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The Laryngoscope Jun 2019Tissue engineering of the larynx requires a complex, multiple tissue layer design. Additionally, spontaneous reinnervation of the larynx after recurrent laryngeal nerve...
OBJECTIVE
Tissue engineering of the larynx requires a complex, multiple tissue layer design. Additionally, spontaneous reinnervation of the larynx after recurrent laryngeal nerve (RLN) injury is often disorganized, resulting in subpar function. This study investigates use of tissue-engineered cartilage and motor endplate-expressing (MEE) tissue-engineered skeletal muscle implants for laryngeal reconstruction and the promotion of organized reinnervation after RLN injury.
METHODS
F344 rat primary muscle progenitor cells (MPCs) were isolated. Three-dimensional muscle constructs were created by encapsulating MPCs in type I oligomeric collagen under passive tension. Constructs were then cultured in differentiation medium (MPC control constructs) or induced to form motor endplates (MEE constructs) with neurotrophic agents. Three-dimensional cartilage constructs were created with adipose stem cells differentiated in chondrocyte medium. The muscle and cartilage constructs were implanted into surgically created myochondral defects in the F344 rat larynx with injured or intact (control) RLN. At 1-, 3-, and 6-month timepoints, videolaryngoscopy, electromyography (EMG), histology, and immunohistochemistry were used to assess outcomes.
RESULTS
At all timepoints, cartilage-muscle implants were well integrated into host tissue. Functionally, there was increased vocal fold adduction and EMG activity in nerve-injured rats treated with the MEE constructs when compared to those treated with the MPC control constructs. Motor endplate-expressing constructs had increased myofiber cross-sectional area compared to MPC control constructs.
CONCLUSION
Although our laboratory previously demonstrated that muscle and cartilage constructs could be used separately for hemilaryngeal reconstruction, this study suggests combining them with the modification of MEEs rather than MPCs, resulting in improved muscle recovery after recurrent laryngeal nerve injury.
LEVEL OF EVIDENCE
NA Laryngoscope, 129:1293-1300, 2019.
Topics: Animals; Cartilage; Disease Models, Animal; Electromyography; Laryngeal Muscles; Laryngoplasty; Male; Motor Endplate; Muscle, Skeletal; Nerve Regeneration; Phonation; Rats; Rats, Inbred F344; Recurrent Laryngeal Nerve; Recurrent Laryngeal Nerve Injuries; Tissue Engineering
PubMed: 30548608
DOI: 10.1002/lary.27575 -
Current Biology : CB Jul 2021The motor control resolution of any animal behavior is limited to the minimal force step available when activating muscles, which is set by the number and size...
The motor control resolution of any animal behavior is limited to the minimal force step available when activating muscles, which is set by the number and size distribution of motor units (MUs) and muscle-specific force. Birdsong is an excellent model system for understanding acquisition and maintenance of complex fine motor skills, but we know surprisingly little about how the motor pool controlling the syrinx is organized and how MU recruitment drives changes in vocal output. Here we developed an experimental paradigm to measure MU size distribution using spatiotemporal imaging of intracellular calcium concentration in cross-sections of living intact syrinx muscles. We combined these measurements with muscle stress and an in vitro syrinx preparation to determine the control resolution of fundamental frequency (f), a key vocal parameter, in zebra finches. We show that syringeal muscles have extremely small MUs, with 40%-50% innervating ≤3 and 13%-17% innervating a single muscle fiber. Combined with the lowest specific stress (5 mN/mm) known to skeletal vertebrate muscle, small force steps by the major f controlling muscle provide control of 50-mHz to 7.3-Hz steps per MU. We show that the song system has the highest motor control resolution possible in the vertebrate nervous system and suggest this evolved due to strong selection on fine gradation of vocal output. Furthermore, we propose that high-resolution motor control was a key feature contributing to the radiation of songbirds that allowed diversification of song and speciation by vocal space expansion.
Topics: Animals; Laryngeal Muscles; Nervous System Physiological Phenomena; Songbirds; Vocalization, Animal
PubMed: 34089645
DOI: 10.1016/j.cub.2021.05.008 -
Journal of Anatomy Sep 2021High-resolution, noninvasive and nondestructive imaging of the subepithelial structures of the larynx would enhance microanatomic tissue assessment and clinical decision...
High-resolution, noninvasive and nondestructive imaging of the subepithelial structures of the larynx would enhance microanatomic tissue assessment and clinical decision making; similarly, in situ molecular profiling of laryngeal tissue would enhance biomarker discovery and pathology readout. Towards these goals, we assessed the capabilities of high-resolution magnetic resonance imaging (MRI) and matrix-assisted laser desorption/ionisation-mass spectrometry (MALDI-MS) imaging of rarely reported paediatric and adult cadaveric larynges that contained pathologies. The donors were a 13-month-old male, a 10-year-old female with an infraglottic mucus retention cyst and a 74-year-old female with advanced polypoid degeneration and a mucus retention cyst. MR and molecular imaging data were corroborated using whole-organ histology. Our MR protocols imaged the larynges at 45-117 μm in-plane resolution and capably resolved microanatomic structures that have not been previously reported radiographically-such as the vocal fold superficial lamina propria, vocal ligament and macula flavae; age-related tissue features-such as intramuscular fat deposition and cartilage ossification; and the lesions. Diffusion tensor imaging characterised differences in water diffusivity, primary tissue fibre orientation, and fractional anisotropy between the intrinsic laryngeal muscles, mucosae and lesions. MALDI-MS imaging revealed peptide signatures and putative protein assignments for the polypoid degeneration lesion and the N-glycan constituents of one mucus retention cyst. These imaging approaches have immediate application in experimental research and, with ongoing technology development, potential for future clinical application.
Topics: Aged; Child; Diffusion Tensor Imaging; Female; Humans; Infant; Laryngeal Muscles; Larynx; Magnetic Resonance Imaging; Male; Mass Spectrometry
PubMed: 34032275
DOI: 10.1111/joa.13451 -
The Laryngoscope Jan 2019Laryngeal function requires neuromuscular activation of the intrinsic laryngeal muscles (ILMs). Rapid activation of the ILMs occurs in cough, laughter, and...
OBJECTIVES
Laryngeal function requires neuromuscular activation of the intrinsic laryngeal muscles (ILMs). Rapid activation of the ILMs occurs in cough, laughter, and voice-unvoiced-voiced segments in speech and singing. Abnormal activation is observed in hyperfunctional disorders such as vocal tremor and dystonia. In this study, we evaluate the dynamics of ILM contraction.
STUDY/DESIGN
Basic science study in an in vivo canine model.
METHODS
The following ILMs were stimulated: thyroarytenoid (TA), lateral cricoarytenoid/interarytenoid (LCA/IA), cricothyroid (CT), all laryngeal adductors (LCA/IA/TA), and the posterior cricoarytenoid (PCA). Neuromuscular stimulation was performed via the respective nerves at current levels needed to achieve maximum vocal fold posture change. Muscle contraction and posture changes were recorded with high speed video (HSV). HSV frames were then analyzed to measure response times required from the onset of muscle contraction to the time the vocal folds achieved maximum posture change.
RESULTS
In all muscles, the onset of posture change occurred within 10 to 12 milliseconds after neuromuscular stimulation. The average times ( ± standard deviation) to achieve final posture were as follows: TA 34.5 ± 6 ms (N = 15), LCA/IA 55 ± 12 ms (N = 14), recurrent laryngeal nerve 43 ± 8 ms (N = 18), CT 100.8 ± 17 ms (N = 26), and PCA 91.2 ± 8 ms (N = 3). Data distribution appeared normal.
CONCLUSION
Results showed a difference in muscle activation time between different ILMs consistent with reported differences in muscle fiber composition. These data also provide an estimate of the limits of laryngeal contraction frequency in physiologic and pathologic laryngeal states.
LEVEL OF EVIDENCE
NA Laryngoscope, 129:E21-E25, 2019.
Topics: Animals; Biomechanical Phenomena; Dogs; Electric Stimulation; Laryngeal Muscles; Muscle Contraction; Prospective Studies; Time Factors; Tracheostomy; Vocal Cords
PubMed: 30325497
DOI: 10.1002/lary.27353 -
Case Reports in Neurology 2020This case report presents oropharyngeal dysphagia due to oromandibular and cervical dystonia, a rare consequence of aseptic meningitis. A 19-year-old male who was...
This case report presents oropharyngeal dysphagia due to oromandibular and cervical dystonia, a rare consequence of aseptic meningitis. A 19-year-old male who was diagnosed with aseptic meningitis visited the rehabilitation outpatient clinic for a sense of foreign body in his throat and odynophagia. Repetitive involuntary movements of his facial, tongue, and laryngeal muscles accompanied by lateroanterior torticollis were observed. Videofluoroscopic swallowing study showed inefficient bolus formation due to repetitive rolling of his tongue and vallecular stasis without penetration or aspiration. Dysphagia and odynophagia had brought the patient significant weight loss and frustration. We provided swallowing training to improve the efficiency and safety of swallowing. The patient's symptoms improved gradually along with body weight gain and emotional stability. Acute-onset oropharyngeal dysphagia is devastating for young adults. A multidisciplinary approach is mandatory for optimal outcome. We share our experience as a team work and emphasize the rehabilitation aspect.
PubMed: 33362519
DOI: 10.1159/000507242 -
Journal of Applied Physiology... May 2019Neuromuscular pathology is found in the larynx and pharynx in humans with Parkinson disease (PD); however, it is unknown when this pathology emerges. We hypothesized...
Neuromuscular pathology is found in the larynx and pharynx in humans with Parkinson disease (PD); however, it is unknown when this pathology emerges. We hypothesized that pathology occurs in early (premanifest) stages. To address this, we used the rat model of PD, which shows age-dependent dopaminergic neuron loss, locomotor deficits, and deficits related to laryngeal function. We report findings in the thyroarytenoid muscle (TA) in rats compared with wild-type (WT) control rats at 4 and 6 mo of age. TAs were analyzed for force production, myosin heavy chain isoform (MyHC), centrally nucleated myofibers, neural cell adhesion molecule, myofiber size, and muscle section size. Compared with WT, TA had reductions in force levels at 1-Hz stimulation and 20-Hz stimulation, increases in relative levels of MyHC 2L, increases in incidence of centrally nucleated myofibers in the external division of the TA, and reductions in myofiber size of the vocalis division of the TA at 6 mo of age. Alterations of laryngeal muscle biology occur in a rat model of premanifest PD. Although these alterations are statistically significant, their functional significance remains to be determined. Pathology of peripheral nerves and muscle has been reported in the larynx and pharynx of humans diagnosed with Parkinson disease (PD); however, it is unknown whether differences of laryngeal muscle occur at premanifest stages. This study examined the thyroarytenoid muscles of the rat model of PD for differences of muscle biology compared with control rats. Thyroarytenoid muscles of rats at premanifest stages show differences in multiple measures of muscle biology.
Topics: Animals; Disease Models, Animal; Laryngeal Muscles; Male; Myofibrils; Myosin Heavy Chains; Parkinson Disease; Protein Kinases; Rats; Rats, Long-Evans
PubMed: 30844333
DOI: 10.1152/japplphysiol.00557.2018 -
Sisli Etfal Hastanesi Tip Bulteni 2021The use of intraoperative neuromonitoring (IONM) is getting more common in thyroidectomy. The data obtained by the usage of IONM regarding the laryngeal nerves' anatomy... (Review)
Review
The use of intraoperative neuromonitoring (IONM) is getting more common in thyroidectomy. The data obtained by the usage of IONM regarding the laryngeal nerves' anatomy and function have provided important contributions for improving the standards of the thyroidectomy. These evidences obtained through IONM increase the rate of detection and visual identification of recurrent laryngeal nerve (RLN) as well as the detection rate of extralaryngeal branches which are the most common anatomic variations of RLN. IONM helps early identification and preservation of the non-recurrent laryngeal nerve. Crucial knowledge has been acquired regarding the complex innervation pattern of the larynx. Extralaryngeal branches of the RLN may contribute to the motor innervation of the cricothyroid muscle (CTM). Anterior branch of the extralaryngeal branching RLN has always motor function and gives motor branches both to the abductor and adductor muscles. In addition, up to 18% of posterior branches may have adductor and/or abductor motor fibers. In 70-80% of cases, external branch of superior laryngeal nerve (EBSLN) provides motor innervation to the anterior 1/3 of the thyroarytenoid muscle which is the main adductor of the vocal cord through the human communicating nerve. Furthermore, approximately 1/3 of the cases, EBSLN may contribute to the innervation of posterior cricoarytenoid muscle which is the main abductor of ipsilateral vocal cord. RLN and/or EBSLN together with pharyngeal plexus usually contribute to the motor innervation of cricopharyngeal muscle that is the main component of upper esophageal sphincter. Traction trauma is the most common reason of RLN injuries and constitutes of 67-93% of cases. More than 50% of EBSLN injuries are caused by nerve transection. A specific point of injury on RLN can be detected in Type 1 (segmental) injury, however, Type 2 (global) injury is the loss of signal (LOS) throughout ipsilateral vagus-RLN axis and there is no electrophysiologically detectable point of injury. Vocal cord paralysis (VCP) develops in 70-80% of cases when LOS persists or incomplete recovery of signal occurs after waiting for 20 min. In case of complete recovery of signal, VCP is not expected. VCP is temporary in patients with incomplete recovery of signal and permanent VCP is not anticipated. Visual changes may be seen in only 15% of RLN injuries, on the other hand, IONM detects 100% of RLN injuries. IONM can prevent bilateral VCP. Continuous IONM (C-IONM) is a method in which functional integrity of vagus-RLN axis is evaluated in real time and C-IONM is superior to intermittent IONM (I-IONM). During upper pole dissection, IONM makes significant contributions to the visual and functional identification of EBSLN. Routine use of IONM may minimalize the risk of nerve injury. Reduction of amplitude more than 50% on CTM is related with poor voice outcome.
PubMed: 34349588
DOI: 10.14744/SEMB.2021.45548 -
Journal of Speech, Language, and... Mar 2019Purpose The purpose of this tutorial is to summarize how sex hormones affect both laryngeal senescence and neuromuscular response to exercise, highlighting the... (Review)
Review
Purpose The purpose of this tutorial is to summarize how sex hormones affect both laryngeal senescence and neuromuscular response to exercise, highlighting the importance of considering sex differences in developing treatment for the senescent voice. Conclusion Men and women's voices are sexually dimorphic throughout the life span, including during the laryngeal adaptations observed during senescence. Therefore, presbyphonia (age-related dysphonia) likely clinically manifests differently for men and women due to differences in how the male and the female larynx change in response to aging. Because sexual dimorphism is evident in both laryngeal aging and response to exercise, voice therapy programs aimed at treating the typical and disordered aged voice should consider sex differences in their design.
Topics: Adult; Aged; Aging; Exercise; Female; Gonadal Steroid Hormones; Humans; Laryngeal Muscles; Larynx; Male; Middle Aged; Sex Characteristics; Voice
PubMed: 30950744
DOI: 10.1044/2018_JSLHR-S-18-0179 -
Experimental Brain Research Jul 2015Motor unit recruitment was assessed in two muscles with similar muscle fiber-type compositions and that participate in skilled movements: the tongue muscle, genioglossus...
Motor unit recruitment was assessed in two muscles with similar muscle fiber-type compositions and that participate in skilled movements: the tongue muscle, genioglossus (GG), and the hand muscle, first dorsal interosseous (FDI). Our primary objectives were to determine in the framework of a voluntary movement whether muscle force is regulated in tongue as it is in limb, i.e., via processes of rate coding and recruitment. Recruitment in the two muscles was assessed within each subject in the context of ramp force (FDI) and in the tongue (GG) during vowel production and specifically, in the context of ramp increases in loudness, and subsequently expressed relative to the maximal. The principle findings of the study are that the general rules of recruitment and rate coding hold true for both GG and FDI, and second, that average firing rates, firing rates at recruitment and peak firing rates in GG are significantly higher than for FDI (P < 0.001) despite tasks performed across comparable force ranges (~2-40 % of max). The higher firing rates observed in the tongue within the context of phonation may be a function of that muscle's dual role as (prime) mover and hydrostatic support element.
Topics: Action Potentials; Adult; Electromyography; Female; Hand; Humans; Laryngeal Muscles; Male; Motor Neurons; Muscle Contraction; Phonation; Recruitment, Neurophysiological; Tongue; Young Adult
PubMed: 25899868
DOI: 10.1007/s00221-015-4284-y -
The Laryngoscope Aug 2017The human voice is sexually dimorphic in obvious ways, such as differences in fundamental frequency and gross laryngeal anatomy, but also in less apparent ways, such as... (Comparative Study)
Comparative Study
OBJECTIVE
The human voice is sexually dimorphic in obvious ways, such as differences in fundamental frequency and gross laryngeal anatomy, but also in less apparent ways, such as in the prevalence and types of voice disorders and the manifestation of voice changes in advanced age. Differences between males and females are rarely explored, however, in mechanistic animal studies. The goal of this study was to explore sexual dimorphism in laryngeal function and structure in adult rats by examining ultrasonic vocalization acoustics and muscle fiber size and type in the thyroarytenoid muscle.
STUDY DESIGN
Animal group comparison.
METHODS
Spontaneous ultrasonic vocalizations from 10 male adult rats and 10 female adult rats were recorded, classified, and acoustically analyzed. Cross-sections of the thyroarytenoid muscle were stained and imaged for analysis of muscle fiber size and type. Acoustic and muscle parameters were statistically compared between sexes.
RESULTS
Male rats had a lower mean frequency of short ultrasonic vocalizations. Male rats also had a larger mean fiber size in the external division of the thyroarytenoid and larger overall muscle area in both the vocalis and external divisions of the thyroarytenoid. However, muscle fiber type compositions were similar between sexes in both the vocalis and external division of the thyroarytenoid muscles.
CONCLUSION
Functional and structural laryngeal differences exist between adult male and female rats; therefore, the rat model can be used to further study sexual dimorphism of the voice.
LEVEL OF EVIDENCE
NA. Laryngoscope, 127:E270-E276, 2017.
Topics: Age Factors; Animals; Female; Laryngeal Muscles; Male; Rats; Rats, Long-Evans; Sex Characteristics; Ultrasonics; Vocalization, Animal
PubMed: 28304076
DOI: 10.1002/lary.26561