Physiology and information processing of the OCD circuit

项目摘要（P2）。对适应性行为的控制，在最基本的层面上， 权衡回报和厌恶的结果，并决定何时冒险以获得最大回报， 为了安全起见这些过程中的功能障碍与精神障碍和适应不良有关。 行为状态，如强迫症（OCD）和焦虑。但尽管它们在 日常决策和临床设置，很少有人知道如何令人厌恶的结果影响价值- 基于决策。特别是，在非人类灵长类动物中，最接近人类的动物模型， 大脑如何评估和预测令人厌恶的事件的神经元机制知之甚少。P2将 (1)评估大脑如何控制决策的风险和不确定性下，令人厌恶的结果，在非 人类灵长类动物和（2）与康特中心的其他项目合作，将利用这些信息， 揭示了电路机制，和新的疗法，强迫症和相关的病理。目标1将 利用功能靶向的体内顺行追踪来鉴定vlPFC、VEGF 1和其他 从ACC中的一个区域接收输入的区域，该区域在功能上与处理价值有关， 不确定性的负面结果。在相同的动物中，我们将进行电生理检查， 新发现的大脑区域，并评估它们是否以及如何有助于处理估值， 不确定性，以及收到令人厌恶的增援。通过P1，我们将了解 强迫症相关脑区的功能特性及其解剖连接。对于P3-P5，我们将 非人类灵长类动物的单神经元数据，以进行治疗开发和电路映射工作， 人类目标二。将利用计算和实验方法的结合来评估 厌恶性强化信息的神经编码可能导致强迫症样适应不良行为 在不确定性的情况下。该目标将利用概率接近-回避任务（PAAT）， 我们与P3一起开发的，以确定参与厌恶决策的心理算法， 不确定性，并推导出其在ACC-vPFC-PWM电路中的神经基础。然后它会扰乱神经 活动在电路的确定的子区域，以获得因果关系的证据，其贡献的具体 PAAT中的行为控制方面。这个目标中前所未有的单神经元记录精度将 通知其他项目中成像数据的解释。此外，广泛的直接操纵 将探索调节强迫症相关回路的方法，以促进新治疗方法的开发 强迫症的治疗总而言之，这些与中心一体化的目标是我们理解 强迫症的神经生物学和更普遍的将扩大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，他们将阐明大脑区域如何 在强迫症中起着关键作用的神经元参与了我们的日常决策。

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.