BASAL GANGLIA FUNCTION IN OBSESSIVE COMPULSIVE DISORDER

该项目的目标是使用功能性 MRI (fMRI) 和认知神经科学方法来测试有关强迫症 (OCD) 病理生理学的具体假设。 基底神经节与强迫症的病理生理学以及内隐（即无意识）学习的正常介导解剖学有关。 我们开发了一种功能磁共振成像范式来测量执行内隐学习任务期间基底神经节各组成部分内的活动。 在初步的功能成像研究中，我们观察到患有当前强迫症的未接受药物治疗的受试者存在异常的激活特征。具体来说，与正常对照受试者相比，强迫症患者表现出无法激活右侧纹状体，并且不存在丘脑失活，以及异常的内侧颞叶激活（即在正常受试者中未发现）。 这些结果与不断发展的强迫症和基底神经节功能的神经生物学模型一致。 目前的提案旨在：1）使用这种功能磁共振成像范式在更大的一组未接受药物治疗的活动性强迫症患者和匹配的正常对照受试者中复制并详细阐述上述发现； 2）通过研究精神病学比较对象来确定强迫症研究结果的特异性； 3）进一步研究强迫症中观察到的异常激活谱的神经心理学后果。 预计这种方法将产生有关强迫症和相关疾病的病理生理学的新信息，同时提供有关基底神经节正常功能和正常学习的中介解剖结构的新见解。

The goals of this project are to test specific hypotheses about the pathophysiology of obsessive compulsive disorder (OCD) using functional MRI (fMRI) and cognitive neuroscience methods. The basal ganglia have been implicated in the pathophysiology of OCD and also in the normal mediating anatomy of implicit (i.e., nonconscious) learning. We have developed an fMRI paradigm to measure activity within components of the basal ganglia during the performance of an implicit learning task. In preliminary functional imaging studies, we have observed an abnormal activation profile in medication-free subjects with current OCD. Specifically, in comparison to normal control subjects, patients with OCD exhibit a failure to activate right striatum, and an absence of thalamic deactivation, as well as aberrent medial temporal activation (i.e., not found in normal subjects). These results are consistent with evolving neurobiological models of OCD and basal ganglia function. The current proposal aims to: 1) use this fMRI paradigm to replicate and elaborate upon the above findings in a larger cohort of medication-free patients with active OCD and matched normal comparison subjects; 2) determine the specificity of the findings in OCD by studying psychiatric comparison subjects; and 3) further investigate the neuropsychological consequences of the abnormal activation profile observed in OCD. It is anticipated that this approach will yield new information regarding the pathophysiology of OCD and related disorders, while providing new insights about the normal function of the basal ganglia and the mediating anatomy of normal learning.