Direct Dopamine Recording From Humans Engaging Working Memory

人类工作记忆的直接多巴胺记录

• 批准号: 10803720
• 负责人: P Read Montague
• 金额: $ 69.42万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10803720
• 关键词: Address; Anterior; Area; Attention deficit hyperactivity disorder; Behavioral; Brain region; Color; Communication; Confusion; Data; Disease; Dopamine; Elasticity; Electrodes; Epilepsy; Goals; Hippocampus; Hospitals; Human; Implant; Implanted Electrodes; Individual; Individual Differences; Lateral; Machine Learning; Maintenance; Measurement; Measures; Memory; Memory impairment; Mental disorders; Methodology; Methods; Midbrain structure; Modeling; Monitor; Neuromodulator; Operative Surgical Procedures; Participant; Patients; Performance; Periodicity; Pharmaceutical Preparations; Phase; Prefrontal Cortex; Prosencephalon; Research; Resistance; Resolution; Rewards; Role; Sampling; Scanning; Schizophrenia; Seizures; Short-Term Memory; Signal Transduction; Stimulus; Techniques; Testing; Time; Visual; awake; cingulate cortex; cognitive control; cognitive process; dopaminergic neuron; interest; memory process; metropolitan; neural; novel; resilience; response; temporal measurement; theories; time use

PROJECT SUMMARY Dopaminergic signaling is proposed to be critical for gating items into working memory and for maintaining representational content over delays in the presence of distracting information. Working memory deficits due to dysregulated dopaminergic signaling are associated with a broad range of psychiatric illnesses. However, the precise role of dopamine in working memory has yet to be fully understood due to limits on our ability to measure it in humans. Recent advances by PI Montague’s research group allow for tracking neuromodulator release in epilepsy patients using fast-scan cyclic voltammetry augmented with machine learning (elastic net regression). Our team can now measure dopamine responses in awake humans with sub-second temporal resolution, allowing for precise characterization of phasic and tonic dopamine release in cortical areas that have been associated with cognitive processes that constitute working memory. This application merges this technique with measurement of working memory processes to test fundamental predictions about dopamine’s function in cognitive control. We will record dopamine release in the lateral prefrontal cortex, anterior cingulate cortex, and hippocampus during performance of a set of working memory tasks. Medication-resistant epilepsy patients will participate in the study during phase-II monitoring for seizure activity with surgically implanted electrodes. These electrodes will be implanted at Banner Hospital in the Phoenix metropolitan area (Co-I Bina). During recording, patients will complete Delay Match-to-Sample and Delayed Estimation Visual Working Memory tasks. Our research group (Co-I Brewer, Co-I Bae, and Co-I McClure) has used these tasks to characterize individual differences in working memory and to explore the neural basis of working memory for the past 15 years. The overall goal of this project is to collect and model direct dopamine recordings during stimulus presentation, distractor presentation, and delay periods of canonical working memory tasks to better characterize the role of phasic and tonic dopamine release in working memory.

项目摘要 提议多巴胺能信号传导对于进入工作记忆和对 在存在分散注意力的信息的情况下，在延误中保持代表性内容。工作记忆 由于多巴胺能信号失调而引起的缺陷与多种精神病有关。 但是，由于我们的限制，多巴胺在工作记忆中的精确作用尚未完全理解 在人类中测量它的能力。 Pi Montague研究小组的最新进展允许跟踪神经调节剂的释放 使用机器学习（弹性净回归）增强使用快速扫描环状伏安法的癫痫患者。 现在，我们的团队可以通过以下临时分辨率来衡量醒着人的多巴胺反应， 允许精确表征在已经 与构成工作记忆的认知过程相关联。该应用程序合并了此技术 通过测量工作记忆过程，以测试有关多巴胺功能的基本预测 认知控制。 我们将在前额叶皮层，前扣带回皮质和 在执行一组工作记忆任务的过程中，海马。耐药性癫痫患者将 在II期监测期间，通过手术植入电子的癫痫发作活性参加研究。 这些电子将植入凤凰城都会区（Co-I Bina）的横幅医院。期间 记录，患者将完成延迟匹配样本和延迟估计的视觉工作记忆 任务。我们的研究小组（Co-I Brewer，Co-I Bae和Co-I McClure）使用这些任务来表征 工作记忆中的个体差异并探索过去15次工作记忆的神经基础 年。该项目的总体目标是在刺激过程中收集和建模直接多巴胺记录 呈现，干扰物的演示和规范工作记忆任务的延迟期 表征了阶段性和滋补多巴胺在工作记忆中的作用。