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

自闭症是一种普遍的儿童发育障碍，其特征是社会交往、语言、刻板行为和兴趣范围有限。最近对死后组织的研究表明，自闭症与皮层细胞结构异常有关。简而言之，关于独立人群的报告显示，小柱周围的神经细胞空间减少。在这个隔室中，侧抑制使小柱的边界变得尖锐，并增加了它们的定义。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本质上可重复的模式排列，在15 ？M和30 ？M宽，垂直于皮质表面。这项拨款试图优先加强抑制包围的微型柱利用双花束细胞的几何优势。我们将利用感应原理在双花束细胞中感应电流，通过应用由电容器（经颅磁刺激器或TMS）通电的线圈来提供与线圈平面正交的磁场。慢频或低频经颅磁刺激将增强神经元间的抑制作用，从而增强优化小柱单元功能识别所需的空间对比。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，我们的项目将把认知测试中的行为、临床和神经生理（qEEG、ERP）反应和经颅磁刺激治疗结果与我们实验室研究得出的潜在神经病理学模型（小柱病理学和侧抑制缺陷）联系起来。本研究的结果将有助于理解与皮层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础。该建议代表了将经颅磁刺激与功能结果测量（认知ERP， EEG）相结合的新发展，将经颅磁刺激作为一种理论指导的自闭症精神治疗方法。

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.