Laryngeal function is vital to airway protection. While swallow is mediated by the brainstem, mechanisms underlying increased risk of dysphagia after cervical spinal cord injury (SCI) are unknown. We hypothesized that loss of descending phrenic drive affects swallow and breathing differently, and loss of ascending spinal afferent information alters swallow regulation. We recorded electromyograms from upper airway and chest wall muscles in freely breathing pentobarbital-anesthetized cats and rats. Inspiratory laryngeal activity increased ~two-fold following C2 lateral-hemisection. Ipsilateral to the injury, crural diaphragm EMG amplitude was reduced during breathing (62 ± 25% change post-injury), but no animal had complete termination of activity; 75% of animals increased contralateral diaphragm recruitment, but this did not reach significance. During swallow, laryngeal adductor and pharyngeal constrictor muscles increased activity, and diaphragm activity was bilaterally suppressed. This was unexpected because of the ipsilateral-specific response during breathing. Swallow-breathing coordination was also disrupted and more swallows occurred during early expiration. Finally, to determine if the chest wall is a major source of feedback for laryngeal regulation, we performed T1 total transections in rats. As in the C2 lateral-hemisection, inspiratory laryngeal recruitment was the first feature noted. In contrast to the C2 lateral-hemisection, diaphragmatic drive increased after T1 transection. Overall, we found that SCI alters laryngeal drive during swallow and breathing, and reduced swallow-related diaphragm activity. Our results show behavior-specific effects, suggesting SCI affects swallow more than breathing, and emphasizes the need for additional studies on the effects of ascending afferents from the spinal cord on laryngeal function.

Swallow is a complex behavior that consists of three coordinated phases: oral, pharyngeal, and esophageal. Esophageal distension (EDist) has been shown to elicit pharyngeal swallow, but the physiologic characteristics of EDist-induced pharyngeal swallow have not been specifically described. We examined the effect of rapid EDist on oropharyngeal swallow, with and without an oral water stimulus, in spontaneously breathing, sodium pentobarbital anesthetized cats (n = 5). Electromyograms (EMGs) of activity of 8 muscles were used to evaluate swallow: mylohyoid (MyHy), geniohyoid (GeHy), thyrohyoid (ThHy), thyropharyngeus (ThPh), thyroarytenoid (ThAr), cricopharyngeus (upper esophageal sphincter: UES), parasternal (PS), and costal diaphragm (Dia). Swallow was defined as quiescence of the UES with overlapping upper airway activity, and it was analyzed across three stimulus conditions: 1) oropharyngeal water infusion only, 2) rapid esophageal distension (EDist) only, and 3) combined stimuli. Results show a significant effect of stimulus condition on swallow EMG amplitude of the mylohyoid, geniohyoid, thyroarytenoid, diaphragm, and UES muscles. Collectively, we found that, compared to rapid cervical esophageal distension alone, the stimulus condition of rapid distension combined with water infusion is correlated with increased laryngeal adductor and diaphragm swallow-related EMG activity (schluckatmung), and post-swallow UES recruitment. We hypothesize that these effects of upper esophageal distension activate the brainstem swallow network, and function to protect the airway through initiation and/or modulation of a pharyngeal swallow response.

Laryngeal dysfunction is a common symptom following cervical spinal cord injury (cSCI) and currently there are no effective pharmacological interventions or behavioral treatments. The larynx is the primary valve controlling entrance into the trachea and lungs via opening and closing of the vocal folds. Although not well studied following cSCI, it is understood that laryngeal deficits during swallow often produce aspiration of food/liquid, significantly increasing risk of pneumonia. Our previous terminal electrophysiology experiments using freely breathing sodium pentobarbital anesthetized cats with acute hemisections at the 3rd cervical spinal level (C3) showed immediate alterations in laryngeal activity. These alterations persisted for 4 hours (testing duration). The serotonin (5‐HT1A) receptor agonist 8‐OH‐DPAT was delivered via the vertebral artery at low (3 □g/kg) and/or high (30 □g/kg) doses. This agonist altered behavior‐specific muscle recruitment patterns. In particular, the high dose restored laryngeal activity across breathing and swallow, which could be reversed with the competitive antagonist WAY100635 (0.5 mg/kg). In the current study, we tested if alterations seen acutely in laryngeal activity persist chronically, and if the 8‐OH‐DPAT clinical‐correlate buspirone (Buspar) would produce similar therapeutic results. Adult female cats underwent C3 hemisections and recovered for 4 or 8 weeks. Laryngeal endoscopy was performed weekly under isofluorane (3%) during normocapnia and hypercapnia (5% CO2). Asynchronous vocal fold movement was seen in all animals, defined by unilateral movement delays, and the extent of opening and closing of the glottis became variable. In a subset of animals, oral buspirone (5 mg) was given with food. One hour later, repeat endoscopic evaluation revealed full resolution of laryngeal function with synchronized movements during normocapnia and hypercapnia. Most importantly, with termination of buspirone dosing, laryngeal dysfunction returned. This work shows that the anesthetized preparation effectively identifies upper airway dysfunction early and chronically after C3 SCI, and that it can be used as a pre‐clinical model for novel therapeutic interventions. Results also indicate that buspirone is a high‐priority target for additional investigation as a therapeutic intervention after cSCI. Support or Funding Information This work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Veterans Affairs Rehabilitation, Research and Development RCSB9249S (DRH), Kentucky Spinal Cord and Head Injury Research Trust, Rebecca F. Hammond Endowment (DRH), and the Commonwealth of Kentucky Challenge for Excellence.

This study utilized a convenience sample (n = 510) to investigate misconceptions of traumatic brain injury (TBI) among first and second year graduate students in physical therapy (PT), occupational therapy (OT), and speech-language pathology (SLP) training programs. Eighty-six-point-seven percent of participants were female, and 87.70% were white. All participants completed a survey comprised of items relating to general information about TBI, coma and unconsciousness, memory loss, recovery, and concussion. Descriptive and summary statistics indicated the persistence of misconceptions regarding coma and unconsciousness, memory loss, recovery, and concussion among graduate students in PT, OT, and SLP training programs. Group comparisons were conducted to identify differences according to discipline (PT, OT, or SLP) and university designation (first or second year graduate student). Kruskall-Wallis vi analyses revealed no statistically significant difference in knowledge across disciplines regarding general information about TBI or recovery, however there was a statistically significant difference regarding knowledge of coma and unconsciousness, memory loss, and concussion. Mann-Whitney analyses revealed no significant difference in knowledge of general information about TBI, coma and unconsciousness, or recovery according to university designation, however there was a statistically significant difference in knowledge of memory loss and concussion. vii

Airway protection is maintained through a constellation of behaviors. The laryngeal adductor reflex (LAR) responds to mechanical or chemical stimulation of the laryngeal orifice with rapid adduction of the vocal folds. While there are abundant serotonin receptors on laryngeal motoneurons, the effects of serotonin agents on the LAR have not been investigated. To this end, a dose response protocol of 8‐OH‐DPAT (5HT1A receptor agonist) was performed on adult cats (n = 2). Animals were anesthetized using an intravenous dose of sodium pentobarbital and then tracheostomized. Electromyogram (EMG) activity of laryngeal muscles was recorded and LARs were induced by infusing water into the larynx during both normocapnia (0% CO2) and hypercapnia (10% CO2) conditions. A series of six cumulative doses (1 – 300 μg/kg) were delivered intra‐venously. 8‐OH‐DPAT is thought to activate the serotonergic raphe neuron autoreceptors at lower doses and the post‐synaptic receptors on target neurons at higher doses. LAR occurred as a response to water stimulus in 50±23% of control trials. LAR occurrence was modulated by 8‐OH‐DPAT in a dose‐dependent manner: LAR frequency at lower doses may have decreased but this was variable, and LAR frequency appeared to be increased at higher doses (LAR occurred in 13±18%, 17±23%, 50±70%, 57±9%, 84±7%, and 60±4% of stimulus trials at 1, 3, 10, 30, 100, and 300 μg/kg doses, respectively). LAR can be used as a strong clinical predictor of swallow impairment; while other airway protective behaviors require activity across multiple cranial nerves, the LAR is regulated by only laryngeal branches of the vagus nerve. Thus, the LAR is a promising biomarker for testing novel therapeutic agents. These results suggest that pharmacological interventions may be capable of facilitating laryngeal function in patients suffering from dysphagia.

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Opioid use is associated with increased risk of chest infection due to opioid suppression of immune function, ventilation, cough, and secretion mobilization. Buprenorphine is a highly lipophilic, semi‐synthetic partial agonist of the mu opioid receptor. Intramuscular buprenorphine is commonly used for post‐operative analgesia at a dose range of 0.01‐0.04 mg/kg in the cat. While buprenorphine is considered to have a low side effect profile, its effects on the pharyngeal phase of swallow are unknown. We hypothesized that administration of opioid would result in clinically meaningful decline of pharyngeal swallow function. Experiments were performed on healthy adult cats (12 months old). Animals were administered intramuscular buprenorphine (0.015 mg/kg) q12 hours for 48 hours. One hour after the last dose was given, videofluoroscopic swallow studies were performed to evaluate the effects of the drug on swallow function. Animals were presented with 40% by volume barium sulfate in tuna water mixed to a thin consistency, and all animals ate voluntarily. Images were recorded in the lateral plane at 30 frames/second and compared to control feeding assessments using the Global Dysphagia Scale (GDS), a novel tool developed to rate swallow function in the cat. The GDS consists of an Airway Invasion Scale (AIS) and relevant components of the Modified Barium Swallow Impairment Profile (MBSImP), a standardized protocol for swallow assessment. The AIS is a 10‐point scale where scores of 0‐1 are normal, scores of 2‐4 indicate laryngeal penetration, and scores of 5‐9 indicate tracheobronchial aspiration. Four components of the MBSImP were included: Initiation of the pharyngeal swallow, pharyngeal stripping wave, pharyngoesophageal segment opening, and pharyngeal residue. The GDS rating was derived by adding the AIS and MBSImP sub‐totals. During control assessments mean GDS was 5.5 ± 1.3, and aspiration was not detected in any animal. On buprenorphine, mean GDS was 11.25 ± 4.2, and 50% of animals exhibited large volume tracheobronchial aspiration. In conclusion, after 48 hours on buprenorphine, airway protection during swallow failed without appreciable response in 50% of animals (no cough, throat clear, or cessation of eating). Our success in producing dysphagia (significant but varying by animal) with relatively small doses of opioid has potential implications for predicting aspiration pneumonia in post‐surgical clinical cases.

Swallow is a critical behavior for sustaining life, important for both for the ingestion of nutrients and for protecting the airways. To produce an effective swallow, neural circuits must coordinate over 20 muscles across multiple cranial/spinal nerves to produce a rostral‐caudal pressure gradient to move the bolus from the mouth to the stomach. The medullary raphe nuclei are the main source of serotonin in the brainstem, and this region has been implicated in modulation of swallow and other airway protective behaviors. In order to explore the role of serotonin in swallow, we conducted experiments in adult cats (n = 6). Animals were anesthetized with intravenous sodium pentobarbital and tracheostomized. Fine wire intramuscular electromyograms (EMGs) were recorded from swallow and respiratory related muscles. The 5‐HT1A receptor agonist 8‐OH‐DPAT was delivered either intravenously through the femoral artery (n = 3) or intra‐arterially through the vertebral artery (n = 3) as a series of six cumulative doses (0.1‐30 ug/kg i.v.; 1‐300 ug/kg i.a.). Swallow was elicited by oral infusion water (3 ml) via syringe and was confirmed by the presence coordinated activity on swallow‐related EMGs. EMG amplitude was normalized prior to analysis. Administration of 8‐OH‐DPAT demonstrated a significant effect on the two primary submental muscles responsible for hyolaryngeal elevation necessary for full occlusion of the airway by the epiglottis. Mylohyoid amplitude increased by 45% (p = 0.006) and geniohyoid amplitude increased by 64% (p = 0.04) at the highest dose when compared to control. This is evidence of the raphe and its serotonergic network coordinating distributed aspects of the swallow control network as these two muscles are innervated via separate cranial nerves: the trigeminal for the mylohyoid and hypoglossal for the geniohyoid. Disordered hyolaryngeal function is a leading cause of aspiration across a multitude of neuro‐ degenerative and ‐traumatic diseases, and pharmacologic intervention with serotonergic agonists represents a promising agent for therapeutic interventions.