Direct Dopamine Recording From Humans Engaging Working Memory

项目摘要 多巴胺能信号被认为是至关重要的门控项目进入工作记忆， 在存在分散注意力的信息的情况下在延迟上保持代表性内容。工作记忆 由于多巴胺能信号传导失调引起的缺陷与广泛的精神疾病有关。 然而，多巴胺在工作记忆中的确切作用还没有完全理解，因为我们对多巴胺的认识有限。 在人类身上测量的能力。 PI Montague研究小组的最新进展允许跟踪神经调节剂的释放， 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测量清醒人类的多巴胺反应，时间分辨率为亚秒， 允许精确地表征已经在大脑皮层区域中的阶段性和紧张性多巴胺释放， 与构成工作记忆的认知过程相关。此应用程序将此技术 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层，前扣带皮层， 海马在一组工作记忆任务的性能。抗癫痫药患者会 在II期监测期间使用手术植入电极参与研究。 这些电极将在凤凰城都会区的Banner医院（Co-I Bina）植入。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麦克卢尔）使用这些任务来描述 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和模拟刺激过程中的直接多巴胺记录 呈现、干扰物呈现和延迟期的规范工作记忆任务，以更好地 描述了工作记忆中阶段性和紧张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.