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

自闭症是一种普遍存在的儿童发育障碍，其特征是社交、语言、刻板印象行为和兴趣范围受限。最近对身体组织的研究表明，自闭症与皮质细胞结构异常有关。简而言之，有关独立人群的报告显示，微柱外围的神经纤维空间减少。这是侧向抑制使微柱边缘锐化并提高其清晰度的隔室。这种抑制作用的主要来源是双花束细胞的轴突束。双束细胞的轴突基本上以可重复的方式排列，宽度在15m到30m之间，垂直于皮质表面。这项资助试图通过利用双花束细胞的几何结构来优先加强微柱的抑制环绕。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)供电的导线线圈来提供与线圈平面垂直的磁场，从而在双花束电池中感应电流。慢或低频率的TMS将加强神经元间抑制，这反过来将增强空间对比度，这是优化小柱单位功能辨别所需的。这项试验将招募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。总体而言，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TMS治疗结果与来自我们实验室调查的潜在神经病理学模型(微柱病理和侧向抑制缺陷)联系起来。这项拟议的研究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交和认知缺陷，从而有助于理解自闭症典型行为障碍的大脑基础。该提案代表了将TMS与功能结果测量(认知事件相关电位，EEG)相结合的新发展，将TMS用作自闭症的理论指导的精神治疗。

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.