Clinical neurophysiology of apnea.

Understanding the clinical neurophysiology of apnea generation encompasses discussion of the neuroanatomic aspects of central respiratory rhythm and pattern generation, including the central respiratory control networks, central and peripheral chemoreceptors, mechanisms of respiratory muscles, and sleep state dependent differences. Anatomical and functional links to apnea also involve central respiratory motor output recruited from the hypoglossal nerve, which has led to novel treatments for obstructive sleep apnea. Autonomic fluctuations occur in relation to sleep-wake and sleep states (i.e., REM vs NREM sleep), with both parasympathetic and sympathetic contributions. Finally, our understanding of the pathophysiology of obstructive sleep apnea now includes concepts of critical closing pressure of the upper airway, increased loop gain as reflected by high responsiveness to external perturbations, inadequate responsiveness of upper airway muscle recruitment, and reductions in arousal threshold leading to ventilatory instability. In turn, these concepts have led to the development of novel therapies such as hypoglossal nerve stimulation and targeting key culprit physiologic mechanisms specific to the individual.