Direct Dopamine Recording From Humans Engaging Working Memory

项目总结 多巴胺能信号被认为是门控项目进入工作记忆和 在出现令人分心的信息的情况下，在延迟情况下维护代表性内容。工作记忆 多巴胺能信号失控导致的缺陷与一系列精神疾病有关。 然而，多巴胺在工作记忆中的确切作用还没有完全了解，因为我们的 在人类身上测量它的能力。 皮蒙塔古研究小组的最新进展使追踪神经调节剂的释放成为可能 使用快速扫描循环伏安法的癫痫患者增加了机器学习(弹性网络回归)。 我们的团队现在可以用亚秒的时间分辨率测量清醒人类的多巴胺反应， 从而能够精确地表征在已经被认为是 与构成工作记忆的认知过程相关的。此应用程序合并了此技术 通过测量工作记忆过程来测试关于多巴胺功能的基本预测 认知控制。 我们将记录外侧前额叶皮质、前扣带回皮质和 在一组工作记忆任务的执行过程中，海马体。耐药癫痫患者将 在使用外科植入电极监测癫痫发作活动的第二阶段期间参与研究。 这些电极将被植入凤凰城大都市区的班纳医院(Co-I Bina)。在.期间 记录下来，患者将完成延迟样本匹配和延迟估计视觉工作记忆 任务。我们的研究小组(Co-I Breyer、Co-I Bae和Co-I McClure)使用这些任务来表征 工作记忆的个体差异及过去15年工作记忆的神经基础 好几年了。这个项目的总体目标是收集和模拟刺激过程中的直接多巴胺记录。 典型工作记忆任务的呈现、分心呈现和延迟时间更好 描述工作记忆中时相性和强激性多巴胺释放的作用。

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.