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

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 5 mg donepezil or placebo for 15 days 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.