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

Abstract

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.