Nicotinic Modulation of the Default Network of Resting Brain Function
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Observational

Summary: 
      Background:

      - A brain circuit called the default network is the brain circuit that is active when the
      brain is at rest; that is, when individuals are not concentrating on specific tasks. Previous
      research has shown that the default network functions differently in people with
      schizophrenia and Alzheimer s disease, and may contribute to the problems with memory and
      concentration that can affect people who have these conditions. Studies have also shown that
      nicotine affects the default network, but more research is needed on the ways in which
      nicotinic receptors may change activity in these regions and thereby affect individuals
      ability to concentrate on specific tasks.

      Objectives:

      - To determine whether and how nicotine and mecamylamine, a drug that blocks nicotinic
      receptors, affect the default network in nonsmokers in ways that improve thinking and
      concentration.

      Eligibility:

        -  Healthy, right-handed volunteers between 21 and 50 years of age.

        -  Volunteers must not have used any kind of tobacco product in the past 2 years.

      Design:

        -  This study involves an initial screening visit, a training visit, and three testing
           visits.

        -  Participants will be screened with a medical history and physical examination, as well
           as blood and urine samples and questions about smoking history.

        -  Participants will have an initial training session to practice the tasks that will be
           done during magnetic resonance imaging scans at the testing visits. These tasks will
           test participants concentration and memory.

        -  Participants will have three test sessions with the following combinations of study
           drugs: (1) a nicotine patch and a placebo capsule, (2) a placebo patch and a capsule of
           mecamylamine, or (3) a placebo patch and capsule. Different combinations will be given
           at each visit, and participants will not know which one they receive.

        -  Participants will perform the same concentration and memory tasks at each testing visit,
           and will provide a blood sample after each visit to determine levels of nicotine and
           mecamylamine.
    

Detailed description: 
      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.
    

Time perspective: Prospective
Keywords: Nicotine; Mecamylamine; Attention; fMRI; Default Network; Healthy Volunteer; HV