40-Hz auditory stimulation for intracranial interictal activity: A pilot study

Acta Neurol Scand. 2021 Aug;144(2):192-201. doi: 10.1111/ane.13437. Epub 2021 Apr 24.


Objectives: To study the effects of auditory stimuli on interictal epileptiform discharge (IED) rates evident with intracranial monitoring.

Materials and methods: Eight subjects undergoing intracranial EEG monitoring for refractory epilepsy participated in this study. Auditory stimuli consisted of a 40-Hz tone, a 440-Hz tone modulated by a 40-Hz sinusoid, Mozart's Sonata for Two Pianos in D Major (K448), and K448 modulated by a 40-Hz sinusoid (modK448). Subjects were stratified into high- and low-IED rate groups defined by baseline IED rates. Subject-level analyses identified individual responses to auditory stimuli, discerned specific brain regions with significant reductions in IED rates, and examined the influence auditory stimuli had on whole-brain sigma power (12-16 Hz).

Results: All subjects in the high baseline IED group had a significant 35.25% average reduction in IEDs during the 40-Hz tone; subject-level reductions localized to mesial and lateral temporal regions. Exposure to Mozart K448 showed significant yet less homogeneous responses. A post hoc analysis demonstrated two of the four subjects with positive IED responses had increased whole-brain power at the sigma frequency band during 40-Hz stimulation.

Conclusions: Our study is the first to evaluate the relationship between 40-Hz auditory stimulation and IED rates in refractory epilepsy. We reveal that 40-Hz auditory stimuli may be a noninvasive adjunctive intervention to reduce IED burden. Our pilot study supports the future examination of 40-Hz auditory stimuli in a larger population of subjects with high baseline IED rates.

Publication types

  • Clinical Trial

MeSH terms

  • Acoustic Stimulation*
  • Adult
  • Aged
  • Brain / physiopathology*
  • Drug Resistant Epilepsy
  • Electrocorticography / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects