Developing a novel treatment for restricted inflexible behavior

描述（由申请人提供）：自闭症谱系障碍（ASD）的部分定义是可以被描述为受限和不灵活的行为。这种行为以所谓的“高阶”限制性重复行为为例，其特征是坚持千篇一律或抵制改变。以这种方式表现的行为在ASD儿童中普遍存在，并且可能显著干扰发展功能行为和更复杂的技能的机会。因此，受限、不灵活的行为可能对大脑和行为发育产生不利影响，针对此类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个研究项目，以开发一种新的治疗方法来治疗受限、不灵活的行为，这是神经发育障碍和自闭症中普遍存在的一个临床重要且高度未被研究的问题。我们提出的策略不是针对特定的强迫性、限制性或重复性行为进行修改，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，我们提出的项目具有高度的转译性，因为我们的干预方法是基于动物和人类实验室研究，这些研究已经为这种方法建立了经验基础。假设有效的干预措施对发育具有可推广的影响，并将高度可转化为其他神经发育障碍。因此，我们建议评估ASD儿童和典型发展对照的限制性、不灵活行为，然后进行试点测试，以确定它是否会直接促进ASD儿童的可变和灵活的适应性反应。该项目在以灵活性和可变性为干预目标方面具有高度创新性。一般僵硬/不灵活是自闭症的最典型特征，在相关的神经发育障碍中也很常见，目前还没有系统的努力来开发有效的行为治疗方法。最后，拟议的项目代表了一项转化性的努力，将基于实验室的动物和人类研究，并将其应用于针对限制的、不灵活的行为的集中干预，最终可以在社区环境中进行。如果成功，所提出的治疗方法应该有相当大的潜力成为广泛使用的，具有成本效益的治疗方法。

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.