Neuroimaging of Neurotransmitter Release in Humans During Cognitive and Behavioral Tasks

摘要在国家科学基金会的支持下，扎尔德博士和他的同事们将进行一个为期三年的项目，旨在开发一项新的研究计划，将认知神经成像技术与神经递质释放的神经成像相结合。大量的神经药理学证据表明，多巴胺(DA)对情感、运动和认知过程具有深远的影响。要充分了解DA对神经行为系统的影响，需要了解DA是如何以及何时释放的。PET成像的最新进展使安全地测量人类在不同认知或行为任务中的DA释放成为可能。这些数据为DA的功能提供了新的见解，并允许在动物模型缺乏的认知功能期间评估DA。然而，由于这类研究的跨学科性质，很少有认知神经科学家利用这些技术。该项目包括：1)学习部分，以促进获得使用[11C]raclopide PET进行DA释放研究所需的方法学技能；2)旨在测试关于内源性DA何时释放的特定假设的研究计划；以及3)继续发展教学技能，包括开发一门关于情绪认知神经科学的课程。具体研究集中在1)任务反应需求和奖赏偶然性对DA释放的影响，2)新颖性对DA释放的影响，3)集合转移任务中DA是否释放(被DA缺失干扰)，4)纹状体亚区大胆fMRI反应与DA释放的关系。该提案建立了两个主要学术中心之间的合作，使这一新兴领域的思想和技术发展得以交流。由于该领域尚处于初级阶段，在会议和专题讨论会上传播这些想法和技术可能会对指导其他人如何处理这一领域产生重大影响。此外，这项工作的跨学科性质允许将神经科学不同领域的想法整合在一起。这笔赠款还提供了促进研究生一级培训的机会，包括通过范德比尔特-梅哈里医学院联盟让少数族裔医学实习生参加培训。在机构层面，它进一步推动了心理系成为认知神经成像领域领先者的目标，并将促进范德比尔特进行的PET研究类型的扩展。

AbstractWith National Science Foundation support, Dr. Zald and colleagues will conduct a three-year project aimed at developing a novel program of research that fuses cognitive neuroimaging techniques with neuroimaging of neurotransmitter release. A wealth of neuropharmacological evidence indicates that dopamine (DA) exerts a profound influence on affective, motor, and cognitive processes. A full understanding of DA.s influence on neurobehavioral systems requires knowledge of how and when DA is released. Recent advances in PET imaging make it possible to safely measure DA release in humans during different cognitive or behavioral tasks. Such data provide novel insights into the functions of DA, and allows assessment of DA during cognitive functions for which animal models are lacking. However, because of the interdisciplinary nature of such studies, few cognitive neuroscientists have exploited these techniques. The project includes: 1) a learning component to facilitate the acquisition of the methodological skills necessary to perform studies of DA release using [11C]raclopride PET; 2) a program of studies aimed at testing specific hypotheses about when endogenous DA is released; and 3) continuing development of teaching skills, including the development of a course on the cognitive neuroscience of emotion. Specific studies focus on 1) the influence of task response demands and reward contingencies on DA release, 2) the impact of novelty on DA release, 3) whether DA is released during tasks involving set shifting (which is disrupted by DA depletions), and 4) the relationship between BOLD fMRI responses and DA release in striatal subregions. The proposal establishes collaborations between two major academic centers that will allow the exchange of ideas and technical developments in this emerging field. Because the field is in its infancy, dissemination of these ideas and techniques at meetings and symposium is likely to have substantial effects in guiding how others approach this area. Moreover, the interdisciplinary nature of the work allows for the integration of ideas across different fields of neuroscience. The grant also provides the opportunity to facilitate training at the graduate level including participation of minority M.D. trainees through the Vanderbilt-Meharry Medical college alliance. At the institutional level, it furthers the department of psychology's goal of becoming a leader in cognitive neuroimaging and will facilitate the expansion of the types of PET studies performed at Vanderbilt.