Cortical Plasticity in Autism Spectrum Disorders

自闭症谱系障碍中的皮质可塑性

基本信息

批准号：
9267535
负责人：
Alvaro Pascual-Leone
金额：
$ 43.77万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-15 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9267535
关键词：
21 year old 5 year old Address Adult Affect Age Animal Model Animals Area Asperger Syndrome Attention Autistic Disorder Behavior Behavioral Biological Markers Brain Cerebral Palsy Child Childhood Clinical Clinical Trials Cognitive Complex Data Detection Development Diagnosis Disease model Early Diagnosis Early Intervention Etiology Functional disorder Future Gender Goals Guidelines Human In Vitro Incidence Individual Institutional Review Boards Intellectual functioning disability Knowledge Lead Life Link Longevity Measures Methodology Methods Modification Molecular Motor Motor Cortex Motor Evoked Potentials Neurobiology Neurosciences Participant Patients Phenotype Physiologic pulse Physiological Prevention Protocols documentation Publishing Research Risk Factors Rodent Secure Specificity Symptoms Synaptic plasticity Techniques Testing TimeLine Training Transcranial magnetic stimulation Treatment Efficacy Work autism spectrum disorder base clinical Diagnosis cognitive ability cohort developmental disease effective therapy endophenotype in vivo indexing neuroimaging neurophysiology novel potential biomarker predictive of treatment response public health relevance repetitive transcranial magnetic stimulation research study response safety and feasibility social trait treatment response

项目摘要

DESCRIPTION (provided by applicant): The clinical, social and financial burden of Autism Spectrum Disorders (ASD) is staggering. They are the most prevalent of the developmental disorders and their incidence is rising. However, the ASD phenotype variability is large, and ASD symptoms can manifest over a range of ages and to different degrees. In part for these reasons, the ASD clinical diagnosis is challenging and often is not made until 3-5 years of age. Thus, there remains an unmet need for a valid and reliable endophenotype which would facilitate ASD diagnosis early in life, enable efficient study of ASD risk factors, and eventually serve as a useful biomarker to inform the development of effective therapies and assess treatment response in future clinical trials. The overarching goal of this proposal is to explore te utility of transcranial magnetic stimulation (TMS) measures of brain plasticity as a novel neurophysiologic endophenotype in high- and low-functioning adults and children with ASD. Our work to date demonstrates the potential utility of these measures in higher-functioning adults with ASD, and pilot data support the feasibility and safety of applying the same measures to children and lower functioning individuals in whom the value of such an endophenotype would be particularly high. We thus propose to apply single-pulse TMS to evaluate the modulation in corticospinal reactivity induced by a specific repetitive TMS protocol known as theta burst stimulation (TBS). The comparison of the motor responses induced by single-pulse TMS before and following TBS is a unique noninvasive measure of brain plasticity in humans, and we have found that it shows a reliable abnormality in high-functioning adult individuals with ASD. Our hypothesis is that the alteration of TBS-induced modulation of TMS responses is a common neuropathophysiologic trait that is reliably linked to the ASD phenotype, and that will not be limited to high functioning adults but be also valid in children and low-functioning individuals. W thus anticipate that data from the proposed studies will address an important need for a rapid, noninvasive, reliable and safe endophenotype available to patients with ASD across ages and level of function.

描述（由申请人提供）：自闭症谱系障碍的临床，社会和财务负担（ASD）令人震惊。它们是发育障碍中最普遍的，其发病率正在上升。但是，ASD表型的变异性很大，ASD症状可以在各个年龄和不同程度上表现出来。部分原因是ASD临床诊断具有挑战性，通常要等到3-5岁才能进行。因此，对有效可靠的内表型的需求仍未满足，这将促进生命早期ASD诊断，有效地研究ASD危险因素，并最终成为有效的生物标志物，以告知有效疗法的开发并评估未来临床试验中的治疗反应。该提案的总体目标是探索脑颅磁刺激（TMS）的实用性（TMS），以作为一种新型的神经生理性内表型，在具有ASD的高功能和低功能的成年人和儿童中。迄今为止，我们的工作证明了这些措施在具有ASD的高功能成年人中的潜在效用，而PILOT数据支持对儿童应用相同措施的可行性和安全性，而在这种情况下，这种内型型的价值将特别高。因此，我们建议使用单脉冲TMS来评估由特定重复的TMS方案诱导的皮质脊髓反应性的调节，称为theta爆发刺激（TBS）。 TBS之前和之后由单脉冲TMS引起的运动反应的比较是人类脑可塑性的独特无创，我们发现它在具有ASD的高功能成年人中显示出可靠的异常。我们的假设是，TBS诱导的TMS反应的调节的改变是一种常见的神经病理生理学性状，可可靠地与ASD表型相关，并且不限于高功能的成年人，但在儿童和低功能的个体中也有效。 w因此预见到拟议研究的数据将解决对ASD跨年龄和功能水平的患者可用的快速，无创，可靠和安全的内表型的重要需求。