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Timing, reward processing and choice

时间安排、奖励处理和选择

基本信息

批准号：
10299282
负责人：
Kimberly Kirkpatrick
金额：
$ 37.02万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-20 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10299282
关键词：
Animals Attention deficit hyperactivity disorder Behavior Behavioral Borderline Personality Disorder Cognitive Compulsive Behavior Corpus striatum structure Coupled Diffusion Magnetic Resonance Imaging Discrimination Disease Drug Exposure Due Process Functional disorder Future Gambling Goals Health Human Impulsivity Individual Individual Differences Intervention Lead Link Measures Medial Mental Depression Mental disorders Mission Modeling National Institute of Mental Health Neurobiology Obesity Parkinson Disease Pathological Gambling Pathway interactions Pattern Pharmaceutical Preparations Pre-Clinical Model Process Progress Reports Psyche structure Public Health Rattus Research Rewards Rodent Rodent Model Role Schizophrenia Self-control as a personality trait Structure Substance abuse problem System Techniques Testing Therapeutic Intervention Time Translational Research Treatment outcome base comorbidity designer receptors exclusively activated by designer drugs disability effective intervention effective therapy endophenotype experience improved innovation intervention effect neurobiological mechanism neuromechanism novel programs relating to nervous system reward processing substance abuse treatment therapeutic candidate

项目摘要

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.

项目总结冲动的选择涉及到在数量和延迟之间进行权衡，通过交付更小-更快(SS)与较大-较晚(LL)奖励。当个人频繁地选择党卫军时，就会出现冲动的选择这样做并不是最好的。冲动的选择被认为是一种跨疾病过程，因为他们的与多种疾病和障碍有关，包括药物滥用、赌博、肥胖、以及注意力缺陷/多动障碍。冲动的选择既可以是光标的前置，也可以是适应不良的行为。我们研究计划的首要目标是确定潜在的通过干预来促进自我控制的冲动选择机制，并针对这些机制。时间歧视缺陷和延迟不耐受可预测稳定的个体差异在大鼠临床前模型中的冲动选择。据称，时机不佳和不容忍拖延。注意缺陷/多动障碍的内表型，提供了与啮齿动物临床前模型的重要联系。基于时间的干预成功地缓和了冲动的选择并改善了啮齿动物的时间辨别能力。以时间为基础的干预在促进自我控制方面最为成功在最冲动的人身上。最重要的是，涉及积极等待的干预措施所需时间辨别是最有效的，这表明计时过程在以时间为基础的干预。在前人研究成果的基础上，时间功能障碍模型(TDM)提出冲动的选择产生于扭曲的计时过程，这可能导致不精确或不准确时机到了。失灵的计时过程可能会导致冲动的选择。因此，TDM建议计时过程是治疗干预的主要候选方法。此外，不同的神经生物学机制可能对特定时间的不同贡献负责冲动的选择的过程。目标1将演示特定计时过程的不同角色促进自制力。这一目标将确定TDM，并明确基于时间的机制干预对未来神经科学和翻译研究的冲动选择的影响。目标2将评估干预措施对皮质-纹状体通路结构连通性的影响，这是最重要的基于时间的干预对时间选择和冲动选择的影响。这一目标将使用扩散张量成像(DTI)用于测量结构连通性。AIM 3将使用设计者受体仅由特制药物(DREADD)激活，以抑制神经生物学通路中的活动，很可能是基于时间的干预效应的候选者。这三个目标将确定具体的认知以及基于时间的干预的神经机制。这项研究意义重大，因为迫切需要有效的干预措施来缓和冲动的选择。作为一个跨疾病的过程，冲动的选择有对人类健康具有广泛的相关性，并与NIMH任务具有重大相关性。