Evaluating a Brief Intensive Intervention for Children with Fragile X Syndrome

描述(申请人提供)：这个导师临床科学家研究职业发展奖(K08)的长期目标是发展候选人的技能，将多模式神经成像与行为分析研究相结合，使他可能成为在严重神经发育障碍儿童的研究中将应用行为分析与临床神经科学研究相结合的首批独立科学家之一。候选人的具体研究目标是应用神经成像技术评估针对脆性X综合征儿童的特定靶向行为分析干预。为了实现这一目标，候选人将接受行为神经遗传学和神经成像领域的专家的指导，并将继续进行一项教育计划，其中包括神经成像方面的高级研讨会以及认知心理学、遗传学和神经科学领域的正式课程。这项拟议的研究项目的主要目标是针对脆性X综合征患者表现出的特定认知和行为弱点(数学和金钱技能)，进行强化行为干预。这种干预的效果将使用特定的神经成像指标以及行为指标进行评估。通过了解行为变化的神经关联，这些神经成像指标将被用于统计模型，以改善对反应结果的预测。两个受试组将接受干预：一组患有脆性X综合征(FXS)的儿童，以及一组年龄、性别和智商匹配的非特定形式发育障碍(NSDD)的受试者。在斯坦福大学进行的为期三天的密集干预之前和之后，这两组人都将接受神经成像。据假设，有效的干预(如显著的行为或认知变化所证明的)将与反映功能连接和/或代偿性激活的“正常化”的大脑激活曲线相关联。候选人还将调查基线时的特定激活曲线是否能预测反应。关于增强FXS患者认知能力的最佳方法，只有有限的信息可用。如果这种干预被发现是FXS患者学习的有效方法，这项技术可以迅速转化为临床和教育环境，从而使许多患有FXS的儿童和青少年受益。

DESCRIPTION (provided by applicant): The long-term objective of this Mentored Clinical Scientist Research Career Development (K08) Award is to develop the candidate's skills in combining multi-modal neuroimaging with behavior analytic research so that he may become one of the first independent scientists to integrate applied behavioral analysis with clinical neuroscience investigation in the study of children with serious neurodevelopmental disorders. The candidate's specific research goal is to apply neuroimaging techniques to evaluate specific targeted behavior analytic interventions for children with fragile X syndrome. To accomplish this goal, the candidate will be mentored by experts in the fields of behavioral neurogenetics and neuroimaging and will pursue an educational program that includes advanced seminars in neuroimaging as well as formal coursework in the areas of cognitive psychology', genetics and neuroscience. The primary goal of the proposed research project is to target specific cognitive and behavioral weaknesses shown by individuals with fragile X syndrome (math and money skills) for intensive behavioral intervention. The efficacy of this intervention will be evaluated using specific neuroimaging metrics as well as behavioral measures. By understanding the neural correlates of behavior change, these neuroimaging metrics will be employed in statistical models to improve prediction of response outcome. Two subject groups will be exposed to the interventions: a group of children with fragile X syndrome (FXS), and a group of age- gender and IQ-matched subjects with a non-specific form of developmental disability (NSDD). Both groups will receive the neuroimaging prior to and following the intensive intervention conducted at Stanford over three days. It is hypothesized that effective intervention (as demonstrated by significant behavioral or cognitive change) will be associated with profiles of brain activation reflecting "normalization" of functional connectivity and/or compensatory activation. The candidate will also investigate whether particular profiles of activation at baseline predict response. Only limited information is available concerning optimal methods for enhancing cognitive abilities in individuals with FXS. If this intervention is found to be an effective method for learning in individuals with FXS, the technique could be rapidly translated into the clinical and educational environments, thus benefiting many children and adolescents with this disorder.