Nicotine replacement in abstinent smokers improves cognitive withdrawal symptoms with modulation of resting brain network dynamics

Neuroimage. 2010 Aug 15;52(2):590-9. doi: 10.1016/j.neuroimage.2010.04.251. Epub 2010 May 2.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / drug effects*
  • Brain / physiopathology
  • Brain Mapping
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Cross-Over Studies
  • Double-Blind Method
  • Executive Function / drug effects
  • Executive Function / physiology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Neuropsychological Tests
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Smoking / drug therapy*
  • Smoking / physiopathology
  • Substance Withdrawal Syndrome / complications
  • Substance Withdrawal Syndrome / drug therapy*
  • Young Adult


  • Nicotinic Agonists
  • Nicotine