Research Project
10299282
PROJECT SUMMARY Impulsive choices involve trade-offs between amount and delay by delivering smaller-sooner (SS) versus larger-later (LL) rewards. Impulsive choices occur when individuals frequently choose the SS when it is suboptimal to do so. Impulsive choices have been identified as a trans-disease process due to their association with a wide range of diseases and disorders including substance abuse, gambling, obesity, and attention-deficit/hyperactivity disorder. Impulsive choice can be both a pre-cursor to and product of maladaptive behaviors. The overarching goal of our research program is to identify the underlying mechanisms of impulsive choices and target those mechanisms using interventions to promote self-control. Time discrimination deficits and delay intolerance predicted stable individual differences in impulsive choice in the rat pre-clinical model. Poor timing and delay intolerance are purported endophenotypes in attention-deficit/hyperactivity disorder, providing important links with the rodent pre-clinical model. Time-based interventions have successfully moderated impulsive choices and improved time discrimination in rodents. Time-based interventions were most successful in promoting self-control in the most impulsive individuals. Most importantly, interventions that involved active waiting and that required time discrimination were most effective, suggesting a causal role for timing processes in the time-based interventions. Based on the previous results, the timing dysfunction model (TDM) proposes that impulsive choices arise from distorted timing processes, which may result in imprecise or inaccurate timing. Dysfunctional timing processes can lead to impulsive choices. Thus, the TDM proposes that timing processes are a primary candidate for therapeutic interventions. In addition, different neurobiological mechanisms may be responsible for the different contributions of specific timing processes to impulsive choices. Aim 1 will demonstrate distinct roles for specific timing processes in promoting self-control. This aim will confirm the TDM and pinpoint the mechanisms of time-based intervention effects on impulsive choices for future neuroscientific and translational research. Aim 2 will assess effects of the interventions on structural connectivity in cortico-striatal pathways, which are prime candidates for the time-based intervention effects on timing and impulsive choices. This aim will use diffusion tensor imaging (DTI) to measure structural connectivity. Aim 3 will use Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to depress activity in neurobiological pathways that are likely candidates for the time-based intervention effects. The three aims will identify specific cognitive and neural mechanisms of time-based interventions. This research is significant due the critical need for effective interventions to moderate impulsive choices. As a trans-disease process, impulsive choice has broad relevance for human health and is of significant relevance to the NIMH mission.
