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: 7874720
• 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/7874720
• 关键词: Age; Applications Grants; Asperger Syndrome; Autistic Disorder; Autopsy; Axon; Behavioral; Brain; Cells; Clinical; Cognitive; Cognitive deficits; Development; Discrimination; 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; socioeconomics; 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.

自闭症是一种普遍存在的儿童期发育障碍，其特征是社会互动，语言和刻板的行为和利益范围限制范围。关于死后组织的最新研究表明，自闭症与皮质细胞结构异常有关。简而言之，关于独立人群的报告显示，微型列的外围的神经胶体空间减少了。这是一个隔室，侧向抑制作用逐渐增强微型列的边界并增加其定义。这种抑制作用的主要来源来自双构细胞的轴突束。双束式细胞的轴突以基本可重复的模式排列在15米至30米之间，宽度垂直于皮质表面。该赠款试图通过利用双束式细胞的几何形状来优先增强微型级的抑制性周围。我们将使用诱导原理通过施加通过电容器（经颅磁刺激器或TMS）源的电线线圈来诱导双束细胞中的电流，以提供与线圈平面正交的磁场。慢速或低频TMS将增强中间神经元的抑制作用，这反过来将增强在微型典型单元中优化功能歧视所需的空间对比度。该试验将招募70名自闭症患者和30个对照，以匹配年龄，性别，智商和社会经济类别。结果指标将包括行为和电生理措施。总体而言，我们的项目将在认知测试和TMS治疗结果期间将行为，临床和神经生理学（QEEG，ERP）与我们的实验室研究中从研究中得出的潜在神经病理学模型（微型牙术病理学和横向抑制缺陷）联系起来。拟议的研究的结果将有助于了解与皮质回路内功能的发育异常相关的特定社会交流和认知缺陷，从而有助于理解自闭症典型的行为功能障碍的大脑底物。该提案代表了将TMS与功能性结果指标（认知ERP，EEG）相结合的新发展，它使用TMS作为自闭症理论引导的精神疗法。