Authors :
Presenting Author: Zoé Dary, PhD – Brigham and Women's hospital, Harvard Medical School
Aaron Warren, PhD – Brigham and Women's Hospital, Harvard Medical School
Matthew Hook, - – University of Florida
Martha Morrell, MD – NeuroPace
Lise Johnson, PhD – NeuroPace, Inc.
Christopher Butson, PhD – University of Florida
John Rolston, MD, PhD – Brigham and Women's hospital, Harvard Medical School
Rationale:
Lennox–Gastaut syndrome (LGS) is a severe childhood-onset epilepsy characterized by drug-resistant seizures and generalized EEG abnormalities, which complicate accurate seizure monitoring. Traditional methods, such as patient-reported seizure diaries, are often unreliable due to high seizure frequency and cognitive deficits commonly associated with LGS. Objective, biomarkers are needed to reliably track seizure burden and guide treatment. Among thalamic structures, the centromedian nucleus (CM) has emerged as a key therapeutic target for LGS (Warren et al, Brain Communications, Volume 6, Issue 3, 2024; Dalic et al, Epilepsia. 2020 Oct;61(10):2214-2223). Here, we investigated electrophysiological features of the CM and surrounding thalamic nuclei that may serve as biomarkers of seizure susceptibility. We analyzed recordings from responsive neurostimulation devices (RNS System, NeuroPace, Inc.) implanted in patients with LGS as part of a multicenter feasibility trial evaluating thalamocortical network stimulation as an adjunctive therapy for LGS (NCT05339126). We focused on the aperiodic exponent, which is thought to reflect, in part, neural excitation-inhibition balance (Charlebois et al, Epilepsia. 2024 May;65(5):1360-1373). Methods:
Nineteen patients (9 females; mean age ± SD: 29.4 ± 10.3 years) with LGS implanted with the RNS System targeting the bilateral CM and premotor cortex were included. Electrode positions were determined from post-operative CT. Electrophysiological data were analyzed 80 days post-implantation, when stimulation was not active and devices were programmed to record activity only. We focused on scheduled, 90-second recordings acquired approximately every 12 hours twice a day, which reflect baseline interictal activity. The aperiodic exponent was extracted using SpecParam, a Python-based toolbox.
Results:
Of the 80 electrode contacts, 33 were located within the CM and adjacent parafasicular nucleus (CM-Pf); the remaining electrodes were located in the ventral lateral (VL), mediodorsal (MD), central lateral (CL), and ventral posterior (VP) nuclei. A significant difference in the distribution of the aperiodic exponent was seen across nuclei (H = 17.92, p = 0.001). Dunn’s post hoc tests showed that the exponent was highest in the CM-Pf and was significantly lower in the VL (p = 0.0015) and MD (MD; p = 0.0458). No other nucleus pairs showed significant differences after correction.Conclusions:
These preliminary findings suggest that the CM may exhibit distinct electrophysiological characteristics compared to other thalamic regions, potentially reflecting its unique role in seizure dynamics in LGS. This may serve as a marker to improve CM targeting or electrode selection when programming neuromodulatory therapies. Funding:
Research reported in this abstract was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number UH3NS109557. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
This research was also supported by the grant R01NS136297.