Direct Dopamine Recording From Humans Engaging Working Memory

项目概要 多巴胺能信号被认为对于将项目门控到工作记忆和 在分散注意力的信息存在的情况下，在延迟的情况下保持代表性内容。工作记忆 多巴胺能信号失调导致的缺陷与多种精神疾病有关。 然而，由于我们的能力有限，多巴胺在工作记忆中的确切作用尚未完全了解。 在人类中测量它的能力。 PI Montague 研究小组的最新进展允许追踪神经调节剂的释放 癫痫患者使用快速扫描循环伏安法增强机器学习（弹性网络回归）。 我们的团队现在可以以亚秒时间分辨率测量清醒人类的多巴胺反应， 允许精确表征皮质区域的阶段性和强直性多巴胺释放 与构成工作记忆的认知过程相关。该应用程序融合了该技术 通过测量工作记忆过程来测试有关多巴胺功能的基本预测 认知控制。 我们将记录外侧前额皮质、前扣带皮层和 执行一组工作记忆任务期间的海马体。难治性癫痫患者会 参与通过手术植入电极监测癫痫活动的 II 期研究。 这些电极将被植入凤凰城都市区的班纳医院 (Co-I Bina)。期间 记录，患者将完成延迟匹配样本和延迟估计视觉工作记忆 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 工作记忆的个体差异并探讨过去15年工作记忆的神经基础 年。该项目的总体目标是收集刺激期间的直接多巴胺记录并对其进行建模 演示、干扰演示和典型工作记忆任务的延迟期，以更好地 描述工作记忆中阶段性和强直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.