Functional Connectivity in the Thalamocortical Network Using Intracranial iEEG in Lennox-Gastaut Syndrome
Abstract number :
1.142
Submission category :
3. Neurophysiology / 3C. Other Clinical EEG
Year :
2023
Submission ID :
249
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Lise Johnson, PhD – NeuroPace, Inc.
Thomas Tcheng, PhD – NeuroPace, Inc.; Aaron Warren, PhD – Brigham and Women's Hospital; Sharanya Arcot Desai, PhD – NeuroPace, Inc.; David Greene, BS – NeuroPace, Inc.; Robert Gross, MD, PhD – Emory University; Katie Bullinger, MD – Emory University; Jerzy Szaflarski, MD, PhD – The University of Alabama at Birmingham; J Nicole Bentley, MD – The University of Alabama at Birmingham; Zeenat Jaisani, MD – The University of Alabama at Birmingham; Daniel Friedman, MD – NYU Grossman School of Medicine; Vikram Rao, MD, PhD – University of California, San Francisco; Edward Chang, MD – University of California, San Francisco; Saadi Ghatan, MD – Icahn School of Medicine at Mount Sinai; Ji Yeoun Yoo, MD – Icahn School of Medicine at Mount Sinai; Andrew Cole, MD – Massachusetts General Hospital; Matthew Hook, MS – University of Florida; Christopher Butson, PhD – University of Florida; John Rolston, MD, PhD – Brigham and Women's Hospital; Martha Morrell, MD – NeuroPace, Inc.; Stanford University
Rationale: Patients have received RNS® System implants as part of an ongoing early feasibility IDE clinical trial to evaluate thalamocortical responsive neurostimulation for Lennox-Gastaut Syndrome (LGS). LGS is a severe epilepsy syndrome characterized by multiple different seizure types with broad involvement of cortical and sub-cortical areas. In this study, thalamic depth leads are placed bilaterally in the centromedian nucleus and cortical strip leads are placed bilaterally over a previously identified premotor frontal cortical “hot-spot” in the LGS network.
Methods: For this analysis, intracranial EEG (iEEG) records representing electrographic seizures were identified by a board-certified epileptologist who also marked seizure onset times and locations (frontal or thalamic). Functional connectivity was evaluated using mean-squared coherence and generalized partial directed coherence.
Results: In all subjects (N= 7), seizure activity was detected on both the frontal cortical and thalamic leads. Seizures typically manifested as high frequency activity which subsequently evolved into rhythmic delta discharges in both the neocortical and thalamic channels. The RNS® System was configured to identify and treat these patterns. The regional, temporal and spectral characteristics of seizures were consistent within each subject but variable between subjects. In all but one subject (6/7), seizure onsets were first seen in the neocortical contacts in both hemispheres. In the remaining subject, the seizure onset appeared simultaneously in the thalamus and the neocortex in one hemisphere; the onset was neocortical in the other hemisphere. Coherence between the two channels on each frontal or thalamic lead always increased at seizure onset. Coherence between the thalamic and premotor frontal channels was also increased, although not to the same extent in all subjects. Patterns of generalized directed coherence were not consistent across subjects. Increases in directional connectivity from the frontal cortex to the thalamus, from the thalamus to the frontal cortex, and between the channels in the frontal cortex or the thalamus were all observed. This suggests subject-specific dynamic bidirectional changes in thalamocortical communication during seizures.
Conclusions: LGS arises from multiple etiologies but affects a common thalamocortical network. Simultaneous electrophysiological recordings from the thalamus and the premotor frontal cortex reveal the network behavior during seizures in this patient population. Understanding these dynamic interactions not only contributes to a fundamental understanding of the disease but may help guide therapy decisions.
Funding: NIH BRAIN Initiative NINDS (FAIN UH3NS109557)
Neurophysiology