Editorial: Craniofacial Neuroscience

Alyssa A Huff^1*Kei A Katsura²Teresa Pitts³

• ¹Seattle Children's Research Institute, Seattle, United States
• ²University of California San Francisco, San Francisco, California, United States
• ³Univeristy of Missouri, Columbia, Missouri, United States

Upper airway dysfunction continues to be detailed in a number of neurodegenerative and neurotraumatic diseases. Song et al. reports the prevalence of post stroke dysphagia is 47% with associated risk factors such as hypertension, previous stroke, and atrial fibrillation. The authors also reported the persistence of dysphagia at discharge and 1 month post to be 75% and 51%, respectively. Martinez-Peña et al. also reported a high prevalence of dysphagia in older individuals with mild cognitive impairment and dementia. Suggesting early identification and intervention is key in preventing serious health outcomes. Liu et al. reports the association of lower income levels with increased oropharyngeal dysphagia, highlighting the complex challenges of health care accessibility, nutritional adequacy and stress. The authors also call for a sex-specific approach in early intervention in the aging population.Preclinical animal models are investigating a number of potential mechanisms for dysphagia and upper airway dysfunction. Motoneuron (MN) death associated with amyotrophic lateral sclerosis (ALS) disrupts orolingual and aerodigestive behaviors such as speech and swallowing, as well as ventilatory and non-ventilatory behaviors, breathing and coughing, respectively. These deficits also result in an increased risk of airway protection and aspiration pneumonia. By using a mouse model of ALS, Fogarty et al. investigated a timeline for sizedependent XII MN loss and tongue innervation in SOD1 mice. They saw a significant reduction in larger XII MN at mid-and end-stage disease with no difference at presymptomatic and onset ages. Specific disruption to tongue neuromuscular junctions did not occur until end-stage timepoints leading the authors to the conclusion that denervation of tongue neuromuscular junctions may be a consequence not a cause of MN deficits in SOD1 mice. While Keilholz et al. used a different rodent model to induce XII MN death and investigated the use of strength endurance tongue exercise program as a potential therapy for patients with motoneuron disease and ALS. They found that tongue exercise mitigated airflow deficits and preserved the upper airway and ultrafine structures in the tongue, suggesting that high-repetition low endurance tongue exercise program could be an effective therapeutic to maintain upper airway patency.Persons with Down Syndrome experience dysphagia across all three swallow phases: oral, pharyngeal, and esophageal, likely due to disordered tongue function, uncoordinated swallow and breathing, and esophageal dysmotility. Glass et al. utilized clinical techniques in a mouse model of Down Syndrome (Ts65Dn). They found that adult Ts65Dn mice have significantly slower swallow rates and longer time intervals between consecutive swallows. Adult Ts65Dn mice also have slower rates of developing tongue force and a more rapid onset of tongue muscle fatigue. Conclud ing that heightened susceptibility to tongue muscle fatigue could contribute to increased duration of the oral phase and decrease the efficacy of deglutition (swallowing).Opioids, specifically morphine and remifentanil, use has been associated with aspiration and swallow dysfunction. However, the influence of codeine, the most abused opioid drug worldwide, on swallowing is unknown. Bolser et al. reported that intravenous codeine induced spontaneous swallowing in vagal intact and vagally denervated cats, suggesting that swallowpromoting actions of this drug do not require sensory feedback from the vagus to occur. Though there was an increase in the amplitude of upper airway muscles during water induced swallows, swallow frequency did not change. This continues to support the concept that swallow frequency and swallow amplitude are independently regulated.While swallowing is thought to predominately be controlled by the brainstem, there is strong evidence the spinal cord also plays an important role. Kitamura et al. utilized Gaussian frequency stimulation applied to the skin surface of the back over the ribs in a rodent model to activate sensory spinal pathways as a possible therapeutic to improve swallow activity. Stimulation at the T9-T10 level significantly increased swallow related muscle amplitudes of the mylohyoid, thyroarytenoid, and thyropharyngeus. The mylohyoid is a laryngeal elevator muscle, while the thyropharyngeus is a pharyngeal constrictor muscle crucial for swallow related bolus transfer. The thyroarytenoid is a laryngeal adductor muscles that activates during swallow to close the airway and prevent food or liquid from entering. Hashimoto et al. sought to develop a new dysphagia model with reduced pharyngeal constriction during the pharyngeal phase of swallow in a guinea pig. Denervation of the pharyngeal branch of the vagus nerve significantly impacted the expiratory and swallow related activity of the thyropharyngeus and disrupted swallow function one month after injury. This new experimental model could provide insight into dysphagia therapeutic development and mechanisms associated with cranial nerve injury, reinnervation, and regeneration. The motor neurons that regulate these pharyngeal and laryngeal muscles are located within the nucleus ambiguus. M Fogarty et al. characterized the dendritic morphology of the MNs and non-MNs within the compact, semi-compact, and loose formation of the nucleus ambiguus in the brainstem. These findings introduce valuable insight into the inter-network connection of these neurons that must coordinate for proper swallow function.Beyond ingestion, the trigeminal nerve is responsible for both sensory and motor functions of the face, by providing motor innervation to the muscles of mastication and sensory feedback from the jaws and teeth. The mesencephalic trigeminal nucleus, a key portion of the CN V, is activated during bruxism, which is the repetitive clenching or grinding of the teeth. This behavior can occur during awake and sleep states and affects up to 30% of the population. Uchima Koecklin et al. described the current understanding of brain regions and neurotransmitters involved in bruxism, as well as psychological traits and clinical implications. The authors encourage continued animal and human studies on bruxism, specifically the trigeminal system, to improve treatment approaches and understanding of this multifactorial condition. In dental procedures, damage to branches of the trigeminal nerve (inferior alveolar nerve and lingual nerve) are often the major complications following lower jaw surgeries and 3 rd molar extractions and can lead to temporary and/or permanent numbness in the lower lip and tongue.Facial Palsy refers to weakness or paralysis of the facial muscles caused by damage to the facial nerve. While facial synkinesis is a complication that can develop after facial palsy which refers to involuntary simultaneous movements of the facial muscles. These conditions can affect facial expressions, eating, drinking, speech, and eye closure, hindering daily activities and quality of life. Machetanz et al. draws attention to the lack of specialized treatment options for facial palsy and how the vast number of specialists required to treat facial palsy contributes to treatment satisfaction and quality of life. Di Stadio et al. presented the idea of pairing physical facial nerve rehabilitation with early lower eyelid surgery to improve or prevent synkinesis. They reported that patients that underwent eyelid surgery along with physical facial nerve rehabilitation had faster and better recovery of facial movements, along with no synkinesis even 24 months after surgery. Whereas 37% of patients who did not have surgery and only participated in physical facial nerve rehabilitation developed synkinesis.While the primary focus of craniofacial neuroscience research is to support the understanding of human populations, our knowledge is extremely valuable in the rehabilitation of other species including harbor seals. Thousands of infant harbor seals have been admitted to the Vancouver Aquarium's Marine Mammal Rescue center and other rehabilitation centers world wild. The primary cause of death in seal pups is malnutrition and in adults, pneumonia. Skoretz et al. describes the novel ability to use clinical Videofluoroscopic Swallow Studies (VFSS) in seal pups to identify 4 distinct swallow phases, vastly expanding the understanding of airway protection in independently feeding seals.This collection of articles draws attention to the wide variety of specialties associated with all 12 cranial nerves across many different behaviors and disorders. Continued collaboration in both the basic science and clinical sciences are necessary to improve our understanding of craniofacial neuroscience.