Normative high-frequency oscillation phase-amplitude coupling and effective connectivity under sevoflurane

Area of Science:

• Neuroscience
• Epileptology
• Anesthesiology

Background:

• Pediatric drug-resistant focal epilepsy surgery requires invasive intracranial electroencephalography (iEEG) for accurate epileptogenic zone localization.
• Current diagnostic methods involve multiple surgeries and prolonged inpatient evaluations, highlighting a need for less burdensome, objective epilepsy biomarkers.
• Preliminary studies suggest sevoflurane anesthesia can activate specific iEEG biomarkers, including phase-amplitude coupling (PAC) and effective connectivity (EC).

Purpose of the Study:

• To elucidate the normative distribution and propagation pathways of sevoflurane-activated PAC and EC biomarkers across different anesthetic stages.
• To determine if these sevoflurane-enhanced biomarkers can intraoperatively localize epileptogenic sites in pediatric epilepsy patients.
• To establish a baseline understanding for the prospective use of these biomarkers in guiding epilepsy surgery.

Main Methods:

• iEEG data were recorded from 19 pediatric epilepsy patients (ages 4-18) undergoing focal resection with seizure control.
• Recordings included an isoflurane baseline, stepwise sevoflurane increases, and extraoperative slow-wave sleep.
• Normative electrode sites were mapped, white matter pathways connecting augmented biomarker sites were traced using dynamic tractography, and biomarker values were analyzed for localization accuracy.

Main Results:

• Normative iEEG biomarkers (PAC and EC) increased with sevoflurane concentration, particularly in bilateral frontal and parietal regions (p<0.05).
• Callosal and superior longitudinal fasciculus tracts connected regions with elevated PAC and EC, respectively.
• Higher biomarker values at 3-4% sevoflurane significantly correlated with epileptogenicity and seizure-onset zones (p<0.05).

Conclusions:

• Sevoflurane anesthesia reliably enhances iEEG biomarkers (PAC and EC) in a predictable, dose-dependent manner.
• Specific white matter tracts facilitate the propagation of these activated biomarkers across the brain.
• Sevoflurane-activated biomarkers show promise for intraoperative localization of the epileptogenic zone in pediatric epilepsy surgery.