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，其特征是社交互动、语言和刻板行为缺陷以及兴趣范围受限。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，关于独立群体的报告表明，微柱外围的神经纤维空间减少。这是侧向抑制使微型柱的边界变得锐利并增加其清晰度的隔室。这种抑制作用的主要来源是双花束细胞的轴突束。双花束细胞的轴突以基本上可重复的模式排列，宽度在 15 微米到 30 微米之间变化，垂直于皮质表面。该资助试图通过利用双花束细胞的几何形状来优先加强微型柱的抑制周围。我们将利用感应原理，通过应用由电容器（经颅磁刺激器或 TMS）供电的线圈来提供与线圈平面正交的磁场，从而在双束细胞中感应电流。慢速或低频 TMS 将增强中间神经元抑制，进而增强优化微柱状单元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者。结果测量将包括行为和电生理测量。总体而言，我们的项目将认知测试期间的行为、临床和神经生理学（qEEG、ERP）反应和 TMS 治疗结果与我们实验室研究得出的潜在神经病理学模型（微柱病理学和侧向抑制缺陷）联系起来。拟议研究的结果将有助于了解与皮质回路内功能发育异常相关的特定社会沟通和认知缺陷，从而有助于了解自闭症典型行为功能障碍的大脑基础。该提案代表了 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。