Clinical Symptons & Brain Abnormalities in Schizophrenia

描述(由申请者提供)：这是NIMH高级科学家奖(K05)的申请。该候选人之前曾获得两个K02独立科学家奖(1994-1999年和1999-2004年)和一项导师研究科学家发展奖(1988-1993年)的资助。候选人的长期目标是调查精神分裂症和其他精神障碍的临床症状、认知障碍以及大脑结构和功能异常。她还致力于进一步的技术培训和开发，以便将神经成像领域的新进展和神经成像数据的最新处理纳入她的研究计划。她的短期目标是申请K05奖，以支持她在职业发展的关键时刻所做的研究工作。该研究计划的主要目标是开发进一步的扩散张量成像方法及其在精神分裂症中的应用。在这里，将评估额叶-颞叶白质连接，包括钩状、弓状和扣带束，其中预测决策和情景/言语记忆的损害将与钩状异常相关，语义启动异常将与弓状异常相关，错误检测和自我监控异常将与扣带异常相关。此外，我们还将评估胼胝体和内囊前肢，预测异常将分别与大脑半球间的异常(双耳听融合押韵任务)以及言语和空间工作记忆任务的损害有关。其他职业提升计划包括：(1)开发进一步的形状分析工具，包括更多局部而不是全球的形状变形测量中线结构，包括尾状核、丘脑、杏仁-海马体复合体和可能受神经发育因素影响的穹窿-大脑区域；(2)在体内开发进一步的大脑皮质厚度测量方法。在这里，计划对首发精神分裂症、首发情感性精神病、慢性精神分裂症和对照组的患者进行前额叶和颞叶厚度的纵向研究。(3)开发进一步的自动分割方法，以识别感兴趣的小脑区域，如高级颞叶回。将使用结合地图集信息的非刚性配准方法，该方法将扩展到其他大脑区域。(4)与Pitman博士、Gilbertson博士和Shalev博士进一步合作开展PTSD研究，包括对部署在海湾战争中患有PTSD的护士进行检查；(5)与Deutsch博士进一步合作研究大脑异常及其与面部畸形的关联；(6)与Gonalves博士开发一个新的调查领域，研究威廉综合征患者的叙事和认知异常及其与语言相关区域的脑异常的关联。最后，(7)在1.5T和3T磁体上测试MR和MR DTI协议，以便在未来3到5年内自信地将协议转移到3T磁体。

DESCRIPTION (provided by applicant): This is a request for an NIMH Senior Scientist Award (K05). The candidate has been funded previously by two K02 Independent Scientist Awards (1994-1999 and 1999-2004) and by a Mentored Research Scientist Development Award (1988-1993). The candidate's long-term objective is to investigate clinical symptoms, cognitive impairments, and structural and functional brain abnormalities in schizophrenia and other psychiatric disorders. She is also committed to the further technical training and development needed to incorporate new advances i n n euroimaging and t he p ostprocessing of neuroimaging data into her research program. Her short-term objective is to apply for a K05 Award to support her research efforts at a crucial time in her career development. The main goal of the Research Plan is to develop further Diffusion Tensor Imaging measures and their application to schizophrenia. Here, frontal-temporal white matter connections will be evaluated, including the uncinate, arcuate, and cingulate fasciculi, where it is predicted that impairments in decision making and in episodic/verbal memory will be associated with uncinate abnormalities, that semantic priming abnormalities will be associated with arcuate abnormalities, and that error detection and self monitoring abnormalities will be associated with cingulate abnormalities. Additionally, the corpus callosum and the anterior limb of the internal capsule will be evaluated, where it is predicted that abnormalities will be associated with interhemispheric abnormalities (Dichotic Listening Fused Rhymed Task) and impairments in verbal and spatial working memory tasks, respectively. Other career enhancement plans include: (1) to develop further shape analysis tools that include more local rather than global measures of shape deformation midline structures including caudate nucleus, thalamus, amygdala-hippocampal complex, and corpus callosum -brain regions likely influenced by neurodevelopmental factors; (2) to develop further cortical thickness measures of the brain, in vivo. Here, longitudinal studies of prefrontal and temporal lobe thickness are planned in patients with first episode schizophrenia, first episode affective psychoses, chronic schizophrenia, and in controls. (3) To develop further automated segmentation methods for identifying small brain regions of interest such as the superior temporal gyms. Non-rigid registration methods that incorporate atlas information will be used, and this method will be extended to other brain regions. (4) To develop further collaborative PTSD studies with Drs. Pitman, Gilbertson, and Shalev, including an examination of nurses deployed in the Gulf War with PTSD; (5) to develop further collaborative studies with Dr. Deutsch investigating brain abnormalities and their association with facial dysmorphology; (6) to develop a new area of investigation with Dr. Gonalves investigating narrative productions and cognitive anomalies and their association with brain abnormalities in language related areas in William's Syndrome patients. Finally, (7) to test MR and MR DTI protocols on 1.5T and 3T magnets in order to confidently move protocols to the 3T over the next 3 to 5 years.