Nahas Ziad, George Mark S, Horner Michael D, Markowitz John S, Li Xingbao, Lorberbaum Jeffrey P, Owens Susan D, McGurk Susan, DeVane Lindsay, Risch S Craig
Brain Stimulation Laboratory, Center for Advanced Imaging Research, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA.
Neurocase. 2003 Jun;9(3):274-82. doi: 10.1076/neur.9.3.274.15563.
Cognitive impairments are cardinal features of schizophrenia and predictors of poor vocational and social outcome. Imaging studies with verbal fluency tasks (VFT) lead some to suggest that in schizophrenia, the combination of a failure to deactivate the left temporal lobe and a hypoactive frontal lobe reflects a functional disconnectivity between the left prefrontal cortex and temporal lobe. Others have theorized that an abnormal cingulate gyrus modulates such fronto-temporal connectivity. Thus addition of a cognitive enhancing medication to current antipsychotic therapy might improve functionality of networks necessary in working memory and internal concept generation. To test this hypothesis, we serially measured brain activity in 6 subjects on stable atypical antipsychotics performing a VFT, using BOLD fMRI. Measurements were made at baseline and again after groups were randomized to receive 12 weeks of donepezil (an acetylcholinesterase inhibitor) and placebo in a blind cross-over design. Donepezil addition provided a functional normalization with an increase in left frontal lobe and cingulate activity when compared to placebo and from baseline scans. This pilot study supports the cingulate's role in modulating cognition and neuronal connectivity in schizophrenia.
认知障碍是精神分裂症的主要特征，也是职业和社会结局不佳的预测因素。使用言语流畅性任务（VFT）的影像学研究使一些人认为，在精神分裂症中，左颞叶失活失败与额叶活动减退相结合反映了左前额叶皮层与颞叶之间的功能断开连接。其他人则推测异常的扣带回调节这种额颞连接。因此，在当前的抗精神病治疗中添加认知增强药物可能会改善工作记忆和内部概念生成所需网络的功能。为了验证这一假设，我们使用BOLD功能磁共振成像对6名服用稳定非典型抗精神病药物并执行VFT的受试者的大脑活动进行了连续测量。在基线时进行测量，并在将各组随机分配接受12周多奈哌齐（一种乙酰胆碱酯酶抑制剂）和安慰剂的盲法交叉设计后再次测量。与安慰剂和基线扫描相比，添加多奈哌齐可使左额叶和扣带回活动增加，从而实现功能正常化。这项初步研究支持扣带回在调节精神分裂症认知和神经元连接中的作用。
