Canadian Association of Neuroscience Review: Respiratory Control and Behavior in Humans: Lessons from Imaging and Experiments of Nature

Abstract

The purpose of this review is to demonstrate that respiration is a complex behavior comprising both brainstem autonomic control and supramedullary influences, including volition. Whereas some fundamental mechanisms had to be established using animal models, this review focuses on clinical cases and physiological studies in humans to illustrate normal and abnormal respiratory behavior. To summarize, central respiratory drive is generated in the rostroventrolateral medulla, and transmitted to both the upper airway and to the main and accessory respiratory muscles. Afferent feedback is provided from lung and muscle mechnoreceptors, peripheral carotid and aortic chemoreceptors, and multiple central chemoreceptors. Supramedullary regions, including cortex and subcortex, modulate or initiate breathing with volition, emotion and at the onset of exercise. Autonomic breathing control can be perturbed by brainstem pathology including space occupying lesions, compression, congenital central hypoventilation syndrome and sudden infant death syndrome. Sleep-wake states are important in regulating breathing. Thus, respiratory control abnormalities are most often evident during sleep, or during transition from sleep to wakefulness. Previously undiagnosed structural brainstem pathology may be revealed by abnormal breathing during sleep. Ondine's curse and 'the locked-in syndrome' serve to distinguish brainstem from supramedullary regulatory mechanisms in humans: The former comprises loss of autonomic respiratory control and requires volitional breathing for survival, and the latter entails loss of corticospinal or corticobulbar tracts required for volitional breathing, but preserves autonomic respiratory control.