Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis
Pharmacological modulation of the neural basis underlying inhibition of return (IOR) in the human 5-HT2A agonist and NMDA antagonist model of psychosis
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DOI：
10.1007/s00213-008-1237-1
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Gouzoulis-Mayfrank, Euphrosyne
中科院分区：
文献类型：
--
作者：
Daumann, Joerg;Heekeren, Karsten;Gouzoulis-Mayfrank, Euphrosyne
基本原理 注意力缺陷是精神分裂症的常见症状。最近的证据表明，精神分裂症患者在注意力的空间定向方面表现出异常，特别是返回抑制（IOR）缺陷。 IOR 通常被认为反映了一种自动的抑制机制，保护生物体不将注意力转移到之前扫描过的无关紧要的位置。致幻剂的药理学挑战已被用作精神病模型。目的本研究的目的是调查人类 N-甲基-D-天冬氨酸拮抗剂和 5-HT(2A) 激动剂精神病模型中注意力定向的神经相关性。材料和方法 14 名健康志愿者参与了一项使用二甲基色胺的随机、双盲、交叉事件相关功能磁共振成像 (fMRI) 研究（DMT）和S-氯胺酮。我们利用非预测性外围线索进行了一项隐蔽的注意力定向任务，并在至少相隔 14 天的两天内对受试者进行了扫描，每天使用安慰剂和真实条件。结果 DMT（而非 S-氯胺酮）显着减慢了反应时间。 DMT 后 IOR 减弱，但 S-氯胺酮后 IOR 没有减弱。与安慰剂相比，S-氯胺酮增加了右额上回、左颞上回和右额中回 IOR 状态的激活。 结论 行为和功能成像结果之间的差异表明，药理学 fMRI 可能是在没有行为异常的情况下检测药物调节的血氧水平依赖性信号变化的敏感工具。我们的研究结果可能有助于进一步澄清精神分裂症患者 IOR 的矛盾发现，并因此可能为精神分裂症症状可能的差异病理机制提供更多线索。
Rationale Attentional deficits are common symptoms in schizophrenia. Recent evidence suggests that schizophrenic patients show abnormalities in spatial orienting of attention, particularly a deficit of inhibition of return (IOR). IOR is mostly thought to reflect an automatic, inhibitory mechanism protecting the organism from redirecting attention to previously scanned, insignificant locations. Pharmacologic challenges with hallucinogens have been used as models for psychosis.Objectives The aim of this study was to investigate the neural correlates underlying orienting of attention in the human N-methyl-D-aspartic acid antagonist and 5-HT(2A) agonist models of psychosis.Materials and methods Fourteen healthy volunteers participated in a randomized, double-blind, cross-over event-related functional magnetic resonance imaging (fMRI) study with dimethyltryptamine (DMT) and S-ketamine. We administered a covert orienting of attention task with nonpredictive peripheral cues, and we scanned the subjects on two separate days at least 14 days apart with a placebo and a verum condition on each day.Results DMT, but not S-ketamine, slowed down reaction times significantly. IOR was blunted after DMT, but not after S-ketamine. Relative to placebo, S-ketamine increased activation in the IOR condition in the right superior frontal gyrus, left superior temporal gyrus, and right midfrontal frontal gyrus.Conclusions The discrepancy between the behavioral and functional imaging outcome indicates that pharmacological fMRI might be a sensitive tool to detect drug-modulated blood oxygenation level-dependent signal changes in the absence of behavioral abnormalities. Our findings might help to further clarify the contradictory findings of IOR in schizophrenic patients and might, thus, shed more light on possible differential pathomechanisms of schizophrenic symptoms.