Motor Control and Cerebellar Maturation in Autism

描述(由申请者提供)：候选人的长期目标是开发一项独立的研究计划，专注于描述自闭症儿童的大脑和感觉运动技能的发展。为了实现这一目标，候选人组织了一项培训计划，包括课程作业、研讨会和咨询高级专家，重点是运动系统生理学、自闭症的神经生物学、评估眼睛和手动运动控制的方法，以及大脑发育。主办机构伊利诺伊大学芝加哥分校(UIC)提供了许多与该奖项相关的培训活动和资源，包括关于功能磁共振成像方法和数据分析、自闭症研究、神经心理学、神经解剖学以及运动控制和运动障碍的定期研讨会、讲座和期刊俱乐部。这位导师约翰·斯威尼博士从事眼球运动和功能核磁共振研究健康和疾病超过25年，他一直是9K奖的主要导师。他是UIC自闭症卓越中心项目赠款的联席主任。候选人是自闭症卓越中心的研究员，该中心为他提供了与拟议研究的转介来源的直接联系，并接触了芝加哥更广泛的自闭症社区，如中西部自闭症联盟。该候选人将研究自闭症患者的运动控制和大脑系统的发展。虽然这是自闭症研究不足的一个方面，但相当多的证据表明，大多数受影响的人都存在运动障碍。60名年龄在5-25岁之间的自闭症患者将与60名年龄和智商匹配的健康对照组进行比较。受试者将为眼睛和手动系统执行持续和弹道运动控制任务。初步证据表明，自闭症受试者表现出以下方面的降低：a)视觉跟踪准确性，b)手动稳定性，c)跳动准确性，d)弹道力准确性。此外，飞行员数据显示，眼跳和弹道力量精确度的试探性变异性增加，表明小脑的变异性减少。平行的fMRI任务将评估45名自闭症患者和45名8岁对照组的小脑、眼部和手部运动回路的发展。试验数据表明，自闭症患者在眼动任务中中线小脑蠕虫的激活减少，在手动控制时在外侧小脑半球的激活减少。还将进行运动技能的神经心理测试，以及运动功能的临床神经学检查。这些研究有望阐明这种高度流行的神经发育障碍的运动系统功能障碍的性质和发展轨迹。

DESCRIPTION (provided by applicant): The candidate's long-term goal is to develop an independent research program focused on characterizing the development of brain and sensorimotor skills in children with autism. To achieve this goal, the candidate has organized a training program involving coursework, workshops, and consultation with senior experts focused on motor system physiology, the neurobiology of autism, methods for assessing ocular and manual motor control, and brain development. The host institution, the University of Illinois at Chicago (UIC), provides numerous training activities and resources relevant to this award, including regular seminars, lectures and journal clubs on fMRI methods and data analysis, autism research, neuropsychology, neuroanatomy and motor control and movement disorders. The mentor, Dr. John Sweeney, has performed oculomotor and fMRI studies of health and disease for over 25 years, and he has been the primary mentor of 9 K awards. He is co-Director for the UIC Autism Center of Excellence project grant. The candidate is an investigator on the Autism Center of Excellence, which provides him with direct contact with referral sources for the proposed studies and exposure to the broader autism community within Chicago such as the Midwestern Autism Consortium. The candidate will investigate the development of motor control and brain systems in autism. While this is an understudied aspect of autism, considerable evidence suggests motor impairments are present in the majority of affected individuals. Sixty individuals with autism between ages 5-25 years will be compared with 60 age- and IQ- matched healthy controls. Subjects will perform sustained and ballistic motor control tasks for both ocular and manual systems. Preliminary evidence indicates that subjects with autism show reduced: a) visual tracking accuracy, b) manual force stability, c) saccade accuracy, and d) ballistic force accuracy. In addition, the variability-reducing function of the cerebellum is implicated by pilot data showing increased trial- wise variability of saccade and ballistic force accuracy. Parallel fMRI tasks will assess the development of cerebellar ocular and manual motor circuits in the 45 subjects with autism and 45 controls > age 8 years. Pilot data suggest reduced activation in autism within midline cerebellar vermis during eye movement tasks and in lateral cerebellar hemispheres during manual control. Neuropsychological tests of motor skill, as well as clinical neurological examinations of motor function, also will be administered. These studies have promise to clarify the nature and developmental trajectory of motor system dysfunctions in this highly prevalent neurodevelopmental disorder.