Brain Imaging and Cognition in Huntington's Disease

描述(由申请者提供)：这是一份以患者为导向的研究事业发展奖(K23)的申请书。候选人是一名精神病学家，他建议获得成为精神神经成像领域的独立调查员和领导者所需的特定技能和知识。亨廷顿病(HD)是一种典型的神经精神疾病，具有显著的精神和认知功能障碍，是一种已知的遗传异常和一致的结构病理。候选人将在已知认知功能障碍的指导下，使用功能磁共振成像(FMRI)和扩散张量成像(DTI)，研究HD早期和HD基因突变的症状前携带者的结构和功能之间的关系。职业发展活动将强调综合方法，并侧重于研究方法和统计、认知神经心理学以及功能和扩散张量神经成像获取和分析技术。候选人计划通过HD的研究获得技能，这些技能将推广到其他神经精神疾病的研究，如精神分裂症。该研究计划将重点放在HD早期阶段的受试者和有症状的HD突变阳性个体上。受试者将通过约翰霍普金斯大学精神病学系亨廷顿病研究中心招募，在那里他们将接受严格的临床和认知评估。具体目标1将侧重于对认知任务中血流动力学激活的fMRI分析，该任务旨在激活额纹状体回路。特定目标2将利用DTI数据研究额-纹状体部分各向异性(FA)的变化，而特定目标3将研究临床特征、血流动力学激活模式和白质变化之间的关系。未来的方向包括将这种方法扩展到精神分裂症和其他神经精神疾病的患者，这些患者的认知症状表现得很早，对目前的干预措施难以奏效。通过努力了解有助于这些认知过程的生物学，我们可以采取深思熟虑的干预策略，或许还可以进行治疗。相关性：认知功能障碍在神经精神障碍患者中很常见。通过更好地了解这种功能障碍的生物学性质，可以开发特定的干预措施，以减轻患者、照顾者和整个社会的疾病负担。

DESCRIPTION (provided by applicant): This is an application for a mentored Patient-Oriented Research Career Development Award (K23). The candidate is a psychiatrist who proposes to acquire the specific skills and knowledge necessary to become an independent investigator and leader in the field of psychiatric neuroimaging. Huntington's Disease (HD) is a prototypic neuropsychiatric illness with prominent psychiatric and cognitive dysfunction, a known genetic abnormality and consistent structural pathology. The candidate will be guided by known cognitive dysfunction to investigate, using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the relationship between structure and function in early HD and in pre-symptomatic carriers of the HD genetic mutation. Career development activities will emphasize an integrative approach and focus on research methodology and statistics, cognitive neuropsychology, and functional and diffusion tensor neuroimaging acquisition and analysis techniques. The candidate plans to acquire skills through the study of HD that will generalize to the study of other neuropsychiatric conditions like schizophrenia . The research plan will focus on subjects in the early stages of HD and on pre-symptomatic HD mutation-positive individuals. Subjects will be recruited through the Johns Hopkins Department of Psychiatry Huntington's Disease Research Center, where they will have undergone rigorous clinical and cognitive evaluations. Specific Aim 1 will focus on fMRI analysis of hemodynamic activation during cognitive tasks designed to activate fronto-striatal circuits. Specific Aim 2 will use DTI data to study changes of fronto-striatal fractional anisotropy (FA), and Specific Aim 3 will investigate the relationships among clinical features, hemodynamic activation patterns and white matter changes. Future directions include the extension of this approach to patients with schizophrenia and other neuropsychiatric conditions in which cognitive symptoms manifest early and are refractory to current interventions. By working to understand the biology that subserves these cognitive processes we can approach thoughtful strategies for intervention and perhaps cure. RELEVANCE: Cognitive dysfunction is common among patients with neuropsychiatric disorders. By better understanding the biologic nature of this dysfunction, specific interventions may be developed to ease disease burden to patients, caregivers and society as a whole.