Functional Neuroanatomy of Obsessive Compulsive Disorder

描述（由申请人提供）： 大量证据表明，强迫症（OCD）涉及额叶脑回路的功能异常，特别是皮质-纹状体-苍白球-丘脑（CSPT）回路。神经影像学研究表明，在一些边缘相关的组成部分的循环（眶额皮质[OFC]，前扣带回皮质[OFC]，尾状核[CN]）的过度活动，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，脑映射研究表明，内侧额叶结构，如前扣带回，在检测错误中起着核心作用。这种心理过程在强迫症患者中似乎受到干扰，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，强迫症患者的一种电生理电位活动过度，这种电位被认为是由前扣带回产生的，即与错误相关的负性。边缘系统CSPT回路（尤其是眶额皮层和CN）的一个重要功能还涉及对得失的评估和预测，这一过程决定了可能行动的重要性，并指导选择。这个建议将从强迫症患者的理论出发，因为大脑（通过边缘CSPT回路）高估了潜在或实际的损失，所以普通的想法具有病理意义。功能性磁共振成像和事件相关电位研究将用已知在这些大脑区域引起神经反应的简单任务来探测这些CSPT电路，而不会引起强迫症的症状。两个实验将测试假设，强迫症包括异常的大脑活动在这些地区的委员会的错误，当他们预期和响应潜在的金钱损失，使我们能够评估一组假设的功能解剖强迫症。强迫症患者将在药物治疗，相对无症状的样本，以及在未经药物治疗，相对有症状的样本进行研究，以确定疾病的特征相关成分。患者样本将与精神健康的受试者和接受过药物治疗的既往抑郁患者进行比较。该项目的成功完成将导致对特定大脑区域在产生强迫症症状中的作用的更好理解。

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.