fMRI study of developing medial prefrontal cortical function in pediatric OCD

描述(由申请人提供)：强迫症(OCD)是一种常见的致残精神疾病，通常难以获得治疗。儿童和青春期强迫症的发作表明，非典型的大脑成熟可能是这种疾病的基础，并要求对儿科患者进行研究，以确定一个“发育窗口”，在这个窗口，治疗干预可能被定向到中止进展为慢性病。为了探索与儿童强迫症相关的神经行为发育机制，候选人已经开始在功能磁共振成像(FMRI)和儿童精神病学方面的工作。为了满足获得更多技能的需要，5年职业发展计划将为1)儿科神经成像、2)发展神经科学和3)临床研究技能提供基本的基础。职业发展将由一个研究项目决定，该项目旨在通过测试年轻患者大脑皮质-纹状体-苍白丘脑(CSPT)功能和结构假想的成熟异常来扩大儿童强迫症(CSPT)参与的初步发现。当患者在简单的认知任务中犯错误时，成人强迫症患者会出现CSPT元素-嘴前扣带回皮质、额叶后内侧皮质和背外侧前额叶皮质的过度活跃反应。此外，在成人强迫症中已发现CSPT回路中白质连接过度，这可能是由于CSPT功能的过度活动所致，例如对错误的反应。在这项拟议的研究中，将研究青春期前、青春期和青春期CSPT回路的错误处理功能和白质一致性，以开始阐明CSPT异常是如何在强迫症早期出现和进展的。杰出的院系支持；在功能磁共振成像、儿科强迫症、认知-情绪发育和临床研究方面的集体专业知识；以及未来翻译研究的机会，使密歇根大学成为该奖项的理想环境。公共卫生相关性：强迫症影响着数以百万计的美国儿童，了解与早发性疾病相关的大脑成熟异常将有助于促进对这种致残疾病的更好理解、治疗，并最终预防这种疾病。

DESCRIPTION (provided by applicant): Obsessive compulsive disorder (OCD) is a common and disabling psychiatric illness that is often refractory to available treatments. The onset of OCD during childhood and adolescence suggests that atypical brain maturation may underlie the disorder, and mandates the study of pediatric patients to define a "developmental window" at which therapeutic interventions may be directed to abort progression to chronic illness. To probe the mechanisms of neurobehavioral development relevant to pediatric OCD, the Candidate has begun work in functional magnetic resonance imaging (fMRI) and child psychiatry. Addressing the need for additional skill acquisition, a 5-year career development plan will provide an essential grounding in 1) pediatric neuroimaging, 2) developmental neuroscience, and 3) clinical research skills. Career development will be shaped by a research project designed to extend preliminary findings of cortico-striatal-pallidalthalamic (CSPT) involvement in pediatric OCD by testing for hypothesized maturational abnormalities of CSPT function and structure in young patients. Hyperactive response of CSPT elements - the rostral anterior cingulate cortex, posterior medial frontal cortex, and dorsolateral prefrontal cortex - occurs in adult OCD when patients commit errors on simple cognitive tasks. In addition, excessive white matter connectivity within CSPT circuitry has been demonstrated in adult OCD, and could be driven by hyperactivity of CSPT functions, such as the response to errors. In the proposed study, error-processing function and white matter coherence of CSPT circuitry will be studied across prepubertal, pubertal and adolescent stages of development to begin to elucidate how CSPT abnormalities emerge and progress during the early course of OCD. Outstanding departmental support; collective expertise in fMRI, pediatric OCD, cognitive-emotional development, and clinical research; and, opportunities for future translational research make the University of Michigan an ideal environment for this award. PUBLIC HEALTH RELEVANCE: OCD affects millions of American children, and understanding the abnormalities of brain maturation associated with early onset illness will help to foster improved understanding, treatment, and eventually, prevention of this disabling condition.