697: Peak Alpha Frequency Influences Selective Cross-Frequency Coupling during Acute Pain

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Psychology, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS), Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Pain corresponds to electrical brain oscillations across frequency bands. Greater alpha (8-12 Hz) power and faster (10-12 Hz) peak alpha frequency (PAF) correspond to lower pain sensitivity[1], theta (4-8 Hz) power is greater in low-back pain patients than controls[2], and gamma (30-90 Hz) power correlates with pain intensity[3]. Neural pain signals may be integrated across frequencies via phase-amplitude coupling (PAC) – alignment between low-frequency (alpha/theta) phase and high-frequency (gamma) amplitude[4]: Decreased alpha-gamma, and increased theta-gamma coupling is present in neuropathic pain[5]. Here, we tested whether the relationship between PAC and pain generalizes to acute experimental pain in healthy controls.

Methods: We leveraged data from the Comprehensive EEG Dataset of Laser-Evoked Potentials[6], a collection of EEG data from healthy controls (n = 678) undergoing a laser-evoked pain paradigm. Event-related PAC was used to quantify alpha-gamma and theta-gamma coupling at each time point across the laser-evoked pain trials, creating timeseries of PAC time-locked to laser-evoked pain. Then, alpha-gamma and theta-gamma PAC was correlated with individual pain ratings. We further tested whether alpha/theta-gamma PAC related to individual PAF, a trait-like biomarker of pain sensitivity, by testing for differences in PAC strength between slow- and fast-PAF groups (median split).

Results: Preliminary findings in a subset of the data (n = 25) revealed that mean pain ratings were negatively correlated with alpha-gamma PAC (r = -.39) ~250 ms after laser-evoked pain, and with theta-gamma PAC (r = -.36) ~50 ms after laser-evoked pain. The fast PAF group had significantly greater alpha-gamma PAC than the slow PAF group ~250 ms after pain. Further, the slow PAF group had greater theta-gamma PAC than the fast PAF group in a similar timeframe. Final results of the above analysis performed on the full dataset (n ~ 678) are ongoing and will be reported.

Conclusions: Overall, these initial findings extend previous neuropathic patient work by revealing selective alpha- and theta-gamma coupling during pain in healthy controls, suggesting PAC plays a more general role in pain. We additionally report novel evidence that selective PAC coupling relates to subjective pain and PAF.

References: 1. Furman, A. J. et al. Cerebral peak alpha frequency predicts individual differences in pain sensitivity. NeuroImage 167, 203–210 (2018).
2. Kenefati, G. et al. Changes in alpha, theta, and gamma oscillations in distinct cortical areas are associated with altered acute pain responses in chronic low back pain patients. Front. Neurosci. 17, 1278183 (2023).
3. Li, Z., Zhang, L., Zeng, Y., Zhao, Q. & Hu, L. Gamma-band oscillations of pain and nociception: A systematic review and meta-analysis of human and rodent studies. Neurosci. Biobehav. Rev. 146, 105062 (2023).
4. Canolty, R. T. & Knight, R. T. The functional role of cross-frequency coupling. Trends Cogn. Sci. 14, 506–515 (2010).
5. Vanneste, S. & De Ridder, D. Chronic pain as a brain imbalance between pain input and pain suppression. Brain Commun. 3, fcab014 (2021).
6. Zhao, X. et al. A comprehensive EEG dataset of laser-evoked potentials for pain research. Sci. Data 12, 1536 (2025).

Presenting Author: Joshua Hoddinott
Submitting Author: Joshua Hoddinott

Senior Author: Siobhan Schabrun

IASP 2026 Global Year theme of Neuropathic Pain: No

• David Seminowicz: PhD - University of Western Ontario
• Siobhan Schabrun: PhD - University of Western Ontario