The Department of Anatomy and Neuroscience, The University of Melbourne , Parkville, Victoria , Australia.
Monash Biomedicine Discovery Institute and Department of Medical Imaging and Radiation Sciences, Monash University , Clayton, Victoria , Australia.
J Neurophysiol. 2019 Apr 1;121(4):1171-1182. doi: 10.1152/jn.00547.2018. Epub 2019 Jan 16.
Coughing is an airway protective behavior elicited by airway irritation. Animal studies show that airway sensory information is relayed via vagal sensory fibers to termination sites within dorsal caudal brain stem and thereafter relayed to more rostral sites. Using functional magnetic resonance imaging (fMRI) in humans, we previously reported that inhalation of the tussigenic stimulus capsaicin evokes a perception of airway irritation ("urge to cough") accompanied by activations in a widely distributed brain network including the primary sensorimotor, insular, prefrontal, and posterior parietal cortices. Here we refine our imaging approach to provide a directed survey of brain stem areas activated by airway irritation. In 15 healthy participants, inhalation of capsaicin at a maximal dose that elicits a strong urge to cough without behavioral coughing was associated with activation of medullary regions overlapping with the nucleus of the solitary tract, paratrigeminal nucleus, spinal trigeminal nucleus and tract, cardiorespiratory regulatory areas homologous to the ventrolateral medulla in animals, and the midline raphe. Interestingly, the magnitude of activation within two cardiorespiratory regulatory areas was positively correlated ( r = 0.47, 0.48) with participants' subjective ratings of their urge to cough. Capsaicin-related activations were also observed within the pons and midbrain. The current results add to knowledge of the representation and processing of information regarding airway irritation in the human brain, which is pertinent to the pursuit of novel cough therapies. NEW & NOTEWORTHY Functional brain imaging in humans was optimized for the brain stem. We provide the first detailed description of brain stem sites activated in response to airway irritation. The results are consistent with findings in animal studies and extend our foundational knowledge of brain processing of airway irritation in humans.
咳嗽是一种由气道刺激引起的气道保护行为。动物研究表明，气道感觉信息通过迷走感觉纤维传递到背尾脑脑干的终止部位，然后传递到更靠前的部位。我们之前使用功能磁共振成像 (fMRI) 在人类中报告说，吸入促发咳嗽的刺激物辣椒素会引起气道刺激的感觉（“咳嗽冲动”），同时激活包括初级感觉运动、岛叶、前额叶和后顶叶皮层在内的广泛分布的脑网络。在这里，我们改进了我们的成像方法，以提供对被气道刺激激活的脑干区域的定向调查。在 15 名健康参与者中，吸入最大剂量的辣椒素会引起强烈的咳嗽冲动而没有行为性咳嗽，与延髓区域的激活相关，这些区域与孤束核、三叉神经副核、三叉神经脊髓核和束、与动物中腹外侧髓质同源的心肺调节区域以及中缝脑核重叠。有趣的是，两个心肺调节区域内的激活程度与参与者对咳嗽冲动的主观评分呈正相关（r=0.47, 0.48）。在脑桥和中脑也观察到与辣椒素相关的激活。目前的结果增加了人类大脑中关于气道刺激的信息表示和处理的知识，这与寻求新的咳嗽治疗方法有关。新的和值得注意的功能脑成像在脑干中得到了优化。我们提供了对气道刺激反应激活的脑干区域的第一个详细描述。结果与动物研究的结果一致，并扩展了我们对人类气道刺激处理的基础认知。
