title: Nicotine replacement in abstinent smokers improves cognitive withdrawal symptoms with modulation of resting brain network dynamics.
abstract: Symptoms of cognitive impairment during smoking withdrawal can be ameliorated by nicotine replacement. To define brain mechanisms contributing to this therapeutic effect, we conducted a functional connectivity analysis of resting-state fMRI in 17 abstinent smokers following nicotine replacement in a double-blind, placebo-controlled, crossover design. We found that individual differences in cognitive withdrawal symptom improvements after nicotine replacement were associated with increased inverse coupling between executive control and default mode brain networks. Furthermore, improvements in withdrawal symptoms were negatively correlated with altered functional connectivity within the default mode network, and with connectivity between the executive control network and regions implicated in reward processing. These findings demonstrate that nicotine administration in abstinent smokers modulates dynamic interactions between large-scale cognitive brain networks in the resting state. We specifically highlight the role of midline and prefrontal network regions in the neurocognitive response to nicotine pharmacotherapy and suggest that altered functional connectivity patterns of these networks reflect their engagement in reward and salience processing during smoking withdrawal. Individual differences in resting brain functional connectivity may predict therapeutic outcomes in nicotine addiction and other conditions associated with cognitive impairments.
authors.affiliation: Department of Clinical Neuroscience, Imperial College London, London, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Cole
authors.forename: Christian F
authors.initials: CF
authors.lastname: Beckmann
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Long
authors.forename: Paul M
authors.initials: PM
authors.lastname: Matthews
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Durcan
authors.forename: John D
authors.initials: JD
authors.lastname: Beaver
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012907:Smoking / Q000188:drug therapy* / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine