Fletcher P C, Frith C D, Grasby P M, Friston K J, Dolan R J
Wellcome Department of Cognitive Neurology, Institute of Neurology, London WC1N 3BG, United Kingdom.
J Neurosci. 1996 Nov 1;16(21):7055-62. doi: 10.1523/JNEUROSCI.16-21-07055.1996.
We used positron emission tomography (PET) to measure brain activity in healthy control subjects and unmedicated patients with schizophrenia. Subjects were scanned in the context of a combined psychological and pharmacological challenge, and we examined the effects of apomorphine, a drug acting on dopamine receptors, on brain systems engaged by a paced verbal fluency task. This factorial design enabled comparison of control subjects and schizophrenics in terms of the activations engendered by the cognitive task and the pharmacological challenge and the interaction of the two. We report a failure of cognitive task-related activation in anterior cingulate cortex and of task-related deactivation in the left superior temporal gyrus in the schizophrenic subjects. Compared with controls, the impaired cingulate activation was significantly reversed by apomorphine. Additionally, there was a trend for the abnormal fronto-temporal pattern of activation in schizophrenic subjects to be normalized by the drug. Overall, in schizophrenic subjects the effect of apomorphine, which we interpret in terms of a net dopaminergic antagonism, was to modify the brain activity, making the pattern more akin to that seen in control subjects. The results indicate both a regionally specific abnormality of brain function in schizophrenia and an abnormal pattern of fronto-temporal interactions.
我们使用正电子发射断层扫描（PET）来测量健康对照受试者和未服药的精神分裂症患者的大脑活动。受试者在心理和药理学联合挑战的背景下接受扫描，我们研究了阿扑吗啡（一种作用于多巴胺受体的药物）对由言语流畅性任务所激活的脑系统的影响。这种析因设计能够在认知任务和药理学挑战所产生的激活以及两者的相互作用方面对对照受试者和精神分裂症患者进行比较。我们报告称，精神分裂症患者的前扣带回皮质中与认知任务相关的激活失败，以及左颞上回中与任务相关的失活失败。与对照组相比，阿扑吗啡显著逆转了扣带回激活受损的情况。此外，药物使精神分裂症患者异常的额颞叶激活模式有正常化的趋势。总体而言，在精神分裂症患者中，我们将其解释为多巴胺能净拮抗作用的阿扑吗啡效应是改变大脑活动，使模式更类似于在对照受试者中看到的模式。结果表明精神分裂症中脑功能存在区域特异性异常以及额颞叶相互作用的异常模式。
