Project Summary Obstructive sleep apnea (OSA) is a major source of cardiovascular morbidity and mortality where the first-line treatment, positive airway pressure, is often poorly tolerated. The development of effective alternative surgical therapies has been hindered by a fundamental lack of insight into the anatomic and neurophysiologic mechanisms responsible for airway patency. A substantial body of physiology literature documents that caudal pharyngeal stretch via tracheal traction is an important stabilizing mechanism of the upper airway, but forty years of surgical interventions for OSA have focused solely on destructive techniques or ventral displacement of pharyngeal soft tissue structures. Our proposal will address this knowledge and therapy gap by elucidating the distinct effects of caudal traction on upper airway patency in OSA patients. Our central hypothesis is the therapeutic stabilizing power of caudal tracheal traction can be harnessed via ansa cervicalis stimulation (ACS) of the sternothyroid muscle, which generates caudal traction on the pharynx by contracting the sternothyroid muscle, replicating many of the well-documented effects of caudal traction on pharyngeal patency. This hypothesis challenges the long-held concept that the genioglossus is the major pharyngeal dilator muscle responsible for the maintenance of pharyngeal patency during sleep. It rests instead on strong evidence that caudal pharyngeal traction, normally mediated by tracheal pull, increases pharyngeal patency during sleep through several distinct mechanisms. In SA1, we will elucidate the physiologic effects of unilateral and bilateral ACS on pharyngeal patency during drug-induced sleep endoscopy (DISE) with and without hypoglossal nerve stimulation (HNS), the current state-of-the-art neurostimulation therapy for the management of OSA (DISE, SA1). In SA2, we will determine the impact of ACS on the maintenance of airway patency in NREM and REM sleep. In both SAs, we will test the impact of anatomic constraints on stimulation responses. We hypothesize that ACS stretches the pharynx caudally, stiffening the soft palate and lateral pharyngeal walls. We additionally hypothesize that the combination of HNS and ACS creates synergistic effects through opposing forces that further stabilize the pharynx against collapse. Our aims challenge the primacy of the genioglossus in the maintenance of airway patency during sleep. This project outlines rigorous approaches for establishing synergistic mechanisms between the genioglossus and sternothyroid muscles based on our proven ability to activate these muscles independently. State-of-the-art physiologic methods will be deployed to probe the effects of muscle stimulation, sleep state, and anatomy on pharyngeal patency. Our findings will (1) transform our understanding of upper airway neuromuscular control during sleep, (2) establish relevant neuromotor targets for neurostimulation, and will (3) identify potential physiologic ...