Dopamine and Frontostriatal Function

多巴胺和额纹状体功能

基本信息

批准号：
9063531
负责人：
MARK D'ESPOSITO
金额：
$ 65.78万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9063531
关键词：
Affect Agonist Attention Deficit Disorder Attention deficit hyperactivity disorder Behavioral Brain Bromocriptine COMT gene Clinical Cognition Cognitive Complex Corpus striatum structure DRD2 gene Data Data Set Diagnosis Disease Dopamine Dopamine D2 Receptor Dopaminergic Agents Drug Addiction Equilibrium Etiology Evaluation Exhibits Functional Magnetic Resonance Imaging Functional disorder Genetic Genetic Polymorphism Genetic Variation Health Human Individual Knowledge Lead Link MRI Scans Maintenance Measurement Measures Mental disorders Mission Nature Neurotransmitters Parkinson Disease Pharmaceutical Preparations Placebos Positron-Emission Tomography Prefrontal Cortex Process Proxy Public Health Research Resistance Rest Role Schizophrenia Short-Term Memory Site System Task Performances Testing Tracer Traumatic Brain Injury Update Variant addiction cognitive control cognitive function cognitive process cognitive system flexibility imaging modality improved inhibitor/antagonist insight interest nervous system disorder novel novel strategies receptor density relating to nervous system response tolcapone transmission process

项目摘要

DESCRIPTION (provided by applicant): This application is directed towards understanding the role of the dopaminergic system in higher cognitive function such as working memory and cognitive control. These somewhat ill-defined terms generally refer to cognitive systems that require two functionally opposing processes: (1) the stable 'on-line' maintenance of information (necessary for "cognitive stability") and (2) the flexible updating of that information in response to novel task-relevant information (necessary for "cognitive flexibility"). We will test the hypothesis that these cognitive processes are highly dependent on precisely balanced dopaminergic transmission within the striatum and prefrontal cortex (PFC). Specifically, we will test the hypothesis that augmentation of dopamine in the PFC promotes cognitive stability by increasing distractor-resistance whereas dopamine augmentation in the striatum promotes cognitive flexibility by allowing the updating of newly relevant representations. Manipulation of the dopaminergic system has been shown to modulate the function of fronto-striatal circuitry, but the direction and extent of these effects vary widely across individuals and tasks. Through pharmacological manipulation and genetic variation of dopamine in humans, and measurements of their effects with both fMRI and PET, we expect to elucidate the factors that determine this large variability in drug effects and characterize the nature of the complex relationship between dopamine and cognition. Dopamine is of fundamental importance to the etiology and clinical manifestations of a wide variety of neurological and psychiatric disorders such as Parkinson's disease, traumatic brain injury, attention deficit hyperactivity disorder, schizophrenia and drug addiction. A further understanding of the relationship between dopamine and cognition should advance our understanding of the mechanisms underlying cognitive and behavioral deficits in these disorders and provide insight into novel approaches to treating such deficits with medications targeted at specific neurotransmitter systems.

描述（由申请人提供）：此申请旨在了解多巴胺能系统在更高的认知功能（例如工作记忆和认知控制）中的作用。这些定义不明的术语通常是指需要两个功能上相反过程的认知系统：（1）稳定的“在线”维护信息（“认知稳定性”所需与新的任务相关信息（“认知灵活性”所需的信息）。我们将检验以下假设：这些认知过程高度依赖于纹状体和前额叶皮层（PFC）中精确平衡的多巴胺能传播。具体而言，我们将测试以下假设：PFC中多巴胺的增强通过增加分散术的耐药性来促进认知稳定性，而纹状体中的多巴胺增加通过允许更新新相关表示形式来促进认知灵活性。已经证明对多巴胺能系统的操纵可以调节额叶纹状体电路的功能，但是这些效果的方向和程度在个人和任务之间差异很大。通过人类多巴胺的药理操作和遗传变异，以及对fMRI和PET的影响的测量，我们希望阐明确定药物效应的较大差异的因素，并表征多巴胺与认知之间复杂关系的性质。多巴胺对多种神经系统和精神疾病的病因和临床表现至关重要，例如帕金森氏病，创伤性脑损伤，注意力缺陷多动障碍，精神分裂症和药物成瘾。对多巴胺与认知之间的关系的进一步理解应提高我们对这些疾病中认知和行为缺陷的机制的理解，并为使用针对特定神经递质系统的药物治疗这种缺陷的新方法提供见解。