Making good decisions often requires inhibiting impulsive responses; and dysfunctions in such inhibitory control cause a wide range of mental health disorders. The long-term goal of the research program is to specify the neuronal mechanisms underlying inhibitory control in primates and to help develop methods for therapeutic intervention in maladaptive decision-making. The objective of the current proposal is to determine how neurons in critical brain structures mediate the inhibition of impulsive responses. Based largely on rodent studies of impulsivity and substance abuse, the central hypothesis is that the orbitofrontal cortex (OFC) and core of the nucleus accumbens (NA-core) inhibit impulsive responses mediated by the shell of the nucleus accumbens (NA-shell). The first specific aim is to test the central hypothesis by recording single-unit activity in these structures as rhesus monkeys perform a task that probes impulsivity. Monkeys will choose between an immediate, but smaller reward and a delayed, but larger reward. The second specific aim examines the generality of this inhibitory control mechanism. Monkeys will choose a larger amount of food over a smaller amount in one task, as they usually do, but in another task they must choose a smaller amount of food to obtain a larger amount. The third specific aim is to test the central hypothesis using reversible inactivation techniques. I am uniquely qualified to undertake these and subsequent, related studies in the long term, but will require specific additional training in neuroanatomy, multiple-electrode neurophysiological methods, and reversible inactivation techniques to do so independently. It is expected that the proposed project will help to characterize the specific neurophysiological mechanisms underlying the inhibition of impulsive responses, and the project should set the stage for further studies designed to determine the best approaches for augmenting inhibitory control when it dysfunctions. ? ? ?
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