Network dynamics predict improvement in working memory performance following donepezil administration in healthy young adults.

Attentional selection in the context of goal-directed behavior involves top-down modulation to enhance the contrast between relevant and irrelevant stimuli via enhancement and suppression of sensory cortical activity. Acetylcholine (ACh) is believed to be involved mechanistically in such attention processes. The objective of the current study was to examine the effects of donepezil, a cholinesterase inhibitor that increases synaptic levels of ACh, on the relationship between performance and network dynamics during a visual working memory (WM) task involving relevant and irrelevant stimuli. Electroencephalogram (EEG) activity was recorded in 14 healthy young adults while they performed a selective face/scene working memory task. Each participant received either placebo or donepezil (5mg, orally) on two different visits in a double-blinded study. To investigate the effects of donepezil on brain network dynamics we utilized a novel EEG-based Brain Network Activation (BNA) analysis method that isolates location-time-frequency interrelations among event-related potential (ERP) peaks and extracts condition-specific networks. The activation level of the network modulated by donepezil, reflected in terms of the degree of its dynamical organization, was positively correlated with WM performance. Further analyses revealed that the frontal-posterior theta-alpha sub-network comprised the critical regions whose activation level correlated with beneficial effects on cognitive performance. These results indicate that condition-specific EEG network analysis could potentially serve to predict beneficial effects of therapeutic treatment in working memory.