Characterization Of Neuropsychological Impairment In Sch

在过去的一年里，这个神经心理学小组试图更全面地描述精神分裂症患者的认知障碍。特别是，我们已经开始研究精神分裂症患者记忆障碍的机制。患者的困难似乎并不是由于对干扰、编码或所谓的虚假记忆问题的易感性的质量异常。 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，以确定它们是由一般噪声还是记忆加工的单个阶段造成的。我们发现，我们的结果的一种可能的解释是上下文信息的编码有缺陷(在我们的模型中，这是一种分配给海马旁回的功能)。我们使用不同的语义处理范式研究了精神分裂症患者的无组织言语。一般来说，患者遇到的困难不是词汇量的大小，而是他们如何自动获取词汇量，正如启动范式所证明的那样。因此，我们设计了一系列新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，将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加工的表征之间的激活完整性进行比较。这项技术绕过了判断单词关联性的问题。我们还开始使用一种计算丰富的技术，称为“潜在语义分析”，它使用可靠的计算机控制方法来判断精神分裂症患者话语的连贯性。我们发现，在不同的篇幅上，出现了奇怪的联想和连贯性减弱。重要的是，这项技术是高度可靠的；因为它与采访中的临床评分高度相关，我们也认为它是有效的。 此外，我们正在使用N-back任务来评估大样本精神分裂症患者、他们的好兄弟姐妹和健康对照受试者的工作记忆和注意力处理。这项研究表明，与精神分裂症遗传风险增加相关的认知缺陷涉及与目标选择和记忆操作有关的子过程，而不是负荷、延迟或注意力处理的速度。 最后，一项强调中间表型的精神分裂症的遗传学研究正在进行中。我们正在使用大量的神经认知测量方法来描述这种“中间”表型。我们基于这样的理论基础，即患者本身并不遗传精神分裂症，而是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，一些认知测量方法会产生与诊断无关的高相对风险。此外，我们还鉴定了一个基因COMT(儿茶酚-O-甲基转移酶)，它通过多巴胺信号对N-back产生影响。我们还发现了一种对人类海马区功能有重大影响的基因(脑源性坏死营养因子)，包括情景记忆。我们已经检测了第三个基因，称为G72，它证明了上位性，使得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反)。这是文献中第一个这样的报告。 我们将继续获得与精神分裂症相关的其他潜在脑缺陷的新认知数据集，以努力进一步表征其中一些表型的认知神经科学，并通过其他大脑系统检查心理处理。

Over the past year, the neuropsychology group has 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 memory processing. We found that one possible explanation of our results involves defective encoding of context information (a function assigned 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 vocabulary 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 dissociation between vocabulary 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 use 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. Additionally, we are assessing working memory and attention processing in a large sample of schizophrenic patients, their well siblings, and healthy control subjects using the N-Back task to engage the working memory system. This study suggests that cognitive deficits associated with increased genetic risk for schizophrenia involve subprocesses related to target selection and memory manipulation and not load, delay, or speed of processing attention. 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 (Catechol-O-Methyltransferase) that has an impact on the N-Back through dopamine signaling. We have also identified a gene BDNF brain-derived necrotrophic factor) 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. We will continue to acquire new cognitive datasets related to other potential brain deficits associated with schizophrenia in an effort to further characterize the cognitive neuroscience of some of these phenotypes and to examine mental processing through other brain systems.