Functional Neuroanatomy of Obsessive Compulsive Disorder

描述（由申请人提供）：大量证据表明强迫症（OCD）涉及大脑额叶回路的异常功能，特别是皮质-纹状体-苍白质-丘脑（CSPT）回路。神经影像学研究表明，脑回路的一些边缘相关成分（眶额皮质[OFC]、前扣带皮质[OFC]和尾状核[CN]）活动过度，但这些发现的意义尚不清楚。异常的功能活动可能有助于定位失调的电路，但它也可能反映对其他地方异常的反应。然而，脑图研究表明，内侧额叶结构，如ACC，在检测错误中起着核心作用。这种心理过程似乎在强迫症患者身上受到干扰，他们倾向于过度关注不犯错误和避免潜在的不良后果。初步数据显示，强迫症患者的电生理电位过度活跃被认为是由与错误相关的负性脑皮层（ACC）产生的。边缘CSPT回路（尤其是OFC和CN）的一个关键功能还涉及对收益和损失的评估和预期，这一过程决定了可能行动的重要性并指导选择。这一建议将从以下理论出发：在强迫症患者中，由于大脑（通过边缘CSPT回路）高估了潜在的或实际的损失，常见的想法获得了病理意义。功能性磁共振成像和事件相关电位研究将通过已知的简单任务来探测CSPT回路，这些任务可以在这些大脑区域引起神经反应，而不会引起强迫症的症状。两项实验将验证以下假设，即强迫症是由这些区域的异常大脑活动组成的：在犯错期间，当他们预测和应对潜在的金钱损失时，这使我们能够评估关于强迫症功能解剖学的一系列假设。强迫症患者将在药物治疗的、相对无症状的样本和未药物治疗的、相对有症状的样本中进行研究，以确定该疾病的特征相关成分。这些患者样本将与精神健康的受试者和先前接受过药物治疗的抑郁症患者进行比较。该项目的成功完成将使人们更好地了解特定大脑区域在产生强迫症症状中的作用。

DESCRIPTION (provided by applicant): Considerable evidence suggests that obsessive compulsive disorder (OCD) involves abnormal function in frontal brain circuits, specifically the cortico-striatal-pallidal-thalamic (CSPT) loops. Neuroimaging studies demonstrate excessive activity in some of the limbic-related components of the loops (orbitofrontal cortex [OFC], anterior cingulate cortex [OFC], and caudate nucleus [CN]), but the significance of these findings remains unclear. Aberrant functional activity may help localize dysregulated circuitry, but it could also reflect responses to abnormalities elsewhere. However, brain mapping studies have demonstrated that medial frontal structures, such as the ACC, play a central role in detecting errors. This psychological process appears to be disturbed in patients with OCD, who tend to over-focus on not making mistakes and avoiding potential bad outcomes. Preliminary data shows hyperactivity of an electrophysiological potential thought to be generated by the ACC, the error-related negativity, in patients with OCD. A critical function of the limbic CSPT loops (especially the OFC and CN) also involves the evaluation and anticipation of gains and losses, processes which determine the significance of possible actions and guide choice. This proposal will work from the theory that in patients with OCD, common thoughts acquire a pathological significance because the brain (through limbic CSPT circuits) over-estimates potential or actual losses. Functional magnetic resonance imaging and event-related potential studies will probe these CSPT circuits with simple tasks known to elicit neural responses in these brain areas, without eliciting symptoms of OCD. Two experiments will test hypotheses that OCD consists of abnormal brain activity in these regions during the commission of errors and when they anticipate and respond to potential monetary losses, allowing us to evaluate a cluster of hypotheses about the functional anatomy of OCD. Patients with OCD will be studied in medicated, relatively unsymptomatic samples, as well as in unmedicated, relatively symptomatic samples in order to identify trait-related components of the illness. The patient samples will be compared with psychiatricallyhealthy subjects and medicated, previously depressed patients. Successful completion of the project should lead to an improved understanding of the role of specific brain regions in generating the symptoms of OCD.