Drug abuse costs our nation in excess of $450 billion dollars a year, including health care expenditures, accidents, and crime, a sum that is more than double the costs associated with either cancer or diabetes. One of the most damaging health consequences of drug addiction is its effects on executive functioning: the capacity to flexibly select rules for appropriate behavior and to maintain them even when distracting stimuli prime inappropriate behavioral rules or responses. Drugs alter the brain's internal reward circuitry, increasing the value and salience of illicit substances for decision-making, attentional, and response mechanisms. This change enables drug stimuli, or even thoughts about drugs, to hijack these executive systems, leading to increased drug use and to an inability to sustain more productive activities. Although our understanding of executive deficits in drug abuse is growing, it has been difficult to isolate the precise neural substrates of executive processes that select and maintain a rule for upcoming behavior in the context of distracting stimuli that prime a competing rule. The current project uses event-related functional magnetic resonance imaging to isolate the neural mechanisms that enable these crucial executive processes. The behavioral paradigm cues participants on a trial-by-trial basis to use one of two possible rules in an upcoming task, while varying whether a distracting stimulus primes the same rule or a different rule. In Experiment 1, the distracting stimulus is presented simultaneously with the instructional cue, enabling the identification of brain regions that select a rule in the context of a distracter that primes a competing rule. In Experiment 2, the distracting stimulus is presented after the instructional cue, enabling the identification of brain regions that maintain a previously-selected rule in the context of a distracter that primes a competing rule. Prior evidence implicating the frontal lobes as a major neural substrate for executive processing suggests that dorsolateral and ventrolateral frontal lobe regions, respectively, will underlie rule selection and rule maintenance. By identifying the normal patterns of brain activity for executive processing in non-addicts, this project will inform current neurological models of executive control, indicate possible brain regions to target when developing treatments for drug addiction, and provide proof-of-concept data for future proposals aimed at directly investigating the neural substrates of executive deficits in drug-addicted populations. ? ?
