Physiology and information processing of the OCD circuit

强迫症回路的生理学和信息处理

基本信息

批准号：
10594000
负责人：
Ilya E. Monosov
金额：
$ 34.09万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10594000
关键词：
Adaptive Behaviors Agonist Algorithms Anatomy Animal Model Animals Anxiety Area Axon Behavior Behavior Control Behavioral Brain Brain region Clinical Collaborations Computer Analysis Data Decision Making Dedications Desire for food Development Electrophysiology (science)Event Grant Histologic Human Image Analysis Incentives Insula of Reil Internal Capsule Laboratories Magnetic Resonance Imaging Maps Measures Mediating Mental disorders Methods Monkeys Muscimol Negative Reinforcements Neurobiology Neurons Obsessive-Compulsive Disorder Outcome Pathology Pathway interactions Patients Physiology Play Prefrontal Cortex Procedures Process Property Psyche structure Psychological reinforcement Publications Rewards Risk Role Symptoms Uncertainty Work design expectation experimental study in vivo information processing maladaptive behavior mind control motivated behavior neural neural circuit neurotransmission nonhuman primate novel novel therapeutics optogenetics therapy development willingness

项目摘要

Project Summary (P2). The control of adaptive behavior, at its most fundamental level, relies on appropriately weighting the rewards and aversive outcomes, and deciding when to take a risk to maximize reward, and when to play it safe. Malfunctions in these processes are associated with psychiatric disorders and maladaptive behavioral states, such Obsessive-Compulsive Disorder (OCD) and anxiety. But despite their importance in everyday decision making and clinical settings, little is known about how aversive outcomes influence value- based decision making. In particular, in non-human primates, the closest animal model to humans, the neuronal mechanisms of how the brain evaluates and anticipates aversive events is poorly understood. P2 will (1) assess how the brain controls decision making under the risk and uncertainty of aversive outcomes in non- human primates and (2) in collaboration with other projects in the Conte Center, will utilize this information to shed light on the circuit mechanisms of, and novel therapies for, OCD and related pathologies. Aim 1 will utilize functionally targeted in-vivo anterograde tracing to identify regions within vlPFC, insula, and other regions that receive inputs from an area in ACC that has been functionally implicated in processing value and uncertainty of aversive outcomes. In the same animals, we will perform electrophysiological examinations of newly identified brain regions and assess whether and how they contribute to the processing of valuation, uncertainty, and receipt of aversive reinforcements. With P1, we will understand the relationship between functional properties of the OCD related brain areas and their anatomic connectivity. With P3-P5, we will relate single neuron data in non-human primates to ongoing therapy development and circuit mapping efforts in humans. Aim 2. will utilize a combination of computational and experimental methods to assess how the neural encoding of information about aversive reinforcements could give rise to OCD-like maladaptive behavior under aversive-outcome uncertainty. This Aim will utilize the probabilistic approach-avoidance task (PAAT), that we developed with P3, to determine the mental algorithms involved in aversive decision making under uncertainty and derive their neural underpinnings in the ACC-vlPFC-insula circuit. It will then disrupt the neural activity in identified sub regions of the circuit to obtain causal evidence for their contributions to specific aspects of behavioral control in PAAT. The unprecedented precision of single neuron recordings in this Aim will inform the interpretation of imaging data in other Projects. Furthermore, a wide range of direct manipulation methods for mediating OCD-related circuitry will be explored to facilitate the development of novel treatments for OCD in P5. In sum, these Center-integrated Aims represent crucial steps for our understanding of the neurobiology of OCD and more generally will broaden our understanding of the mechanisms of decision making. Particularly, in collaboration with other projects of the Center, they will shed light on how brain areas known to be crucially involved in OCD mediate our everyday decision making.

项目摘要（P2）。适应性行为的控制，在其最基本的层面上，依赖于适当的权衡奖励和厌恶结果，并决定何时冒险以最大化奖励，以及何时为了安全起见。这些过程中的故障与精神疾病和适应不良有关行为状态，例如强迫症（OCD）和焦虑。但尽管它们在在日常决策和临床环境中，人们对厌恶结果如何影响价值知之甚少—— 为基础的决策。特别是在非人类灵长类动物中，最接近人类的动物模型人们对大脑如何评估和预测厌恶事件的神经机制知之甚少。 P2将（1）评估大脑如何在非预期的厌恶结果的风险和不确定性下控制决策人类灵长类动物以及 (2) 与 Conte 中心的其他项目合作，将利用这些信息揭示了强迫症和相关病理学的循环机制和新疗法。目标1将利用功能性靶向体内顺行追踪来识别 vlPFC、岛叶和其他区域内的区域从 ACC 中的某个区域接收输入的区域，该区域在功能上与处理值有关，并且厌恶结果的不确定性。在相同的动物中，我们将进行电生理检查新识别的大脑区域并评估它们是否以及如何有助于评估处理，不确定性，以及收到厌恶的强化。有了P1，我们就会明白它们之间的关系强迫症相关大脑区域的功能特性及其解剖连接。通过 P3-P5，我们将联系起来非人类灵长类动物的单个神经元数据用于正在进行的治疗开发和电路图绘制工作人类。目标 2. 将结合计算和实验方法来评估有关厌恶强化信息的神经编码可能会引起类似强迫症的适应不良行为在厌恶结果的不确定性下。该目标将利用概率回避任务（PAAT），我们用 P3 开发的，以确定在以下情况下参与厌恶决策的心理算法不确定性并得出 ACC-vlPFC-insula 回路中的神经基础。然后它会破坏神经循环中确定的子区域的活动，以获得其对特定区域的贡献的因果证据 PAAT 中行为控制的各个方面。该目标中单神经元记录的前所未有的精度将为其他项目中成像数据的解释提供信息。此外，广泛的直接操纵将探索介导强迫症相关电路的方法，以促进新疗法的开发 P5 中的强迫症。总之，这些中心综合目标代表了我们理解强迫症的神经生物学，更广泛地说，将拓宽我们对决策机制的理解制作。特别是，与该中心的其他项目合作，他们将揭示大脑区域如何已知与强迫症密切相关的物质会调节我们的日常决策。