Functional Neuroanatomy of Obsessive Compulsive Disorder

描述(申请人提供)：大量证据表明，强迫症(OCD)涉及额叶大脑回路的异常功能，特别是皮质-纹状体-苍白球-丘脑(CSPT)回路。神经成像研究表明，在脑环的一些与边缘相关的部分(眼眶额叶皮质[OFC]、前扣带回[OFC]和尾状核[CN])中存在过度活动，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，但它也可能反映出对其他地方异常的反应。然而，大脑地形图研究表明，额叶内侧结构，如ACC，在检测错误方面发挥着核心作用。这一心理过程似乎在强迫症患者中受到干扰，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，在强迫症患者中，被认为是由ACC产生的电生理电位(错误相关的负波)活动过度。边缘CSPT循环(特别是OFC和CN)的一个关键功能还涉及对得失的评估和预期，这是确定可能行动的重要性和指导选择的过程。这一建议的理论基础是，在强迫症患者中，普通思维具有病理学意义，因为大脑(通过边缘CSPT回路)高估了潜在或实际的损失。功能磁共振成像和事件相关电位研究将通过简单的任务来探测这些CSPT电路，这些简单的任务可以在这些大脑区域引发神经反应，而不会引发强迫症症状。两个实验将测试假设，即强迫症包括在犯错误期间以及当他们预测和应对潜在的金钱损失时，这些区域的异常大脑活动，使我们能够评估关于强迫症功能解剖的一系列假说。强迫症患者将在有药物的、相对没有症状的样本中进行研究，以及在没有药物的、相对有症状的样本中进行研究，以确定疾病的特征相关部分。患者样本将与精神健康的受试者和服用药物的既往抑郁症患者进行比较。该项目的成功完成将有助于更好地理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.