Clinical Symptons & Brain Abnormalities in Schizophrenia

描述（由申请人提供）：这是一个NIMH高级科学家奖（K 05）的请求。候选人曾获得两次K 02独立科学家奖（1994-1999年和1999-2004年）和一次指导研究科学家发展奖（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疾病的临床症状，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发展，将神经成像和神经成像数据后处理的新进展纳入她的研究计划。她的短期目标是申请K 05奖，以支持她的研究工作，在她的职业发展的关键时刻。研究计划的主要目标是进一步开发扩散张量成像措施及其在精神分裂症中的应用。在此，将评价额颞白色物质连接，包括钩状束、弓状束和扣带束，其中预测决策和情景/言语记忆的损伤将与钩状束异常相关，语义启动异常将与弓状束异常相关，错误检测和自我监测异常将与扣带束异常相关。此外，将评价胼胝体和内囊前肢，其中预测异常将分别与半球间异常（双耳分听融合押韵任务）以及言语和空间工作记忆任务中的损伤相关。其他职业发展计划包括：（1）开发进一步的形状分析工具，包括更多的局部而不是整体测量形状变形中线结构，包括尾状核，丘脑，杏仁核-海马复合体和胼胝体-可能受神经发育因素影响的脑区域;（2）开发进一步的大脑皮质厚度测量，在体内。在这里，纵向研究的前额叶和颞叶厚度计划在首发精神分裂症，首发情感性精神病，慢性精神分裂症患者，并在控制。(3)开发进一步的自动分割方法，用于识别感兴趣的小大脑区域，如上级颞回。将使用包含图谱信息的非刚性配准方法，并且该方法将扩展到其他大脑区域。(4)与皮特曼、吉尔伯特森和沙莱夫博士开展进一步的创伤后应激障碍研究，包括对海湾战争中部署的患有创伤后应激障碍的护士进行检查;（5）与多伊奇博士开展进一步的合作研究，调查大脑异常及其与面部畸形的关系;（6）与戈恩博士开发一个新的调查领域alves研究了威廉氏综合征患者的叙事作品和认知异常及其与语言相关脑区异常的关系。最后，（7）在1.5T和3 T磁体上测试MR和MR DTI协议，以便在未来3至5年内有信心地将协议转移到3 T。

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.