Saturday, May 10, 2025
5/10/2025
Intraoperative Localization of Epileptic Brain Regions Under Sevoflurane Anesthesia. - Drug-resistant, focal epilepsy impacts millions of children, and treatment often requires invasive evaluation. This process entails identification of intracranial electroencephalography (iEEG) biomarkers such as spike-and-wave discharges (SWDs), to guide surgical removal of the presumed epileptogenic zone responsible for generating habitual seizures. In pediatric patients, extra-operative iEEG evidence indicated that a SWD proxy measuring coupling between delta wave phase and high-frequency oscillation (HFO) amplitude – Modulation Index (MI) – accurately tracks epileptogenicity. Since MI does not detail the causality of neural propagations, it’s powerful to also consider iEEG Transfer Entropy (TE), which measures effective connectivity, and dynamic tractography to provide plausible propagation pathways. Granted, capturing adequate interictal and ictal epileptic events often requires days of extra-operative iEEG recording, and this procedure is grueling, expensive, and replete with major risk factors. Thus, development of intra-operative techniques for induction and reliable measurement of epileptic iEEG biomarkers is imperative to avoid the above pitfalls and help expand utility of one-stage procedures. Pertinently, sevoflurane anesthesia reversibly activates spike activity, but there is much debate over its specificity. Preliminary iEEG results in children suggest that sevoflurane may intra-operatively augment both MI and HFO effective connectivity (TE) in seizure foci. However, large cohort studies are needed to validate this finding, as it is unknown how sevoflurane impacts intra-operative MI and HFO-TE in healthy versus epileptogenic brain areas and if these signals spread via major white matter tracts. Thus, the main aims of the current proposal are to: 1) build normative atlases of intra-operative MI and HFO-TE, at varying concentrations of sevoflurane, and 2) determine if sevoflurane-induced modulation of these features can localize seizure foci and predict seizure outcomes. To accomplish these aims, the trainee will map patient electrodes to 3-dimensional magnetic resonance brain images, quantify the intra-operative iEEG metrics at stepwise increases of sevoflurane, and combine iEEG effective connectivity with white matter tractography (i.e. dynamic tractography). Characterizing the endogenous distribution of MI and HFO effective connectivity, with and without sevoflurane, will provide critical baseline reference for iEEG interpretation. In addition, understanding how sevoflurane impacts these metrics in epileptic networks is expected to improve interictal localization efforts during surgery, reduce invasive diagnostic burden by mitigating the need for extra-operative recording, optimize treatment cost effectiveness, and ultimately improve seizure outcomes. Through this project, the trainee will: (1) gain insight into and help refine clinical epilepsy treatment, (2) enhance scientific understanding of how neural oscillatory coupling and effective connectivity respond under sevoflurane, and (3) will undergo a training regimen to foster development of critical thinking and hypothesis-driven, ethical research design. The cumulative effect of the research and didactics will provide a critical foundation for the trainee’s career as a physician-scientist.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).