Frequency-tagging captures distinct neural responses elicited by bilateral periodic thermonociceptive stimulation

Abstract Sustained periodic stimuli are known to elicit a periodic neural response (i.e. steady-state evoked potential) in the EEG frequency spectrum. These responses can easily be traced at their frequency of stimulation and corresponding harmonics using a frequency-tagging approach. To date, sustained periodic thermonociceptive stimuli have only been used on one extremity (e.g. right volar forearm) at a time. Extending this procedure to sustained stimulation applied concomitantly to distinct limbs would allow us to study the mechanisms of integration or competition between sensory signals from these different body locations. This study demonstrates that slow, sustained, sinusoidal thermonociceptive stimuli, bilaterally applied using two different stimulation frequencies (i.e. f1, f2, one on each forearm), elicit two distinct neural periodic responses at the respective frequency of stimulation and their harmonics. Additionally, we showed preliminary evidence for an interaction between the neural populations involved in the response to these stimuli, marked by neural activity at intermodulation frequencies (n* f1 ± m* f2). So far, this non-linear integration of sensory information has already been observed following visual and auditory stimuli but not yet following thermonociceptive stimuli. New and noteworthy This study demonstrates that sustained, slow, sinusoidal thermonociceptive stimulation applied simultaneously to both forearms at different frequencies elicits distinct neural responses at each stimulation frequency and its harmonics. Moreover, we provide preliminary evidence for interaction between the neural populations involved in the response to these stimuli during bilateral thermonociceptive stimulation. These findings extend frequency-tagging approaches in pain research and reveal potential non-linear sensory integration of distinct thermo-nociceptive inputs. Competing Interest Statement The authors have declared no competing interest. Footnotes Adapted manuscript to submission requirements of the journal to which this preprint is being submitted; updated phrasing mainly in discussion section to improve clarity, simplification of statistical assessment of aggregated harmonics; addition of link to datasets in OSF repository.