Sensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r = −0.48, p < 0.05) and positively with somatosensory glutamate (r = 0.68, p < 0.01). Further, in the ASD group, thalamic GABA concentration predicted altered connectivity with regions previously implicated in SOR. These variations in GABA and associated network connectivity in the ASD group highlight the potential role of GABA as a mechanism underlying individual differences in SOR, a major source of phenotypic heterogeneity in ASD. In ASD, abnormalities of the thalamic neurochemical balance could interfere with the thalamic role in integrating, relaying, and inhibiting attention to sensory information. These results have implications for future research and GABA-modulating pharmacologic interventions.

感觉过度反应（SOR），对感觉刺激（例如刮擦的织物，响亮的声音）的极端敏感或避免，是神经发育障碍（例如自闭症谱系障碍（ASD），焦虑症和ADHD）的高度流行和削弱的特征。先前的研究发现，对ASD中的轻度厌恶感觉刺激作出反应时，大脑反应过度活跃，丘脑皮质连接性的调节降低。这些发现表明，丘脑感觉门控改变可能与兴奋性/抑制性神经化学失衡有关，但是这种丘脑神经化学从未与SOR相关地进行过研究。在这里，我们利用磁共振波谱和静止状态功能磁共振成像来检查丘脑与体感皮层抑制物（γ-氨基丁酸，GABA）和兴奋性（谷氨酸）神经化学物质，它们具有35个ASD和35个典型发展中的儿科受试者的那些区域的内在功能连接。尽管ASD组中任一区域的神经化学浓度均无诊断组差异，但AOR组中SOR严重程度与丘脑GABA呈负相关（r  = -0.48，p  <0.05），体感谷氨酸盐阳性（r  = 0.68，p  <  0.01）。此外，在ASD组中，丘脑GABA浓度预测与先前涉及SOR的区域的连接性改变。GABA的这些变化以及ASD组中的相关网络连接性凸显了GABA作为潜在机制的潜在作用，该机制是SOR中个体差异的基础，而SOR是ASD表型异质性的主要来源。在ASD中，丘脑神经化学平衡的异常可能会干扰丘脑在整合，传递和抑制对感觉信息的注意力中的作用。这些结果对未来的研究和调节GABA的药理干预措施具有影响。