吸烟者脑咳嗽抑制网络中神经活动的改变
2020/05/14
摘要
咳嗽对呼吸道防御很重要，对健康动物和人类的研究表明，多个大脑网络与气道刺激、咳嗽诱发和咳嗽抑制的感知密切相关。咳嗽敏感性的变化和/或伴随肺部病理抑制咳嗽的能力表明这些中枢神经回路可能具有一定的可塑性。但是，关于肺部持续输入如何改变调节咳嗽的大脑过程知之甚少。在本研究中，我们使用人类功能性大脑成像技术来研究吸烟者咳嗽敏感性改变时的中枢神经反应。在非吸烟者中，吸入气道刺激性辣椒素会引起短暂的急促咳嗽，这与包括感觉、前额叶和运动皮层区域在内的分布式脑网络的激活有关。吸烟者结果表明辣椒素引起的急促咳嗽的阈值明显更高，这与起到刺激的敏感性降低相一致。有趣的是，这伴随着已知参与咳嗽感觉处理（主要感觉运动皮层）和咳嗽抑制（背外侧前额叶皮层和楔形中脑核）的大脑区域激活的增加。吸烟行为最少的参与者中前额叶皮层的激活最高，而中脑的激活与更严重的吸烟行为有关。这些结果表明，吸烟引起的中枢咳嗽神经回路敏感性被同时增强的中枢抑制作用所抵消。此外，随着吸烟严重性的变化，中枢抑制机制可能会改变，随吸烟增加，中枢抑制从最初的前额抑制变为更原始的中脑过程。
Altered Neural Activity in Brain Cough Suppression Networks in Cigarette Smokers
Ayaka Ando , Stuart B Mazzone , Michael J Farrell
Abstract
Cough is important for airway defence, and studies in healthy animals and humans have revealed multiple brain networks intimately involved in the perception of airway irritation, cough induction and cough suppression. Changes in cough sensitivity and/or the ability to suppress cough accompany pulmonary pathologies, suggesting a level of plasticity is possible in these central neural circuits. However, little is known about how persistent inputs from the lung might modify the brain processes regulating cough. In the present study, we used human functional brain imaging to investigate the central neural responses that accompany an altered cough sensitivity in cigarette smokers. In nonsmokers, inhalation of the airway irritant capsaicin induced a transient urge-to-cough associated with the activation of a distributed brain network that included sensory, prefrontal and motor cortical regions. Cigarette smokers demonstrated significantly higher thresholds for capsaicin-induced urge-to-cough, consistent with a reduced sensitivity to airway irritation. Intriguingly, this was accompanied by increased activation in brain regions known to be involved in both cough sensory processing (primary sensorimotor cortex) and cough suppression (dorsolateral prefrontal cortex and the midbrain nucleus cuneiformis). Activations in the prefrontal cortex were highest among participants with the least severe smoking behaviour, whereas those in the midbrain correlated with more severe smoking behaviour. These outcomes suggest that smoking-induced sensitisation of central cough neural circuits is offset by concurrently enhanced central suppression. Furthermore, central suppression mechanisms may evolve with the severity of smoke exposure, changing from initial prefrontal inhibition to more primitive midbrain processes as exposure increases.
咳嗽对呼吸道防御很重要，对健康动物和人类的研究表明，多个大脑网络与气道刺激、咳嗽诱发和咳嗽抑制的感知密切相关。咳嗽敏感性的变化和/或伴随肺部病理抑制咳嗽的能力表明这些中枢神经回路可能具有一定的可塑性。但是，关于肺部持续输入如何改变调节咳嗽的大脑过程知之甚少。在本研究中，我们使用人类功能性大脑成像技术来研究吸烟者咳嗽敏感性改变时的中枢神经反应。在非吸烟者中，吸入气道刺激性辣椒素会引起短暂的急促咳嗽，这与包括感觉、前额叶和运动皮层区域在内的分布式脑网络的激活有关。吸烟者结果表明辣椒素引起的急促咳嗽的阈值明显更高，这与起到刺激的敏感性降低相一致。有趣的是，这伴随着已知参与咳嗽感觉处理（主要感觉运动皮层）和咳嗽抑制（背外侧前额叶皮层和楔形中脑核）的大脑区域激活的增加。吸烟行为最少的参与者中前额叶皮层的激活最高，而中脑的激活与更严重的吸烟行为有关。这些结果表明，吸烟引起的中枢咳嗽神经回路敏感性被同时增强的中枢抑制作用所抵消。此外，随着吸烟严重性的变化，中枢抑制机制可能会改变，随吸烟增加，中枢抑制从最初的前额抑制变为更原始的中脑过程。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Eur Respir J. 2019 Sep 19;54(3):1900362. doi: 10.1183/13993003.00362-2019.)
(Eur Respir J. 2019 Sep 19;54(3):1900362. doi: 10.1183/13993003.00362-2019.)
Altered Neural Activity in Brain Cough Suppression Networks in Cigarette Smokers
Ayaka Ando , Stuart B Mazzone , Michael J Farrell
Abstract
Cough is important for airway defence, and studies in healthy animals and humans have revealed multiple brain networks intimately involved in the perception of airway irritation, cough induction and cough suppression. Changes in cough sensitivity and/or the ability to suppress cough accompany pulmonary pathologies, suggesting a level of plasticity is possible in these central neural circuits. However, little is known about how persistent inputs from the lung might modify the brain processes regulating cough. In the present study, we used human functional brain imaging to investigate the central neural responses that accompany an altered cough sensitivity in cigarette smokers. In nonsmokers, inhalation of the airway irritant capsaicin induced a transient urge-to-cough associated with the activation of a distributed brain network that included sensory, prefrontal and motor cortical regions. Cigarette smokers demonstrated significantly higher thresholds for capsaicin-induced urge-to-cough, consistent with a reduced sensitivity to airway irritation. Intriguingly, this was accompanied by increased activation in brain regions known to be involved in both cough sensory processing (primary sensorimotor cortex) and cough suppression (dorsolateral prefrontal cortex and the midbrain nucleus cuneiformis). Activations in the prefrontal cortex were highest among participants with the least severe smoking behaviour, whereas those in the midbrain correlated with more severe smoking behaviour. These outcomes suggest that smoking-induced sensitisation of central cough neural circuits is offset by concurrently enhanced central suppression. Furthermore, central suppression mechanisms may evolve with the severity of smoke exposure, changing from initial prefrontal inhibition to more primitive midbrain processes as exposure increases.
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