Abstract:
Deficits in early auditory sensory processing in schizophrenia have been linked to N-methyl-D-aspartate receptor (NMDAR) hypofunction, but the role of NMDARs in aberrant auditory sensory gating (SG) in this disorder is unclear. This study, conducted in 22 healthy humans, examined the acute effects of a subanesthetic dose of the NMDAR antagonist ketamine on SG as measured electrophysiologically by suppression of the P50 event-related potential (ERP) to the second (S2) relative to the first (S1) of two closely paired (500 ms) identical speech stimuli. Ketamine induced impairment in SG indices at sensor (scalp)-level and at source-level in the auditory cortex (as assessed with eLORETA). Together with preliminary evidence of modest positive associations between impaired gating and dissociative symptoms elicited by ketamine, tentatively support a model of NMDAR hypofunction underlying disturbances in auditory SG in schizophrenia.
摘要:
精神分裂症早期听觉感觉加工的缺陷与N-甲基-D-天冬氨酸受体(NMDAR)功能减退有关,但NMDAR在该疾病异常听觉感觉门控(SG)中的作用尚不清楚。这项研究,在22名健康人类中进行,通过抑制相对于两个紧密配对(500ms)相同的言语刺激中的第一个(S1)的P50事件相关电位(ERP)对第二个(S2)的电生理测量,检查了亚麻醉剂量的NMDAR拮抗剂氯胺酮对SG的急性影响。氯胺酮在听觉皮层的传感器(头皮)水平和来源水平诱导SG指数受损(如eLORETA评估)。加上初步证据表明,门控受损和氯胺酮引起的解离症状之间存在适度的正相关,暂时支持精神分裂症患者听觉SG中NMDAR功能减退的模型。