BASAL GANGLIA FUNCTION IN OBSESSIVE COMPULSIVE DISORDER

本项目的目的是利用功能磁共振成像（fMRI）和认知神经科学的方法来检验强迫症（OCD）病理生理学的特定假设。基底神经节与强迫症的病理生理有关，也与内隐（即无意识）学习的正常中介解剖有关。我们已经开发了一种功能磁共振成像范式来测量在执行内隐学习任务期间基底神经节各部分的活动。在初步的功能成像研究中，我们观察到患有当前强迫症的无药物受试者的异常激活谱。具体来说，与正常对照组相比，强迫症患者表现出右侧纹状体无法激活，丘脑没有失活，以及内侧颞叶异常激活（即在正常受试者中未发现）。这些结果与强迫症和基底神经节功能的进化神经生物学模型是一致的。目前的建议旨在：1)使用fMRI范式在更大的无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和详细阐述上述发现；2)通过对精神病学比较对象的研究，确定强迫症症状的特异性；3)进一步研究强迫症患者异常激活谱的神经心理学后果。预计该方法将为强迫症和相关疾病的病理生理学提供新的信息，同时为基底神经节的正常功能和正常学习的中介解剖提供新的见解。

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.