Characterization Of Neuropsychological Impairment In Sch

学校神经心理障碍的特征

• 批准号: 6823939
• 负责人: Terry E Goldberg
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6823939
• 关键词: behavioral genetics; brain injury; clinical research; cognition; cognition disorders; disease /disorder proneness /risk; dopamine; genetic markers; human subject; memory; mental disorder diagnosis; neural information processing; neuropsychological tests; neuropsychology; schizophrenia; semantics

Over the past year we have attempted to characterize more completely the cognitive disturbances in schizophrenia. In particular we have begun work on the mechanisms accounting for failures in memory in schizophrenia. Patients' difficulties do not appear to be due to qualitative abnormalities in susceptibility to interference, encoding, or so called false memory problems. We have begun to computationally model the episodic memory impairments in schizophrenia in order to determine if they are due to general noise or a single stage in mnemonic processing. We found that one possibile explanation of our results involves defective encoding of context information (a function asigned to the parahippocampal gyrus in our model. We have examined disorganized speech in schizophrenia using various semantic processing paradigms. In general patients have difficulties not with the size of their lexicon but rather how they access it automatically, as evidenced in priming paradigms. Thus, we have devised a battery of novel experimental tasks to assess whether schizophrenic patients show a dissociation between lexical integrity and semantic abnormality. We have completed work on a study which compares the integrity of the internal representation itself to the integrity of activation among representations using various types of number priming and quantity processing. This technique circumvents problems in judging the relatedness of words. We have also begun to employ a computationally rich technique called "latent semantic analysis" which judges the coherence of schizophrenic discourse using reliable computer controlled methods. We have found odd associations and diminished coherence over various discourse lengths. Importantly the technique is highly reliable; because it was highly correlated with clinical ratings from interviews we also think that it is valid. Finally, a genetic study of schizophrenia with an emphasis on intermediate phenotypes is ongoing. We are using a large battery of neurocognitive measures to characterize this "intermediate" phenotype. We base this on the rationale that patients do not inherit schizophrenia per se but a variety of susceptibilities to cognitive impairments and their attendant neurophysiologic abnormalities. We have already found that some cognitive measures yield high relative risks that are not redundant with diagnosis.Moreover, we have identified a gene (COMT) that has an impact on the N Back through dopamine signaling. We have also identified a gene (BDNF) that has significant impact on human hippocampal function, including episodic memory. We have examined a third gene, called G72, that demonstrates epistasis such that its effect on cognition was amplified in a group of schizophrenia patients (in contrast to controls and siblings). This is the first such report in the literature.

在过去的一年里，我们试图更全面地描述精神分裂症的认知障碍。特别是，我们已经开始研究精神分裂症记忆障碍的机制。患者的困难似乎不是由于对干扰、编码或所谓的错误记忆问题的敏感性的定性异常。我们已经开始对精神分裂症患者的情景记忆障碍进行计算建模，以确定它们是由于一般噪音还是记忆处理的单一阶段。我们发现，我们的结果的一个可能的解释涉及有缺陷的编码的背景信息（一个功能分配给海马旁回在我们的模型。我们已经研究了混乱的言语精神分裂症使用各种语义加工范式。在一般情况下，患者有困难，而不是他们的词汇量的大小，而是他们如何访问它自动，证明在启动范例。因此，我们设计了一系列新颖的实验任务来评估精神分裂症患者是否表现出词汇完整性和语义异常之间的分离。我们已经完成了一项研究，比较了内部表征本身的完整性与使用各种类型的数字启动和数量处理的表征之间激活的完整性。这种技术避免了判断单词相关性的问题。我们还开始采用一种称为“潜在语义分析”的计算丰富的技术，使用可靠的计算机控制的方法来判断精神分裂症话语的连贯性。我们发现，在不同的话语长度上，存在着奇怪的联想和连贯性的减弱。重要的是，该技术是高度可靠的;因为它与访谈的临床评分高度相关，我们也认为它是有效的。最后，精神分裂症的遗传研究，重点是中间表型正在进行中。我们正在使用一个大电池的神经认知措施，以表征这种“中间”表型。我们的理论基础是，患者本身并不遗传精神分裂症，而是遗传了各种认知障碍及其伴随的神经生理异常的易感性。我们已经发现，一些认知指标产生的相对风险很高，这与诊断无关。此外，我们已经确定了一个基因（COMT），它通过多巴胺信号对N Back产生影响。我们还发现了一个基因（BDNF），对人类海马功能有显着影响，包括情节记忆。我们已经研究了第三个基因，称为G72，它证明了上位性，以至于它对认知的影响在一组精神分裂症患者中被放大（与对照组和兄弟姐妹相比）。这是文献中的第一份此类报告。