Effects of ketamine on prefrontal and striatal regions in an overt verbal fluency task: a functional magnetic resonance imaging study
Effects of ketamine on prefrontal and striatal regions in an overt verbal fluency task: a functional magnetic resonance imaging study
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DOI：
10.1007/s00213-005-0154-9
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发表时间：
2005-11-01
影响因子：
3.4
通讯作者：
McGuire, PK
中科院分区：
文献类型：
--
作者：
Fu, CHY;Abel, KM;McGuire, PK
基本原理：N-甲基-D-天冬氨酸（NMDA）受体的谷氨酸能功能障碍已被提出作为精神分裂症的神经化学模型。这种疾病的一个关键特征是认知功能受损。目的：本研究旨在探讨氯胺酮，一种NMDA拮抗剂，对性能和语言流畅性，一个任务，涉及执行功能的神经相关的影响。研究方法：在两次功能性磁共振成像过程中，10名健康右侧男性志愿者接受静脉注射安慰剂生理盐水或氯胺酮（0.23 mg/kg推注和0.65 mg/kg输注），以双盲、随机顺序给药。在扫描过程中，受试者执行了一项语言流畅性任务。在任务中检查了两个水平的认知负荷，并获得了明显的反应，以测量受试者的性能在线。结果：氯胺酮在健康个体中引起的症状与急性精神病状态相当。虽然氯胺酮没有显着损害任务性能相对于安慰剂，任务需求与氯胺酮的相互作用，观察到在前扣带回，前额，纹状体区。结论：氯胺酮对健康个体言语流畅性的行为和功能影响与精神分裂症患者的明显影响相当。这些发现支持了精神分裂症的病理生理学中多巴胺能功能障碍的作用。
Rationale: Glutamatergic dysfunction at N-methyl-D-aspartate (NMDA) receptors has been proposed as a neurochemical model for schizophrenia. A key feature of this disorder is impairments in cognitive function. Objective: The present study sought to investigate the effects of ketamine, an NMDA antagonist, on the performance and neural correlates of verbal fluency, a task that engages executive function. Methods: Ten healthy dextral male volunteers received intravenous placebo normal saline or ketamine (bolus of 0.23 mg/kg and infusion of 0.65 mg/kg), administered in a double-blind, randomized order, during two functional magnetic resonance imaging sessions. During scanning, subjects performed a verbal fluency task. Two levels of cognitive load were examined in the task, and overt responses were acquired in order to measure subject performance on-line. Results: Ketamine induced symptoms in the healthy individuals comparable to an acute psychotic state. Although ketamine did not significantly impair task performance relative to placebo, an interaction of task demand with ketamine was observed in the anterior cingulate, prefrontal, and striatal regions. Conclusions: The behavioural and functional effects of ketamine during verbal fluency in healthy individuals were comparable to those evident in patients with schizophrenia. The findings support a role for glutamatergic dysfunction in the pathophysiology of schizophrenia.