Nicotinic Modulation of the Default Network of Resting Brain Function

Objective: To evaluate the potential of manipulating activity in the so-called default network of resting brain function by nicotinic ligands. Default network activity modulates cognitive functioning, and effects of nicotine thereon may motivate smoking behavior. In the future, this mechanism could become a novel approach to improving cognition in disease populations that show dysfunction of this network, such as schizophrenia or Alzheimer s disease. Study population: 27 healthy non-smokers. Design: A double-blind, placebo-controlled, within-subject fMRI study, evaluating regional brain activation and cognitive functions under conditions of transdermal nicotine (7 mg/day), oral mecamylamine (a nicotinic antagonist, 7.5 mg), and placebo. Outcome measures: Activity and functional connectivity of default regions during cognitive task performance, measures of cognitive task performance, measures of subjective state, and plasma concentrations of nicotine, nicotine metabolites and mecamylamine.