Stimulation Of Laryngeal Nerve Research Articles

Normative electromyography data and influencing factors in intraoperative neuromonitoring using adhesive skin electrodes during thyroid surgery.

Skin electrodes have been reported to be a useful alternative recording method for intraoperative neuromonitoring (IONM) and show typical electromyography (EMG) waveforms while overcoming the shortcomings of the EMG endotracheal tube. However, the skin electrodes showed relatively lower evoked amplitudes than other recording methods. In this study, we analyzed normative EMG data using skin electrodes and factors that affect the evoked amplitude of thyroid IONM. In total, 167 patients [242 nerves at risk (NAR)] who underwent thyroidectomy under IONM with adhesive skin electrodes were analyzed. A pair of skin electrodes was attached to the lateral border of the lamina of the thyroid cartilage. Evoked EMG data, including mean amplitude and latency, obtained after stimulation of the recurrent laryngeal nerve (RLN) and vagus nerve (VN), were collected and analyzed. The mean amplitudes of RLN and VN recorded via skin electrodes were 255.48±96.53 and 236.15±69.72 μV, respectively. The mean latency of the right and left RLN was 3.22±0.03 and 3.49±0.08 mS, respectively. The mean latency of the right and left VN was 5.37±0.80 and 7.57±0.10 mS, respectively. The mean amplitude was significantly lower in the obesity, male, and total thyroidectomy (TT) groups. As body mass index (BMI) and age increased, the amplitude of EMG tended to decrease significantly. The evoked amplitude recorded with the skin electrodes was relatively low. A larger surgical extent, obesity, male sex, and age >55 years showed significantly lower evoked amplitudes.

Modulation of the swallowing reflex by stimulation of the gigantocellular reticular nucleus in the rat

ObjectivesThe gigantocellular reticular nucleus (Gi) projects to the nuclues of the solitary tract nucleus (NTS) and the lateral reticular formation (LRF) above the nucleus ambiguus. The swallowing central pattern generator comprises the NTS and the LRF. The present study examined whether stimulation of the Gi affects the swallowing reflex. MethodsExperiments were performed on urethane-anesthetized rats. The swallowing reflex was evoked by repetitive electrical stimulation of the superior laryngeal nerve and responses were recorded from the mylohyoid muscle on an electromyogram. The Gi was stimulated electrically. In addition, glutamate was injected into the Gi. The Friedman's test, followed by the Wilcoxon signed-rank test with Bonferroni correction, were used to assess the effects of electrical stimulation of the Gi. The Wilcoxon signed-rank test was used to assess the effects of glutamate injection into the Gi. Differences were considered significant at the P < 0.05 level. ResultsThe number of swallows was significantly increased or decreased by electrical stimulation of the Gi or after injection of glutamate into the Gi. In both electrical stimulation of the Gi and injection of glutamate into the Gi, the onset latency of the first swallow was prolonged when the number of swallows was decreased but showed no change when the number of swallows was increased. ConclusionsThe present results suggest that the Gi is involved in the control of swallowing.

Sustained Effects of Capsaicin Infusion into the Oropharynx on Swallowing in Perfused Rats.

To examine the sustained effects of oropharyngeal capsaicin stimulation on the regulation of swallowing, we recorded the swallowing-related nerve activities during continuous infusion of capsaicin solution into the oropharynx. In 33 in situ perfused brainstem preparation of rats, we recorded the activities of the vagus, hypoglossal, and phrenic nerves during fictive swallowing. The interburst intervals (IBIs) of the swallowing-related nerves during sequential pharyngeal swallowing (sPSW) elicited by electrical stimulation of the superior laryngeal nerve (SLN) during concurrent capsaicin stimulation of 10, 1, and 0.1 μM (n = 28) were compared with those during oropharyngeal infusion of saline (control) (n = 5). The IBIs during SLN-induced sPSW were reduced at 5 min after initiation of continuous infusion of 10 and 1 μM capsaicin solution. The IBIs showed significant decreases to -25.8 ± 6.9%, -25.9 ± 5.3, -18.3 ± 3.7, and -12.0 ± 1.6 at 30 min following 1 μM capsaicin stimulation at SLN stimulus conditions at 5 Hz of 1.2 times threshold, 10 Hz of 40 μA, 5 Hz of 60 μA, and 10 Hz of 60 μA, respectively. Continuous capsaicin stimulation of 0.1 μM solution did not show significant sustained effects. Pharmacological stimulation of capsaicin could provide time-dependent effects on the likelihood of swallowing, particularly subserving sustained facilitation of swallowing reflex with appropriate concentration of capsaicin. NA Laryngoscope, 134:305-314, 2024.

Atropine facilitates water-evoked swallows via central muscarinic receptors in anesthetized rats.

Anticholinergic medication causes impaired swallowing with hyposalivation. However, the underlying mechanisms by which these drugs modulate the swallowing reflex remain unclear. This study investigated the effects of the muscarinic acetylcholine receptor (mAChR) nonspecific antagonist atropine on the initiation of swallowing. Experiments were performed on 124 urethane-anesthetized rats. A swallow was evoked by either topical laryngeal application of a small amount of distilled water (DW), saline, citric acid, or capsaicin; upper airway distention with a continuous airflow; electrical stimulation of the superior laryngeal nerve (SLN); or focal microinjection of N-methyl-d-aspartate (NMDA) into the lateral region of the nucleus of the solitary tract (L-nTS). Swallows were identified by electromyographic bursts of the digastric and thyrohyoid muscles. Either atropine, the peripheral mAChR antagonist methylatropine, or antagonists of mAChR subtypes M1-M5 were intravenously delivered. Atropine at a dose of 1 mg/kg increased the number of DW-evoked swallows compared with baseline and did not affect the number of swallows evoked by saline, citric acid, capsaicin, or upper airway distention. Methylatropine and M1-M5 antagonists did not significantly change the number of DW-evoked swallows. Bilateral SLN transection completely abolished DW-evoked swallows, and atropine decreased the swallowing threshold of SLN electrical stimulation. Finally, microinjection of NMDA receptor antagonist AP-5 into the L-nTS inhibited DW-evoked swallows, and atropine facilitated the initiation of swallowing evoked by NMDA microinjection into this region. These results suggest that atropine facilitates DW-evoked swallows via central mAChR actions.NEW & NOTEWORTHY Atropine facilitated the distilled water (DW)-evoked swallows in anesthetized rats. Atropine decreased the swallowing threshold evoked by electrical stimulation of the superior laryngeal nerve, which is a primary sensory nerve for the initiation of DW-evoked swallows. Atropine facilitated the swallows evoked by N-methyl-d-aspartate microinjection into the lateral region of the nucleus of the solitary tract, which is involved in the DW-evoked swallows. We speculate that atropine facilitates the DW-evoked swallows via central muscarinic receptor actions.

Response patterns of NTS neurons during electrical stimulation of the superior laryngeal nerve: Influence of codeine

Electrical or mechanical activation of laryngeal afferents elicits the laryngeal adductor reflex (LAR), an airway defensive behavior that adducts the vocal folds to protect the airway from aspiration. This behavior is mediated, in part, by neurons in the NTS (nucleus of the solitary tract) and is sensitive to suppression by codeine. We hypothesized that NTS neuron responses to electrical stimulation of the superior laryngeal nerve (SLN) would be reduced by codeine, consistent with an action of the drug at this level of the brainstem to suppress the LAR. We recorded extracellular activity of multiple NTS neurons simultaneously in three anesthetized, spontaneously breathing cats using multiple microelectrode arrays. We also recorded bilateral EMG activity of upper airway and chest wall muscles. The neurons were tested with electrical stimulation of the SLN (2 Hz, 0.1 ms pulse duration, 1.5X threshold for inducing the LAR) during vehicle and a cumulative dose response to codeine (0.1-10.0 mg/kg iv). A total of 35 NTS neurons were recorded; some were identified as premotor to laryngeal or upper airway motoneuron pools by spike triggered averaging. Prior to codeine administration, approximately 30% of cells had short latency excitatory responses to electrical stimulation of the SLN; no inhibitory responses were observed. After codeine doses, changes in spontaneous activity were observed in most neurons (~80%). In response to codeine, both enhancement and suppression of short latency excitatory responses were observed in cells that were excited by SLN stimulation during vehicle. The data support complex actions of codeine on NTS neurons that do not easily account for opioid-suppression of the LAR. T32 HL134621, and NIH HL155721 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Optical imaging of neurons related to fictive swallowing using GCaMP6f in an arterially perfused rat preparation

ObjectiveIt is difficult to comprehensively study the activity patterns and distribution of neurons in the brainstem that control the act of swallowing, as they are located deep in the brain. In this study, we aimed to evaluate the usefulness of calcium imaging using GCaMP6f in arterially perfused preparations to study the activity of swallowing-related neurons in the brainstem. MethodsArterially perfused rat preparations were prepared 3–4 weeks after the injection of a neuron-specific virus expressing GCaMP6f. Fictive swallowing was induced by repetitive electrical stimulation of the superior laryngeal nerve (SLN). Simultaneously, the activity of GCaMP6f-expressing neurons in the dorsal brainstem, between 0.1 and 4.8 mm rostral to the obex, was assessed by changes in the intracellular calcium concentration using confocal laser microscopy. ResultsNeurons responding to stimulation of the SLN included swallowing-related neurons (48%), which showed an increase in fluorescence intensity at the time of swallowing bursts in the cervical vagus nerve, and stimulation-related neurons (52%), which showed an increase in fluorescence intensity through stimulation, regardless of the swallowing bursts. Despite a broad search area, swallowing-related neurons were localized exclusively in and around the solitary nucleus. In contrast, most stimulation-related neurons were located in the brainstem reticular formation, which is more rostral than the solitary nucleus. ConclusionsCalcium imaging using GCaMP in arterially perfused rat preparations is useful for an efficient search of the activity pattern and distribution of neurons located in a wide area of the brainstem.

The advantage of the combined use of intraoperative neuromonitoring and percutaneous ultrasonography of the larynx as a screening for postoperative vocal cord paresis

Background. One of the most common complications during thyroid surgery after hypoparathyroidism is a violation of the mobility of the vocal folds - paresis or paralysis of the larynx. The incidence of damage to the recurrent laryngeal nerves during primary surgical interventions can vary from 1 to 30%. Intraoperative neuromonitoring is the most effective method to reduce the amount of damage to the laryngeal nerves during surgical interventions on the thyroid and parathyroid glands. Assessment of the state of the vocal cords in the preoperative and postoperative period is crucial. In the preoperative period, this helps establish baseline characteristics and identify pre-existing laryngeal paresis, while postoperative early identification of vocal cord paresis helps develop a rapid treatment plan. Indirect laryngoscopy is still considered the reference standard for vocal cord examination. The main advantage is the ability to visualize the vocal cords in 99% of cases. However, this is an invasive procedure that can be painful and uncomfortable for patients, and increases medical costs and lead time.Materials and methods. The results of intraoperative neuromonitoring were analyzed in 25 patients who underwent total thyroidectomy according to indications (diffuse nodular non-toxic goiter — 17 patients (68%), diffuse nodular toxic goiter — 4 patients (16%), autoimmune thyroiditis, diffuse — nodular form — 4 patients (16%)), from September 2021 to February 2022. The patients’ age ranged from 18 to 73 years. There were 23 women (92%), men — 2 (8%). In the study, a C2 neuromonitor (InoMed, Germany), an electrode for EMG recording on an endotracheal tube, and a bipolar forked stimulating probe were used. To assess the mobility of the vocal folds, all patients underwent percutaneous ultrasonography before and after thyroid surgery.Results and discussion. In 20 patients (80%) before surgery on transcutaneous ultrasound of the larynx, the visualization of the structures of the larynx was good (grade 4-5), in 2 male patients (8%), the visualization of the structures of the larynx was satisfactory (grade 3), in 3 women (older than 45 years (12%)) — visualization of the structures of the larynx was satisfactory (grade 3), in all 25 patients (100%) — complete or normal symmetrical movement of the vocal folds (grade I). During the performance of precision extrafascial thyroidectomy in 3 patients (12%), a decrease in the amplitude of oscillations was recorded during stimulation of the left recurrent laryngeal nerve and the left vagus nerve, in order to prevent bilateral paresis of the larynx, it was decided to confine ourselves to hemithyroidectomy followed by a staged right-sided hemithyroidectomy. A day after the performed left-sided hemithyroidectomy, percutaneous ultrasound of the larynx in 2 patients showed a violation of the mobility of the vocal fold on the left (grade II), in 1 patient — symmetrical movement of the vocal folds (grade I) — a false positive reaction. In 22 patients (88%) who underwent total thyroidectomy on percutaneous ultrasound of the larynx, complete or normal symmetrical movement of the vocal folds (I degree).Conclusion. Intraoperative neuromonitoring is an effective tool to localize the recurrent laryngeal nerves regardless of whether a loss of signal (LOS) has occurred, as well as to determine the type of LOS (LOS 1, LOS 2) and staged thyroidectomy in the presence of LOS. Percutaneous vocal cord ultrasonography is currently an effective screening tool, saving 80% of patients from unnecessary invasive laryngoscopy. The complex of these methods should be an obligatory component in surgical interventions on the thyroid and parathyroid glands.

Stimulation of the center of the lateral reticular nucleus suppresses the swallowing reflex in rats

Morphological studies have demonstrated that the lateral reticular nucleus (LRt) receives fibers projected from sites that are related to control of the swallowing reflex. Although the LRt may therefore be related to control of the swallowing reflex, the functional role of the LRt in the swallowing reflex remains unknown. The present study examined whether the swallowing reflex is modulated by stimulation of the LRt. These experiments were performed on rats anesthetized by urethane. The swallowing reflex was evoked by repetitive electrical stimulation of the superior laryngeal nerve (SLN) and was identified by electromyographic activities from the mylohyoid muscle. Electrical stimulation was applied to the LRt or glutamate was injected into the LRt. The number of swallows was reduced, and the latency of the onset of the first swallow was increased during electrical stimulation near the middle of the rostrocaudal direction of the LRt. The number of swallows was reduced, and the latency of onset of the first swallow increased after microinjection of glutamate near the rostrocaudal center of the LRt. The present study suggests that the LRt is involved in control of the swallowing reflex.

Involvement of ghrelin in the regulation of swallowing motor activity in an arterially perfused rat preparation

Ghrelin, a peripheral peptide produced in the stomach, is involved in the neural networks that control food intake. Alterations in motor components, such as swallowing, are believed to be significant in the regulation food intake by orexigenic signals. However, there has been no detailed investigation of the relationship between ghrelin and swallowing activities induced in motor nerves innervating the pharyngeal and laryngeal muscles. In this study, we examined the effects of ghrelin administration on swallowing motor activity in arterially perfused rats. Injection of distilled water (0.5 ml) into the oral cavity or electrical stimulation of the superior laryngeal nerve evoked swallowing motor activity in the cervical vagus nerve. Administration of ghrelin (6 nM), but not des-acylated ghrelin (6 nM), into the perfusate increased the peak burst amplitude and burst duration, and shortened the first burst interval of water injection-induced swallowing. These ghrelin-induced changes in swallowing motor activity were blocked by the administration of JMV2959 (6 µM), a growth hormone secretagogue receptor antagonist. In preparations in which the hypothalamus was removed, ghrelin had no effect on swallowing motor activity. Furthermore, ghrelin-induced changes were counteracted by the administration of BIBO3304 (1 µM) or L-152,804 (1 µM), antagonists of neuropeptide Y Y1 and Y5 receptors, respectively, which are essential for ghrelin-induced enhancement of food intake. Ghrelin also increased the peak burst amplitude and burst duration of the swallowing motor activity evoked by electrical stimulation of the superior laryngeal nerve, although the effects of ghrelin on the number of swallowing bursts and burst intervals varied with stimulus intensity. These results suggest that ghrelin enhances the magnitude and frequency of bursts of swallowing motor activity by acting via the hypothalamic neural network, and that neuropeptide Y Y1 and Y5 receptors are involved in this enhancement.

Effect of pharmacological inhibition of the pontine respiratory group on swallowing interneurons in the dorsal medulla oblongata

ObjectivesTo examine the role of neurons of the pontine respiratory group (PRG) overlapping with the Kölliker-Fuse nucleus in the regulation of swallowing, we compared the activity of swallowing motor activities and interneuron discharge in the dorsal swallowing group in the medulla before and after pharmacological inhibition of the PRG. MethodsIn 23 in situ perfused brainstem preparation of rats, we recorded the activities of the vagus (VNA), hypoglossal (HNA), and phrenic nerves (PNA), and swallowing interneurons of the dorsal medulla during fictive swallowing elicited by electrical stimulation of the superior laryngeal nerve or oral water injection. Subsequently, respiratory- and swallow-related motor activities and single unit cell discharge were assessed before and after local microinjection of the GABA-receptor agonist muscimol into the area of PRG ipsilateral to the recording sites of swallowing interneurons. ResultsAfter muscimol injection, the amplitude and duration of swallow-related VNA bursts decreased to 71.3 ± 2.84 and 68.1 ± 2.76 % during electrically induced swallowing and VNA interburst intervals during repetitive swallowing decreased. Similar effects were observed for swallowing-related HNA. The swallowing motor activity was similarly qualitatively altered during physiologically induced swallowing. All 23 neurons were changed in either discharge duration or frequency after PRG inhibition, however, the general discharge patterns in relation to the motor output remained unchanged. ConclusionDescending synaptic inputs from PRG provide control of the primary laryngeal sensory gate and synaptic activity of the PRG partially determine medullary cell and cranial motor nerve activities that govern the pharyngeal stage of swallowing.

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.

The rostral brainstem's pivotal role in swallow‐breathing coordination

Respiration and swallowing are motor behaviours that require the interaction of two brainstem central pattern generators (r‐CPG, sw‐CPG). Previously we studies the interaction of swallowing and breathing in the in situ perfused brainstem preparation that identified a pivotal role of the pontine Kolliker‐Fuse nuclei for the mediation of protective glottal closure. We recently developed a computational model to further aid and test network connectivity and neural interaction between sw‐ and r‐CPGs. The model is based on a stepwise integration of synaptic connectivity between central sensory relay, sw‐ and r‐CPG neuron populations. The model is validated by experimental data obtained in situ. In the model and experimental data, stimulation of the superior laryngeal nerve (SLN, 10s) reliably triggers sequential swallowing with concomitant swallowing‐related glottal closure and suppression of inspiratory activity. Short SLN stimulation (100ms) evokes single swallows and respiratory phase resetting in the model and in situ yielding comparable phase response curves. Consistent with experiments, numerical circuit‐busting simulations show that deletion of ponto‐medullary synaptic interactions triggers apneusis and eliminates swallowing‐related glottal closure during sequential swallowing. Additionally, systematic variations of the synaptic strengths of distinct network connections predict vulnerable network connections that can mediate clinically relevant breathing‐swallowing disorders observed in the elderly and patients with neurodegenerative disease. Thus, the present model provides novel insights that can guide future experiments and the development of efficient treatments for prevalent breathing‐swallowing disorders.

Rabbit model with vocal fold hyperadduction

ObjectiveAdductor spasmodic dysphonia (AdSD) is caused by hyperadduction of the vocal folds during phonation, resulting in a strained voice. Animal models are not yet used to elucidate this intractable disease because AdSD has a difficult pathology without a definitive origin. For the first step, we established an animal model with vocal fold hyperadduction and evaluated its validity by assessing laryngeal function. MethodsIn this experimental animal study, three adult Japanese 20-week-old rabbits were used. The models were created using a combination of cricothyroid approximation, forced airflow, and electrical stimulation of the recurrent laryngeal nerves (RLNs). Cricothyroid approximation was added to produce a glottal slit. Thereafter, both RLNs were electrically stimulated to induce vocal fold hyperadduction. Finally, the left RLN was transected to relieve hyperadduction. The sound, endoscopic images, and subglottal pressure were recorded, and acoustic analysis was performed. ResultsSubglottal pressure increased significantly, and the strained sound was produced after the electrical stimulation of the RLNs. After transecting the left RLN, the subglottal pressure decreased significantly, and the strained sound decreased. Acoustic analysis revealed an elevation of the standard deviation of F0 (SDF0) and degree of voice breaks (DVB) through stimulation of the RLNs, and degradation of SDF0 and DVB through RLN transection. Formant bands in the sound spectrogram were interrupted by the stimulation and appeared again after the RLN section. ConclusionThis study developed a rabbit model with vocal fold hyperadduction . The subglottal pressure and acoustic analysis of this model resembled the characteristics of patients with AdSD. This model could be helpful to elucidate the pathology of the larynx caused by hyperadduction, and evaluate and compare the treatments for strained phonation.

Evaluation of the Cricothyroid Muscle Innervation Pattern Through Intraoperative Electromyography

Objectives:We observed significant contractions in the cricothyroid muscle (CTM) after recurrent laryngeal nerve (RLN) stimulation in some patients. We aimed to evaluate whether these contractions resulted from the laryngeal-muscle movement due to the contraction of other intrinsic muscles or actual CTM contraction, with objective real-time intraoperative electromyography (EMG) recordings.Methods:This study was performed prospectively in 106 consecutive patients who underwent intraoperative neural monitoring-guided primary thyroid surgery due to various thyroid diseases between February-2015 and February-2016. After completion of the thyroidectomy procedure; the RLN, vagus nerve (VN), external branch of the superior laryngeal nerve (EBSLN), plexus pharyngeus (PP), and contralateral EBSLN (CEBSLN) were stimulated and the responses from the CTM and CPM were recorded and evaluated by EMG through needle electrodes.Results:182 CTMs of 106 patients, with the mean age of 45, were evaluated regarding their innervation patterns. Positive EMG waveforms were achieved from 181 CTMs with EBSLN stimulation. A total of 132 (74%) positive EMG responses were recorded after the stimulation of 179 RLNs. The mean amplitude obtained with CTM EMG with RLN stimulation was 5.5% of that with EBSLN stimulation. The CTM amplitude was 39% of the vocal cord amplitude with RLN stimulation. Positive EMG responses of 96 CTMs (55%) with VN stimulation were recorded. The mean amplitude through CTM EMG with VN stimulation was 6% of that with EBSLN stimulation. Positive EMG responses were achieved from 10 (0.6%) CTMs with the stimulation of 170 PPs. The mean amplitude obtained from CTMs with PP stimulation was 4.3% of that with EBSLN stimulation. Positive EMG amplitudes of 35 (67%) CTMs were obtained with stimulation of 52 CEBSLN. Temporary vocal cord paralysis was detected in six patients (5% of patients and 3.3% of the nerves) postoperatively.Conclusion:The RLN contributes significantly to the innervation of the CTM. Despite the findings associated with the contribution of the PP and CEBSLN to the CTM innervation, further studies are needed. We are of the opinion that these are among the significant factors that contribute to the differences in clinical findings between patients with EBSLN injuries.

Experience of using a neuromonitor during thyroid surgery in children

Background. Thyroid surgery is associated with the risk of complications that worsen the course of the postoperative period and lead to disability of patients. One of these complications is damage to the recurrent laryngeal nerve, causing impaired phonation, and in the case of bilateral lesions, respiratory impairment.&#x0D; The aim of this work was to study the features of the technique and the effectiveness of the use of neuromonitoring during operations on the thyroid gland.&#x0D; Materials and methods. The study was conducted on a series of 55 clinical observations of thyroid diseases in children. Intraoperative monitoring was performed using the Inomed C2 Nerve Monitor, which records the action potential on the vocal folds caused by electrical stimulation of the recurrent laryngeal nerve.&#x0D; Results. In 52 cases, no decrease in the amplitude of the neuromonitor signal was observed during surgical interventions. In two cases, intraoperatively, a decrease in the signal amplitude associated with excessive traction of the nerve was revealed. Another observation noted the absence of a signal at the end of the operation and the preservation of the mobility of the vocal cords in the postoperative period, probably due to technical errors in performing intraoperative monitoring. In one patient, during the operation, changes in the neuromonitor signal did not occur, but after surgery, a violation of the vocal function was noted, which fully recovered within 3 months. In all likelihood, these changes are due to the technique of tracheal intubation.&#x0D; Conclusions. Neuromonitoring is an additional method for finding the recurrent laryngeal nerve, but in no way replaces the need for delicate anatomical identification of the latter.

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.

Phonation Threshold Pressure Revisited: Effects of Intrinsic Laryngeal Muscle Activation.

Phonation threshold pressure (Pth ) is the minimum subglottic pressure required to reach phonation onset and is considered a marker for vocal efficiency and health. We investigated the effects of intrinsic laryngeal muscle (ILM) activation on Pth . In vivo animal study. In an in vivo canine phonation model, laryngeal adductor muscles were activated together by stimulation of the recurrent laryngeal nerves (RLNs) and individually via stimulation of respective terminal nerve branches. Cricothyroid (CT) muscles were activated via stimulation of the superior laryngeal nerves. ILMs were activated in a graded manner at various combinations as transglottal airflow was gradually increased. Aerodynamic and glottal posture parameters were measured at phonation onset. Graded RLN stimulation decreased glottal distance and increased Pth . Thyroarytenoid (TA) muscle activation alone increased Pth . Lateral cricoarytenoid (LCA) muscle activation alone had minimal effects. However, graded TA activation as a function of LCA activation level revealed a synergistic relationship between the two muscles in increasing Pth . Effects of CT activation were dependent on adductor stimulation level: CT activation increased Pth at low RLN stimulation levels and decreased Pth at high RLN levels. The effects of ILM activation on Pth were consistent with their expected effects on vocal fold stiffness and tension. TA was the primary adductor controlling Pth . While LCA alone had minimal effects on Pth , it enhanced the role of TA in controlling Pth . TA and CT have antagonistic roles in controlling Pth . These relationships should be considered in clinical efforts to improve ease of phonation and vocal efficiency. NA, basic science Laryngoscope, 132:1427-1432, 2022.

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.

Drawbacks of neural monitoring troubleshooting algorithms in transoral endoscopic thyroidectomy

The application of intraoperative neural monitoring (IONM) trouble-shooting algorithms procedures in transoral endoscopic thyroidectomy vestibular approach (TOETVA) was investigated. Loss of signal (LOS) is defined as a loss of the primary electromyographic (EMG) normal biphasic waveform with reduced amplitude response to less than 100μV with a stimulation level intensity of 1-2mA. A systematic review of the IONM system at LOS was covered methodically: (i) correct endotracheal tube verification, (ii) stimulation of the recurrent laryngeal nerve (RLN) at entry point, (iii) ipsilateral or contralateral vagal nerve (VN) stimulation, and (iv) laryngeal twitch (LT). The function of 223 nerves at risk (NAR) was recorded with IONM. Twenty-seven (12%) NAR experienced a suspected LOS. LT could not be appreciated. In 15/27 (55%) cases, the application of the IONM trouble-shooting algorithm revealed upward displacement of the EMG tube (all orotracheal intubations). In 9 (4%) NAR, VN stimulation was not accomplished. In detail, there were n.5 left and n. 4 right VNs. Two VNs were ipsilateral, and 7 VNs contralateral. For EMG tube displacement, because the oral/nasal area is included in the aseptic field, it is less possible to re-check by the laryngoscope or fiberscope. A limit for applying the IONM trouble-shooting algorithm to TOETVA is determined by (a) inability to appreciate the LT, (b) difficulty in stimulating the ipsilateral and contralateral VN, and (c) remodeling EMG endotracheal tube position. A modified IONM trouble-shooting algorithm for TOETVA is proposed.