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

## TL;DR

This study uses a new EEG analysis method to explore how the brain balances pain and pain relief during anesthesia.

## Contribution

The study introduces Holo-Hilbert spectral analysis to reveal nonstationary EEG modulation patterns linked to nociception during anesthesia.

## Key findings

- HHSA identified two dominant alpha-band modulation patterns under anesthesia.
- Nociceptive states increased alpha and high-delta modulation power while reducing theta and low-delta modulation.
- Alpha-band modulation power correlates with SPI and inversely with MAC.

## 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.