Motor Control and Cerebellar Maturation in Autism

自闭症的运动控制和小脑成熟

• 批准号: 8331592
• 负责人: MATTHEW W MOSCONI
• 金额: $ 15.71万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331592
• 关键词: 8 year old; Adult; Affect; Age; Autistic Disorder; Autopsy; Award; Ballistics; Brain; Cell Nucleus; Cerebellar Diseases; Cerebellar vermis structure; Cerebellum; Chicago; Child; Clinical; Communities; Consultations; Data; Data Analyses; Development; Diagnosis; Diagnostic; Disease; Dysmetria; Educational workshop; Equipment and supply inventories; Exposure to; Eye Movements; Family member; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Grant; Health; Illinois; Image; Impairment; Individual; Institution; Journals; K-Series Research Career Programs; Knowledge; Laboratories; Lateral; Lobule; Manuals; Measures; Mentors; Methods; Modeling; Motor; Motor Pathways; Motor Skills; Movement Disorders; Nature; Neuroanatomy; Neurobiology; Neurodevelopmental Disorder; Neurologic; Neurologic Examination; Neuropsychological Tests; Neuropsychology; Neurosciences; Neurosciences Research; Pathology; Performance; Physiology; Relative (related person); Reporting; Research; Research Design; Research Personnel; Resources; Saccades; Sampling; Schedule; Severities; Smooth Pursuit; Source; Symptoms; System; Systems Development; Testing; Training; Training Activity; Training Programs; Universities; Work; age related; base; career development; experience; lectures; motor control; motor deficit; motor impairment; neurophysiology; novel; oculomotor; programs; public health relevance; relating to nervous system; sensorimotor system; skills; visual tracking

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制定一个独立的研究计划，旨在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，候选人组织了一项培训计划，涉及课程工作，讲习班，并与专注于运动系统生理学的高级专家，自闭症的神经生物学，评估眼部和手动运动控制的方法以及大脑发育。东道国伊利诺伊大学芝加哥大学（UIC）提供了与该奖项相关的众多培训活动和资源，包括定期研讨会，讲座和期刊俱乐部，涉及FMRI方法和数据分析，自闭症研究，神经心理学，神经性神经术，神经术以及运动控制和运动障碍。这位导师约翰·斯威尼（John Sweeney）博士已经对健康和疾病进行了眼球磁共振成像研究，已有25年以上，他一直是9 K奖的主要导师。他是UIC自闭症卓越项目赠款中心的联合主任。候选人是自闭症卓越中心的调查员，该调查员使他与拟议的研究和接触芝加哥境内更广泛的自闭症社区（例如中西部自闭症财团）的推荐来源直接接触。 候选人将研究自闭症运动和大脑系统的发展。尽管这是自闭症的一个研究，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5-25岁年龄段的自闭症患者将与60岁和IQ匹配的健康对照组进行比较。受试者将针对眼部和手动系统执行持续的弹道运动控制任务。初步证据表明，自闭症受试者显示出降低：a）视觉跟踪精度，b）手动力稳定性，c）扫视精度和d）弹道力精度。此外，小脑的可变性功能与试验数据有关，显示出扫视和弹道力准确性的试验变异性增加。平行FMRI任务将评估45名患有自闭症的受试者和45个控制> 8岁的45名受试者中小脑眼和手动电机电路的发展。试验数据表明，在手动控制过程中，在眼动任务和小脑半球的中线小脑vermis中自闭症的激活降低。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也将进行。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。 公共卫生相关性：大多数自闭症患者迄今为止研究的大脑的运动障碍和细胞异常已记录在小脑中。拟议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，这反过来又可以为自闭症中的病理生理机制提供线索，有助于更可靠的诊断，并为针对小脑系统的新型治疗方法提供了开发。