Stimulation Of Superior Laryngeal Nerve Research Articles

Neurophysiology of the Superior Laryngeal Nerve in an In Vivo Rat Model.

The superior laryngeal nerve (SLN) is fundamental in laryngeal sensation, cough reflex, and pitch control. SLN injury has substantial consequences including altered sensation, aspiration, and dysphonia. To date, in vivo measurement of the SLN remains elusive. The purpose of this study was to assess the feasibility of recording motor and sensory evoked potentials in a rat SLN model. Twenty-two rat hemi-laryngeal preparations (n = 11) were obtained from 4-month-old Sprague-Dawley rats and included in this study. Compound motor action potentials (CMAPs) and motor unit number estimation (MUNE) were calculated by stimulating the SLN at the point of medial extension near the carotid artery and by placing a recording electrode on the cricothyroid muscle. Sensory response was determined through stimulation of the SLN and laryngoscopic visualization of a laryngeal adductor reflex (LAR). SLN and cricothyroid muscle cross-sections were stained and histologic morphometrics were quantified. Laryngeal evoked potentials were successfully obtained in all trials. Mean CMAP latency and negative durations were 0.99 ± 0.57 ms and 1.49 ± 0.57 ms, respectively. The median MUNE was 2.06 (IQR 1.88, 3.51). LAR was induced with a mean intensity of 0.69 ± 0.20 mV. Mean axon count, myelin thickness, and g-ratio were 681 ± 192.2, 1.72 ± 0.26, and 0.45 ± 0.04, respectively. This study demonstrates the feasibility of recording evoked response potentials following SLN stimulation. We hypothesize that this work will provide a tractable animal model to study changes in laryngeal sensation and cricothyroid motor function with aging, neurodegenerative disease, aspiration, or nerve injury. NA Laryngoscope, 134:1778-1784, 2024.

Inhibition of Water-Evoked Swallowing During Noxious Mechanical Stimulation of Tongue in Anesthetized Rats.

Dysphagia is sometimes accompanied by pain. Because orofacial structures subserve mastication and swallowing, orofacial pain might impair both functions. Tongue biting can occur not only accidentally while eating but also in some pathological conditions. However, it remains unclear whether noxious mechanical stimulation of the tongue affects swallowing. To explore this question, we evaluated the effects of lingual pinch stimulation on the initiation of swallowing evoked by distilled water (DW) infusion with a flow rate of 5.0µL/s for 20s into the pharyngolaryngeal region in anesthetized rats. The swallowing reflex was identified by electromyographic (EMG) bursts in the suprahyoid muscles which include the anterior belly of the digastric muscle, mylohyoid and geniohyoid muscles, and laryngeal elevation by visual inspection. The number of DW-evoked swallows during pinch stimulation was significantly smaller than that in a control condition or during pressure stimulation. The onset latency of the first swallow during pinch stimulation was significantly longer than that in the control condition. DW-evoked swallowing was almost abolished following bilateral transection of the superior laryngeal nerve (SLN) compared with the control condition, suggesting that the SLN plays a crucial role in the initiation of DW-evoked swallowing. Finally, electrophysiological data indicated that some SLN-responsive neurons in the nucleus tractus solitarii (nTS) exhibited delayed latency from a single SLN stimulation during lingual pinch stimulation. These results suggest that noxious mechanical stimulation of the tongue inhibits the initiation of swallowing and modulates neuronal activity in the nTS.

3D Reconstruction of Phonatory Glottal Shape and Volume: Effects of Neuromuscular Activation.

Although phonatory glottal posture and airflow pulse shape affect voice quality, studies to date have been limited by visualization of vocal fold (VF) vibration from a superior view. We performed a 3D reconstruction of VF vibratory motion during phonation from a medial view and assessed the glottal volume waveform and resulting acoustics as a function of neuromuscular stimulation. In vivo canine hemilarynx phonation. Across 121 unique combinations of the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) stimulation, the hemilarynx was excited to the oscillation with airflow. VF medial surface reference points were tracked on high-speed video, mapped into 3D space, and surface shape was restored using cubic spline interpolation. Glottal surface shape, reconstruction-based parameters, and glottal volume waveform were calculated. Fundamental frequency (F0), cepstral peak prominence (CPP), and harmonic amplitude (H1-H2) were measured from high-quality audio samples. The glottis was convergent during opening and divergent during closing. Neuromuscular activation changed phonatory glottal shape and reduced glottal volume. Significant reduction in glottal volume and closing quotient were present with SLN stimulation. RLN stimulation significantly increased F0 and CPP and decreased H1-H2 (constricted glottis), while SLN effects were similar and synergistic with concurrent RLN stimulation. 3D reconstruction of in vivo medial surface vibration revealed effects of laryngeal nerve stimulation on glottal vibratory pattern and acoustic correlates of voice quality. SLN activation resulted in significantly quicker glottal closure per cycle, decreased glottal volume, and higher-pitched, less breathy, and less noisy voice. RLN had a similar effect on acoustic measures. NA, Basic Science Laryngoscope, 133:357-365, 2023.

EndoFLIP Topography: Motor Patterns in an Obstructed Esophagus

Esophageal distension–induced secondary peristalsis plays an important role in the clearance of gastric contents refluxed into the esophagus and in the expulsion of food residues left behind by swallow-induced primary peristalsis. Esophageal motor responses to distension have been investigated using water-filled balloons monitoring esophageal pressures proximal and distal to the balloon. Recently, motor patterns using a fluid-filled obstructing balloon with or without recording pressures proximal or distal to the balloon have measured impedance that may provide information on the luminal cross-sectional area (CSA).1Gregersen H. Andersen M.B. Impedance measuring system for quantification of cross-sectional area in the gastrointestinal tract.Med Biol Eng Comput. 1991; 29: 108-1010Crossref PubMed Scopus (85) Google Scholar Functional lumen imaging probe (FLIP) records luminal CSAs per diameter using 17 ring electrodes spaced 1 cm apart to provide impedance data from 16 sites in a long balloon filled with fluid.2Carlson D.A. Lin Z. Rogers M.C. et al.Utilizing functional lumen imaging probe topography to evaluate esophageal contractility during volumetric distention: a pilot study.Neurogastroenterol Motil. 2015; 27: 981-989Crossref PubMed Scopus (55) Google Scholar FLIP planimetry reporting some “unique” motor patterns such as distension-induced repetitive contractions in health and disease3Carlson D.A. Baumann A.J. Prescott J.E. et al.Validation of secondary peristalsis classification using FLIP panometry in 741 subjects undergoing manometry.Neurogastroenterol Motil. 2022; 34e14192Crossref Scopus (15) Google Scholar,4Carlson D.A. Kahrilas P.J. Ritter K. et al.Mechanisms of repetitive retrograde contractions in response to sustained esophageal distension: a study evaluating patients with post fundoplication dysphagia.Am J Physiol Gastrointest Liver Physiol. 2018; 314: G334-G340Crossref PubMed Scopus (16) Google Scholar has been proposed as an alternative to high-resolution manometry topography. However, the pathophysiologic basis of findings and their relationship to previously described motor patterns remains unknown. The esophagus is wired to elicit either centrally organized swallow-associated primary peristalsis, locally regulated secondary esophageal peristalsis, or related abnormalities. It may also exhibit spontaneous, disorganized contractions termed tertiary contractions. Esophageal distension may augment these contractions. It is not clear whether the motor patterns recorded by endoluminal FLIP (EndoFLIP) are extensions of known pathophysiologic or any novel patterns. The swallowing reflex produces primary peristalsis that can be elicited by the stimulation of either the superior laryngeal nerve (SLN) or recurrent laryngeal nerve. Although a solitary simulation of the SLN causes a single primary peristaltic sequence, sustained afferent nerve stimulation may cause repeated swallows.5Sang Q. Goyal R.K. Swallowing reflex and brainstem neurons activated by superior laryngeal nerve stimulation in mouse.Am J Physiol Gastrointest Liver Physiol. 2001; 280: G191-G200Crossref PubMed Google Scholar,6Tsuji K. Tsujimura T. Magara J. et al.Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.Brain Res Bull. 2015; 111: 53-61Crossref PubMed Scopus (21) Google Scholar One circuit involves the nucleus ambiguous that by activating lower motor neurons elicits primary peristalsis in the striated muscle of the oral cavity, pharynx, upper esophageal sphincter, and cervical esophagus. This sequence of events results in the delivery of a food bolus into the cervical esophagus.7Doty R.W. Neural organization of deglutition.in: Code CF (ed). Handbook of physiology: the alimentary canal. American Physiological Society, Washington, DC1968: 1861-1902Google Scholar The other circuit involves inhibitory and excitatory parasympathetic preganglionic neurons in the dorsal motor nucleus of the vagus. Swallowing causes prompt activation of intramural inhibitory and sequential activation of the excitatory neurons responsible for the peristalsis in the esophageal smooth muscle.8Gidda J.S. Goyal R.K. Swallow-evoked action potentials in the vagal preganglionic efferents.J Neurophysiol. 1984; 52: 1169-1180Crossref PubMed Scopus (39) Google Scholar The inhibitory circuit is responsible for the so-called deglutitive inhibition and thus for the latency of onset of contraction and the rebound contraction.9Yamato S. Spechler S.J. Goyal R.K. Role of nitric oxide in esophageal peristalsis in the opossum.Gastroenterology. 1992; 103: 197-204Abstract Full Text PDF PubMed Scopus (140) Google Scholar,10Sifrim D. Janssens J. Vantrappen G. A wave of inhibition precedes primary peristaltic contractions in the human esophagus.Gastroenterology. 1992; 103: 876-882Abstract Full Text PDF PubMed Scopus (104) Google Scholar The excitatory circuit influences latency and contributes to the contraction.11Goyal R.K. Chaudhury A. Physiology of normal esophageal motility.J Clin Gastroenterol. 2008; 42: 610-619Crossref PubMed Scopus (183) Google Scholar The peristaltic response in the smooth muscle part of the esophagus resembles that of vagal efferent stimulation except that the swallow-induced peristalsis has a slower speed of propagation.8Gidda J.S. Goyal R.K. Swallow-evoked action potentials in the vagal preganglionic efferents.J Neurophysiol. 1984; 52: 1169-1180Crossref PubMed Scopus (39) Google Scholar Swallow-induced esophageal peristalsis is generally similar in awake or anesthetized subjects.12Schoeman M.N. Holloway R.H. Stimulation and characteristics of secondary oesophageal peristalsis in normal subjects.Gut. 1994; 35: 152-158Crossref PubMed Scopus (89) Google Scholar In some cases, however, the peristaltic wave may show a delay at the junction of the upper one-third vs the lower two-thirds of the esophagus. Multiple repetitive 2-mL swallows at shorter intervals (as during rapid drinking of water) suppresses contractile responses to all swallows except for the last one. In healthy subjects, an interval of about 8 seconds was found to be optimal for the complete peristaltic sequence. Behar and Biancani13Behar J. Biancani P. Pathogenesis of simultaneous esophageal contractions in patients with motility disorders.Gastroenterology. 1993; 105: 111-118Abstract Full Text PDF PubMed Scopus (73) Google Scholar reported that paired swallows 5 seconds apart in control subjects with a normal rate of peristalsis (with the latency of contraction at the distal-most part of the esophagus of 6.4 seconds) elicited only 1 contraction at the end of the second swallow. However, rapid peristalsis (with a latency of 2.9 seconds), presumably because of loss of inhibitory neuromuscular transmission, elicited 2 contractions, 2 each to 2 swallows. Behar and Biancani13Behar J. Biancani P. Pathogenesis of simultaneous esophageal contractions in patients with motility disorders.Gastroenterology. 1993; 105: 111-118Abstract Full Text PDF PubMed Scopus (73) Google Scholar suggested that the interswallow interval is critical in documenting impaired inhibitory neurotransmission. Differences in the duration of latency of contraction at different esophageal sites may explain the shorter interval for the full contractions in the proximal vs distal part. Fornari et al14Fornari F. Bravi I. Penagini R. et al.Multiple rapid swallowing: a complementary test during standard oesophageal manometry.Neurogastroenterol Motil. 2009; 21: 718Crossref PubMed Scopus (134) Google Scholar observed that the last contraction after repetitive swallows is usually larger than that with single swallows. The mechanism of the large contraction (also known as reserve contraction) is not known. Swallowing-induced activation of the longitudinal muscle may support peristaltic contraction mediated by the circular muscle. In addition, contraction of the longitudinal muscle by an overall shortening of the esophagus may cause retrograde displacement of the lower esophageal sphincter (LES).15Sugarbaker D.J. Rattan S. Goyal R.K. Swallowing induces sequential activation of esophageal longitudinal smooth muscle.Am J Physiol. 1984; 247: G515-G519PubMed Google Scholar,16Park S. Zifan A. Kumar D. et al.Genesis of esophageal pressurization and bolus flow patterns in patients with achalasia esophagus.Gastroenterology. 2018; 155: 327-336Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar In the smooth muscle part of the esophagus, transient balloon distension elicits secondary peristalsis that is characterized by isolated esophageal peristalsis without a pharyngeal or cricopharyngeal response,12Schoeman M.N. Holloway R.H. Stimulation and characteristics of secondary oesophageal peristalsis in normal subjects.Gut. 1994; 35: 152-158Crossref PubMed Scopus (89) Google Scholar with variable responses in the upper esophageal sphincter.17Babaei A. Dua K. Naini S.R. et al.Response of the upper esophageal sphincter to esophageal distension is affected by posture, velocity, volume, and composition of the infusate.Gastroenterology. 2012; 142: 734-743Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Esophageal pressure recording at sites proximal and distal to the balloon shows that secondary peristaltic contractions involve both striated and smooth muscle portions of the esophagus. Additionally, the junctional area between the proximal and distal esophagus shows a delay in the progress of the peristaltic contraction that is exaggerated by atropine (in experimental animals and humans) in response to swallowing.18Paterson W.G. Rattan S. Goyal R.K. Esophageal responses to transient and sustained esophageal distension.Am J Physiol. 1988; 255: G587-G595PubMed Google Scholar Simultaneous recordings of intraluminal pressures and membrane potentials revealed that hyperpolarization (indicating muscle inhibition) is responsible for the latency of contraction or depolarization.19Paterson W.G. Electrical correlates of peristaltic and nonperistaltic contractions in the opossum smooth muscle esophagus.Gastroenterology. 1989; 97: 665-675Abstract Full Text PDF PubMed Scopus (28) Google Scholar Repeated successive transient balloon distension caused an inhibition during the period of stimulation followed by a prominent contraction to the last distension.18Paterson W.G. Rattan S. Goyal R.K. Esophageal responses to transient and sustained esophageal distension.Am J Physiol. 1988; 255: G587-G595PubMed Google Scholar This response is similar to that of primary peristalsis in humans. In some cases, however, a peristaltic response to the first stimulus in the series was observed. These studies are consistent with the view that the motor part of esophageal peristalsis uses the same neural circuits for primary or secondary peristalsis. However, the contribution of the cholinergic component in the 2 contractions may differ.20Paterson W.G. Hynna-Liepert T.T. Selucky M. Comparison of primary and secondary esophageal peristalsis in humans: effect of atropine.Am J Physiol. 1991; 260: G52-G57PubMed Google Scholar Sustained esophageal distension elicits contraction proximally and inhibition distally, dissecting the excitatory and inhibitory components of the peristalsis. This sequence of events facilitates the movement of the bolus retained in the esophagus. Winship and Zboralske21Winship WH Zboralske F.F. Esophageal propulsive force: esophageal response to acute obstruction.J Clin Invest. 1967; 46: 1391-1401Crossref PubMed Scopus (39) Google Scholar reported that in the human esophagus longer distensions using large volumes evoked aboral force to propel the obstructing balloon into the stomach. The propulsive force occurred promptly and was sustained until the balloon was deflation. Conversely, the detachment of the obstructing balloon converted the stationary propulsive force to a propagating type, leading to the forward propulsion of the balloon at a speed of 4 to 8 cm/s. Arresting the balloon movement also arrested the propagating force and converted it into a stationary propulsive force until the balloon was freed when the propagating force delivered the balloon to the stomach. Esophageal obstruction promotes a collection of secretions proximal to the obstruction inducing swallowing, which initially inhibits but later at the time of contraction wave augments the propulsive force.21Winship WH Zboralske F.F. Esophageal propulsive force: esophageal response to acute obstruction.J Clin Invest. 1967; 46: 1391-1401Crossref PubMed Scopus (39) Google Scholar Paterson and colleagues18Paterson W.G. Rattan S. Goyal R.K. Esophageal responses to transient and sustained esophageal distension.Am J Physiol. 1988; 255: G587-G595PubMed Google Scholar recorded esophageal pressures distal to a distended balloon, mimicking transient obstruction. Distal to the balloon, esophageal motor activity was inhibited at the onset and for the duration of the balloon distension. The inhibition extended to the LES. The pressure sensor was pinned to the sphincter to ensure that the LES relaxation was not a movement artifact. Simultaneous membrane potential recording using suction electrodes showed that early and late inhibition during maintained distension were associated with smooth muscle membrane hyperpolarization.19Paterson W.G. Electrical correlates of peristaltic and nonperistaltic contractions in the opossum smooth muscle esophagus.Gastroenterology. 1989; 97: 665-675Abstract Full Text PDF PubMed Scopus (28) Google Scholar Deflation of the balloon led to the peristaltic contractile activity distal to the balloon and LES relaxation followed by its contraction. These observations agree with the initial reports that in vitro sustained distension elicits contractions on termination of esophageal circular smooth muscle distension.18Paterson W.G. Rattan S. Goyal R.K. Esophageal responses to transient and sustained esophageal distension.Am J Physiol. 1988; 255: G587-G595PubMed Google Scholar These observations correlate with those of esophageal propulsive force.21Winship WH Zboralske F.F. Esophageal propulsive force: esophageal response to acute obstruction.J Clin Invest. 1967; 46: 1391-1401Crossref PubMed Scopus (39) Google Scholar Esophageal obstruction elicits secondary peristalsis proximally up to the point of obstruction, which is converted into stationary esophageal propulsive force once the obstruction is removed, denoted by the peristaltic contraction. The distal inhibition was dependent on the degree of distension. However, the secondary peristaltic wave continued over the balloon onto the esophagus beyond the balloon. The authors noted that almost one-third of the secondary peristaltic contractions may be expressed in the distended balloon extending to the distal esophagus. Rao et al22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar investigated the effect of intraesophageal balloon distension on esophageal contractions over, proximal, and distal to the balloon. A 4-fold increase in the CSA of the balloon was associated with a 20-fold increase in the motility index over the balloon related to the frequency, amplitude, and duration of contractions. The motor activity increased proximal to the balloon but not so much distally. The authors recognized 3 types of contractions: swallow-induced primary and distension-induced secondary peristaltic contractions, and distension-induced and spontaneous, nonperistaltic tertiary contractions.22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar The distension-induced and spontaneous tertiary contractions are confined to the balloon and are also called localized, nonpropagating pressure waves. Primary and secondary peristaltic contractions start and are arrested proximal to the balloon and contribute to the esophageal propulsive force. However, they may continue over the balloon and beyond it to the distal esophagus.18Paterson W.G. Rattan S. Goyal R.K. Esophageal responses to transient and sustained esophageal distension.Am J Physiol. 1988; 255: G587-G595PubMed Google Scholar Esophageal distension-induced secondary peristaltic contraction is associated with distal inhibition, and it is usually expressed distally only after balloon deflation. When secondary peristaltic contraction continues over and beyond a distended balloon, its amplitude is reduced consistent with persistent distal inhibition.18Paterson W.G. Rattan S. Goyal R.K. Esophageal responses to transient and sustained esophageal distension.Am J Physiol. 1988; 255: G587-G595PubMed Google Scholar,23Orvar K.B. Gregersen H. Christensen J. Biomechanical characteristics of the human esophagus.Dig Dis Sci. 1993; 38: 197-205Crossref PubMed Scopus (57) Google Scholar Sustained esophageal distension has an inhibitory effect on primary as well as secondary peristalsis distal to the balloon. Sustained balloon distension is associated with esophageal obstruction and difficulty in handling salivary secretion.21Winship WH Zboralske F.F. Esophageal propulsive force: esophageal response to acute obstruction.J Clin Invest. 1967; 46: 1391-1401Crossref PubMed Scopus (39) Google Scholar,23Orvar K.B. Gregersen H. Christensen J. Biomechanical characteristics of the human esophagus.Dig Dis Sci. 1993; 38: 197-205Crossref PubMed Scopus (57) Google Scholar Pharyngeal collection of secretion may elicit swallow-induced primary peristalsis by stimulating the SLN and recurrent laryngeal nerve.6Tsuji K. Tsujimura T. Magara J. et al.Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.Brain Res Bull. 2015; 111: 53-61Crossref PubMed Scopus (21) Google Scholar Because the expression of the peristaltic waves depends on the interswallow interval, only swallows with a sufficient interval may be fully expressed, whereas others are suppressed. Swallow-induced primary peristalsis may be arrested proximal to the balloon and augment the esophageal propulsive force. However, many primary peristaltic waves may be expressed over and beyond the distended balloon. Interestingly, a 9-second stimulation of the SLN is reported to elicit 2 full primary peristaltic contractions.5Sang Q. Goyal R.K. Swallowing reflex and brainstem neurons activated by superior laryngeal nerve stimulation in mouse.Am J Physiol Gastrointest Liver Physiol. 2001; 280: G191-G200Crossref PubMed Google Scholar Barium swallow and barium videography have been used for the estimation of esophageal diameter and progress of intraluminal contents. Impedance planimetry, on the other hand, has been introduced as a nonradiologic technique to study the luminal diameter and contractile patterns during the movements of luminal contents.1Gregersen H. Andersen M.B. Impedance measuring system for quantification of cross-sectional area in the gastrointestinal tract.Med Biol Eng Comput. 1991; 29: 108-1010Crossref PubMed Scopus (85) Google Scholar It may also provide data on the mechanical properties of the muscular wall. This technique identified 2 types of motor activities in the intestine: lumen-occluding motor patterns and myogenic rhythmic myogenic contractions. Lumen-occluding motor patterns with large changes in the CSAs were associated with the movement of intraluminal contents. These neural reflexes were blocked by a ganglionic blocker, hexamethonium. Different parts of the gut revealed distinct neurogenic motor patterns. The second, type, myogenic rhythmic myogenic contractions (resistant to hexamethonium), was associated with the pendular movements involved in the mixing of luminal contents. Such myogenic contractions may be coupled with interstitial cells of Cajal when present.24Costa M. Wiklendt L. Arkwright J.W. et al.An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility.Front Syst Neurosci. 2013; https://doi.org/10.3389/fnsys.2013.00007Crossref PubMed Scopus (43) Google Scholar Orvar et al23Orvar K.B. Gregersen H. Christensen J. Biomechanical characteristics of the human esophagus.Dig Dis Sci. 1993; 38: 197-205Crossref PubMed Scopus (57) Google Scholar found that inflation of the balloon causes volume-dependent transient decreases in the CSA that correlate with an increase in intraballoon pressure. The contraction waves augmented on increasing pressures were called reactive contractions. The reactivity was prominent in subjects with chest pain.22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar,23Orvar K.B. Gregersen H. Christensen J. Biomechanical characteristics of the human esophagus.Dig Dis Sci. 1993; 38: 197-205Crossref PubMed Scopus (57) Google Scholar The authors22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar,23Orvar K.B. Gregersen H. Christensen J. Biomechanical characteristics of the human esophagus.Dig Dis Sci. 1993; 38: 197-205Crossref PubMed Scopus (57) Google Scholar also carefully monitored swallow and esophageal contractions proximal to the balloon and noted that many contractions over the balloon were associated with swallows or secondary peristalsis. Using EndoFLIP planimetry Carlson et al2Carlson D.A. Lin Z. Rogers M.C. et al.Utilizing functional lumen imaging probe topography to evaluate esophageal contractility during volumetric distention: a pilot study.Neurogastroenterol Motil. 2015; 27: 981-989Crossref PubMed Scopus (55) Google Scholar recorded changes in the CSA from 16 points, 1 cm apart covering the distal esophagus, LES, and stomach. The transient changes in the CSA represented the intraluminal pressure. They recorded a spectrum of distension-associated esophageal contractions. In healthy subjects, distension elicited anterograde waves, which appeared to start at the proximal end of the balloon, progressing distally. The anterograde progression was due to a progressive increase in the latency of contraction distally along the esophagus. These waves were associated with the LES opening and migrating proximally with the onset of the contraction wave and finally closing on the arrival of the contraction wave. Such waves could represent primary or secondary peristaltic contractions over the balloon.22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar These waves occurred singly or in groups. When this cluster of waves fulfilled certain criteria such as the so-called rule of 6, they were named anterograde rhythmic contractions (ARCs).3Carlson D.A. Baumann A.J. Prescott J.E. et al.Validation of secondary peristalsis classification using FLIP panometry in 741 subjects undergoing manometry.Neurogastroenterol Motil. 2022; 34e14192Crossref Scopus (15) Google Scholar The high-resolution motility study showed normal primary peristalsis missed ARCs in most subjects (8/10). The presence of ARCs was correlated with repeated swallows greater than 8 seconds apart, and EndoFLIP planimetry was proposed to avoid a separate high-resolution manometry topography study. Swallow-induced primary peristalsis on an obstructed balloon has been attributed to difficulty in handling secretions triggering the swallowing reflex.21Winship WH Zboralske F.F. Esophageal propulsive force: esophageal response to acute obstruction.J Clin Invest. 1967; 46: 1391-1401Crossref PubMed Scopus (39) Google Scholar,22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar Interestingly, persistent stimulation of the SLN may elicit repeated swallowing at intervals of 6 seconds, which may explain the ARC pattern.5Sang Q. Goyal R.K. Swallowing reflex and brainstem neurons activated by superior laryngeal nerve stimulation in mouse.Am J Physiol Gastrointest Liver Physiol. 2001; 280: G191-G200Crossref PubMed Google Scholar,6Tsuji K. Tsujimura T. Magara J. et al.Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.Brain Res Bull. 2015; 111: 53-61Crossref PubMed Scopus (21) Google Scholar Esophageal distension may also produce repetitive contractions. However, primary peristaltic contractions over a distended esophageal balloon are associated with swallow-induced primary and secondary peristaltic contractions proximal and distal to the balloon22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar and are linked with esophageal propulsive force proximal to the balloon.21Winship WH Zboralske F.F. Esophageal propulsive force: esophageal response to acute obstruction.J Clin Invest. 1967; 46: 1391-1401Crossref PubMed Scopus (39) Google Scholar In the absence of pressure data proximal and distal to the EndoFLIP, the relationship of the anterograde contractions, including ARCs, primary peristalsis, and secondary peristalsis, remains speculative and requires validation. The ARC may represent a novel response to EndoFLIP,2Carlson D.A. Lin Z. Rogers M.C. et al.Utilizing functional lumen imaging probe topography to evaluate esophageal contractility during volumetric distention: a pilot study.Neurogastroenterol Motil. 2015; 27: 981-989Crossref PubMed Scopus (55) Google Scholar possibly restricted to the distended balloon. However, no currently known neural circuit can explain repetitive primary or secondary peristalsis on the esophageal balloon. Balloon distension-induced contractions that are restricted to the balloon are nonpropagating spontaneous “tertiary: contractions22Rao S.S. Gregersen H. Hayek B. et al.Unexplained chest pain: the hypersensitive, hyperreactive, and poorly compliant esophagus.Ann Intern Med. 1996; 124: 950-958Crossref PubMed Scopus (164) Google Scholar that are present as irregular, disorganized, and retrograde contractions.4Carlson D.A. Kahrilas P.J. Ritter K. et al.Mechanisms of repetitive retrograde contractions in response to sustained esophageal distension: a study evaluating patients with post fundoplication dysphagia.Am J Physiol Gastrointest Liver Physiol. 2018; 314: G334-G340Crossref PubMed Scopus (16) Google Scholar The ARC pattern also does not resemble migrating motor complex in which the cluster of contractions moves as a group without any preceding inhibition. The ARC may represent a version of a normal motor pattern. Alternatively, the ARC may provide information on the propulsive force of the esophagus, either relevant to clearing the esophagus of food residues, obstructing solid bolus, or an interesting experimental finding relevant only to pressure dynamics in a fluid-filled obstructing esophageal balloon.25Acharya S. Estimation of mechanical work done to open the esophagogastric junction using functional lumen imaging probe panometry.Am J Physiol Gastrointest Liver Physiol. 2021; 320: G780-G790Crossref PubMed Google Scholar All these important hypotheses are testable and deserve to be validated. Active marketing has led to the clinical use of EndoFLIP for the diagnosis of esophageal motility disorders. However, the results yielded by this technique are not based on the pathophysiologic understanding of esophageal motility disorders, and their significance is unknown. Therefore, the use of this inadequately evaluated,26Massey B.T. Clinical functional lumen probe testing in esophageal disorders: a need for better quality evidence.Am J Gastroenterol. 2020; 115: 1799-1801Crossref PubMed Scopus (3) Google Scholar expensive, and potentially risky technique for the investigation of esophageal motility disorders is not justified.

Targeted Electrical Stimulation of the Superior Laryngeal Nerve – A Potential Treatment for Dysphagia in ALS

Electrical stimulation (ES) is a treatment for swallowing impairment (dysphagia) that uses surface electrodes on the anterior neck to repeatedly contract and strengthen swallowing musculature without evoking swallows. This treatment approach is generally avoided in ALS patients due to concerns over rapid muscle fatigue that may further compromise swallowing, breathing, and airway protection. However, swallowing is a sensorimotor reflex that relies on several “upstream” sensory, motor, and interneuron components that are also affected by ALS. We hypothesize that ES can be optimized for ALS by selectively stimulating the superior laryngeal nerve (SLN) to activate and treat the entire swallow reflex circuitry, rather than only the swallowing muscles. Our rationale is based on general knowledge that SLN stimulation reliably evokes swallowing in experimental studies. Here, our translational work establishes a safe and reliable ES‐SLN protocol in a mouse model of ALS with dysphagia, and then adapts the protocol for use in humans. For protocol development, ALS mice (transgenic SOD1‐G93A) underwent an invasive survival surgery at 6 months of age (clinical disease onset) for 30 minutes of direct ES‐SLN based on our prior work: 40 Hz; anodal, charge balanced rectangular pulses (400 µs pulse width, 400 µs interphase delay); up to 800 uA intensity and continuous trains of 20‐seconds ON, 10‐seconds OFF. Respiratory rate was monitored via an abdominal pneumatic sensor. Swallowing function was assessed via monthly videofluoroscopy. For translation to humans we used a noninvasive transcutaneous ES (tES) approach in five healthy adults (18‐30 years; 3 F, 2 M) using identical stimulus parameters as mice, except with a shorter pulse duration (100 µs pulse width, 25 μs interphase delay) to eliminate perceived muscle fatigue and higher stimulus intensity (up to 10 mA). Physiological monitoring (pulse oximetry, respiratory and heart rate) occurred throughout the 30‐minute session. Results showed that direct ES‐SLN in mice consistently evoked 2‐4 swallows per 20 second stimulus train without decay or adverse effects on respiratory rate (p>0.05). Moreover, this single treatment session nearly preserved lick and swallow rates at disease end stage. In humans, tES‐SLN reliably evoked 3‐6 saliva swallows per 20 second stimulus train without decay or adverse effects on physiological measures (p>0.05). However, trials were successful only in females likely due to differences in male anatomy and electrical impedance that we are troubleshooting. This preliminary work demonstrates ES can be adapted for targeted, noninvasive SLN stimulation to evoke swallowing in humans. Moreover, our preliminary work with ALS mice suggests an untapped therapeutic benefit of ES‐SLN, which provides rationale for proceeding with clinical trials for ALS patients as well as other neurological diseases. Continued investigations in mice will be essential to understand the treatment mechanisms of SLN stimulation for further optimization.

Firing characteristics of swallowing interneurons in the dorsal medulla during physiologically induced swallowing in perfused brainstem preparation in rats

Oropharyngeal swallowing is centrally mediated by a swallowing central pattern generator (Sw-CPG) in the medulla oblongata. The activity of the Sw-CPG depends on the sensory inputs determined by physical and chemical bolus properties. Here we investigate the sensory-motor integration during swallowing arising from different sensory sources. To do so we electrically stimulated the superior laryngeal nerve and we triggered swallowing with oral injections of distilled water or capsaicin solution and extracellularly recorded from swallowing interneurons in arterially perfused brainstem preparations of rats. We recorded the activities of 40 neurons, while monitoring the motor activities of the phrenic, vagal and hypoglossal nerves. Eighteen neurons responded to electrical stimulation of the ipsilateral superior laryngeal nerve, and 6 neurons were excited by oral fluid injection, while 16 non-respiratory neurons did not receive afferent inputs to either electrical or physiological stimuli. The cellular activities displayed by swallowing interneurons during electrical and physiological stimulation of pharyngeal and laryngeal afferent input reveal complex adaptations of the timing of firing patterns and frequencies. The modulation of neuronal activity is likely to contribute to the coordination of efficient bolus transfer during the pharyngeal stage of swallowing.

Investigation of potential neuropharmacological activity of neostigmine-glycopyrrolate for intraoperative neural monitoring in thyroid surgery.

Intraoperative neuromonitoring (IONM) is frequently used in thyroid surgery to reduce recurrent laryngeal nerve injury. The use of neuromuscular blockade agent to facilitate tracheal intubation, is a common cause of IONM failure. We performed a retrospective analysis to assess the efficacy of neostigmine-glycopyrrolate as a neuromuscular blockade reversal agent for IONM during thyroid surgery. Rocuronium (0.6mg/kg) was administered for muscle relaxation. Neostigmine (2mg) and glycopyrrolate (0.4mg) were administered immediately after intubation. Cricothyroid muscle-twitch response upon external branch of superior laryngeal nerve stimulation and electromyography amplitudes of vagal and recurrent laryngeal nerves before (V1, R1) and after thyroid resection (V2, R2) were recorded. Fifty patients (23 males, 27 females) were included in the analysis. The diagnoses comprised 43 papillary thyroid carcinomas and seven benign diseases. The mean time between rocuronium injection and neostigmine-glycopyrrolate injection was 5.1 ± 1.2min, and the mean time from neostigmine-glycopyrrolate injection to successful cricothyroid muscle twitching upon external branch of superior laryngeal nerve stimulation was 21.0 ± 4.5min. All patients had V1 and R1 amplitudes of more than 500 μV each, with mean V1 and R1 amplitudes of 985.3 ± 471.6μV and 1177.2 ± 572.7μV, respectively. Neostigmine-glycopyrrolate was effectively used as a neuromuscular blockade reversal agent for IONM in thyroid surgeries without a significant increase in bucking events. Administration of neostigmine-glycopyrrolate immediately after intubation can be recommended for successful NMB reversal to facilitate IONM during thyroid surgery.

Perceptual Evaluation of Vocal Fold Vibratory Asymmetry

Laryngeal vibratory asymmetry occurring with paresis may result in a perceptually normal or abnormal voice. The present study aims to determine the relationships between the degree of vibratory asymmetry, acoustic measures, and perception of sound stimuli. Animal Model of Voice Production, Perceptual Analysis of Voice. In an in vivo canine model of phonation, symmetric and asymmetric laryngeal vibration were obtained via graded unilateral recurrent laryngeal nerve (RLN) stimulation simulating near paralysis to full activation. Phonation was performed at various contralateral RLN and bilateral superior laryngeal nerve stimulation levels. Naïve listeners rated the perceptual quality of 182 unique phonatory samples using a visual sort-and-rate task. Cepstral peak prominence (CPP) was calculated for each phonatory condition. The relationships among vibratory symmetry, CPP, and perceptual ratings were evaluated. A significant relationship emerged between RLN stimulation and perceptual rating, such that sound samples from low RLN levels were preferred to those from high RLN levels. When symmetric vibration was achieved at mid-RLN stimulation, listeners preferred samples from symmetric vibration over those from asymmetric vibration. However, when symmetry was achieved at high RLN levels, a strained voice quality resulted that listeners dispreferred over asymmetric conditions at lower RLN levels. CPP did not have a linear relationship with perceptual ratings. Laryngeal vibratory asymmetry produces variable perceptual differences in phonatory sound quality. Though CPP has been correlated with dysphonia in previous research, its complex relationship with quality limits its usefulness as clinical marker of voice quality perception. NA, basic science Laryngoscope, 131:2740-2746, 2021.

Chronic Electrical Stimulation of the Superior Laryngeal Nerve in the Rat: A Potential Therapeutic Approach for Postmenopausal Osteoporosis.

Electrical stimulation of myelinated afferent fibers of the superior laryngeal nerve (SLN) facilitates calcitonin secretion from the thyroid gland in anesthetized rats. In this study, we aimed to quantify the electrical SLN stimulation-induced systemic calcitonin release in conscious rats and to then clarify effects of chronic SLN stimulation on bone mineral density (BMD) in a rat ovariectomized disease model of osteoporosis. Cuff electrodes were implanted bilaterally on SLNs and after two weeks recovery were stimulated (0.5 ms, 90 microampere) repetitively at 40 Hz for 8 min. Immunoreactive calcitonin release was initially measured and quantified in systemic venous blood plasma samples from conscious healthy rats. For chronic SLN stimulation, stimuli were applied intermittently for 3–4 weeks, starting at five weeks after ovariectomy (OVX). After the end of the stimulation period, BMD of the femur and tibia was measured. SLN stimulation increased plasma immunoreactive calcitonin concentration by 13.3 ± 17.3 pg/mL (mean ± SD). BMD in proximal metaphysis of tibia (p = 0.0324) and in distal metaphysis of femur (p = 0.0510) in chronically SLN-stimulated rats was 4–5% higher than that in sham rats. Our findings demonstrate chronic electrical stimulation of the SLNs produced enhanced calcitonin release from the thyroid gland and partially improved bone loss in OVX rats.

Suppression of the Swallowing Reflex during Rhythmic Jaw Movements Induced by Repetitive Electrical Stimulation of the Dorsomedial Part of the Central Amygdaloid Nucleus in Rats.

A previous study indicated that the swallowing reflex is inhibited during rhythmic jaw movements induced by electrical stimulation of the anterior cortical masticatory area. Rhythmic jaw movements were induced by electrical stimulation of the central amygdaloid nucleus (CeA). The swallowing central pattern generator is the nucleus of the solitary tract (NTS) and the lateral reticular formation in the medulla. Morphological studies have reported that the CeA projects to the NTS and the lateral reticular formation. It is therefore likely that the CeA is related to the control of the swallowing reflex. The purpose of this study was to determine if rhythmic jaw movements driven by CeA had inhibitory roles in the swallowing reflex induced by electrical stimulation of the superior laryngeal nerve (SLN). Rats were anesthetised with urethane. The SLN was solely stimulated for 10 s, and the swallowing reflex was recorded (SLN stimulation before SLN + CeA stimulation). Next, the SLN and the CeA were electrically stimulated at the same time for 10 s, and the swallowing reflex was recorded during rhythmic jaw movements (SLN + CeA stimulation). Finally, the SLN was solely stimulated (SLN stimulation following SLN + CeA stimulation). The number of swallows was reduced during rhythmic jaw movements. The onset latency of the first swallow was significantly longer in the SLN + CeA stimulation than in the SLN stimulation before SLN + CeA stimulation and SLN stimulation following SLN + CeA stimulation. These results support the idea that the coordination of swallowing reflex with rhythmic jaw movements could be regulated by the CeA.

Effects of Arytenoid Adduction Suture Position on Voice Production and Quality.

Arytenoid adduction (AA) is performed to treat unilateral vocal fold paralysis with a large posterior glottal gap. However, the voice effects of AA suture position remain unclear. This study aimed to evaluate voice production and quality as a function of AA suture position on the thyroid ala in a neuromuscularly intact in vivo larynx. Animal model. Unilateral recurrent laryngeal nerve and vagal paralysis were modeled in two canines. AA suture position was varied across five equidistant positions on the anterior inferior thyroid ala, from a paramedian position anteriorly to the oblique line posteriorly. Phonation was performed over 8 × 8 graded level combinations of recurrent and superior laryngeal nerve stimulation per suture position. The primary outcome was percent successful phonatory conditions. Secondary outcomes included fundamental frequency (F0), phonation onset pressure (PTP), cepstral peak prominence (CPP), and laryngeal posture. Anterior suture positions resulted in a greater percentage of successful phonatory conditions compared to posterior sutures. Suture position 2, located at the anterior inferior thyroid ala, resulted in the highest percentage of successful phonatory conditions, lowest PTP, and lower muscle activation levels to achieve higher CPP. Posterior sutures resulted in wider glottal gap and more effective F0 and vocal fold strain increase with cricothyroid muscle contraction, but with fewer successful phonatory conditions and higher PTP. Trends were consistent across both paralysis types. AA suture placed in the anterior inferior thyroid ala resulted in the best acoustic, aerodynamic, and voice quality outcomes. This study provides scientific evidence for maintaining current clinical practice. NA Laryngoscope, 131:846-852, 2021.

Codeine Asymmetrically Inhibits The Laryngeal Adductor Reflex

The laryngeal adductor reflex (LAR) is a fundamental airway protective behavior that prevents penetration of material from the upper airway into the trachea. Aspiration risk increases in humans after a single dose of an opioid and pneumonia is a common occurrence in opioid users. The LAR consists of a short latency (~10 ms), short duration (~10 ms) burst (R1) and a longer latency (~40ms) burst (R2) in laryngeal electromyogram (EMG) activity. The R1 LAR is thought to be primarily a brainstem reflex. We hypothesized that systemic administration of codeine, one of the most commonly prescribed opioids, would suppress the R1 LAR in an animal model that robustly expresses airway protective behaviors. The LAR was elicited in anesthetized, spontaneously breathing cats (n=13) by electrical stimulation (2 Hz, 0.1 ms pulse duration) of the superior laryngeal nerve (SLN) or mechanical stimulation of the vocal folds with a von Frey filament. Bilateral thyroarytenoid (TA) and midline posterior cricoarytenoid (PCA) muscle electromyograms (EMGs) were recorded. The R1 LAR manifested as a short latency (approx. 10 ms) evoked response consisting of peaks and troughs in both the TA and the PCA EMGs. Codeine (0.1–10 mg/kg, iv) dose dependently inhibited the magnitude of the contralateral TA and PCA LAR by approximately 60% but had no significant effect on the LAR in the ispilateral TA EMG. Similar lateralization of the effect of codeine was observed in animals in which the LAR was elicited by mechanical stimulation of the vocal folds. These effects were similar in animals whether only one or both SLNs were sectioned. In separate animals, the codeine dose response was conducted after pretreatment with the NMDA antagonist, MK‐801 (10 μg/kg) via the vertebral artery. MK‐801 enabled depression of the TA LAR on the ipsilateral side by iv codeine, but did not enhance the reduction in the contralateral TA or PCA LAR relative to animals that only received this opioid. These findings support lateralized suppression of the LAR by opioids that is mediated by central NMDA receptors. The differing effects of codeine on the LAR in the PCA and ipsilateral TA EMGs suggest that opioids may disrupt laryngeal protective actions through asymmetric positioning of the vocal folds.Support or Funding InformationSupported by NIH HL131716 and 3OT2OD023854

Anterior laryngeal electrodes for recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: New expanded options for neural monitoring.

Intraoperative neural monitoring is a useful adjunct for the laryngeal nerve function assessment during thyroid and parathyroid surgery. Typically, monitoring is performed by measurement of electromyographic responses recorded by endotracheal tube (ETT) surface electrodes. Tube position alterations during surgery can cause displacement of the electrodes relative to the vocal cords, leading to false positive loss of signal. Numerous reports have denoted monitoring equipment-related issues, especially endotracheal tube displacement, as the dominant source of false positive error. The false positive error may result in inappropriate decisions by the surgeon. This study tests the hypothesis that anterior laryngeal electrodes (ALEs) can help reduce this error. Placement of ALEs directly onto the thyroid cartilage represent an adjunctive and possible alternative method to standard ETT surface electrodes. Retrospective review. Fifteen consecutive patients undergoing thyroid and parathyroid surgery with intraoperative neuromonitoring using both ETT electrodes and ALEs were studied. Data collected included site of neural stimulation, laterality, and electromyographic parameters. With vagal and recurrent laryngeal nerve stimulation, the ALEs recorded mean vocalis muscle waveform amplitude within 83% of that recorded with standard ETT electrodes. The latency measurements with the anterior laryngeal and endotracheal electrodes were similar, with both electrodes recording significantly longer latency for the left vagus nerve as compared to the right vagus nerve. With superior laryngeal nerve stimulation, the ALEs recorded a 800% greater mean amplitude than the ETT electrodes. The ALEs demonstrated similar sensitivity to stimulation at low current as ETT electrodes and provided stable intraoperative monitoring information. Compared to ETT surface electrodes, the ALEs provide similar and stable electromyographic responses with equal sensitivity for recording evoked responses during neural monitoring in thyroid and parathyroid surgery. The ALEs offer significantly more robust monitoring of the external branch of the superior laryngeal nerve. Furthermore, ALEs are contained within the operative field, are totally surgeon controlled, and are unaffected by the potential vicissitudes of ETT position during surgery. 4 Laryngoscope, 128:2910-2915, 2018.

Original Research: Aerosolized Lidocaine: Effective for Safer Arousal After Suspension Laryngoscopy

To examine the systemic and local effects of the lidocaine on the larynx and trachea which is applied after the end of the surgery and through various application methods. Randomized controlled prospective study. The study is composed of patients who underwent suspension laryngoscopy (SL) for benign laryngeal diseases (cysts, polyp, granuloma, etc) and American Society of Anesthesiologists (ASA) I, between January 2017 and January 2018. The patients were randomly divided into 3 groups. In the first group nothing is applied at the end of the surgery and called as control group, second group received 7 pufs of aerosolized 10% lidocaine solution (70 mg) over larynx and trachea and third group received cotton swaps that impregnated in 1 ml of 20 mg lidocaine solution over surgical area for 1 minutes. Operation and arousal times, heart rate and mean arterial blood pressure levels were noted and compared. Also laryngospasm, cough, and agitation scores were obtained during arousal. 64 patients were included in the study. Laryngospasm was not observed in any of the patients. In group 2 (aerosolized lidocaine group), patients' blood pressure remained similar while increased in other groups (P < 0.05). Agitation scores were significantly lower in group 2 compared to the other groups (P = 0.012). Cough reflex is observed less in group 2 but result was not statistically significant (P = 0.13) CONCLUSION: The usage of aerosolized lidocaine after suspension laryngoscopy is very effective in blocking the stimulation of superior laryngeal nerve and sympathetic nerves which were responsible for the pressor reflexes. The inhibition of these reflexes before or during arousal could secure a safer arousal.

Unearthing a consistent bilateral R1 component of the laryngeal adductor reflex in awake humans.

The laryngeal adductor reflex (LAR) is an essential tracheobronchial protective mechanism resulting in vocal fold adduction to laryngeal stimulation. It was thought to consist of an early ipsilateral R1 component and a later, bilateral but highly centrally modulated R2 component. We recently demonstrated that bilateral R1 responses are robustly present in humans under general anesthesia. We herein give evidence that the R1 response is also bilateral in awake humans and is likely the primary component responsible for initiating the LAR. Seven volunteers were included (3 males, 4 females). The reflex was elicited by direct percutaneous monopolar needle stimulation of the internal superior laryngeal nerve. Electromyography traces from bilateral lateral cricoarytenoid muscles were recorded using hookwire electrodes. Reflex responses to variations in stimulus intensity and duration were evaluated. Bilateral R1 responses were recorded in all patients, even during deep inspiration when the vocal folds were maximally abducted. R1, but not R2, responses increased linearly in amplitude, with sequential increases in both stimulation intensity (1-8 mA) and duration (100-500 µsec) (Pearson correlation 0.94). Contradicting over 40 years of research, we demonstrate that the R1 LAR component is consistently bilateral in awake humans. It increases linearly with stimulus intensity and is unaffected by conscious state suggesting minimal central control. These findings may provide a means to objectively stratify patients for risk of laryngeal aspiration, even in unconscious states, and its potentially cardinal role in disease states such as laryngospasm and sudden infant death needs to be reevaluated. 4. Laryngoscope, 2581-2587, 2018.

Effect of peripherally and cortically evoked swallows on jaw reflex responses in anesthetized rabbits

This study aimed to investigate whether the jaw-opening (JOR) and jaw-closing reflexes (JCR) are modulated during not only peripherally, but also centrally, evoked swallowing. Experiments were carried out on 24 adult male Japanese white rabbits. JORs were evoked by trigeminal stimulation at 1 Hz for 30 s. In the middle 10 s, either the superior laryngeal nerve (SLN) or cortical swallowing area (Cx) was simultaneously stimulated to evoke swallowing. The peak-to-peak JOR amplitude was reduced during the middle and late 10-s periods (i.e., during and after SLN or Cx stimulation), and the reduction was dependent on the current intensity of SLN/Cx stimulation: greater SLN/Cx stimulus current resulted in greater JOR inhibition. The reduction rate was significantly greater during Cx stimulation than during SLN stimulation. The amplitude returned to baseline 2 min after 10-s SLN/Cx stimulation. The effect of co-stimulation of SLN and Cx was significantly greater than that of SLN stimulation alone. There were no significant differences in any parameters of the JCR between conditions. These results clearly showed that JOR responses were significantly suppressed, not only during peripherally evoked swallowing but also during centrally evoked swallowing, and that the inhibitory effect is likely to be larger during centrally compared with peripherally evoked swallowing. The functional implications of these results are discussed.

Contribution of intraoperative neuromonitoring to the identification of the external branch of superior laryngeal nerve.

We evaluated the contribution of intraoperative neuromonitoring to the visual and functional identification of the external branch of the superior laryngeal nerve. The prospectively collected data of patients who underwent thyroid surgery with intraoperative neuromonitoring for external branch of the superior laryngeal nerve exploration were assessed retrospectively. The surface endotracheal tube-based Medtronic NIM3 intraoperative neuromonitoring device was used. The external branch of the superior laryngeal nerve function was evaluated by the cricothyroid muscle twitch. In addition, contribution of external branch of the superior laryngeal nerve to the vocal cord adduction was evaluated using electromyographic records. The study included data of 126 (female, 103; male, 23) patients undergoing thyroid surgery, with a mean age of 46.2±12.2 years (range, 18-75 years), and 215 neck sides were assessed. Two hundred and one (93.5%) of 215 external branch of the superior laryngeal nerves were identified, of which 60 (27.9%) were identified visually before being stimulated with a monopolar stimulator probe. Eighty-nine (41.4%) external branch of the superior laryngeal nerves were identified visually after being identified with a probe. Although 52 (24.1%) external branch of the superior laryngeal nerves were identified with a probe, they were not visualized. Intraoperative neuromonitoring provided a significant contribution to visual (p<0.001) and functional (p<0.001) identification of external branch of the superior laryngeal nerves. Additionally, positive electromyographic responses were recorded from 160 external branch of the superior laryngeal nerves (74.4%). Intraoperative neuromonitoring provides an important contribution to visual and functional identification of external branch of the superior laryngeal nerves. We believe that it can not be predicted whether the external branch of the superior laryngeal nerve is at risk or not and the nerve is often invisible; thus, intraoperative neuromonitoring may routinely be used in superior pole dissection. Glottic electromyography response obtained via external branch of the superior laryngeal nerve stimulation provides quantifiable information in addition to the simple visualization of the cricothyroid muscle twitch.

Innervation of the human posterior cricoarytenoid muscle by the external branch of the superior laryngeal nerve.

The posterior cricoarytenoid muscle is the abductor muscle for the vocal cords and is innerved by the recurrent laryngeal nerve (RLN). The purpose of this study was to present our determination if the external branch of the superior laryngeal nerve (SLN) contributes to the motor innervation of the posterior cricoarytenoid muscle. We performed electromyographies (EMGs) via needle electrodes on 47 posterior cricoarytenoid muscles from 28 patients during thyroidectomy (9 lobectomies and 19 total thyroidectomies) with intraoperative neural monitoring. The RLN, vagus nerve, and external branch of the SLN were stimulated intraoperatively and the responses were evaluated by EMG. Positive EMG responses were obtained from 16 (34%) of 47 posterior cricoarytenoid muscles after external branch of the SLN stimulation. The EMG of the posterior cricoarytenoid muscle was unilaterally positive in 8 of 19 patients (42%) with total thyroidectomy, and 2 of 19 patients (10.5%) were bilaterally positive. The external branch of the SLN contributes to the ipsilateral posterior cricoarytenoid muscle innervation in one-third of the cases. This contribution is usually unilateral, but is occasionally bilateral.

Cannabinoids facilitate the swallowing reflex elicited by the superior laryngeal nerve stimulation in rats.

Cannabinoids facilitate the swallowing reflex elicited by the superior laryngeal nerve stimulation in rats.

Frequency Dependent Inhibitory Mechanisms Controlling the Laryngeal Adductor Response (LAR)

Electrical stimulation of the superior laryngeal nerve (SLN) has been used to induce behaviors with airway protective components, such as the LAR. The LAR has both short (R1) and long latency (R2) peaks in response to stimulation, but the neuronal pathways that produce and modulate the LAR are not well understood. It has been reported that there exists a frequency‐dependent suppression of R2 for SLN stimulation frequencies above 2.5 Hz. The R1 can follow frequencies of electrical stimulation of the SLN approaching 200 Hz, suggesting a high fidelity of brainstem neuronal pathways, but to our knowledge there is no report on whether R1 exhibits frequency‐dependent depression. We hypothesized that the R1 would exhibit frequency‐dependent depression consistent with the existence of modulatory short latency inhibitory mechanisms. To test this hypothesis, we monitored EMG activity from the thyroarytenoid (TA) muscle and electrically stimulated the SLN unilaterally with a range of frequencies between 1 and 40 Hz. All frequencies employed induced both repetitive swallowing and LAR. The R1 peak of the LAR was time‐locked to each stimulus pulse (peak R1 latencies were 13.7±0.5 ms (5–10 Hz) and 14.2±0.6 ms (35–40 Hz)), and the R2 peak was not observed. Lower frequency stimulations (5–10 Hz) of the SLN elicited significantly higher LAR amplitudes (52.8 ±2.9 % max) than higher frequency stimulations (35–40 Hz; 36.8±3.2 % max). In other experiments, analysis of neuronal responses recorded in the ventral respiratory column revealed evidence of stimulus‐induced synchrony as well as disruption of concurrent functional relationships among respiratory‐modulated neurons. These observations suggest that more complex regulatory mechanisms exist in addition to frequency‐dependent depression of the LAR.Support or Funding InformationSupported by NIH HL 103415, HL 111215, HL109025.