Motor Control and Cerebellar Maturation in Autism

自闭症的运动控制和小脑成熟

• 批准号: 8028652
• 负责人: MATTHEW W MOSCONI
• 金额: $ 5.96万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 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 2011-04-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8028652
• 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计划，重点是表征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，候选人组织了一个培训计划，包括课程，研讨会，以及与高级专家的咨询，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）提供了与该奖项相关的许多培训活动和资源，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。导师John Sweeney博士从事眼科和fMRI健康和疾病研究超过25年，他一直是9 K奖的主要导师。他是UIC自闭症卓越中心项目赠款的共同主任。候选人是自闭症卓越中心的调查员，该中心为他提供了与拟议研究的转介来源的直接联系，并接触到芝加哥内更广泛的自闭症社区，如中西部自闭症联盟。 候选人将研究自闭症的运动控制和大脑系统的发展。虽然这是自闭症的一个未充分研究的方面，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5-25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。受试者将执行眼睛和手动系统的持续和弹道运动控制任务。初步证据表明，患有自闭症的受试者表现出降低的：a）视觉跟踪准确性，B）手动力稳定性，c）扫视准确性，和d）弹道力准确性。此外，小脑的可变性减少功能与飞行员数据有关，飞行员数据显示扫视和弹道力准确性的试验可变性增加。平行的fMRI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视觉和手动运动回路的发育。试验数据表明，减少激活自闭症中线小脑蚓部在眼球运动任务和手动控制过程中，在小脑外侧半球。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。这些研究有希望澄清这种高度流行的神经发育障碍中运动系统功能障碍的性质和发展轨迹。 公共卫生关系：迄今为止，大多数自闭症患者都有小脑运动障碍和细胞异常的记录。拟议中的研究将检查自闭症的运动和小脑发育。这些研究有可能阐明运动和小脑系统的异常发育途径，从而为自闭症的病理生理机制提供线索，有助于更可靠的诊断，并为开发针对小脑系统的新型治疗方法提供信息。