients with thalamic recordings documented. These findings inform pre-surgical assessments, aiding in identifying patients unsuitable for surgery and suggesting alternative interventions like DBS. Additionally, diminished thalamic activity and connectivity associated with epilepsy duration and age prompt speculation on the role of the thalamus as a pivotal hub in aging-related processes. Vigilance state-dependent insights from the thalamus underscore the necessity for comprehensive analyses to tailor stimulation protocols, facilitating a personalized therapeutic approach. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### 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: IRB of AP-HM (Assistance Publique - Hopitaux de Marseille) 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 data produced in the present study are available upon reasonable request to the authors