PREDICTING OUTCOME IN CHILDREN WITH TIC DISORDERS USING NEUROIMAGING DATA

描述（由申请人提供）：多达25%的儿童在某个时候有抽搐（短暂的，重复的动作或噪音），但个体有很大的不同抽搐。即使在抽搐发作后的第一年内，一些儿童也会改善，没有明显的损害，而另一些儿童则会发展成慢性疾病（抽动秽语综合征：TS），严重影响他们的生活质量。了解大脑的特点，目前在早期的过程中， TS介导或预测这些不同的结果可能会彻底改变预后和治疗。这个指导研究科学家发展奖（K 01）的目的是为申请人提供必要的培训，以过渡到独立的研究计划，重点是TS和相关疾病的大脑机制（例如，注意力缺陷/多动障碍：ADHD，强迫症：OCD）。申请人的长期目标是鉴定可以帮助指导预后和治疗的预测性生物标志物。为了实现这些目标，申请人将获得TS和神经成像方法学专家的无与伦比的指导（Drs. K。黑色，B。Schlaggar，E.索厄尔河Poldrack和T.好时），并将获得华盛顿大学一流的临床和成像资源。拟议的培训计划将使申请人能够实现促进其长期目标所需的几个短期目标，包括结构MRI方法、高级分析策略和纵向研究设计方面的新培训，以及静息状态功能连接MRI和TS及其共病疾病临床方面的持续培训。这些培训目标将通过拟议的研究来推进。首先，监督学习方法将用于识别大脑结构和功能的模式，这些模式可以将个体儿童分类为患有TS或没有，为探索预测生物标志物提供原则性的起点（目标1）。其次，无监督学习方法将用于识别TS的基于大脑的表型亚组，有助于更好地解释TS的异质性（目标2）。最后，监督学习方法将用于预测儿童首次出现抽搐时的症状进展，使用抽搐发作后第一年的儿童纵向随访（目标3）。因此，该项目是对抽搐儿童进行基于大脑的个性化预测的第一步.值得注意的是，所提出的方法可以扩展到其他儿童神经精神障碍（例如，自闭症，多动症），为早期治疗奠定基础，以及发现潜在的机制。作为该奖项的一部分，收集的纵向数据将成为未来针对TS发展轨迹的R 01应用的基础。本申请中提出的培训和研究计划将有助于申请人过渡到翻译发育神经科学的独特和独立的研究生涯。通过采用多种融合技术和分析方法来询问TS和相关疾病的生物标志物的研究计划，申请人将在整个独立职业生涯中继续解决与NIMH相关的研究问题。

DESCRIPTION (provided by applicant): As many as 25% of all children have tics (brief, repetitive movements or noises) at some point, yet individuals have greatly varying prognoses. Even within the first year after tic onset, some children improve and experience no significant impairment, while others develop a chronic disorder (Tourette syndrome: TS) that can severely impinge upon their quality of life. Understanding the brain features present early in the course of TS that mediate or predict these different outcomes could revolutionize prognosis and treatment. The purpose of this Mentored Research Scientist Development Award (K01) is to provide the applicant with the training necessary to transition to independence with a research program focused on the brain mechanisms underlying TS and related disorders (e.g., attention-deficit/hyperactivity disorder: ADHD, obsessive-compulsive disorder: OCD). The applicant's long-term goal is to identify predictive biomarkers that can help guide prognosis and treatment. In order to achieve such goals, the applicant will receive unparalleled mentorship by experts in TS and neuroimaging methodologies (Drs. K. Black, B. Schlaggar, E. Sowell, R. Poldrack, and T. Hershey) and will have access to superb clinical and imaging resources at Washington University. The proposed training plan will enable the applicant to achieve several short-term goals necessary to facilitate her long-term goals, including new training in structural MRI methods, advanced analytic strategies, and longitudinal study design, and continued training in resting state functional connectivity MRI and in the clinical aspects of TS and its comorbid conditions. These training goals will be advanced through the proposed research. First, supervised learning methods will be used to identify patterns of brain structure and function that can classify an individual child as having TS or not, providing a principled starting point for exploring predictive biomarkers (Aim 1). Second, unsupervised learning methods will be used to identify brain-based phenotypic subgroups of TS, helping to better account for the heterogeneity of TS (Aim 2). Finally, supervised learning methods will be used to predict symptom progression for children when they first present with tics, using longitudinal follow-up of children during ther first year after tic onset (Aim 3). Thus, the proposed project is a first step toward brain- based individualized predictions for children with tics. Notably, the proposed methods can be extended to other childhood neuropsychiatric disorders (e.g., autism, ADHD), setting the stage for early treatment, as well as discovery of the underlying mechanisms. The longitudinal data collected as part of this award will be foundational for future R01 applications targeting the developmental trajectory of TS. The training and research plan proposed in this application will facilitate the applicant's transition to a unique and independent research career in translational developmental neuroscience. With a research program that employs multiple converging techniques and analysis methods to interrogate biomarkers of TS and related disorders, the applicant will continue to address research questions relevant to the NIMH throughout her independent career.