Thalamocortical Phase-amplitude Coupling in Lennox-gastaut Syndrome
Abstract number :
3.182
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2024
Submission ID :
1241
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Thomas Tcheng, PhD – NeuroPace
Lise Johnson, PhD – NeuroPace, Inc.
Sharanya Arcot Desai, PhD – NeuroPace, Inc.
Muhammad Furqan Afzal, PhD – NeuroPace, Inc.
Aaron Warren, PhD – Brigham and Women's Hospital, Harvard Medical School
Matthew Hook, MS – University of Florida
Christopher Butson, PhD – University of Florida
John Rolston, MD, PhD – Brigham and Women's Hospital, Harvard Medical School
David Greene, BS – NeuroPace, Inc.
Katie Bullinger, MD, PhD – Emory University School of Medicine
Robert Gross, MD, PhD – Rutgers New Jersey Medical School
Jerzy Szaflarski, MD, PhD – University of Alabama
Nicole Bentely, MD – University of Alabama, Birmingham
Zeenat Jaisani, MD – University of Alabama, Birmingham
Daniel Friedman, MD – New York University Grossman School of Medicine, NYU Langone Health
Vikram Rao, MD, PhD – University of California San Francisco
Edward Chang, MD – University of California, San Francisco
Saadi Ghatan, MD – Mount Sinai Health System
Jiyeoun (Jenna) Yoo, MD – Icahn School of Medicine at Mount Sinai
Mark Richardson, MD, PhD – Massachusetts General Hospital
Martha Morrell, MD – NeuroPace
Rationale: Lennox-Gastaut Syndrome (LGS) is a severe childhood-onset epilepsy with electrophysiological signatures corresponding to broad involvement of the frontal cortex. The centromedian nucleus of the thalamus (CM) is diffusely and reciprocally connected to the frontal cortex and has been identified as a potentially important node within the broader LGS network. Thalamocortical responsive neurostimulation targeting the frontal cortex and the CM is being evaluated in an IDE feasibility clinical study (clinicaltrials.gov, NCT05339126) as an adjunctive therapy option for patients 12 years and older with pharmacologically uncontrolled LGS.
Phase amplitude coupling (PAC) is one mechanism by which different nodes within a distributed brain network can be functionally coordinated. The thalamic local field potential is characterized by multiple low-frequency oscillations, and cross-frequency interactions in thalamocortical oscillations may facilitate thalamic regulation of sleep and wake states. Seizures represent an additional, pathological, brain state in the LGS population that may be associated with an enhanced or alternative pattern of PAC.
Methods: Trial participants (N=12) receive two neurostimulator implants, one in each hemisphere, each with a lead targeting the CM and a lead in the frontal cortex. The PAC between the CM and the neocortex was calculated bilaterally for the LGS trial participants during several different brain states. Scheduled, interictal recordings were collected during both day and night; electrographic seizures were identified in each hemisphere independently using a previously described machine learning-based seizure classifier (Barry et al., Front. Neurosci., 2021, v15). Recordings that were classified by the model as having an electrographic seizure on both the cortical and thalamic leads were included in this analysis.
Results: Low frequency phase modulation of higher frequency activity was observed within and across brain areas in all participants. As expected, the specific patterns of cross-frequency interactions were different between times of putative wake, sleep, and seizure. A high degree of variability was also observed across subjects, and within subjects different patterns were sometimes observed on neighboring channels on the same lead. These differences reflect potential differences in the lead’s anatomical location and/or underlying network organization.
Conclusions: These results illuminate some of the ways in which the different nodes are coordinated both during and between times of pathological expression. In addition to contributing to our understanding of the network, the ability to distinguish between normal and abnormal brain states may serve as a biomarker to guide therapy decisions.
Funding: NIH NINDS UH3NS109557
Translational Research