A 15-day course of donepezil modulates spectral EEG dynamics related to target auditory stimuli in young, healthy adult volunteers

Clin Neurophysiol. 2019 May;130(5):863-875. doi: 10.1016/j.clinph.2015.11.018. Epub 2015 Nov 27.

Abstract

Objective: To identify possible electroencephalographic (EEG) markers of donepezil's effect on cortical activity in young, healthy adult volunteers at the group level.

Methods: Thirty subjects were administered a daily dose of either 5mg donepezil or placebo for 15days in a double-blind, randomized, cross-over trial. The electroencephalogram during an auditory oddball paradigm was recorded from 58 scalp electrodes. Current source density (CSD) transformations were applied to EEG epochs. The event-related potential (ERP), inter-trial coherence (ITC: the phase consistency of the EEG spectrum) and event-related spectral perturbation (ERSP: the EEG power spectrum relative to the baseline) were calculated for the target (oddball) stimuli.

Results: The donepezil and placebo conditions differed in terms of the changes in delta/theta/alpha/beta ITC and ERSP in various regions of the scalp (especially the frontal electrodes) but not in terms of latency and amplitude of the P300-ERP component.

Conclusion: Our results suggest that ITC and ERSP analyses can provide EEG markers of donepezil's effects in young, healthy, adult volunteers at a group level.

Significance: Novel EEG markers could be useful to assess the therapeutic potential of drug candidates in Alzheimer's disease in healthy volunteers prior to the initiation of Phase II/III clinical studies in patients.

Keywords: Donepezil; EEG markers; Event-related potential; Event-related spectral perturbation; Inter-trial coherence.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Adult
  • Brain / drug effects*
  • Cross-Over Studies
  • Donepezil / pharmacology*
  • Double-Blind Method
  • Electroencephalography
  • Evoked Potentials / drug effects*
  • Healthy Volunteers
  • Humans
  • Male
  • Nootropic Agents / pharmacology*
  • Young Adult

Substances

  • Nootropic Agents
  • Donepezil