EEG frequency-tagging captures the neural integration of bilateral periodic thermonociceptive stimulation

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 paradigm to a bilateral application would enable its use to study the sensory integration of concomitant nociceptive stimuli and cognitive modulations during e.g. spatial attention tasks. This study demonstrates that bilaterally applied slow sustained periodic sinusoidal thermonociceptive stimuli using two different frequencies of stimulation (i.e. f 1 , f 2 , one on each forearm) can indeed be differentiated at the neural level by eliciting two distinct periodic responses at the respective frequency of stimulation and their harmonics. Additionally, we showed that there seems to be an interaction between the neural populations involved in the response to these stimuli, marked by neural activity at intermodulation frequencies (n* f 1 ± m* f 2 ). So far, this non-linear integration of sensory information has already been observed following visual and auditory stimuli, but never following thermonociceptive stimuli.