Imaging and Genetic Investigation of Learning and Decision Making
Condition: Polymorphism- Genetic; Reward Mediating System
Study type: Observational

Summary: 
      Background:

      - Previous research has shown that dopamine, a brain chemical, is involved in decision
      making. Different genes influence how much dopamine people have in their brains and how that
      affects their behavior. Researchers will study if genes associated with dopamine affect
      decision making and impulsiveness. All participants will take tests; some will have brain
      images taken. Researchers will study the test responses and images; they will look for how
      differences in these genes affect different types of decision making.

      Objectives:

      - To see if genes involved in a brain chemical, dopamine, are related to impulsiveness on
      behavioral tests.

      Eligibility:

      - Healthy adults ages 18 to 55.

      Design:

        -  Participants will be screened with a medical history and physical exam.

        -  All participants in this study will have at least 1 outpatient visit to the NIH Clinical
           Center. Each visit will last 2 4 hours. At the first visit:

        -  A blood sample will be taken only from participants that have not been previously
           enrolled in 95-M-0150

        -  Participants will be given tests of their memory, attention, concentration, and
           thinking.

        -  Some participants will have a second visit. It will be scheduled as soon as possible
           after the first. At the second visit:

        -  Participants will have an MRI (magnetic resonance imaging). They will have to lie in a
           scanner for up to 2 hours. The MRI uses magnets, radio waves, and computers to produce
           detailed pictures of the brain.

        -  Participants will repeat the tests from the first visit. Some will be done during the
           MRI.
    

Detailed description: 
      The objective of this study is to examine the effects of genetic variability in the dopamine
      signaling pathway on metric measures of impulsivity. Our hypothesis is that increased
      dopamine levels or conversion of dopamine to intracellular signals, brought about by specific
      variants of genes in this pathway, will increase impulsivity in our behavioral tasks. We will
      examine variability by recruiting up to 400 ethnically and racially diverse healthy adult
      male and female volunteers aged 18 to 55. We will carry out genotyping, behavioral testing
      and functional magnetic resonance imaging on this group. We will initially recruit a large
      pool of subjects for behavioral testing and genotyping. Behavioral tests will include various
      laboratory tasks related to impulsivity. We have recently developed a series of tasks that we
      have used in a group of Parkinson s patients with impulsive/compulsive behaviors (PD+ICBs).
      Several tasks have shown large group effects between Parkinson s patients with and without
      ICBs (PD +/- ICBs). We will focus on those tasks in the present study. Specific examples
      include information sampling tasks and measures of novelty preference. If genetic effects on
      behavior in the large sample are found, we will ask a subset of the original sample to return
      for fMRI testing. The subset will be selected to allow us to examine the neural circuits that
      operate differently as a function of genotype. In other words, they will be selected on the
      basis of their genotype. The outcome measure in this case will be differences in brain
      activity as a function of genotype, during performance of our behavioral task.
    

Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Healthy Volunteers
      
Keywords: Dopamine Transporter; D2 Dopamine Receptor Subtype; Dopamine; Dopamine Genes; Dopaminergic Mechanisms; Natural History