Characterization Of Neuropsychological Impairment In Sch

在过去的一年里，神经心理学小组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上下文信息（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。一般来说，患者的困难不是他们的词汇量的大小，而是他们如何自动访问它，如启动范式所示。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。我们也开始使用一种称为“潜在语义分析”的计算丰富的技术，它使用可靠的计算机控制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。 此外，我们正在评估工作记忆和注意力处理的精神分裂症患者的大样本，他们的同胞和健康的控制对象使用N-Back任务，从事工作记忆系统。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纵相关的子过程，而不是处理注意力的负荷、延迟或速度。 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，与诊断无关。此外，我们已经确定了一个基因COMT（儿茶酚-O-甲基转移酶），它通过多巴胺信号传导对N-Back产生影响。我们还鉴定了一个基因BDNF（脑源性坏死营养因子），该基因对人类海马功能（包括情景记忆）具有显著影响。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。 我们将继续获取与精神分裂症相关的其他潜在脑缺陷相关的新认知数据集，以进一步表征其中一些表型的认知神经科学，并通过其他脑系统检查心理加工。

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.