NEUROPHYSIOLOGICAL STUDIES OF SCHIZOPHRENIA

精神分裂症的神经生理学研究

• 批准号: 3379200
• 负责人: Robert W McCarley
• 金额: $ 22.88万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3379200
• 关键词: antipsychotic agents; attention; bipolar depression; brain electrical activity; brain interhemispheric activity; clinical depression; cognition disorders; cues; electrophysiology; evoked potentials; handedness; human subject; male; mental disorder diagnosis; mental process; neurophysiology; neuropsychological tests; performance; psychological tests; schizophrenia; speech; statistics /biometry; stimulus /response; stimulus interval; temporal lobe /cortex disorder; visual fields; visual stimulus

The broad goal of this work is to define neurophysiological abnormalities in schizophrenia, and thus to lay a foundation for a more rational approach to treatment. A first group of studies will examine the characteristics of our thrice-replicated findings of a topographic asymmetry of the auditory P300 event-related potential (ERP) in schizophrenics, referred to as the "left temporal feature" (LTF) and consisting of an amplitude reduction at T3 that maximally differentiates schizophrenics from normals. Its presence in a larger unmedicated schizophrenic group will be determined. A longitudinal study will investigate the state-trait nature of the LTF in schizophrenics and its covariation with changes in clinical status, including positive symptoms. Its diagnostic specificity will be examined in contrast groups of patients with major mood disorders with psychotic features (bipolar and unipolar). This application also proposes new ERP and attentional measures bearing on left hemisphere and attentional pathology in schizophrenia that will both complement and contrast with the P300 LTF. The visual N400, and ERP associated with semantic incongruity, will be used as a possible convergent measure, since both N400 and P300 may have temporal lobe sources and both may be associated with positive symptoms. The N400 will be studied in schizophrenics and contrast groups of normal controls and of bipolar and unipolar mood disorders with psychotic features. It is further proposed to develop "manic-specific" and "schizophrenic-specific" anomalous sentence completions that will have N400 effects specific to each diagnostic group, and to determine the relationship of thought disorder in individual patients (cloze probabilities of speech) to the N400 ERP abnormalities. As a contrasting measure, the application proposes to investigate whether the P200 abnormalities and their correlations with negative symptoms reported by us will replicate in unmedicated schizophrenic subjects. A computerized visual continuous performance task using degraded stimuli to match initial performance of patients and normals will determine if the P300 LTF is related to a schizophrenic deficit in sustained attention. Visual P300 ERPs to the target stimuli of the CPT will be examined to determine if amplitude and topographic abnormalities covary with a decline in performance. Finally, to contrast with our auditory tasks, and as a complementary and contrasting measure of hemispheric pathology, the "Posner paradigm" of visual attention testing will be utilized in unmedicated schizophrenics and normals to determine if there is a right hemisphere visual attention deficit, as preliminary data suggest. Methodological features of the studies proposed include 28-electrode scalp recordings, age-matched normal control groups, unmedicated patients (except for the longitudinal study), and the use of multivariate statistics for hypothesis testing.

这项工作的主要目标是定义神经生理学异常 从而为更理性的方法奠定基础 接受治疗 第一组研究将检查 我们三次重复的发现， 精神分裂症患者的P300事件相关电位（ERP），简称P300。 “左颞特征”（LTF），由在左颞叶的振幅降低组成。 最大程度区分精神分裂症患者和正常人的T3。 它的存在 在一个更大的未经药物治疗的精神分裂症组将被确定。 一 纵向研究将调查LTF的状态-特质性质， 精神分裂症及其与临床状态变化的协变， 包括阳性症状。 将检查其诊断特异性 在对照组中， 特性（双极和单极）。 本申请还提出了新的ERP和注意力措施， 精神分裂症患者的左半球和注意力病理学， 与P300 LTF形成互补和对比。 可视化N400和ERP 与语义不一致，将被用作一个可能的收敛 测量，因为N400和P300都可能有颞叶源， 可能与阳性症状有关。 N400将在 精神分裂症和对照组的正常对照组和双相情感障碍， 具有精神病特征的单极情绪障碍。 还拟 发展出“躁狂症特异性”和“精神分裂症特异性”异常语句 将对每个诊断组产生特定N400效应的完井， 并确定思维障碍与个体 患者（完形填空概率）的N400 ERP异常。 作为 作为对比措施，申请书建议调查 P200异常及其与阴性症状的相关性 会在未服药的精神分裂症患者身上复制 计算机化 使用降级刺激匹配初始刺激的视觉连续执行任务 患者和正常人的表现将决定P300 LTF是否 与精神分裂症持续注意力缺陷有关 视觉P300 将检查CPT目标刺激的ERP，以确定是否 振幅和地形异常协变， 性能 最后，与我们的听觉任务相比， 半球病理学的互补和对比测量，“波斯纳 视觉注意力测试的“范例”将在未用药的 精神分裂症患者和正常人来确定是否有一个右半球 视觉注意力缺陷，初步数据显示。 方法学 所提出的研究的特征包括28个电极的头皮记录， 年龄匹配的正常对照组，未用药的患者（除了 纵向研究），并使用多变量统计假设 试验.