687: Entrainment of Pain-Related Insular Oscillations by Intracerebral Periodic Stimulation in Humans

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Non -specific to any diagnosis, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS), Assessment and Measurement of Pain/Nociception, Neuromodulation (e.g. rTMS, tDCS, FUS, DBS, biofeedback)

Background and Aims: The insula shows enhanced high-frequency oscillations under periodic thermonociceptive stimuli perceived as painful, an effect not observed for innocuous non-nociceptive stimuli. [1] Multicontact depth electrodes implanted in epileptic patients offer the unique opportunity to modulate oscillations through Intracerebral Periodic Stimulation (iPS), consisting of biphasic squared pulses delivered to neural tissues at a specific frequency. In this study, insular iPS will be delivered while recording intracerebral EEG to validate entrainment effects on insular oscillations [2] and assess whether the iPS-induced modulation of neural activity affects pain perception. This approach aims to directly test the causal relationship between insular oscillations and pain.

Methods: 60-Hz iPS is delivered to insular contacts in a double-blind, sham-controlled design. Phasic thermonociceptive stimulation is delivered before, during and after iPS on the forearm contralateral to the stimulation site. It consists of 30-40 transient heat stimuli, after which participants rate intensity (0-10) and painfulness (yes/no). Amplitude and contacts are selected depending on clinical evaluation, and stimulation intensity is set at 80% of the threshold eliciting somatic sensations, if present. [3] Active and sham stimulation sessions are performed, and data is acquired while patients are under antiseizure medications. The current dataset includes two pilot sessions and one enrolled participant.

Results: Preliminary results confirm the increase in spectral power at the frequency of stimulation during iPS, compatible with neural entrainment. Effects on pain perception will be assessed as enrollment progresses. As data acquisition has only recently begun, these preliminary observations demonstrate that the experimental design is feasible and safe, supporting continued enrollment and validation of the paradigm.

Conclusions: While validating iPS-induced entrainment effect found in a previous pilot study, [2] this study can help clarifying the functional role of insular neural activity by testing the causal relationship between high-frequency insular oscillations and pain perception. iPS allows to stimulate and investigate deep brain regions and their connections, which are normally inaccessible with traditional scalp EEG. On the other hand, the focality of the stimulation makes it possible to target the specific cortical area of interest. Together, these features give the project the potential to guide novel applications of non-invasive neurostimulation techniques (such as tACS) for chronic pain.

References: [1] G. Liberati et al., ‘Insular responses to transient painful and non-painful thermal and mechanical spinothalamic stimuli recorded using intracerebral EEG’, Sci Rep, vol. 10, no. 1, p. 22319, Dec. 2020, doi: 10.1038/s41598-020-79371-2.
[2] J. L. Amengual, M. Vernet, C. Adam, and A. Valero-Cabré, ‘Local entrainment of oscillatory activity induced by direct brain stimulation in humans’, Sci Rep, vol. 7, no. 1, p. 41908, Mar. 2017, doi: 10.1038/srep41908.
[3] D. J. Denis, R. Marouf, P. Rainville, A. Bouthillier, and D. K. Nguyen, ‘Effects of insular stimulation on thermal nociception’, Eur J Pain, vol. 20, no. 5, pp. 800–810, May 2016, doi: 10.1002/ejp.806.

Presenting Author: Gloria Ricci
Submitting Author: Gloria Ricci

Senior Author: Giulia Liberati

IASP 2026 Global Year theme of Neuropathic Pain: No

• Gloria Ricci - Institute of Neuroscience, UCLouvain
• Susana Ferrao Santos - Department of Neurology, Saint-Luc University Hospital
• Alexane Fierain - Department of Neurology, Saint-Luc University Hospital
• Patrice Finet - Department of Neurology, Saint-Luc University Hospital
• Vincent Joris - Department of Neurology, Saint-Luc University Hospital
• André Mouraux - Institute of Neuroscience, UCLouvain
• Giulia Liberati - Institute of Neuroscience, UCLouvain