Developing a novel treatment for restricted inflexible behavior

描述(由申请人提供)：自闭症谱系障碍(ASD)部分由可被描述为受限和僵化的行为来定义。这种行为的例证是所谓的“更高层次的”限制性重复行为，其特征是坚持相同或抵制改变。以这种方式表现的行为在ASD儿童中很普遍，可能会严重干扰发展功能性行为和更复杂的曲目的机会。因此，受限、僵化的行为可能会对大脑和行为发育产生不利影响，针对这种行为的干预应该对神经可塑性和神经发育轨迹产生显著的积极影响。拟议项目的总体目标是启动一项研究计划，以开发一种新的治疗方法来治疗受限的、僵硬的行为，这是一个在一般神经发育障碍和特定的自闭症中具有重要临床意义和高度未被研究的问题。我们建议的策略不是针对特定的强迫、限制或重复的行为进行修改，而是通过适合年龄的功能性活动来促进灵活性和可变性的发展。因此，拟议的项目具有很高的翻译性，因为我们的干预方法基于一系列动物和人类实验室研究，这些研究为这种方法奠定了经验基础。有效的干预措施被认为对发育具有普遍的影响，并将高度可翻译到其他神经发育障碍。因此，我们建议评估ASD儿童的限制性、顽固性行为，并典型地发展对照，然后试行经验性干预，以确定它是否将直接促进ASD儿童的可变和灵活的适应性反应。该项目在将灵活性和可变性作为干预目标方面具有很高的创新性。目前还没有系统的努力来开发有效的行为治疗方法来治疗一般的僵硬/僵硬，这是自闭症的最大特征，在相关的神经发育障碍中很常见。最后，拟议的项目代表了一项转化努力，即进行以实验室为基础的动物和人类研究，并将其应用于针对受限的、僵化的行为的重点干预，这些行为最终可以在社区环境中进行。如果成功，建议的治疗方法应该有相当大的潜力成为一种广泛使用的、具有成本效益的治疗方法。 公共卫生相关性：自闭症谱系障碍(ASD)的定义在一定程度上是由可以被描述为受限和僵化的行为来定义的。对于自闭症最具特征的高阶仪式性重复行为和一般僵硬/僵硬的行为/教育治疗，还没有系统的尝试开发有效的方法。为受限、僵化的行为和干预措施建立评估方法，以增加反应的可变性和灵活性，将对自闭症患者及其家庭有重大好处。

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) are defined, in part, by behavior that can be characterized as restricted and inflexible. Such behavior is exemplified by the so-called "higher order" restricted repetitive behaviors characterized by their insistence on sameness or resistance to change. Behaviors characterized in this way are pervasive in children with ASD and can significantly interfere with opportunities to develop functional behaviors and more complex repertoires. Thus, restricted, inflexible behavior likely adversely impacts brain and behavioral development, and intervention directed toward such behavior should have significant positive impact on neuroplasticity and neurodevelopmental trajectories. The overall goal of the proposed project is to initiate a program of research to develop a novel treatment approach to restricted, inflexible behavior, a clinically important and highly understudied problem in neurodevelopmental disorders in general and autism in specific. Rather than target a particular compulsive, restricted, or repetitive behavior for modification, our proposed strategy is to promote the development of flexibility and variability using age appropriate, functional activities. As such, the proposed project is highly translational as our approach to intervention is based on a body of animal and human laboratory studies that have established the empirical foundation for such an approach. Effective interventions are hypothesized to have generalizable effects on development and will be highly translatable to other neurodevelopmental disorders. Thus, we propose to assess restricted, inflexible behavior in children with ASD and typically developing controls and then pilot test an experiential intervention to determine if it will directly promote variable and flexible adaptive responding in children with ASD. This project is highly innovative in targeting flexibility and variability as goals of the intervention. No systematic efforts have been made to develop effective methods for the behavioral treatment of the general rigidity/inflexibility that is most characteristic of autism and common in related neurodevelopmental disorders. Finally, the proposed project represents a translational effort to take laboratory-based animal and human studies and apply them to a focused intervention directed at restricted, inflexible behavior that can ultimately be conducted in a community setting. If successful, the proposed treatment approach should have considerable potential for becoming a widely used, cost effective treatment approach. PUBLIC HEALTH RELEVANCE: Autism spectrum disorders (ASD) are defined, in part, by behavior that can be characterized as restricted and inflexible. No systematic attempts have been made to develop effective methods for the behavioral/educational treatment of the higher-order ritualistic repetitive behaviors and general rigidity/inflexibility that are most characteristic of autism. Establishing assessment methods for restricted, inflexible behavior and interventions to increase variability and flexibility in responding will be of significant benefit to individuals with autism and their families.