Building a Selective Inhibitory Control Tone in Autism: An rTMS Study

建立自闭症的选择性抑制控制基调：一项 rTMS 研究

• 批准号: 7714488
• 负责人: Manuel F Casanova
• 金额: $ 22.2万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7714488
• 关键词: Age; Applications Grants; Asperger Syndrome; Autistic Disorder; Autopsy; Axon; Behavioral; Brain; Cells; Clinical; Cognitive; Cognitive deficits; Development; Discrimination; Economics; Electroencephalography; Environment; Frequencies; Functional disorder; Grant; Interneurons; Intervention; Investigation; Laboratories; Language; Lateral; Link; Magnetism; Measures; Modeling; Neuropil; Outcome Measure; Pathology; Patients; Pattern; Persons; Pervasive Child Development Disorders; Population; Psychiatric therapeutic procedure; Recruitment Activity; Reporting; Rett Syndrome; Sensory Process; Social Interaction; Source; Stereotyped Behavior; Surface; Symptoms; Testing; Therapeutic Intervention; Thinking; Tissues; Transcranial magnetic stimulation; Treatment outcome; functional outcomes; interest; magnetic field; neuropathology; neurophysiology; response; sex; social communication; theories

Autism is a pervasive developmental disorder of childhood characterized by deficits in social interaction, language, and stereotyped behaviors and restricted range of interests. Recent studies on postmortem tissue suggest that autism is associated with cortical cytoarchitectural abnormalities. In brief, reports on independent populations have shown a reduction in the neuropil space at the periphery of the minicolumn. This is the compartment where lateral inhibition sharpens the borders of minicolumns and increases their definition. The primary source of for this inhibitory effect is derived from axon bundles of double-bouquet cells. The axons of double bouquet cells arrange themselves in essentially repeatable patterns varying between 15 ?m and 30 ?m wide, perpendicular to the cortical surface. This grant attempts to preferentially strengthen the inhibitory surround of minicolumns by taking advantage of the geometry of double bouquet cells. We will use the principle of induction to induce electrical currents in double bouquet cells by applying a coil of wire energized by a capacitor (Transcranial Magnetic Stimulator or TMS) to provide a magnetic field orthogonal to the plane of the coil. Slow or low frequency TMS will enhance interneuron inhibition which in turn will enhance spatial contrast needed to optimize functional discrimination in minicolumnar units. The trial will recruit 70 autistic patients and 30 controls matched for age, sex, IQ, and socio-economic class. Outcome measures will include behavioral and electrophysiological measures. Overall, our project will link behavioral, clinical, and neurophysiological (qEEG, ERP) responses during cognitive tests and TMS treatment outcomes with an underlying neuropathology model (minicolumnar pathology and lateral inhibition deficits) derived from investigations in our laboratory. The results of the proposed study will help understand the specific social communication and cognitive deficits associated with developmental abnormalities of functions within cortical circuitry, and thereby contribute to understanding the brain substrates of behavioral dysfunctions typical for autism. The proposal represents a new development in combining TMS with functional outcome measures (cognitive ERP, EEG), using TMS as a theory-guided psychiatric therapy in autism.

孤独症是一种广泛性的儿童发育障碍，其特征是社会交往、语言和刻板行为的缺陷以及兴趣范围的限制。最近对死后组织的研究表明，自闭症与皮质细胞结构异常有关。简而言之，独立人群的报告显示，在微柱周围的神经间隙减少。这是侧抑制使微柱的边界变尖并增加其清晰度的隔室。这种抑制作用的主要来源是来自双束细胞的轴突束。双束细胞的轴突安排自己在基本上可重复的模式之间变化15？m和30？m宽，垂直于皮质表面。该授权试图通过利用双花束细胞的几何形状来优先加强微柱的抑制性周围。我们将使用感应原理，通过施加由电容器（经颅磁刺激器或TMS）激励的线圈来在双束细胞中感应电流，以提供与线圈平面正交的磁场。慢或低频率TMS将增强中间神经元抑制，这反过来将增强优化微柱单元中的功能辨别所需的空间对比度。该试验将招募70名自闭症患者和30名年龄、性别、智商和社会经济阶层相匹配的对照组。结果测量将包括行为和电生理测量。总的来说，我们的项目将在认知测试和TMS治疗结果期间将行为，临床和神经生理（qEEG，ERP）反应与我们实验室研究中得出的基础神经病理学模型（微柱病理学和侧抑制缺陷）联系起来。这项研究的结果将有助于理解与皮质回路功能发育异常相关的特定社会沟通和认知缺陷，从而有助于理解自闭症典型行为功能障碍的大脑基底。该提案代表了将TMS与功能结果测量（认知ERP，EEG）相结合的新发展，使用TMS作为自闭症的理论指导精神治疗。