663: Modulatory Effects of Non-invasive Posterior Insular Stimulation on Oscillatory Alpha Activity

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS), Pain models (e.g. saline injection, capsaicin, UVB, HFS, incision, exercise, itch), Neuromodulation (e.g. rTMS, tDCS, FUS, DBS, biofeedback)

Background and Aims: Repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex and dorsolateral prefrontal cortex reduces pain and affects oscillatory alpha activity. The primary objective of this pre-registered secondary analysis was to investigate whether rTMS delivered to the posterior superior insula (PSI), an emerging target in rTMS pain treatment, has modulatory effects on specific resting-state oscillatory alpha features (i.e. peak alpha frequency (PAF), power, and frontal alpha asymmetry). Secondary objectives explored associations between alpha features and effects of PSI-rTMS on experimental pain, and whether baseline alpha features predict individual responses to PSI-rTMS.

Methods: Twenty healthy adults (10 females) attended two sessions receiving active or sham rTMS (randomised) during experimentally induced pain. Facilitatory rTMS was delivered to the left PSI (10Hz, 100 pulses/train, 15 trains) ~50 minutes after application of a capsaicin patch to the forearm. Pain intensity was scores on a numerical rating scale (NRS). Eyes-closed resting-state electroencephalography (EEG, 64 channels) was recorded at baseline, during capsaicin-induced pain prior to rTMS, and after rTMS. Global alpha band (8–13Hz) power and PAF derived from centre of gravity (CoG) and peak finding (max) methods were extracted using the DISCOVER-EEG pipeline, alongside aperiodic-adjusted PAF.

Results: An increase was found in global aperiodic-adjusted and CoG-PAF post-rTMS relative to pre-rTMS regardless of active/sham condition (P<0.040), while after active rTMS only, aperiodic-adjusted and max-PAF increased locally over frontal-central and right-frontal channels, respectively (P<0.024). A significant timepoint-by-condition interaction effect on alpha power was found (P=0.027), indicating a decrease after sham but not active rTMS. For sham rTMS, greater increases in pain NRS ratings were associated with greater decreases in global aperiodic-adjusted and CoG-PAF. Moreover, baseline max-PAF closer to the 10Hz stimulation frequency and greater frontal asymmetry scores independently predicted greater reductions in pain scores (P<0.027).

Conclusions: This study showed that PSI-rTMS influences some key resting-state EEG alpha features. Alpha power was maintained at baseline levels with active PSI-rTMS, suggesting the effect of pain on alpha power may have been mitigated by rTMS. Our results suggest localised PAF increases after active PSI-rTMS. This aligns with previous work on PAF-pain associations, as the main study also showed decreased pain after active PSI-rTMS, although our PAF observations were not consistent across PAF-estimation methods. There is a continued need to investigate how alpha features are associated with pain sensitivity and the effects of treatment on pain.

References: Chowdhury, N. S., Millard, S. K., de Martino, E., Larsen, D. B., Seminowicz, D. A., Schabrun, S. M., de Andrade, D. C., & Graven-Nielsen, T. (2025). Posterior-superior insula repetitive transcranial magnetic stimulation reduces experimental tonic pain and pain-related cortical inhibition in humans. Pain, 166(6), 1314–1327. https://doi.org/10.1097/j.pain.0000000000003488

Chowdhury, N. S., Taseen, K. J., Chiang, A. KI., Chang, W.-J., Millard, S. K., Seminowicz, D. A., & Schabrun, S. M. (2025). A 5-day course of repetitive transcranial magnetic stimulation before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency. Pain, 166(6), 1382–1394. https://doi.org/10.1097/j.pain.0000000000003484

Furman, A. J., Meeker, T. J., Rietschel, J. C., Yoo, S., Muthulingam, J., Prokhorenko, M., Keaser, M. L., Goodman, R. N., Mazaheri, A., & Seminowicz, D. A. (2018). Cerebral peak alpha frequency predicts individual differences in pain sensitivity. NeuroImage, 167, 203–210. https://doi.org/10.1016/j.neuroimage.2017.11.042

Millard, S. K., Chiang, A. K. I., Chowdhury, N., Chang, W., Furman, A. J., De Martino, E., Graven‐Nielsen, T., Schabrun, S. M., & Seminowicz, D. A. (2025). Peak Alpha Frequency Is Not Significantly Altered by Five Days of Experimental Pain and Repetitive Transcranial Stimulation of the Left Dorsolateral Prefrontal Cortex. European Journal of Neuroscience, 62(4), e70219. https://doi.org/10.1111/ejn.70219

Okamura, H., Jing, H., & Takigawa, M. (2001). EEG Modification Induced by Repetitive Transcranial Magnetic Stimulation. Journal of Clinical Neurophysiology, 18(4), 318–325. https://doi.org/10.1097/00004691-200107000-00003

Presenting Author: Bárbara Silva-Passadouro
Submitting Author: Bárbara Silva-Passadouro

Senior Author: Thomas Graven-Nielsen

IASP 2026 Global Year theme of Neuropathic Pain: No

• Samantha K. Millard: PhD - Aalborg University
• Nahian S. Chowdhury: PhD - University of New South Wales
• Enrico De Martino: MD, PhD - Aalborg University
• Dennis Boye Larsen: PhD - Aalborg University
• Daniel Ciampi de Andrade: MD, PhD - Aalborg University
• Thomas Graven-Nielsen: PhD, DMSc - Aalborg University