Evaluating a Brief Intensive Intervention for Children with Fragile X Syndrome

描述（由申请人提供）：本指导临床科学家研究职业发展（K08）奖的长期目标是培养候选人将多模态神经影像学与行为分析研究相结合的技能，使他有可能成为第一批将应用行为分析与临床神经科学研究结合起来研究严重神经发育障碍儿童的独立科学家之一。候选人的具体研究目标是应用神经影像学技术来评估脆性X综合征儿童的特定目标行为分析干预措施。为了实现这一目标，候选人将由行为神经遗传学和神经影像学领域的专家指导，并将进行包括神经影像学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在内的教育计划。拟议研究项目的主要目标是针对脆性X综合征患者（数学和金钱技能）所表现出的特定认知和行为弱点进行强化行为干预。这种干预的效果将使用特定的神经影像学指标和行为指标进行评估。通过了解行为改变的神经相关因素，这些神经影像学指标将被用于统计模型，以提高对反应结果的预测。两组受试者将接受干预：一组患有脆性X染色体综合征（FXS）的儿童，以及一组年龄-性别和智商匹配的患有非特异性发育障碍（NSDD）的受试者。在斯坦福大学进行为期三天的强化干预之前和之后，两组患者都将接受神经影像学检查。假设有效的干预（通过显著的行为或认知改变证明）将与反映功能连接和/或代偿激活“正常化”的大脑激活概况相关。候选人还将研究基线激活的特定剖面是否可以预测反应。关于增强FXS个体认知能力的最佳方法，目前的信息有限。如果这种干预被发现是FXS患者学习的有效方法，该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。

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.