Effects of Nicotine on Cognitive Task Performance and Brain Activity as Measured by fMRI
Condition: Nicotine Dependence; Drug Abuse
MeSH terms: Tobacco Use Disorder; Substance-Related Disorders
Study type: Observational

Summary: 
      Background:

      - Many cigarette smokers claim that smoking improves their ability to think and concentrate,
      and have reported problems in thinking and concentration after quitting smoking. Some
      research has indicated that nicotine can enhance certain aspects of attention and memory in
      humans. However, more research is needed to determine how nicotine affects different elements
      of the brain s ability to think, pay attention, respond to rewards, and make decisions.
      Researchers are interested in using functional magnetic resonance imaging (fMRI) to study the
      effects of nicotine on brain function and activity.

      Objectives:

      - To determine the effects of nicotine on attentional and other thinking processes, including
      reward-seeking behavior.

      Eligibility:

      - Individuals between 18 and 50 years of age who are either current smokers (10 or more
      cigarettes per day for at least 1 year) or nonsmokers.

      Design:

        -  The study has four experiments. Each experiment requires two MRI scanning sessions and a
           training session. Participant can do one or all of the experiments.

        -  Participants will receive training on the types of computerized tests that will be given
           during the active portion of the study. Participants will also fill out questionnaires
           on nicotine use and other alcohol and drug use, and provide breath and urine samples.

        -  During the test sessions, participants will have fMRI scanning while performing up to
           four different sets of tasks that test attention, memory, concentration, reward-seeking
           behavior, and decision making. Smokers will wear a nicotine patch or placebo patch
           during the test sessions, but will not be told which patch they are receiving. The order
           of these sessions will be different for individual participants.

        -  Participants will provide blood and urine samples throughout the research study for
           evaluation purposes.
    

Detailed description: 
      Objective:

      Experiments in this protocol employ fMRI to address the interactions of nicotine with such
      cognitive processes as working memory, attention, and the executive functions of inhibitory
      control, conceptual reasoning and attention switching, in addition to reward and temporal
      error reward processing. The effects of nicotine on these cognitive processes will also be
      assessed outside the MRI scanner. Assessments of genetic variants will be done with the
      hypothesis that these will account for some inter-individual differences in the brain imaging
      data.

      Study Population:

      The study population will consist of adult (18-50 y.o.) non-treatment seeking smokers and age
      and gender matched non-smoking control subjects. The control subjects will provide normative
      data on cognitive task performance and corresponding neural activation, as well as providing
      control for any time effects (e.g. practice effect on repeated cognitive task performance).
      Smokers will smoke at least 10 cigarettes per day for a period of 1 year. Both smokers and
      controls will be suitable for fMRI scanning. Subjects may not be dependent on any other drug
      except nicotine or caffeine.

      Design:

      In a within subjects design, experienced smokers will perform cognitive tasks involving
      memory encoding and consolidation, selective/divided and sustained attention, as well as
      reward and temporal error reward processing two hours following single blind application of a
      nicotine patch (21 mg/24 hr) and during a separate session on a different day, following
      application of a placebo patch. The tasks will be performed during fMRI scanning. Not all of
      the tasks will be done at the same time, rather, groups of tasks are run in series as task
      sets: Task set A: Selective/divided attention task and Intention/ attention task; Task set B:
      The SARAT (Spatial Attentional Resource Allocation task) which is designed to enable
      dissociation of top-down and stimulus driven processes of visuospatial selective attention as
      well as the CEFER task which is a measure of central executive function task which isolates
      the allocation of attentional resources within working memory; Task set C: Monetary Incentive
      Delay and Temporal Delay Error processing tasks; Task set D: Affective Forecasting and Loss
      Aversion task. Control subjects will do the tasks during scanning without a patch. Blood will
      be drawn from all participants for analysis of genetic variants and for smokers, plasma
      nicotine and cotinine will be measured.

      Outcome:

      We will determine the acute effects of nicotine on attentional and other cognitive mechanisms
      and how emotional processes such as the anticipation and receipt of reward affects the
      neuronal activation properties of acute nicotine administration in experienced smokers. In
      addition, we will determine whether genetic polymorphisms predict BOLD response during
      cognitive tasks pertinent to nicotine addiction. Plasma nicotine and cotinine will be
      included as a factor in analyses of nicotine-induced effects on fMRI signal to take account
      of potentially large inter-individual variability in circulating nicotine concentrations.
    

Time perspective: Other
Keywords: Attention; Working Memory; Central Executive Processes; Response Preparation; Cigarettes