Cognitive and Neural Correlates in Obsessive Compulsive Disorder

描述（由申请人提供）：病理性不确定性是强迫症（OCD）的一个关键特征，除了驱动特定的强迫和强迫外，还会损害日常决策。作为强迫症潜在的核心过程，不确定性的增加可能是一种独立于症状激发而发生的特征特征，可能是强迫症治疗和预防研究的重点。虽然先前的研究表明强迫症患者比健康对照组获得更多的信息来做出决定，但很少有工作集中在阐明强迫症患者异常决策相关的认知和神经机制。在我们的初步研究中，为了减少不确定性并做出决定，我们需要连续的证据。结果表明，获取新信息的成本和信息呈现环境的模糊性是影响控制被试主观不确定性和证据积累的重要因素。在三项研究中，我们将测试一系列假设，这些假设预测强迫症患者的长期信息获取是由对这些因素的相对不敏感所驱动的。在第一项行为研究中，我们预测，无论背景和信息搜索的成本如何，OC症状严重程度的增加将与更大的不确定性和更多的证据积累相关。在第二和第三项研究中，将使用功能磁共振成像（fMRI）检查健康对照和强迫症患者的神经活动，目的是确定异常认知体验或不确定性情绪评估的神经机制。特别是，与强迫症病理有关的额叶区域，如背内侧前额叶皮层/前扣带皮层和眶额叶皮层的过度活跃，可能分别是不确定性处理的不同认知和情感方面的增加的基础。这些研究的结果将提供oc相关决策行为的全面表征，使临床医生能够改进治疗耐药患者的治疗技术。此外，研究这些过程的神经基础可能有助于识别强迫症的生物学内表型，并进一步研究该疾病的遗传易感性。强迫症病理性优柔寡断导致的严重残疾和情绪困扰是患者和卫生保健界关注的重要问题。对不确定性作为强迫症核心过程的研究是推进治疗策略和确定影响该疾病发展的遗传因素的有希望的一步。

DESCRIPTION (provided by applicant): Pathological uncertainty is a key feature of obsessive compulsive disorder (OCD), impairing everyday decision-making in addition to driving specific obsessions and compulsions. As a potential core process in OCD, increased uncertainty may be a trait characteristic that occurs independently of symptom provocation and could be the focus of research into treatment and prevention of the disorder. Although previous research has shown that OCD patients acquire more information in order to reach a decision than healthy controls, little work has focused on elucidating the cognitive and neural mechanisms associated with abnormal decision-making in OCD. In our preliminary study, sequential pieces of evidence were requested in order to reduce uncertainty and reach a decision. Results revealed that the cost of acquiring new information and the ambiguity of the context in which information was presented were important factors influencing subjective uncertainty and evidence accumulation among control subjects. In three studies, we will test a series of hypotheses predicting that prolonged information acquisition in OCD is driven by a relative insensitivity to these factors. In the first behavioral study, we predict that increasing OC symptom severity will be associated with greater uncertainty and increased evidence accumulation, regardless of the context and cost of information search. In the second and third studies, neural activity will be examined in healthy controls and OCD patients using functional magnetic resonance imagining (fMRI), with the aim of identifying the neural mechanisms underlying the abnormal cognitive experience or emotional appraisal of uncertainty. In particular, hyperactivity in frontal regions implicated in the pathology of OCD, such as dorsomedial prefrontal cortex/anterior cingulate cortex and orbitofrontal cortex, may underlie increases in distinct cognitive and affective aspects of uncertainty processing, respectively. Results from these studies will provide a thorough characterization of OC-related decision-making behavior, enabling clinicians to refine therapeutic techniques for treatment-resistant patients. Moreover, investigation into the neural substrates of these processes may lead to the identification of biological endophenotypes of OCD and further research on genetic susceptibilities of the disorder. The significant disability and emotional distress resulting from pathological indecisiveness in OCD constitutes an important concern for the patient as well as the health care community. The investigation of uncertainty as a core process in OCD is a promising step toward advancing treatment strategies and identifying genetic factors influencing the development of the disorder.