NEUROPHYSIOLOGICAL STUDIES OF SCHIZOPHRENIA

精神分裂症的神经生理学研究

• 批准号: 2245050
• 负责人: Robert W McCarley
• 金额: $ 24.17万
• 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 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2245050
• 关键词: attention; auditory cortex; biomarker; brain electrical activity; cerebral dominance; chronic disease /disorder; computer program /software; evoked potentials; handedness; human subject; interview; magnetic resonance imaging; male; memory; mental disorder diagnosis; mood disorders; neural information processing; neuroanatomy; neurophysiology; neuropsychological tests; neuropsychology; performance; schizophrenia; semantics; temporal lobe /cortex disorder

The broad aim of this 5 year research study is to advance understanding of the neurophysiological and biological bases of schizophrenia. The first project proposed is a study of first episode psychotic patients and matched normal controls. The major questions to be addressed are whether the event-related potential (ERP) abnormalities we have found to characterize chronic schizophrenics are present at first hospitalization, without the confounds associated with chronicity. The major ERP paradigm will be the auditory oddball P300, on which chronic schizophrenics have shown both an overall amplitude reduction and a topographic abnormality, a left temporal scalp region amplitude reduction (left temporal feature, LTF). We predict these abnormalities will be present at the first episode and will differentiate those patients diagnosed as schizophrenic on retest one year later vs. those with mood disorder or transient psychosis. The importance of such potential diagnostic predictors is evident. Other ERPs elicited in the oddball paradigm will also be studied (Nl00, P200, N200), as will the N400. These ERPs provide additional indices of information processing abnormalities and thus the determination of their time of onset and prognostic value is also important. The second major project involves correlation of ERP abnormalities in chronic schizophrenics with quantitative volumetric Magnetic Resonance Imaging (MRI) definition of specific regions of interest (ROI) in temporal and frontal lobe. This approach combines the strengths of a technology with high time resolution and functional information (ERPs) with one having a high spatial resolution (MRI). This project takes advantage of the advanced imaging capabilities of the Brigham and Womens Hospital MRI facility. It predicts quite specific sets of correlations between abnormalities in ERPs and clinical features, and of volume reduction in specific MRI ROI in schizophrenics, whereas matched normals are expected to show no MRI-ERP correlations. The paradigmatic prediction is an association between the P300 LTF/clinical thought disorder and volume, reduction of the left posterior superior temporal gyrus (STG) gray matter in right-handed subjects. Our working hypothesis is that part of the pathophysiology of schizophrenic thought is explained by 2 disturbance in the language/auditory -related cortical areas, and that the P300 amplitude reduction reflects a disturbance of memory updating that is dependent on the same brain regions. In left handed subjects we predict the P300 amplitude reduction in the right temporal scalp region will correlate with reduced volume in the right posterior STG; this association with hand dominance may reflect abnormalities associated with schizophrenic hemispheric specialization. Other ERP-MRI associations may also provide clues as to which abnormal brain regions are responsible for abnormalities of information processing. Other components of the research program will examine the association of ERP- and MRI-defined biological abnormalities with neuropsychological/cognitive probes that complement the ERP probes. It is predicted that disturbances of semantic memory and association will be related to hippocampal-auditory association cortex while disturbances of attention apparent in the Posner and computer-controlled Continuous Performance Task will be associated with prefrontal cortex abnormalities, especially on the left (in right-handed subjects) and especially in middle and inferior frontal gyri gray matter.

这项5年研究的广泛目的是提高理解 精神分裂症的神经生理学和生物学基础。 这 提出的第一个项目是对第一集的研究精神病患者和 匹配的正常对照。要解决的主要问题是是否 我们发现的事件相关电位（ERP）异常 慢性精神分裂症患者的特征是在第一次住院时出现 没有与慢性相关的混杂。 主要的ERP范式 将是慢性精神分裂症患者的听觉奇数P300 既显示总体幅度降低和地形异常， 左颞头皮区域振幅降低（左时间特征， LTF）。 我们预测这些异常将在第一次存在 发作并将区分那些被诊断为精神分裂症的患者 一年后的重新测试与患有情绪障碍或瞬态的人 精神病。 这种潜在诊断预测指标的重要性是 明显。 在奇数范式中引起的其他ERP也将是 研究（NL00，P200，N200），N400也是如此。 这些ERP提供 信息处理异常的其他指标，因此 确定其发作时间和预后价值也是 重要的。 第二个主要项目涉及ERP异常的相关性 具有定量容量磁共振的慢性精神分裂药 成像（MRI）对特定感兴趣区域（ROI）的定义（ROI） 颞叶和额叶。 这种方法结合了一个 具有高时间分辨率和功能信息（ERP）的技术 一个具有高空间分辨率（MRI）。 这个项目需要 杨百翰和女子的高级成像功能的优势 医院MRI设施。 它预测了相当具体的相关集 在ERP和临床特征的异常和体积之间 精神分裂症患者中特定的MRI ROI的降低，而匹配的正态 预计不会显示MRI-ERP相关性。 范式 预测是P300 LTF/临床思想之间的关联 障碍和体积，左后颞上的减少 右手受试者中的回（STG）灰质。 我们的工作假设 是否解释了精神分裂症思想的病理生理学的一部分 通过语言/听觉相关的皮质区域的2个干扰， p300幅度降低反映了记忆的干扰 更新取决于相同的大脑区域。 在左手 受试者我们预测右时间的p300幅度降低 头皮区域将与右后方的体积减小相关 STG;这种与手优势的关联可能反映了异常 与精神分裂性半球专业化有关。 其他ERP-MRI 关联还可以提供有关哪些异常大脑区域的线索 负责信息处理的异常。 研究计划的其他组成部分将研究 ERP和MRI定义的生物学异常 与ERP探针相辅相成的神经心理/认知探针。 它 预测语义记忆和关联的干扰将是 与海马审计协会皮质有关，而干扰 Posner和计算机控制连续的注意力明显 性能任务将与前额叶皮层异常相关， 特别是在左侧（右手受试者），尤其是 中间和下部回旋灰质。