Brain circuitry mediating arousal from obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is a disorder of repetitive sleep disruption caused by reduced or blocked respiratory airflow. Although an anatomically compromised airway accounts for the major predisposition to OSA, a patient's arousal threshold and factors related to the central control of breathing (ventilatory control stability) are also important. Arousal from sleep (defined by EEG desynchronization) may be the only mechanism that allows airway re-opening following an obstructive event. However, in many cases arousal is unnecessary and even worsens the severity of OSA. Mechanisms for arousal are poorly understood. However, accumulating data are elucidating the relevant neural pathways and neurotransmitters. For example, serotonin is critically required, but its site of action is unknown. Important neural substrates for arousal have been recently identified in the parabrachial complex (PB), a visceral sensory nucleus in the rostral pons. Moreover, glutamatergic signaling from the PB contributes to arousal caused by hypercapnia, one of the arousal-promoting stimuli in OSA. A major current focus of OSA research is to find means to maintain airway patency during sleep, without sleep interruption.

Figure 1

Typical OSA breathing pattern with recurrent obstructive events. This polysomnogram from a patient with obstructive sleep apnea shows multiple cycles over a four minute period of airway collapse accompanied by hypercapnia and hypoxia and terminating with arousal (A) and airway restoration. Traces show (from top to bottom) EEG, arterial oxygen saturation (SaO₂), airflow (liters/sec), end tidal partial pressure of CO₂ (PetCO₂), ribcage and abdominal movements. Obstructive apneas are characterized by reduced or absent airflow despite attempts to breathe as shown by rib cage and abdominal movements. Hypoxia is measured by a pulse oximeter. The level of CO₂ in exhaled air at the end of an expiratory cycle approximates the partial pressure of CO₂ in arterial blood, whereas the signal drops towards zero during inspiration. In this example airflow was reduced but not completely abolished during the obstructions. The dotted line overlying the trace indicates average end tidal CO₂. Note the rise in CO₂ during the airway obstruction and the large breaths that accompany arousal at apnea termination and that drive the CO₂ below baseline. The two arrows on the trace indicate the PetCO₂ during the last obstructed breath and the first unobstructed breath. The magnitude of the PetCO₂ undershoot is thought to contribute to the likelihood of another obstructive event occurring when the individual falls back to sleep. Adapted from [6].