The human orbitofrontal cortex (OFC) is involved in assessing the emotional significance of events and stimuli, emotion-based learning, allocation of attentional resources, and social cognition. Little is known about the structure, connectivity and excitatory/inhibitory circuit interactions underlying these diverse functions in human OFC, as well as how the circuit is disrupted in individuals with autism spectrum disorder (ASD). We used post-mortem brain tissue from neurotypical adults and individuals with ASD. We examined the morphology and distribution of myelinated axons across cortical layers in OFC, at the single axon level, as a proxy of excitatory pathways. In the same regions, we also examined the laminar distribution of all neurons and neurochemically- and functionally-distinct inhibitory neurons that express the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR). We found that the density of myelinated axons increased consistently towards layer 6, while the average axon diameter did not change significantly across layers in both groups. However, both the density and diameter of myelinated axons were significantly lower in the ASD group compared with the Control group. The distribution pattern and density of the three major types of inhibitory neurons was comparable between groups, but there was a significant reduction in the density of excitatory neurons across OFC layers in ASD. This study is limited by the availability of human post-mortem tissue optimally processed for high-resolution microscopy and immunolabeling, especially from individuals with ASD. The balance between excitation and inhibition in OFC is at the core of its function, assessing and integrating emotional and social cues with internal states and external inputs. Our preliminary results provide evidence for laminar-specific changes in the ratio of excitation/inhibition in OFC of adults with ASD, with an overall weakening and likely disorganization of excitatory signals and a relative strengthening of local inhibition. These changes likely underlie pathology of major OFC communications with limbic or other cortices and the amygdala in individuals with ASD, and may provide the anatomic basis for disrupted transmission of signals for social interactions and emotions in autism.

中文翻译：

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自闭症患者眶额皮质层状特异性兴奋和抑制回路的失衡

人类眶额皮质 (OFC) 参与评估事件和刺激的情感意义、基于情感的学习、注意力资源的分配和社会认知。关于人类 OFC 中这些不同功能背后的结构、连接性和兴奋性/抑制性电路相互作用，以及自闭症谱系障碍 (ASD) 个体的电路如何被破坏，我们知之甚少。我们使用来自神经典型成人和 ASD 个体的死后脑组织。我们在单轴突水平检查了有髓轴突在 OFC 皮质层中的形态和分布，作为兴奋性途径的代表。在同一地区，我们还检查了所有神经元和神经化学和功能上不同的抑制神经元的层状分布，这些神经元表达钙结合蛋白小白蛋白 (PV)、钙结合蛋白 (CB) 和钙视网膜蛋白 (CR)。我们发现有髓轴突的密度向第 6 层持续增加，而两组的平均轴突直径在各层之间没有显着变化。然而，与对照组相比，ASD 组有髓轴突的密度和直径均显着降低。三种主要类型抑制性神经元的分布模式和密度在各组之间具有可比性，但在 ASD 中，跨 OFC 层的兴奋性神经元的密度显着降低。这项研究受到为高分辨率显微镜和免疫标记而优化处理的人类死后组织的可用性的限制，特别是来自 ASD 的个体。OFC 中兴奋和抑制之间的平衡是其功能的核心，评估和整合情绪和社会线索与内部状态和外部输入。我们的初步结果为 ASD 成人 OFC 中兴奋/抑制比率的层流特异性变化提供了证据，兴奋信号整体减弱和可能解体，局部抑制相对增强。这些变化可能是自闭症患者边缘或其他皮质和杏仁核的主要 OFC 通讯病理的基础，