Cortical Plasticity in Autism Spectrum Disorders

自闭症谱系障碍中的皮质可塑性

• 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
• 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

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 (ASD) 的临床、社会和经济负担是惊人的。它们是最普遍的发育障碍，并且其发病率正在上升。然而，自闭症谱系障碍表型变异性很大，并且自闭症谱系障碍症状可以在不同年龄范围内表现出不同程度的症状。部分由于这些原因，自闭症谱系障碍 (ASD) 的临床诊断具有挑战性，通常要到 3-5 岁才能做出。因此，对有效且可靠的内表型的需求仍然未得到满足，这种内表型将有助于生命早期的 ASD 诊断，能够有效研究 ASD 危险因素，并最终作为有用的生物标志物，为有效疗法的开发提供信息并在未来的临床试验中评估治疗反应。该提案的总体目标是探索经颅磁刺激 (TMS) 测量大脑可塑性的效用，作为一种新型神经生理内表型，在高功能和低功能成人和自闭症谱系障碍儿童中的应用。迄今为止，我们的工作证明了这些措施在患有自闭症谱系障碍的高功能成人中的潜在效用，并且试点数据支持将相同措施应用于儿童和低功能个体的可行性和安全性，这些人的内表型价值特别高。因此，我们建议应用单脉冲 TMS 来评估由称为 theta 突发刺激 (TBS) 的特定重复 TMS 协议诱导的皮质脊髓反应性调节。 TBS 前后单脉冲 TMS 诱导的运动反应的比较是人类大脑可塑性的一种独特的非侵入性测量，我们发现它在患有 ASD 的高功能成年个体中显示出可靠的异常。我们的假设是，TBS 诱导的 TMS 反应调节的改变是一种常见的神经病理生理学特征，与 ASD 表型可靠相关，并且不仅限于高功能成人，而且对儿童和低功能个体也有效。因此，我们预计拟议研究的数据将满足不同年龄和功能水平的自闭症谱系障碍患者对快速、无创、可靠和安全的内表型的重要需求。