Minimally Verbal ASD: From Basic Mechanisms to Innovative Interventions

描述：2011年LACC战略计划中确定的一个关键差距是缺乏对未能获得口语的年龄较大的儿童和成年人的知识。人们对这些人知之甚少，因为目前的评估工具和做法不适合这一群体。更重要的是，没有模型可以解释为什么大约30%的自闭症人口仍然保持最低限度的言语，也没有专门针对这一人群的干预措施来促进口语。我们的ACE的目标是解决这些问题，带来从言语、听觉、临床和计算神经科学的其他领域汲取的工具、方法和途径。我们的ACE位于波士顿大学，汇集了来自全校的研究人员以及来自哈佛医学院、东北大学和阿尔伯特·爱因斯坦医学院的合作者。ACE中相互关联的项目包括：促进自闭症学龄儿童口语的新干预措施(项目I)；治疗反应和结果的生物标记物调查(项目I、II和III)；可能导致说话障碍的机制调查，包括：(A)根据DIVA模型，言语产生网络关键节点的结构和功能连接障碍(项目11)；(B)根据电生理反应和神经振荡模式索引的听觉场景的感知、组织和分析异常(项目III)；使用高分辨率方法研究组织样本中的白质和轴突生长蛋白，研究与语言有关的关键前额叶皮质区域兴奋性和抑制性神经元通路的中断(项目IV)。这些项目由行政和数据管理核心(A)、研究培训和教育核心(B)和临床核心(C)联合提供服务，该核心将使用标准和新颖的实验措施进行全面评估，以获取患有自闭症儿童的不同表型，并将用来解释项目中确定的治疗反应和机制因素的变异性。总之，在我们的ACE中进行的研究将极大地促进我们对自闭症谱系中这一被忽视的末端的理解，为评估和治疗提供创新的方法，为识别预测谁将无法获得言语的生物标志物铺平道路，并强调治疗干预的潜在分子靶点。

DESCRIPTION: A critical gap identified in the 2011 lACC Strategic Plan is the dearth of knowledge about older children and adults who fail to acquire spoken language. Little is known about these individuals because current assessment tools and practices are not adequate for this population. More significantly, there are no models that explain why about 30% of the ASD population remains minimally verbal and no interventions that specifically and uniquely target this population in promoting spoken language. The goals of our ACE are to address these issues, bringing tools, methods, and approaches have drawn from others areas of speech, auditory, clinical, and computational neurosciences. Our ACE, located at Boston University, brings together researchers from across the university and collaborators from Harvard Medical School, Northeastern University and Albert Einstein College of Medicine. The interconnected projects in the ACE include: a novel intervention to promote spoken language in school-aged children with ASD (Project I); investigation of biological markers of treatment response and outcome (Projects I, II, and III); investigation of mechanisms that might underlie the failure to speak including (a) structural and functional connectivity impairments in key nodes of the speech production network according to the DIVA model (Project 11); (b) abnormalities in the perception, organization and analysis of auditory scenes as indexed in electrophysiological responses and neural oscillatory patterns (Project III); disruptions in excitatory and inhibitory neuronal pathways in key prefrontal cortical areas associated with language using high resolution methods to investigate white matter and axonal growth proteins in tissue samples (Project IV). The projects are united and served by an Administration and Data Management Core (A), a Research Training and Education Core (B) and a Clinical Core (C), which will carry out comprehensive assessments using standard and novel experimental measures to capture the heterogeneous phenotypes of minimally verbal children with ASD, and that will be used to explain variability in treatment response and mechanistic factors identified in the Projects. Together, the research conducted in our ACE will significantly advance our understanding of this neglected end of the autism spectrum, provide innovative approaches to assessment and treatment, pave the way for identifying biological markers predict who will fail to acquire speech, and highlight potential molecular targets for therapeutic interventions.