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BACK-TRANSLATION OF EEG/ERP MARKERS FROM AMNESTIC MCI PATIENTS TO HEALTHY YOUNG VOLUNTEERS IN THE PHARMACOG PROJECT

      Background

      Abnormality of resting state electroencephalographic (EEG) rhythms and oddball event-related potentials (ERPs) has been shown in amnesic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) patients. This study tested whether these EEG/ERP markers can be back-translated to healthy young volunteers (Healthy) for initial stages of drug discovery in AD.

      Methods

      Resting state eyes-closed EEG and auditory oddball ERP data were collected in the European IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org). The recordings were performed in: (1) 124 aMCI patients classified as 80 prodromal AD (MCI+) and 44 Control (MCI-) based on the Aβ42 level in the cerebrospinal fluid; (2) 30 Healthy subjects after a chronic (15 days) administration of Donepezil or placebo; and (3) 36 Healthy subjects before and after 1 night of sleep deprivation “challenge” (SD), followed by a single psychostimulant (Modafinil) or placebo dose. EEG markers were spectral power density at the standard frequency bands. ERP marker was the greatest positive peak in posterior electrodes (P3b peak). Cortical sources of the EEG/ERP markers were estimated by eLORETA freeware.

      Results

      Statistical results (p<0.05 corrected) showed that cortical sources of P3b peak and resting state delta EEG rhythms were abnormal in MCI+ compared with MCI- subjects. In Healthy subjects, Donepezil induced an amplitude reduction of cortical sources of posterior delta, theta, and alpha EEG rhythms. In addition, SD “challenge” altered cognitive performance and cortical sources of the P3b peak and delta/alpha EEG rhythms, while Modafinil partially recovered them.

      Conclusions

      In Healthy subjects, SD “challenge” made EEG/ERP markers reminiscent of prodromal AD, while a psychostimulant recovered them. Donepezil might induce some “neural efficiency” (i.e. more selective activation in enhanced brain) in the neurophysiological mechanisms generating EEG/ERP markers.