Direct sub-second measurement of neuromodulator signaling during risky decision-making

在风险决策过程中直接亚秒测量神经调节信号

• 批准号: 10579985
• 负责人: Brooks Casas
• 金额: $ 65.87万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-08 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579985
• 关键词: Anhedonia; Anxiety Disorders; Behavioral; Chemicals; Clinic; Computer software; Decision Making; Dopamine; Dorsal; Elasticity; Electrochemistry; Electrodes; Epilepsy; Functional Magnetic Resonance Imaging; Goals; Health; Hospitals; Human; Implant; Implanted Electrodes; Learning; Link; Major Depressive Disorder; Measurement; Measures; Medial; Medical; Mental disorders; Methods; Monitor; Neurobiology; Neuromodulator; Neurosciences; Neurotransmitters; Norepinephrine; Outcome; Participant; Pharmaceutical Preparations; Pharmacology Study; Phase; Play; Prefrontal Cortex; Process; Resistance; Resolution; Rewards; Risk; Risk Behaviors; Role; Serotonin; Signal Transduction; Specificity; Testing; Update; Virginia; Work; arm; awake; experience; in vivo; machine learning algorithm; neural; neurosurgery; new technology; noradrenergic; response; substance use; temporal measurement

PROJECT SUMMARY Much work in decision neuroscience has been predicated on the hypothesis that dopaminergic signaling plays a critical role in value representations and their updating, and recent work has linked abnormalities in such value representations to specific features of psychiatric illness (e.g., anhedonia in major depression). However, despite the fundamental role that risk plays in evaluating choice options as well as the role sensitivity to risk plays in psychiatric illness, including anxiety disorders at one extreme and health risk behaviors like substance use at another other, an understanding of the neurobiology of risk remains elusive. Indirect evidence from pharmacological studies have suggested both serotoninergic and noradrengergic signaling may play roles in representations of risk; however, direct measurement of serotonin or norepinephrine signaling during risky choice has yet to be examined in humans. Recent advances by MPI Montague’s group allow the unprecedented ability to track neuromodulator responses with high temporal resolution and chemical specificity. Specifically, MPI Montague’s team is able to directly and simultaneously measure dopamine and serotonin responses in awake humans with the temporal resolution (~ 1 ms) required to examine the relationship of neuromodulator release with decision-making processes. For signal identification and extraction, the recording method uses machine-learning algorithms (elastic net regression) combined with electrochemistry using only off-the shelf hardware and software. The product of this ‘elastic net electrochemistry’ is recordings of in vivo neuromodulator fluctuations at sub-second resolution. This application merges the decision neuroscience expertise of MPI King-Casas with these advances of MPI Montague to directly examine serotonergic, noradrenergic, and dopaminergic functioning during risky choice. 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. Depth electrodes will be implanted by our neurosurgery colleagues at Virginia Tech’s medical affiliate Carilion Clinic (Carilion Clinic PI: Witcher). During recording, participants will perform i) a risk elicitation task (Holt & Laury type task) and ii) a reward learning task (multi-arm bandit task) that have been shown by our group and others both to reliably evoke neural responses associated with risk and representations as they are monitored in a standard (i.e., non-surgical) hospital suite. Depth recordings will be made using a standard montage that includes multiple contacts along the dorsal-rostral axis of the medial prefrontal cortex.

项目概要 决策神经科学中的许多工作都是基于多巴胺能信号传导的假设 在价值表示及其更新中发挥着关键作用，最近的工作已将此类异常联系起来 然而，精神疾病的特定特征（例如重度抑郁症的快感缺失）的价值表征。 尽管风险在评估选择选项以及对风险的敏感性中发挥着根本作用 与精神疾病有关，包括极端的焦虑症和物质等健康风险行为 在另一个方面，对风险的神经生物学的理解仍然难以捉摸。 药理学研究表明，血清素能和去甲肾上腺素能信号传导可能在 风险的表示；然而，在危险期间直接测量血清素或去甲肾上腺素信号 选择尚未在人类身上得到检验。 MPI Montague 团队的最新进展使得追踪神经调节剂的能力达到前所未有的水平 具体来说，MPI Montague 的团队能够实现具有高时间分辨率和化学特异性的响应。 直接并同时测量清醒人类的多巴胺和血清素反应 检查神经调节剂释放与决策之间的关系所需的分辨率（约 1 毫秒） 对于信号识别和提取，记录方法使用机器学习算法。 （弹性网回归）与电化学相结合，仅使用现成的硬件和软件。 这种“弹性网电化学”的产物是亚秒内体内神经调节剂波动的记录 该应用程序将 MPI King-Casas 的决策神经科学专业知识与这些技术相结合。 MPI Montague 直接检查血清素能、去甲肾上腺素能和多巴胺能功能的进展 在进行危险的选择时。 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 已安装颅内深度电极进行第二阶段监测的癫痫患者将使用深度电极。 由我们弗吉尼亚理工大学医疗附属机构 Carilion Clinic（Carilion Clinic）的神经外科同事植入 PI：《巫师》期间，参与者将执行 i) 风险引发任务（Holt & Laury 类型任务）和 ii) a 奖励学习任务（多臂强盗任务）已被我们的小组和其他人证明是可靠的 当按照标准（即， 深度录音将使用包含多个的标准蒙太奇进行。 沿着内侧前额叶皮层的背侧-喙轴接触。