PREDICTING OUTCOME IN CHILDREN WITH NEW-ONSET TICS USING NEUROIMAGING DATA

 描述(由申请人提供)：儿童期起病的神经精神障碍通常会使人虚弱，并且患病率正在上升。我们认为，抽动症/慢性抽动障碍(TS/CTD)有一个特别适合发现早期诊断和预防发育障碍的最佳策略的过程。常见的临床实践和流行病学数据表明，很大一部分(10%-25%)的儿童在某个年龄段出现运动和/或声带痉挛。然而，在所有儿童中，只有1-3%的儿童在诊断TS/CTD所需的全年内有抽搐。拟议研究的目的是了解新发抽动症(“新抽动”)儿童的结构和功能神经成像特征，因为这一人群的神经生物学尚未进行研究。研究患有新抽动症的儿童应该提供最大的杠杆作用，以理解为什么抽搐会在一些儿童身上发作，而在另一些儿童中不会。这项建议将新抽动症与TS/CTD和对照组的神经成像特征进行比较，实施机器学习工具来预测患有新抽动症的儿童是否会发作或发展为TS/CTD，并利用纵向扫描来识别抽搐缓解或持续时发生的受试者内的变化。拟议的研究将应用静息状态功能连通性磁共振(RS) FcMRI)和结构MRI方法对儿童新抽动症的研究。将对目前新发抽搐的儿童进行神经成像，并将与诊断为TS/CTD的儿童和对照儿童的现有MRI数据进行比较。对新抽动发作后1年的随访评估将使我们能够确定哪些儿童抽动完全缓解，哪些实际上处于TS/CTD的早期阶段，从而将这一组分为缓解的抽动和转换的TS/CTD亚组。根据流行病学数据，我们预计大多数新发TICS患者属于缓解期TICS亚组。对新抽动症儿童的纵向扫描将使我们能够评估抽搐的汇款或持续发生的受试者内的变化。这项研究还将应用机器学习工具，特别是支持向量机(SVMs)，来表征区分汇款TIC和现有TS/CTD组的特征。然后，这些功能将用于预测新TICS组中的TICS是否会汇款(已汇出TICS) 或坚持(转换为TS/CTD)以个别患者为基础。因此，我们将准备确定汇款和TS/CTD的差异，以及潜在的早期预测因素。这项研究将为一种常见的临床表现提供创新的、重要的数据：患有新抽搐的儿童。成功地完成我们的目标将允许个体预测缓解或进展，或者至少将允许丰富新的TICS样本以用于TS/CTD的高风险，这将使TS/CTD的预防研究变得可行。我们还将深入了解New tics的神经生物学。最后，这项研究是迈向明确的纵向研究的必要的第一步，可以提高诊断的准确性并解决因果问题。随着我们目标的成功完成，类似的方法可以应用于其他儿童期起病的神经精神障碍，为早期治疗或预防慢性病奠定基础。

 DESCRIPTION (provided by applicant): Childhood onset neuropsychiatric disorders are often debilitating and are increasing in prevalence. Tourette Syndrome/Chronic Tic Disorder (TS/CTD), we propose, has a course that lends itself especially well to discovering optimal strategies for early diagnosis and prevention of developmental disorders. Common clinical practice and epidemiological data suggest that a large fraction (10-25%) of all children manifest motor and/or vocal tics at some age. Yet only 1-3% of all children have tics for the full year required for diagnosis of TS/CTD. The objective of the proposed research is to understand the structural and functional neuroimaging features of children with new-onset tics ("New Tics"), as the neurobiology of this population has not been investigated. Studying children with New Tics should provide the most leverage in understanding why tics remit in some children but not others. This proposal compares neuroimaging features of New Tics to TS/CTD and to controls, implements machine-learning tools to predict whether children with New Tics will remit or develop TS/CTD, and utilizes longitudinal scans to identify within-subject changes that occur as tics remit or persist. The proposed study will apply resting-state functional connectivity MRI (rs fcMRI) and structural MRI methods to investigate children with New Tics. Neuroimaging will be conducted on children with current, new- onset tics, and comparisons will be made to existing MRI data from children with diagnosed TS/CTD and controls. Follow-up evaluation (1 year after tic onset) of New Tics will allow us to identify which children's tics remitted completely and whic were actually in the earliest stages of TS/CTD, thus sorting this group into Remitted Tics and Converted TS/CTD subgroups. Based on the epidemiological data, we expect most of New Tics subjects to fall in the Remitted Tics subgroup. Longitudinal scans of the New Tics children will enable us to assess within-subject changes that occur with remittance or persistence of tics. This study will also apply machine learning tools, specifically Support Vector Machines (SVMs), to characterize features that distinguish Remitted Tics and Existing TS/CTD groups. Those features will then be used to predict whether tics in the New Tics group will remit (Remitted Tics) or persist (Converted TS/CTD) on an individual patient basis. Thus, we will be poised to identify differences, and potentially early predictors, of remittance and TS/CTD. This study will provide innovative, important data on a common clinical presentation: the child with New Tics. Completing our aims successfully will allow individual prediction of remission or progression, or at least will allow a New Tics sample to be enriched for high risk of developing TS/CTD, which would make prevention studies for TS/CTD feasible. We will also gain insight into the neurobiology of New Tics. Finally, this study is an essential first step towards a definitive longitudinal study that can improve diagnostic accuracy and settle questions of cause and effect. With successful completion of our aims, similar methods can be applied to other childhood onset neuropsychiatric disorders, setting the stage for early treatment or prevention of chronicity.