Project 2_Dougherty: Invasive Recording and Neurostimulation Studies of Approach/Avoidance Behaviors in Humans

项目2_Dougherty：人类接近/回避行为的侵入性记录和神经刺激研究

• 批准号: 10601134
• 负责人: DARIN D DOUGHERTY
• 金额: $ 64.8万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601134
• 关键词: Acute; Affect; Animals; Anterior; Anxiety Disorders; Area; Behavior; Behavior assessment; Behavioral; Brain; Brain region; Cell Nucleus; Chronic; Code; Conflict (Psychology); Corpus striatum structure; Data; Decision Making; Deep Brain Stimulation; Desire for food; Dorsal; Electrodes; Electroencephalography; Epilepsy; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; General Hospitals; Goals; Grant; Human; Implant; Individual; Investigation; Lateral; Link; Major Depressive Disorder; Mammals; Massachusetts; Measurement; Medial; Mediating; Mental Depression; Mental disorders; Midbrain structure; Monitor; Mood Disorders; Nature; Neurons; Nucleus Accumbens; Operative Surgical Procedures; Pathway interactions; Patient Admission; Patients; Performance; Prefrontal Cortex; Punishment; Reaction Time; Resolution; Rewards; Risk; Rodent; Role; Seizures; Signal Transduction; Site; Stimulus; Structure; Task Performances; Testing; Ventral Striatum; Ventral Tegmental Area; approach avoidance behavior; approach behavior; avoidance behavior; awake; capsule; cingulate cortex; depressed patient; experience; human model; imaging study; implantation; insight; millisecond; neural; neural network; neurobiological mechanism; neuroimaging; neuropsychiatric disorder; neuropsychiatry; nociceptin; nonhuman primate; novel; recruit; striosome; synergism; temporal measurement

PROJECT SUMMARY (PROJECT 2, Project Leader: Dougherty, Massachusetts General Hospital) The goal of Project 2 is to causally probe the role of cortico-striatal circuits in approach-avoidance conflict using invasive recording and neurostimulation in awake, behaving humans. Invasive studies in humans serve as a bridge between the complementary invasive animal and non-invasive human studies in other Projects. Noninvasive human functional imaging studies provide valuable insights into the circuitry underlying specific brain functions but – fundamentally – are correlative in nature. Invasive measurements in humans during tasks provide markedly better spatial resolution (down to the single neuron) and temporal resolution (down to 5-10 milliseconds). More critically, the ability to stimulate using the same electrodes allows for unique “backwards neuroimaging”. Instead of performing a task and observing which brain networks are involved, one can stimulate different brain regions at different amplitudes, frequencies and task epochs to observe effects on task performance all while simultaneously recording. In this project we propose to study approach-avoidance conflict in two human models: (1) deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) and (2) surgical epilepsy monitoring. Over five years, we will recruit 20 DBS patients with chronic DBS electrodes in the VC/VS for treatment of neuropsychiatric disorders and 20 patients with epilepsy with acute depth electrodes for seizure monitoring. We will investigate the behavioral and neural effects of DBS on approach-avoidance behavior in patients with major depressive disorder (MDD) with implanted DBS electrodes in the VC/VS. Capitalizing on our prior studies and extensive set of preliminary data we will use an approach/avoidance decision making task to assess behavioral and neural changes associated with stimulation of the ventral striatum (as opposed to no stimulation) in neuropsychiatric patients with implanted DBS depth electrodes. We will also investigate the large- scale neural network of approach-avoidance behavior in epilepsy patients implanted with depth electrodes, and test the hypothesis that closed-loop stimulation targeting key cortico-striatal nodes will bidirectionally modulate approach-avoidance behaviors in depressed patients. Building on our extensive experience in this area we will record simultaneous activity of multiple prefrontal structures and, in some cases, striatum, in patients admitted to the MGH Epilepsy Monitoring Units following implantation of depth electrodes. To maximize synergies across Projects, the task will be identical to the one used in Project 1 (with unmedicated individuals with MDD or anxiety disorders) and functionally analogous to the one in Project 3 (with non-human primates). Contribution to Overall Center Goals & Interactions with Other Center Components. By testing that direct stimulation of both approach-related (e.g., striatum) and avoidance-related (e.g., pregenual anterior cingulate cortex) areas affects approach-avoidance behavior in humans, Project 2 will directly link the non-invasive fMRI studies in individuals with unmedicated MDD (Project 1) with the non-human primate (Project 3) and rodent (Project 4) studies that will mechanistically dissect neurobiological mechanisms governing approach/avoidance behaviors.

项目总结（项目2，项目负责人：Doughman，马萨诸塞州总医院） 项目2的目标是通过使用一种新的方法来探索皮质-纹状体回路在接近-回避冲突中的作用。 侵入性记录和神经刺激在清醒，行为人类。人类的侵入性研究作为一种 在其他项目中，作为补充的侵入性动物和非侵入性人类研究之间的桥梁。 非侵入性的人类功能成像研究提供了有价值的见解电路的具体 大脑功能，但从根本上说，是相互关联的性质。任务期间对人体的侵入性测量 提供明显更好的空间分辨率（低至单个神经元）和时间分辨率（低至5-10 毫秒）。更关键的是，使用相同电极刺激的能力允许独特的“反向”刺激。 神经成像”。我们可以刺激大脑，而不是执行一项任务并观察哪些大脑网络参与其中， 不同的脑区在不同的振幅，频率和任务时期，以观察对任务的影响 所有的表演同时记录。在这个项目中，我们建议研究接近-回避冲突 在两种人体模型中：（1）腹侧囊/腹侧纹状体（VC/VS）的深部脑刺激（DBS）和（2） 外科癫痫监测在五年内，我们将招募20名DBS患者， VC/VS治疗神经精神疾病和20例癫痫患者，急性深部电极用于 缉获监测。我们将研究DBS对接近-回避行为的行为和神经影响 在VC/VS中植入DBS电极的重度抑郁症（MDD）患者中。 我们先前的研究和大量的初步数据，我们将使用一个接近/回避决策任务， 为了评估与腹侧纹状体的刺激相关的行为和神经变化（与没有刺激相反）， 刺激）。我们还将调查大- 植入深度电极的癫痫患者的接近-回避行为的尺度神经网络，以及 测试靶向关键皮质-纹状体节点的闭环刺激将双向调节 抑郁症患者的接近-回避行为。基于我们在这一领域的丰富经验， 记录多个前额叶结构的同时活动，在某些情况下，纹状体，在病人入院 在植入深部电极后，MGH癫痫监测单元。最大限度地发挥各部门的协同作用， 项目，任务将与项目1中使用的任务相同（未用药的MDD或焦虑患者 疾病），并且功能上类似于项目3中的（非人灵长类动物）。贡献 总体中心目标和与其他中心组件的交互。通过测试直接刺激 两者都与接近相关（例如，纹状体）和回避相关（例如，膝前扣带皮层）区 影响人类的接近-回避行为，项目2将直接将非侵入性功能磁共振成像研究， 未用药MDD个体（项目1）与非人灵长类动物（项目3）和啮齿类动物（项目4） 这些研究将从机制上剖析控制接近/回避行为的神经生物学机制。