Therapeutic exposure to intermittent hypoxia leads to long-term facilitation (LTF) of diaphragm and upper airway muscle activity, resulting in sustained increases in minute ventilation and improved upper airway stability (Mateika and Narwani 2009). These findings led to the hypothesis that exposure to intermittent hypoxia, which accompanies hypopneic or apneic events during sleep, could initiate LTF of chest wall (eg diaphragm and inspiratory intercostal muscles) and upper airway muscle activity. Initiation of LTF could serve to stabilize breathing and the upper airway, leading to reductions in breathing events across the night or life-span (Mateika and Narwani 2009). However, there is little support for this hypothesis, since many studies conducted over decades have reported that the severity of sleep apnea increases from the evening to the early morning. The prevailing hypothesis is that LTF does not typically manifest itself in individuals with sleep apnea because of the withdrawal of chemoreceptor input (Harris, Balasubramaniam et al. 2006). This withdrawal is induced by the presence of hypocapnia that occurs in response to hyperventilation that is elicited when emerging from apneic events. However, there are other possibilities that could explain the ineffectiveness of respiratory plasticity in mitigating apneic events during sleep.

Along these lines, Fields and colleagues (2019) explored if initiation of competing forms of plasticity, induced by repetitive apnea, prevent the induction of sustained increases in phrenic nerve activity. In addition to LTF induced by intermittent hypoxia, recurrent reductions in respiratory neural activity initiates another form of plasticity, known as inactivity-induced inspiratory motor facilitation (iMF)(Streeter and Baker-Herman 2014). iMF is robustly expressed in phrenic, inspiratory intercostal and hypoglossal motor pools. Given that central sleep apnea is characterized by periods of reduced or inactive motor activity, and mixed apneic events are characterized by motor inactivity at the onset of an event, the authors proposed that iMF may be initiated during sleep (Fields, Braegelmann et al. 2019). Given that hypoxia typically accompanies motor inactivity, two forms of respiratory plasticity could theoretically be initiated in response to apneic events. However,