Multisine frequency modulation of intra-epidermal electric pulse sequences: A novel tool to study nociceptive processing

Boudewijn van den Berg*, Mana Manoochehri, Mindy Kasting, Alfred C. Schouten, Frans C.T. van der Helm, Jan R. Buitenweg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
91 Downloads (Pure)


A sustained sensory stimulus with a periodic variation of intensity creates an electrophysiological brain response at associated frequencies, referred to as the steady-state evoked potential (SSEP). The SSEPs elicited by the periodic stimulation of nociceptors in the skin may represent activity of a brain network that is primarily involved in nociceptive processing. Exploring the behavior of this network could lead to valuable insights regarding the pathway from nociceptive stimulus to pain perception.

We present a method to directly modulate the pulse rate of nociceptive afferents in the skin with a multisine waveform through intra-epidermal electric stimulation. The technique was demonstrated in healthy volunteers. Each subject was stimulated using a pulse sequence modulated by a multisine waveform of 3, 7 and 13 Hz. The EEG was analyzed for the presence of the base frequencies and associated (sub)harmonics.

Topographies showed significant central and contralateral SSEP responses at 3, 7 and 13 Hz in respectively 7, 4 and 3 out of the 9 participants included for analysis. As such, we found that intra-epidermal stimulation with a multisine frequency modulated pulse sequence can generate nociceptive SSEPs . The possibility to stimulate the nociceptive system using multisine frequency modulated pulses offers novel opportunities to study the temporal dynamics of nociceptive processing.
Original languageEnglish
Article number109106
JournalJournal of neuroscience methods
Early online date21 Feb 2021
Publication statusPublished - 1 Apr 2021


  • UT-Hybrid-D
  • Pain
  • Nociception
  • Nociceptive processing
  • System identification
  • Multisine signal
  • Frequency tagging
  • EEG
  • Electroencephalogram
  • Delay
  • Steady-state evoked response


Dive into the research topics of 'Multisine frequency modulation of intra-epidermal electric pulse sequences: A novel tool to study nociceptive processing'. Together they form a unique fingerprint.

Cite this