Exploring Nociceptive-Analgesic Balance and EEG Modulation Patterns During General Anesthesia Using Holo-Hilbert Spectral Analysis

Abstract

Intraoperative EEG provides a noninvasive window into cortical dynamics under anesthesia, but conventional spectral analysis cannot capture nonstationary modulation patterns linked to nociceptive processing. This study applied Holo-Hilbert spectral analysis (HHSA) to characterize cross-frequency modulation patterns in relation to the Surgical Pleth Index (SPI) during general anesthesia. Frontal EEG from 134 female patients undergoing gynecologic surgery was analyzed. Ten-minute segments were first examined to define canonical modulation structures, followed by one-minute epochs synchronized with SPI values to assess dynamic changes. HHSA decomposed each epoch into amplitude modulation patterns across carrier frequencies (1/64-64 Hz). Group comparisons between pain and no-pain epochs were performed using t-tests with Bonferroni correction. A linear mixed-effects model evaluated the effects of SPI, minimum alveolar concentration (MAC), heart rate (HR), and mean arterial pressure (NIBP-m) on alpha-band modulation (8-16-Hz carrier modulated by 3-8-Hz amplitude). HHSA revealed two dominant cross-frequency interactions within the alpha-carrier band (8-16 Hz): one modulated by 3-6-Hz (high-delta to theta) and another by 1-2-Hz (low-delta) oscillations, indicating layered modulation under anesthesia. During nociceptive states (SPI > 60), modulation power increased in the alpha and high-delta bands, while theta and low-delta modulation weakened. Alpha-band modulation power rose with SPI and declined with MAC. HHSA revealed distinct cross-frequency modulation patterns reflecting the cortical balance between nociception and analgesia. Alpha-band modulation serves as a physiologically grounded EEG marker for individualized nociception monitoring under general anesthesia.