A number of potentially important cognitive deficits have been reported to occur in stimulant dependent men and women. Among areas of cognitive deficits, dysregulations of decision-making have important potential clinical impact, i.e. improving decision-making strategies may help to avoid relapse, but have not been studied carefully. Subjects with stimulant dependence show dysfunctional decision-making not unlike subjects with ventromedial prefrontal cortex lesions. Two research strategies will be used. First, investigators have developed a computerized two-choice paradigm and applied mathematical tools from nonlinear dynamical systems theory to measure decision-making strategies in humans, i.e. 'coming up with rules for actions'. Second, the investigators have begun to use functional neuroimaging techniques to link dysregulations in decision-making in subjects with methamphetamine dependence to patterns of activation in different neural substrates. Both techniques will be used to address the following specific aim: (1) to better define and document the dysregulation of decision-making in the presence of uncertainty in methamphetamine dependent subjects and (2) to determine which neural substrates underlie the decision-making dysregulation in these subjects. Three main hypotheses are addressed: (1) methamphetamine dependent subjects relative to comparison subjects show a decision-making dysfunction that is characterized by an increase dependence on previous stimuli. (2) Methamphetamine-dependent subjects relative to comparison subjects show a decreased activation of the ventromedial prefrontal cortex during the two-choice task relative to the choice reaction task. (3) The behavioral differences on two-choice task and the neural substrate differences between methamphetamine-dependent subjects and comparison subjects do not change over time. The results from these studies will provide important information whether chronic use of methamphetamine is associated with neural substrate changes that impair decision-making. Moreover, this study will provide the basis for future investigations to determine whether the dysregulation in decision-making is a consequence of chronic use or a risk factor for the development of stimulant dependence.
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