Evaluating a Brief Intensive Intervention for Children with Fragile X Syndrome

这项指导临床科学家研究职业发展奖(K08)的长期目标是 培养候选人将多模式神经成像与行为分析研究相结合的技能，以便 他可能成为首批将应用行为分析与临床相结合的独立科学家之一 神经科学在严重神经发育障碍儿童研究中的应用。这个 候选人的具体研究目标是应用神经成像技术来评估特定的目标行为 脆性X综合征儿童的分析性干预。为了实现这一目标，候选人将是 由行为神经遗传学和神经成像领域的专家指导，将致力于 教育计划，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。 拟议的研究项目的主要目标是针对特定的认知和行为弱点。 由患有脆性X综合征(数学和金钱技能)的个人展示，用于强化行为干预。 这种干预的效果将使用特定的神经成像指标以及行为学指标进行评估 措施。通过了解行为变化的神经关联，这些神经成像指标将 在统计模型中使用，以改进对响应结果的预测。两个课题组将是 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。两个小组都将 在斯坦福大学进行的密集干预之前和之后接受神经成像 几天。假设有效的干预(如显著的行为或认知所证明的 变化)将与反映功能连通性“正常化”的大脑激活曲线相关联 和/或补偿激活。候选人还将调查特定的激活配置文件是否在 基线预测响应。只有有限的信息可以获得关于增强 FXS患者的认知能力。如果这种干预被发现是一种有效的学习方法 对于患有FXS的患者，这项技术可以迅速转化为临床和教育 环境，从而使许多患有这种疾病的儿童和青少年受益。

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.