Clinical Symptons & Brain Abnormalities in Schizophrenia

描述（由申请人提供）：这是一份申请NIMH高级科学家奖（K05）的申请书。该候选人曾获得两项K02独立科学家奖（1994-1999和1999-2004）和一项指导研究科学家发展奖（1988-1993）的资助。候选人的长期目标是研究精神分裂症和其他精神疾病的临床症状、认知障碍以及结构和功能脑异常。她还致力于进一步的技术培训和发展，以将神经成像的新进展和神经成像数据的预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的研究工作。研究计划的主要目标是进一步发展扩散张量成像方法及其在精神分裂症中的应用。在这里，将评估额颞白质连接，包括钩状、弓状和扣带束状，预测决策和情景/言语记忆的损伤将与钩状异常有关，语义启动异常将与弓状异常有关，错误检测和自我监测异常将与扣带异常有关。此外，胼胝体和内囊前肢将被评估，预测异常将分别与半球间异常（二元听力融合押韵任务）和言语和空间工作记忆任务的损伤有关。其他职业提升计划包括：(1)开发进一步的形状分析工具，包括更多的局部而不是全局的形状变形中线结构测量，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大脑区域；(2)在体内进一步测量大脑皮层厚度。本研究计划对首发精神分裂症患者、首发情感性精神病患者、慢性精神分裂症患者和对照组进行前额叶和颞叶厚度的纵向研究。(3)进一步开发自动分割方法，用于识别感兴趣的大脑小区域，如颞上脑区。将使用包含图谱信息的非刚性配准方法，并将该方法扩展到其他脑区。(4)与博士开展进一步的PTSD合作研究。Pitman， Gilbertson和Shalev，包括对海湾战争中患有创伤后应激障碍的护士的调查；(5)与Deutsch博士开展进一步的合作研究，研究大脑异常及其与面部畸形的关系；(6)与龚博士（alves）共同开发一个新的研究领域，研究威廉氏综合征患者语言相关区域的叙事产物和认知异常及其与大脑异常的关系。最后，(7)在1.5T和3T磁铁上测试MR和MR DTI协议，以便在未来3到5年内自信地将协议移动到3T。

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.