Motor Control and Cerebellar Maturation in Autism

自闭症的运动控制和小脑成熟

• 批准号: 8299730
• 负责人: MATTHEW W MOSCONI
• 金额: $ 9.44万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-16 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8299730
• 关键词: Motor; Control; Cerebellar; Maturation; Autism

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. PUBLIC HEALTH RELEVANCE: Motor impairments and cellular abnormalities in the cerebellum have been documented in the majority of individuals with autism studied to date. The proposed studies will examine motor and cerebellar development in autism. These studies have the potential to elucidate abnormal developmental pathways of motor and cerebellar systems, which in turn could provide clues to pathophysiological mechanisms in autism, assist in more reliable diagnosis, and inform the development of novel treatments targeting cerebellar systems.

描述（由申请人提供）：候选人的长期目标是开发一个独立的研究项目，重点关注自闭症儿童大脑和感觉运动技能的发展特征。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、研讨会以及与高级专家的咨询，重点关注运动系统生理学、自闭症神经生物学、评估眼部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) 提供了大量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、神经解剖学和运动控制的定期研讨会、讲座和期刊俱乐部，以及运动障碍。导师 John Sweeney 博士从事健康和疾病的动眼神经和功能磁共振成像研究超过 25 年，也是 9 K 奖的主要导师。他是 UIC 自闭症卓越中心项目资助的联合主任。该候选人是自闭症卓越中心的一名调查员，该中心使他能够直接接触拟议研究的推荐来源，并接触芝加哥更广泛的自闭症社区，例如中西部自闭症联盟。 候选人将研究自闭症患者运动控制和大脑系统的发育。虽然这是自闭症的一个尚未得到充分研究的方面，但大量证据表明大多数受影响的个体都存在运动障碍。 60 名年龄在 5 至 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者进行比较。受试者将为视觉和手动系统执行持续的弹道运动控制任务。初步证据表明，患有自闭症的受试者表现出以下方面的下降：a) 视觉跟踪准确性，b) 手力稳定性，c) 扫视准确性，以及 d) 弹道力准确性。此外，试验数据显示小脑的变异性减少功能显示扫视和弹道力精度的试验变异性增加。并行功能磁共振成像任务将评估 45 名自闭症受试者和 45 名 8 岁以上对照者的小脑眼部和手动运动回路的发育情况。试验数据表明，自闭症患者在眼动任务期间小脑蚓部中线内的激活减少，在手动控制期间小脑外侧半球的激活减少。还将进行运动技能的神经心理学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普遍的神经发育障碍中运动系统功能障碍的性质和发育轨迹。 公共健康相关性：迄今为止，大多数自闭症患者的研究都记录了小脑的运动障碍和细胞异常。拟议的研究将检查自闭症患者的运动和小脑发育。这些研究有可能阐明运动和小脑系统的异常发育途径，进而可以为自闭症的病理生理机制提供线索，协助更可靠的诊断，并为针对小脑系统的新疗法的开发提供信息。