Adolescence is a transitional stage hallmarked by decisions that are increasingly impulsive and consequently dangerous. While an increase in impulsive behavior is normal in this stage of development, failure to inhibit inappropriate behaviors, such as experimentation with alcohol or illicit drugs, can lead to detrimental consequences. Differences in the developmental stage of prefrontal cortical and subcortical systems in adolescents might explain the relative increase in risky and impulsive decisions during this period. Specifically, the orbitofrontal region of prefrontal cortex (OFC) has been shown to play a central role in processing value expectation in a delay discounting task. The delay discounting task is a robust translational model used to quantify impulsivity, in which subjects choose between smaller-sooner and larger-later rewards. Elevated preference for smaller-sooner over larger-later rewards indicates impulsive choice. It is unknown whether an immature OFC will process decisions through similar mechanisms. Recent evidence suggests that dopaminergic innervation of the OFC plays an important role in mediating delay-discounting choices and pharmacological treatment with methylphenidate (MPH;an ADHD medication) decreases impulsive behavior in adolescents. Therefore, the goal of this dissertation research is to assess, across the lifespan, how OFC encodes the cues that predict reward availability and the receipt of immediate and delayed rewards. This proposal will also characterize the role of the OFC in delay discounting performance in adolescence. To this end, the first Aim will investigate the neurophysiological changes in OFC activity during Reward Magnitude Discrimination and Delay Discounting tasks in both adolescence and adulthood.
The second Aim will pharmacologically inactivate OFC in adolescent and adult rats prior to performing the Delay Discount task to determine whether OFC activity is necessary for MPH effects on impulse control. Combined, these approaches provide a powerful quantitative and mechanistic assessment of the impact of impulsive behavior across development. Understanding the dynamic processing associated with inhibitory control throughout development represents a significant challenge for researchers, with overarching implications for adolescent public health.
The focus of this proposal is to directly investigate differences in cognitive impulsivity in a Delay Discounting task between adolescents and adults, how impulsive choices are encoded by the firing patterns of neurons in orbitofrontal cortex (OFC) across developmental periods, and whether this signaling is the target of MPH's therapeutic actions on impulsivity. Combined, these approaches provide a powerful quantitative and mechanistic assessment of the impact of OFC on impulsive behavior across development.
|Amodeo, Leslie R; Jacobs-Brichford, Eliza; McMurray, Matthew S et al. (2017) Acute and long-term effects of adolescent methylphenidate on decision-making and dopamine receptor mRNA expression in the orbitofrontal cortex. Behav Brain Res 324:100-108|