Stimulant use and dependence are important problems among young adults in the U.S. It has been suggested that an imbalance between motivational drives for novel experiences and inhibitory control systems could predispose to impulsive and risk-taking behaviors. Decision-making, risk-taking, and error processing are inter-related processes that are important for every-day functioning and have been implicated in subjects with substance dependence. Functional neuroimaging studies have shown that decision-making is critically dependent on the activation of inferior prefrontal cortex, ventromedial and ventrolateral frontal cortex, anterior cingulate, insula, and parietal cortex. Our main goal is to identify differences in brain processes and their underlying neural activation patterns between young adults who use stimulants and are at risk for transition to stimulant dependence and matched comparison subjects. We will use risk-taking decision-making paradigms during functional magnetic resonance imaging (fMRI) to determine the activation patterns related to risk-taking, decision-making, and error processing.
The specific aims are: 1. We will contrast brain functioning during risk-taking decision-making using fMRI in subjects who recently used stimulants (i.e. are at higher risk for developing stimulant dependence) and in subjects who have never used stimulants. 2. We will evaluate the relationship between risk-taking decision-making tasks and the fMRI activation pattern at baseline and the future development of stimulant dependence in stimulant-using subjects. The hypotheses are that stimulant using subjects, relative to subjects who have never taken stimulants, will show more risk-taking behavior during decision-making paradigms and will show less activation of brain areas that are critical for error processing, including the anterior cingulate, insula, inferior prefrontal and medial prefrontal cortex. Moreover, it is hypothesized that subjects who develop dependence relative to those who do not show more rigid stimulus-bond decision-making and less activation in the posterior parietal cortex. Testing these hypotheses will advance the neurobiology of substance dependence by (1) identifying the neural substrates that may differentiate stimulant using versus non-using subjects; (2) relating behavioral characteristics during risk-taking decision-making in stimulant using subjects to patterns of brain activation; (3) identifying patterns of brain activation that are predictive of transition to stimulant dependence. ? ?
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