673: Sex differences in dynamic pain connectome periodic versus aperiodic alpha activity

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Gender/sex differences, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS), Assessment and Measurement of Pain/Nociception

Background and Aims: Sex differences are important in pain research given disparities in chronic pain prevalence[1]. We previously reported sex-specific abnormalities in resting-state alpha oscillations in the dynamic pain connectome (DPC) in people with chronic pain[2-4]. However, interpretation is hindered because periodic and aperiodic components of the power spectral density (PSD) were not dissociated[5], and age-related effects were not considered in heterogenous cohorts. To establish a normative baseline for chronic pain interpretation, our study aim was to differentiate and characterize periodic vs aperiodic contributions to magnetoencephalography (MEG) resting-state alpha activity in the DPC using spectral parameterization[5] and evaluate sex-related differences.

Methods: Healthy male and female adults underwent resting-state MEG. Data preprocessing included a standard PSD pipeline for 19 regions of interest (ROIs) of the DPC including those in the ascending nociceptive and descending antinociceptive pathways, salience and default mode networks[4]. Spectral parameterization[5] was applied to each spectrum to separate the aperiodic background from periodic alpha oscillation features. For each approach, we derived peak alpha frequency (PAF) and total alpha-band power (area under the curve from 8–13 Hz), yielding method-specific estimates for each participant. Sex differences were evaluated within each analytic approach.

Results: At the individual level, PAF and alpha-band power significantly differed between PSD- vs parameterization-based estimates across all ROIs. There was no significant sex differences in the PAF derived from either method. In contrast, regardless of method, the total alpha-band power was greater in males than females in the bilateral dorsolateral and medial prefrontal cortex, midcingulate cortex, subgenual anterior cingulate cortex, thalamus, bilateral temporoparietal junction, precuneus, left posterior insula, right primary somatosensory cortex (S1), and left secondary somatosensory cortex (S2). No significant sex differences were found in left S1, right S2, bilateral anterior insula, right posterior insula, or posterior cingulate cortex.

Conclusions: Given the growing attention and debate regarding the role of alpha oscillations in pain, our findings point to the importance of accounting for aperiodic contributions to MEG resting-state data. Spectral parameterization may be beneficial going forward because it estimates periodic peak features after accounting for aperiodic background signals, improving comparability across individuals and studies. In this study, we highlight that method-driven measurement effects may contribute to an individual’s PAF or total alpha-band power across studies, weakening comparability and reproducibility. Furthermore, our findings of sex differences across analysis methods demonstrate the importance of disaggregated analyses in studies of resting-state alpha activity.

References: 1 Finn, D. P. et al. Recommendations for the inclusion and study of sex and gender in research. Nature Neuroscience 29, 256-266 (2026). https://doi.org:10.1038/s41593-025-02164-1
2 Fauchon, C. et al. Sex differences in brain modular organization in chronic pain. PAIN 162, 1188-1200 (2021). https://doi.org:10.1097/j.pain.0000000000002104
3 Fauchon, C. et al. Exploring sex differences in alpha brain activity as a potential neuromarker associated with neuropathic pain. PAIN 163, 1291-1302 (2022). https://doi.org:10.1097/j.pain.0000000000002491
4 Kucyi, A. & Davis, K. D. The dynamic pain connectome. Trends Neurosci 38, 86-95 (2015). https://doi.org:10.1016/j.tins.2014.11.006
5 Donoghue, T. et al. Parameterizing neural power spectra into periodic and aperiodic components. Nature Neuroscience 23, 1655-1665 (2020). https://doi.org:10.1038/s41593-020-00744-x

Presenting Author: Sushmit Das
Submitting Author: Sushmit Das

Senior Author: Dr. Karen D. Davis

IASP 2026 Global Year theme of Neuropathic Pain: No

• Rima El-Sayed: PhD - University Health Network
• Vaidhehi Veena Sanmugananthan - University Health Network
• Natalie R Osborne: PhD - University Health Network
• Junseok A Kim: PhD - University Health Network
• Rachael L Bosma: PhD - University Health Network
• Karen D. Davis: PhD - University Health Network