title: Network dynamics predict improvement in working memory performance following donepezil administration in healthy young adults.
abstract: 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.
authors.affiliation: ElMindA Ltd., Herzliya, Israel. Electronic address: amit@elminda.com.
authors.forename: A
authors.initials: A
authors.lastname: Reches
authors.affiliation: ElMindA Ltd., Herzliya, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Laufer
authors.affiliation: ElMindA Ltd., Herzliya, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Ziv
authors.affiliation: ElMindA Ltd., Herzliya, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Cukierman
authors.affiliation: University of California, Los Angeles School of Medicine, Los Angeles, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: McEvoy
authors.affiliation: ElMindA Ltd., Herzliya, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Ettinger
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA; Department of Psychology, University of California, Berkeley, CA, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Knight
authors.affiliation: Departments of Neurology, Physiology and Psychiatry, University of California San Francisco, San Francisco, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gazzaley
authors.affiliation: ElMindA Ltd., Herzliya, Israel; Electrical and Computer Engineering, Ben Gurion University of the Negev, Beer Sheba, Israel.
authors.forename: A B
authors.initials: AB
authors.lastname: Geva
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000077265:Donepezil; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D010364:Pattern Recognition, Visual / Q000187:drug effects / Q000502:physiology*; D058573:Performance-Enhancing Substances / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D058573:Performance-Enhancing Substances; D010880:Piperidines; D000077265:Donepezil
keywords: BNA; Cognitive enhancement; Donepezil; EEG; Working memory