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

7.项目摘要 真实的世界中的决策是复杂的，并受到许多因素的影响。我们和其他人发现 强迫症（OCD）患者决策的特定方面是异常的。 我们推测这些异常与神经皮质-基底节回路的功能障碍有关 以及临床诊断学在诸如优柔寡断、行为不确定性等领域的发展， 强迫性的重复动作。强迫症影响约40人中的1人;强迫症和强迫症被发现， 更多.阐明它们与潜在的神经认知异常的关系是至关重要的 重要性，并可能最终导致诊断澄清和新的治疗干预措施。 该建议旨在采用计算漂移扩散模型（DDM）框架来细化和量化 强迫症的皮质基底神经节理论，这是广泛接受的，但仍然定性。我们使用“保持- 你的马”模型的丘脑底核（ESTA）的功能，以表征个体差异的反应， 在行为和神经生物学水平上，任务难度和任务背景的变化，以及它们与 强迫症治疗学该模型表明，活动和连接有助于个人的能力， 调整决策形成的过程，以满足当前的任务需求，通过调整证据的需求量 在做出选择之前积累起来。这有助于行为的灵活性;我们 预期这一功能在强迫症中是异常的。与这一假设相一致，先前的研究和我们的试点数据 表明强迫症患者在做出知觉分类决定之前需要更多证据， 这可能会导致犹豫不决;但他们倾向于在做出基于价值的判断之前积累较少的证据， 决策（当被要求选择两个选项中的哪一个是首选），这可能导致反应抑制减少 和低质量的决策（如我们以前记录的）。决策过程中的差异 这两种背景很少被系统地研究（在强迫症中也从未）。我们的新任务允许直接 比较知觉和价值为基础的决定，而不同的任务难度，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的方法的可行性。 这一建议结合了强迫症神经认知异常的一个新的理论框架， 计算方法，以及一个具体的机械假设，涉及的神经网络和相关的网络， 强迫症的病理生理学这些将使用DDM参数的分层贝叶斯估计进行检验， 结合最先进的功能磁共振成像分析用DDM量化脑血管异常将有助于我们 在基本的神经认知过程中解开强迫症相关的异常，并开始将皮质基底神经元 强迫症的神经节模型进行定量分析在今后的工作中，这些分析可以应用于 transdiagnosis诊断。最终，我们希望这项工作将产生药物治疗的生物标志物 反应，并可能有助于新的治疗调制牵连电路。

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.