fMRI of Cholinergic Dysfunction in Schizophrenia

描述(由申请人提供)：平稳追踪、眼球运动异常和听觉感觉门控缺陷是与精神分裂症相关的两种最具特征性的生理内表型。除了来自流行病学、动物模型、遗传学、分子生物学和死后结合研究的证据外，吸烟使这两种感觉障碍短暂正常化，表明烟碱型胆碱能受体参与了疾病的发生。然而，这种假定的胆碱能功能障碍对精神分裂症患者心理过程的功能影响尚不清楚。这项研究的第一个目的是利用功能磁共振成像(Fmrl)来表征精神分裂症患者和年龄匹配的健康对照组中与平滑追逐眼球运动相关的功能神经解剖学，以确定精神分裂症患者未能正确执行这一任务是否与可检测到的异常神经元激活模式有关。他研究的第二个目的是使用功能磁共振成像来检测对照组和精神分裂症患者由于尼古丁胆碱能受体功能障碍而导致的功能神经解剖学上的差异，方法是检查对照组和精神分裂症患者服用尼古丁后神经元活动的特定变化(平滑追踪眼球运动)。

DESCRIPTION (provided by applicant): Abnormalities in smooth pursuit eye movements and deficits in auditory sensory gating are two of the best characterized physiological endophenotypes associated with schizophrenia. Transient normalization of both of these sensory deficits by smoking, in addition to evidence from epidemiology, animal models, genetics, molecular biology and post-mortem binding studies, suggests involvement of nicotinic cholinergic receptors in the disease. The functional effect of this putative cholinergic dysfunction on mental processes in individuals with schizophrenia, however, remains unknown. This first aim of this study proposes the use of functional magnetic resonance imaging (fMRl) to characterize the functional neuroanatomy associated with smooth pursuit eye movements in patients with schizophrenia and age-matched healthy controls to determine if failure to properly execute this task in patients with schizophrenia is associated with a detectable, abnormal pattern of neuronal activation. The second aim of his study is to use fMRI to detect differences in functional neuroanatomy between control and patients with schizophrenia are due to nicotinic cholinergic receptor dysfunction by examining task-specific (smooth pursuit eye movement) changes in neuronal activity associated with administration of nicotine to controls and patients with schizophrenia.