Evidence accumulation in obsessive-compulsive disorder during perceptual and value-based decisions

在基于知觉和价值的决策过程中强迫症的证据积累

• 批准号: 9755518
• 负责人: Christopher John Pittenger
• 金额: $ 20.94万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-03 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755518
• 关键词: Affect; Anterior; Attenuated; Basal Ganglia; Behavior; Behavior Control; Behavioral; Biological Markers; Blueberries; Brain; Categories; Cognition; Coke; Complex; Compulsive Behavior; Computer Simulation; Corpus striatum structure; Coupling; Data; Decision Making; Deep Brain Stimulation; Development; Diagnosis; Diagnostic; Diffusion; Dimensions; Disease; Distress; Equus caballus; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Heterogeneity; Ice Cream; Impulsivity; Individual; Lead; Link; Maps; Measures; Medial; Modeling; Neurobiology; Neurocognitive; Obsession; Obsessive-Compulsive Disorder; Oranges; Parietal; Persons; Pharmacological Treatment; Population; Prefrontal Cortex; Procedures; Process; Publishing; Refractory; Research; Rest; Role; Sensory; Services; Specific qualifier value; Structure of subthalamic nucleus; Symptoms; Tea; Testing; Time; Transcranial magnetic stimulation; Uncertainty; Work; base; behavioral impairment; biomarker development; cingulate cortex; clinical development; compulsion; disorder control; driving behavior; endophenotype; flexibility; foot; individual variation; interest; neural network; neurofeedback; novel; novel therapeutic intervention; novel therapeutics; potential biomarker; recruit; relating to nervous system; response; symptomatology; theories; treatment response

7. Project Summary Decision making in the real world is complex and is modulated by numerous factors. We and others have found that specific aspects of decision making are abnormal in individuals with obsessive-compulsive disorder (OCD). We hypothesize that these abnormalities are related to both dysfunctions in neural cortico-basal ganglia circuits and the development of clinical symptomatology in such domains as indecisiveness, behavioral inflexibility, and compulsive repetition of actions. OCD affects about 1 person in 40; obsessions and compulsions are found in many more. Elucidating their relationship to underlying neurocognitive abnormalities is of fundamental importance and may ultimately lead to diagnostic clarification and new therapeutic interventions. This proposal seeks to employ the computational drift diffusion model (DDM) framework to refine and quantify the cortico-basal ganglia theory of OCD, which is widely accepted but remains qualitative. We employ the “hold- your-horses” model of subthalamic nucleus (STN) function to characterize individual variation in responses to changes in task difficulty and task context, on both behavioral and neurobiological levels, and their relations to OCD symptomatology. The model suggests that STN activity and connectivity contribute to individual ability to adjust the process of decision formation to meet current task demands, by modulating how much evidence needs to be accumulated before a choice between alternatives is made. This contributes to behavioral flexibility; we expect this STN function to be abnormal in OCD. Consistent with this hypothesis, prior studies and our pilot data suggest that individuals with OCD require more evidence before they make a perceptual categorization decision, which may lead to indecisiveness; but they tend to accumulate less evidence before making an value-based decision (when asked to choose which of two options is preferred), which may lead to reduced response inhibition and poor quality decisions (such as we have previously documented). Differences in decision making across these two contexts have rarely been systematically investigated (and never in OCD). Our novel task allows direct comparison of perceptual and value-based decisions, while varying tasks difficulty, using the rigorous DDM- based analysis on both behavioral and neural levels. Our pilot data demonstrate the feasibility of our approach. This proposal combines a novel theoretical framework of neurocognitive abnormalities in OCD, a sophisticated computational approach, and a specific mechanistic hypothesis implicating the STN and associated networks in OCD pathophysiology. These will be tested using hierarchical Bayesian estimation of DDM parameters in conjunction with state-of-the-art fMRI analyses. Quantifying STN abnormalities with DDM will help us to disentangle OCD-related abnormalities in basic neurocognitive processes and to begin to place the cortico-basal ganglia model of OCD on a more quantitative footing. In future work these analyses can be applied transdiagnostically. Ultimately, we hope this work will produce biomarkers of pharmacological treatment response, and may contribute to novel therapeutics modulating the implicated circuitries.

七、项目概要 现实世界中的决策是复杂的，并且受到许多因素的影响。我们和其他人发现 患有强迫症（OCD）的人决策的某些特定方面是异常的。 我们假设这些异常与神经皮质基底节回路的两种功能障碍有关 以及临床症状学在犹豫不决、行为僵化等领域的发展 强迫性重复动作。大约每 40 人中就有 1 人患有强迫症；强迫观念和强迫行为存在于 还有更多。阐明它们与潜在神经认知异常的关系至关重要 重要性，并可能最终导致诊断澄清和新的治疗干预措施。 该提案旨在采用计算漂移扩散模型（DDM）框架来细化和量化 强迫症的皮质基底节理论，该理论已被广泛接受，但仍然是定性的。我们采用“hold- 你的马”底丘脑核（STN）模型的功能是描述个体反应的差异 任务难度和任务背景在行为和神经生物学层面上的变化及其与 强迫症症状学。该模型表明 STN 活动和连接有助于个体能力 通过调整需要多少证据来调整决策形成过程以满足当前的任务需求 在做出选择之前积累。这有助于提高行为灵活性；我们 预计 OCD 患者的 STN 功能会出现异常。先前的研究和我们的试点数据与这一假设一致 建议强迫症患者在做出知觉分类决定之前需要更多证据， 这可能会导致优柔寡断；但他们在做出基于价值的判断之前往往会积累较少的证据 决定（当被要求选择两个选项中的哪一个时），这可能会导致反应抑制减少 以及低质量的决策（例如我们之前记录的）。不同地区决策的差异 这两种情况很少被系统地研究（并且从未在强迫症中进行过）。我们的新颖任务允许直接 比较感知和基于价值的决策，同时改变任务难度，使用严格的 DDM- 基于行为和神经层面的分析。我们的试点数据证明了我们方法的可行性。 该提案结合了强迫症神经认知异常的新颖理论框架，这是一种复杂的 计算方法，以及涉及 STN 和相关网络的具体机制假设 强迫症病理生理学。这些将使用 DDM 参数的分层贝叶斯估计进行测试 与最先进的功能磁共振成像分析相结合。使用 DDM 量化 STN 异常将有助于我们 解开基本神经认知过程中与强迫症相关的异常，并开始放置皮质基底核 强迫症的神经节模型更加定量。在未来的工作中可以应用这些分析 跨诊断。最终，我们希望这项工作能够产生药物治疗的生物标志物 响应，并可能有助于调节相关电路的新疗法。