Sub-second neurochemistry of error signals and affective processing in depression

抑郁症中错误信号和情感处理的亚秒神经化学

• 批准号: 10665721
• 负责人: PEARL H CHIU
• 金额: $ 77.1万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665721
• 关键词: Affective; Anhedonia; Anterior; Biological; Brain region; Chemicals; Clinic; Clinical; Cognition; Computer software; Conflict (Psychology); Decision Making; Disease; Dopamine; Elasticity; Electrochemistry; Electrodes; Electroencephalography; Emotional; Epilepsy; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Hospitals; Human; Impairment; Implanted Electrodes; Individual; Investigation; Learning; Major Depressive Disorder; Measures; Medical; Mental Depression; Methods; Monitor; Moods; Neuromodulator; Neurotransmitters; Participant; Pharmaceutical Preparations; Phase; Positron-Emission Tomography; Process; Public Health; Resistance; Resolution; Role; Serotonin; Signal Transduction; Specificity; Symptoms; System; Testing; Virginia; affective neuroscience; arm; awake; cingulate cortex; clinical research site; clinically significant; depressive symptoms; in vivo; machine learning algorithm; negative mood; neural; neurochemistry; neuroimaging; neurosurgery; new technology; novel therapeutics; response; symptomatic improvement; temporal measurement

PROJECT SUMMARY Serotonin and dopamine dysfunction have been long implicated in the pathophysiology of major depression. However, to date, delineating the role of these neuromodulators in depression has largely and necessarily relied on inference, with neuroimaging (including PET, fMRI, EEG) studies revealing responses in brain regions associated with dopamine and serotonin release and medications targeting the dopaminergic and serotoninergic systems improving symptoms for some individuals. In order to make significant advances in understanding the neural underpinnings of depression and developing novel therapeutics for the disorder, tracking neuromodulator responses quickly, accurately, and in vivo is required. Recent advances allow exactly the unprecedented ability to track neuromodulator responses with high temporal resolution and chemical specificity. Specifically, we are able to directly and simultaneously measure dopamine and serotonin responses in awake humans with the temporal resolution (~ 10 ms) required to examine the relationship of neuromodulator release with decision-making processes. The product of these advances is recordings of in vivo neuromodulator fluctuations at sub-second resolution. This application merges the clinical and affective neuroscience expertise of MPI Chiu with these advances of MPI Montague to directly examine the relationship of dopamine and serotonin responses to depression. To achieve this goal, we will record neuromodulator responses in participants with medication-resistant epilepsy who already have intracranial depth electrodes in place for phase-II monitoring. The depth electrodes are implanted by our neurosurgery colleagues at Virginia Tech’s medical affiliate Carilion Clinic (Project Co-I Witcher; Carilion Clinic clinical site PI). During recording, participants will be in a standard (i.e., non-surgical) hospital monitoring suite and perform i) an affective processing task (emotional Stroop) and ii) a value-based learning task (two-arm bandit) that have been shown by our group and others both to engage processes thought to be related to serotonin and dopamine function, and also to be related to negative mood and anhedonia symptoms, respectively, of depression.

项目总结 长期以来，5-羟色胺和多巴胺功能障碍一直与抑郁症的病理生理学有关。 然而，到目前为止，描述这些神经调节剂在抑郁症中的作用在很大程度上是必要的。 依靠推理，通过神经成像(包括PET、fMRI、EEG)研究揭示大脑的反应 与多巴胺和5-羟色胺释放相关的区域和靶向多巴胺能和5-羟色胺的药物 5-羟色胺能系统改善某些人的症状。为了在以下方面取得重大进展 了解抑郁症的神经基础并开发治疗这种疾病的新疗法， 需要快速、准确和活体跟踪神经调节剂的反应。 最近的进展使人们能够通过高密度脂蛋白跟踪神经调节剂的反应，这是前所未有的能力 时间分辨率和化学特异度。具体地说，我们能够直接和同时测量 清醒人类的多巴胺和5-羟色胺反应具有所需的时间分辨率(~10ms) 研究神经调节剂的释放与决策过程的关系。这些产品的产品 先进的是以亚秒级分辨率记录体内神经调节剂波动。此应用程序 将MPI Chiu的临床和情感神经科学专业知识与MPI Montague的这些进步相结合，以 直接检查多巴胺和5-羟色胺对抑郁反应的关系。 为了实现这一目标，我们将记录耐药参与者的神经调节剂反应。 已经安装了用于二期监测的颅内深度电极的癫痫患者。深度电极 由弗吉尼亚理工大学附属医疗机构Carilion Clinic(Project Co-I)的神经外科同事植入 Carilion诊所临床站点PI)。在录制过程中，参与者将处于标准状态(即非手术状态) 医院监测套件和执行i)情感处理任务(情绪Stroop)和ii)基于价值的 学习任务(双臂强盗)，我们小组和其他人都展示了参与过程 被认为与5-羟色胺和多巴胺功能有关，也与负面情绪和 快感缺失症状分别为抑郁。