解析精神分裂症错配负波产生的组成振荡动力学:与临床和认知功能的不同关系。

Decomposing the constituent oscillatory dynamics underlying mismatch negativity generation in schizophrenia: Distinct relationships to clinical and cognitive functioning.

机构信息

VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, San Diego, CA, United States of America; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States of America.

Department of Psychiatry, University of California San Diego, La Jolla, CA, United States of America.

出版信息

Int J Psychophysiol. 2019 Nov;145:23-29. doi: 10.1016/j.ijpsycho.2018.12.014. Epub 2018 Dec 23.

Abstract

Abnormalities in early auditory information processing (EAIP) contribute to higher-order deficits in cognition and psychosocial functioning in schizophrenia. A passive auditory oddball paradigm is commonly used to evoke event-related potential (ERP) measures of EAIP reflecting auditory sensory registration and deviance detection, including mismatch negativity (MMN) and P3a responses. MMN and P3a have been extensively studied in healthy subjects and neuropsychiatric patient populations and are increasingly used as translational biomarkers in the development of novel therapeutics. Despite widespread use, relatively few studies have examined the constituent oscillatory elements and the extent to which sensory registration and deviance detection represent distinct or intercorrelated processes. This study aimed to determine the factor structure and clinical correlates of these oscillatory measures in schizophrenia patients (n = 706) and healthy comparison subjects (n = 615) who underwent clinical, cognitive, and functional characterization and EEG testing via their participation in the Consortium of Genomics in Schizophrenia (COGS-2) study. Results revealed significant deficits in theta-band (4-7 Hz) evoked power and phase locking in patients. Exploratory factor analyses of both ERP and oscillatory measures revealed two dissociable factors reflecting sensory registration and deviance detection. While each factor shared a significant correlation with social cognition, the deviance detection factor had a unique relationship to multiple cognitive and clinical domains. Results support the continued advancement of functionally relevant oscillatory measures underlying EAIP in the development of precognitive therapeutics.

摘要

早期听觉信息处理异常(EAIP)导致精神分裂症患者认知和社会心理功能的高级缺陷。被动听觉Oddball 范式通常用于诱发事件相关电位(ERP)测量 EAIP,反映听觉感觉登记和偏差检测,包括失匹配负波(MMN)和 P3a 反应。MMN 和 P3a 在健康受试者和神经精神患者群体中得到了广泛研究,并越来越多地用作新型治疗药物开发中的转化生物标志物。尽管广泛使用,但相对较少的研究检查了组成的振荡元素,以及感觉登记和偏差检测代表不同或相互关联的过程的程度。这项研究旨在确定精神分裂症患者(n=706)和健康对照组受试者(n=615)的这些振荡测量的因子结构和临床相关性,这些患者通过参与精神分裂症基因组联盟(COGS-2)研究进行了临床、认知和功能特征描述和 EEG 测试。结果显示,患者的θ频段(4-7Hz)诱发功率和相位锁定存在显著缺陷。ERP 和振荡测量的探索性因子分析揭示了反映感觉登记和偏差检测的两个可分离因素。虽然每个因素都与社会认知有显著相关性,但偏差检测因素与多个认知和临床领域有独特的关系。研究结果支持在开发前认知治疗药物的过程中,继续推进 EAIP 下功能相关的振荡测量。

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