Synthetic, self-oscillating vocal fold models for voice production researcha).

Sound for the human voice is produced by vocal fold flow-induced vibration and involves a complex coupling between flow dynamics, tissue motion, and acoustics. Over the past three decades, synthetic, self-oscillating vocal fold models have played an increasingly important role in the study of these complex physical interactions. In particular, two types of models have been established: "membranous" vocal fold models, such as a water-filled latex tube, and "elastic solid" models, such as ultrasoft silicone formed into a vocal fold-like shape and in some cases with multiple layers of differing stiffness to mimic the human vocal fold tissue structure. In this review, the designs, capabilities, and limitations of these two types of models are presented. Considerations unique to the implementation of elastic solid models, including fabrication processes and materials, are discussed. Applications in which these models have been used to study the underlying mechanical principles that govern phonation are surveyed, and experimental techniques and configurations are reviewed. Finally, recommendations for continued development of these models for even more lifelike response and clinical relevance are summarized.

Asymmetric triangular body-cover model of the vocal folds with bilateral intrinsic muscle activation.

Many voice disorders are linked to imbalanced muscle activity and known to exhibit asymmetric vocal fold vibration. However, the relation between imbalanced muscle activation and asymmetric vocal fold vibration is not well understood. This study introduces an asymmetric triangular body-cover model of the vocal folds, controlled by the activation of bilateral intrinsic laryngeal muscles, to investigate the effects of muscle imbalance on vocal fold oscillation. Various scenarios were considered, encompassing imbalance in individual muscles and muscle pairs, as well as accounting for asymmetry in lumped element parameters. Measurements of amplitude and phase asymmetries were employed to match the oscillatory behavior of two pathological cases: unilateral paralysis and muscle tension dysphonia. The resulting simulations exhibit muscle imbalance consistent with expectations in the composition of these voice disorders, yielding asymmetries exceeding 30% for paralysis and below 5% for dysphonia. This underscores the relevance of muscle imbalance in representing phonatory scenarios and its potential for characterizing asymmetry in vocal fold vibration.

Principal dimensions of voice production and their role in vocal expression.

How we produce and perceive voice is constrained by laryngeal physiology and biomechanics. Such constraints may present themselves as principal dimensions in the voice outcome space that are shared among speakers. This study attempts to identify such principal dimensions in the voice outcome space and the underlying laryngeal control mechanisms in a three-dimensional computational model of voice production. A large-scale voice simulation was performed with parametric variations in vocal fold geometry and stiffness, glottal gap, vocal tract shape, and subglottal pressure. Principal component analysis was applied to data combining both the physiological control parameters and voice outcome measures. The results showed three dominant dimensions accounting for at least 50% of the total variance. The first two dimensions describe respiratory-laryngeal coordination in controlling the energy balance between low- and high-frequency harmonics in the produced voice, and the third dimension describes control of the fundamental frequency. The dominance of these three dimensions suggests that voice changes along these principal dimensions are likely to be more consistently produced and perceived by most speakers than other voice changes, and thus are more likely to have emerged during evolution and be used to convey important personal information, such as emotion and larynx size.

Mechanotransduction in the Vocal Fold Microenvironment: A Narrative Review.

PURPOSE: The vocal fold tissues undergo nearly continuous and repeated cycles of injury and repair throughout the course of an individual's lifetime. It is well established that certain individuals are at greater risk of lesion development based on personality and behavioral classification. However, these characteristics alone do not wholly predict or explain lesion development or severity. In this review, we discuss current knowledge of mechanotransduction proteins and their potential relevance to tissue homeostasis in the vocal folds. METHOD: A review of literature surrounding mechanotransduction and tissue homeostasis as it relates to the vocal folds was conducted. Review of the literature included searches of PubMed, Google Scholar, and other various online peer-reviewed sources. Search terms pertained to mechanosensation, mechanotransduction, mechanically activated channels, mechanical cellular regulation, and other associated concepts and terms. Additional literature was identified through the reference lists of identified papers. Findings of this literature review were then applied to known physiology and pathophysiology of the vocal folds in order to speculate on the contribution of mechanically mediated mechanisms within the vocal fold. DISCUSSION AND CONCLUSION: Because the vocal folds are such mechanically active structures, withstanding nearly constant external forces, there is strong support for the idea that mechanically sensitive molecular pathways within the vocal fold tissue play a major role in tissue homeostasis in the presence of these considerable forces. As such, mechanotransduction within the vocal fold should be considered and targeted in future biological studies of vocal fold physiology.

Biomechanics of sound production in high-pitched classical singing.

Voice production of humans and most mammals is governed by the MyoElastic-AeroDynamic (MEAD) principle, where an air stream is modulated by self-sustained vocal fold oscillation to generate audible air pressure fluctuations. An alternative mechanism is found in ultrasonic vocalizations of rodents, which are established by an aeroacoustic (AA) phenomenon without vibration of laryngeal tissue. Previously, some authors argued that high-pitched human vocalization is also produced by the AA principle. Here, we investigate the so-called "whistle register" voice production in nine professional female operatic sopranos singing a scale from C6 (≈ 1047 Hz) to G6 (≈ 1568 Hz). Super-high-speed videolaryngoscopy revealed vocal fold collision in all participants, with closed quotients from 30 to 73%. Computational modeling showed that the biomechanical requirements to produce such high-pitched voice would be an increased contraction of the cricothyroid muscle, vocal fold strain of about 50%, and high subglottal pressure. Our data suggest that high-pitched operatic soprano singing uses the MEAD mechanism. Consequently, the commonly used term "whistle register" does not reflect the physical principle of a whistle with regard to voice generation in high pitched classical singing.

Muscular and neuronal control of voice production - forgotten findings, current concepts, and new developments.

Voice production has been an area of interest in science since ancient times, and although advancing research has improved our understanding of the anatomy and function of the larynx, there is still little general consensus on these two topics. This review aims to outline the main developments in this field and highlight the areas where further research is needed. The most important hypotheses are presented and discussed highlighting the four main lines of research in the anatomy of the human larynx and their most important findings: (1) the arrangement of the muscle fibers of the thyroarytenoid muscle is not parallel to the vocal folds in the internal part (vocalis muscle), leading to altered properties during contraction; (2) the histological structure of the human vocal cords differs from other striated muscles; (3) there is a specialized type of heavy myosin chains in the larynx; and (4) the neuromuscular system of the larynx has specific structures that form the basis of an intrinsic laryngeal nervous system. These approaches are discussed in the context of current physiological models of vocal fold vibration, and new avenues of investigation are proposed.

Extrinsic Laryngeal Muscle Activity With Different Diameters and Water Depths in a Semi-Occluded Vocal Tract Exercise.

PURPOSE: Surface electromyography (sEMG) has been used to evaluate extrinsic laryngeal muscle activity during swallowing and phonation. In the current study, sEMG amplitudes were measured from the infrahyoid and suprahyoid muscles during phonation through a tube submerged in water. METHOD: The sEMG amplitude values measured from the extrinsic laryngeal muscles and the electroglottographic contact quotient (CQ) were obtained simultaneously from 62 healthy participants (31 men, 31 women) during phonation through a tube at six different depths (2, 4, 7, 10, 15, and 20 cm) while using two tubes with different diameters (1 and 0.5 cm). RESULTS: With increasing depth, the sEMG amplitude for the suprahyoid muscles increased in men and women. However, sEMG amplitudes for the infrahyoid muscles increased significantly only in men. Tube diameter had a significant effect on the suprahyoid sEMG amplitudes only for men, with higher sEMG amplitudes when phonating with a 1.0-cm tube. CQ values increased with submerged depth for both men and women. Tube diameter affected results such than CQ values were higher for men when using the wider tube and for women with the narrower tube. CONCLUSIONS: Vocal fold vibratory patterns changed with the depth of tube submersion in water for both men and women, but the patterns of muscle activation differed between the sexes. This suggests that men and women use different strategies when confronted with increased intraoral pressure during semi-occluded vocal tract exercises. In this study, sEMG provided insight into the mechanism for differences between vocally normal individuals and could help detect compensatory muscle activation during tube phonation in water for people with voice disorders.

Brainstem control of vocalization and its coordination with respiration.

Phonation critically depends on precise controls of laryngeal muscles in coordination with ongoing respiration. However, the neural mechanisms governing these processes remain unclear. We identified excitatory vocalization-specific laryngeal premotor neurons located in the retroambiguus nucleus (RAmVOC) in adult mice as being both necessary and sufficient for driving vocal cord closure and eliciting mouse ultrasonic vocalizations (USVs). The duration of RAmVOC activation can determine the lengths of both USV syllables and concurrent expiration periods, with the impact of RAmVOC activation depending on respiration phases. RAmVOC neurons receive inhibition from the preBötzinger complex, and inspiration needs override RAmVOC-mediated vocal cord closure. Ablating inhibitory synapses in RAmVOC neurons compromised this inspiration gating of laryngeal adduction, resulting in discoordination of vocalization with respiration. Our study reveals the circuits for vocal production and vocal-respiratory coordination.

Restraining vocal fold vertical motion reduces source-filter interaction in a two-mass model.

Previous experimental studies suggested that restraining the vocal fold vertical motion may reduce the coupling strength between the voice source and vocal tract. In this study, the effects of vocal fold vertical motion on source-filter interaction were systematically examined in a two-dimensional two-mass model coupled to a compressible flow simulation. The results showed that when allowed to move vertically, the vocal folds exhibited subharmonic vibration due to entrainment to the first vocal tract acoustic resonance. Restraining the vertical motion suppressed this entrainment. This indicates that the vertical mobility of the vocal folds may play a role in regulating source-filter interaction.

Analyzing Vocal Fold Frequency Dynamics Using High-Speed 3D Laser Video Endoscopy.

OBJECTIVE: To examine changes in lateral and vertical vibratory motion along the anterior, middle, and posterior sections of the vocal folds, as a function of vocal frequency variations. METHODS: Absolute measurements of vocal fold surface dynamics from high-speed videoendoscopy with custom laser endoscope were made on 23 vocally healthy adults during sustained /i:/ production at 10%, 20%, and 80% of pitch range. The 3D parameters of amplitude (mm), maximum velocity opening/closing (mm/s), and mean velocity opening/closing (mm/s) were computed for the lateral and vertical vibratory motion along the anterior, middle, and posterior sections of the vocal folds. Linear mixed model analysis was conducted to evaluate the differences in (a) vocal frequency levels (high vs. normal vs. low pitch), (b) axis level (vertical vs. lateral), (c) position level (anterior vs. middle vs. posterior), and (d) gender differences (male vs. female). RESULTS: Overall, the superior surface vertical motion of the vocal fold is greater compared with the lateral motion, especially in males. Along the superior surface, the mean and maximum closing velocities are greater posteriorly for low pitch. The location (anterior, middle, and posterior) along the superior surface is relevant only for vocal fold closing rather than opening, as the dynamics are different along the various locations. CONCLUSIONS: The study highlights the significance of assessing the vertical motion of the superior surface of the vocal fold to understand the complex dynamics of voice production. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3267-3276, 2024.

Speaking without vocal folds using a machine-learning-assisted wearable sensing-actuation system.

Voice disorders resulting from various pathological vocal fold conditions or postoperative recovery of laryngeal cancer surgeries, are common causes of dysphonia. Here, we present a self-powered wearable sensing-actuation system based on soft magnetoelasticity that enables assisted speaking without relying on the vocal folds. It holds a lightweighted mass of approximately 7.2 g, skin-alike modulus of 7.83 × 105 Pa, stability against skin perspiration, and a maximum stretchability of 164%. The wearable sensing component can effectively capture extrinsic laryngeal muscle movement and convert them into high-fidelity and analyzable electrical signals, which can be translated into speech signals with the assistance of machine learning algorithms with an accuracy of 94.68%. Then, with the wearable actuation component, the speech could be expressed as voice signals while circumventing vocal fold vibration. We expect this approach could facilitate the restoration of normal voice function and significantly enhance the quality of life for patients with dysfunctional vocal folds.

Vocal fold fibroblasts and exposure to vibration in vitro: Does sex matter?

Studies have shown that certain vocal fold pathologies are more common in one sex than the other. This is often explained by differences in the composition of the lamina propria and anatomical differences between female and male vocal folds, resulting in e.g. different fundamental frequencies. Here, we investigated a potential sex-specific voice frequency effect in an in vitro setting using vocal fold fibroblasts from one male and one female donor with and without cigarette smoke extract (CSE) addition. After exposure to either male or female vibration frequency with or without CSE, cells and supernatants were harvested. Gene and protein analysis were performed by means of qPCR, western blot, ELISA and Luminex. We found that exposure of cells to both male and female vibration pattern did not elicit significant changes in the expression of extracellular matrix-, inflammation-, and fibrosis-related genes, compared to control cells. The addition of CSE to vibration downregulated the gene expression of COL1A1 in cells exposed to the female vibration pattern, as well as induced MMP1 and PTGS2 in cells exposed to both female and male vibration pattern. The protein expression of MMP1 and COX2 was found to be significantly upregulated only in cells exposed to CSE and female vibration pattern. To conclude, different vibration patterns alone did not cause different responses of the cells. However, the female vibration pattern in combination with CSE had a tendency to elicit/maintain more pro-inflammatory responses in cells than the male vibration pattern.

Twin vocal folds as a novel evolutionary adaptation for vocal communications in lemurs.

Primates have varied vocal repertoires to communicate with conspecifics and sometimes other species. The larynx has a central role in vocal source generation, where a pair of vocal folds vibrates to modify the air flow. Here, we show that Madagascan lemurs have a unique additional pair of folds in the vestibular region, parallel to the vocal folds. The additional fold has a rigid body of a vocal muscle branch and it is covered by a stratified squamous epithelium, equal to those of the vocal fold. Such anatomical features support the hypothesis that it also vibrates in a manner like the vibrations that occur in the vocal folds. To examine the acoustic function of the two pairs of folds, we made a silicone compound model to demonstrate that they can simultaneously vibrate to lower the fundamental frequency and increase vocal efficiency. Similar acoustic effects are achieved using different features of the larynx for the other primates, e.g., by vibrating multiple sets of ventricular folds in several species and further by an evolutionary modification of enlarged larynx in howler monkeys. Our multidisciplinary approaches found that these functions were acquired through a unique evolutionary adaptation of the twin vocal folds in Madagascan lemurs.

Reconstruction of Vocal Fold Medial Surface 3D Trajectories: Effects of Neuromuscular Stimulation and Airflow.

INTRODUCTION: Analysis of medial surface dynamics of the vocal folds (VF) is critical to understanding voice production and treatment of voice disorders. We analyzed VF medial surface vibratory dynamics, evaluating the effects of airflow and nerve stimulation using 3D reconstruction and empirical eigenfunctions (EEF). STUDY DESIGN: In vivo canine hemilarynx phonation. METHODS: An in vivo canine hemilarynx was phonated while graded stimulation of the recurrent and superior laryngeal nerves (RLN and SLN) was performed. For each phonatory condition, vibratory cycles were 3D reconstructed from tattooed landmarks on the VF medial surface at low, medium, and high airflows. Parameters describing medial surface trajectory shape were calculated, and underlying patterns were emphasized using EEFs. Fundamental frequency and smoothed cepstral peak prominence (CPPS) were calculated from acoustic data. RESULTS: Convex-hull area of landmark trajectories increased with increasing flow and decreasing nerve activation level. Trajectory shapes observed included circular, ellipsoid, bent, and figure-eight. They were more circular on the superior and anterior VF, and more elliptical and line-like on the inferior and posterior VF. The EEFs capturing synchronal opening and closing (EEF1) and alternating convergent/divergent (EEF2) glottis shapes were mostly unaffected by flow and nerve stimulation levels. CPPS increased with higher airflow except for low RLN activation and very dominant SLN stimulation. CONCLUSION: We analyzed VF vibration as a function of neuromuscular stimulation and airflow levels. Oscillation patterns such as figure-eight and bent trajectories were linked to high nerve activation and flow. Further studies investigating longer sections of 3D reconstructed oscillations are needed. LEVEL OF EVIDENCE: N/A, Basic Science Laryngoscope, 134:1249-1257, 2024.

Effect of Testosterone on the Thyroarytenoid Muscle and Lamina Propria of Female Rat Vocal Folds.

OBJECTIVE: To analyze the effects of androgen therapy on the thyroarytenoid (TA) muscle, expression of androgen receptors (ARs) and hyaluronic acid (HA) concentration in the vocal folds (VFs) of adult female rats. METHODS: Twenty-one adult female Wistar rats were divided into experimental and control groups. The experimental group received weekly intramuscular injections of nandrolone decanoate for 9 weeks. Following euthanasia and dissection of the VFs, histomorphometric analysis of the TA muscle, immunohistochemical evaluation of ARs, and measurement of HA concentration using the ELISA-like fluorimetric method were performed. RESULTS: The experimental group exhibited a significantly larger mean fiber cross-sectional area in the TA muscle compared to the control group (434.3 ± 68.6 µm2 versus 305.7 ± 110.1 µm2; p = 0.029), indicating muscle hypertrophy. There was no significant difference in the number of muscle fibers. The experimental group showed higher expression of ARs in the lamina propria (62.0% ± 30.3% versus 22.0% ± 22.8%; p = 0.046) and in the TA muscle (45.0% ± 22.6% versus 18.3% ± 9.8%; p = 0.024). There was no significant difference in the concentration of HA. CONCLUSION: Exposure of adult female rats to androgen therapy resulted in hypertrophy of the TA muscle and increased expression of ARs in the VFs. The TA muscle seems to be the primary target of testosterone action in the VF, and the up-regulation of ARs might contribute to the persistent deepening of the voice. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2316-2321, 2024.

Histologic Examination of Vocal Fold Mucosal Wave and Vibration.

OBJECTIVES: Despite gross anatomic and histologic differences between human and canine vocal folds, similar wave patterns have been described yet not fully characterized. We reconstructed vocal fold (VF) vibration in a canine hemilarynx and performed histologic examination of the same vocal fold. We demonstrate comparable wave patterns while exploring the importance of certain anatomic architectures. METHODS: An in vivo canine hemilarynx was phonated against a glass prism at low and high muscle activation conditions. Vibration was captured using high-speed video, and trajectories of VF medial surface tattooed landmarks were 3D-reconstructed. The method of empirical eigenfunctions was used to capture the essential dynamics of vibratory movement. Histologic examination of the hemilarynx was performed. RESULTS: Oscillation patterns were highly similar between the in vivo canine and previous reports of ex vivo human models. The two most dominant eigenfunctions comprised over 90% of total variance of movement, representing opening/closing and convergent/divergent movement patterns, respectively. We demonstrate a vertical phase difference during the glottal cycle. The time delay between the inferior and superior VF was greater during opening than closing for both activation conditions. Histological examination of canine VF showed not only a thicker lamina propria layer superiorly but also a distinct pattern of thyroarytenoid muscle fibers and fascicles as described in human studies. CONCLUSIONS: Histologic and vibratory examination of the canine vocal fold demonstrated human vocal fold vibratory patterns despite certain microstructural differences. This study suggests that the multilayered lamina propria may not be fundamental to vibratory patterns necessary for human-like voice production. LEVEL OF EVIDENCE: NA (Basic science study) Laryngoscope, 134:264-271, 2024.

A practical guide to calculating vocal tract length and scale-invariant formant patterns.

Formants (vocal tract resonances) are increasingly analyzed not only by phoneticians in speech but also by behavioral scientists studying diverse phenomena such as acoustic size exaggeration and articulatory abilities of non-human animals. This often involves estimating vocal tract length acoustically and producing scale-invariant representations of formant patterns. We present a theoretical framework and practical tools for carrying out this work, including open-source software solutions included in R packages soundgen and phonTools. Automatic formant measurement with linear predictive coding is error-prone, but formant_app provides an integrated environment for formant annotation and correction with visual and auditory feedback. Once measured, formants can be normalized using a single recording (intrinsic methods) or multiple recordings from the same individual (extrinsic methods). Intrinsic speaker normalization can be as simple as taking formant ratios and calculating the geometric mean as a measure of overall scale. The regression method implemented in the function estimateVTL calculates the apparent vocal tract length assuming a single-tube model, while its residuals provide a scale-invariant vowel space based on how far each formant deviates from equal spacing (the schwa function). Extrinsic speaker normalization provides more accurate estimates of speaker- and vowel-specific scale factors by pooling information across recordings with simple averaging or mixed models, which we illustrate with example datasets and R code. The take-home messages are to record several calls or vowels per individual, measure at least three or four formants, check formant measurements manually, treat uncertain values as missing, and use the statistical tools best suited to each modeling context.

Vocal communication: The enigmatic production of low-frequency purrs in cats.

Cat purring, the unusual, pulsed vibration that epitomizes comfort, enjoys a special status in the world of vocal communication research. Indeed, it has long been flagged as a rare exception to the dominant theory of voice production in mammals. A new study presents histological and biomechanical evidence that purring can occur passively, without needing muscle vibration in the larynx controlled by an independent neural oscillator.

Flow-induced oscillations of vocal-fold replicas with tuned extensibility and material properties.

Human vocal folds are highly deformable non-linear oscillators. During phonation, they stretch up to 50% under the complex action of laryngeal muscles. Exploring the fluid/structure/acoustic interactions on a human-scale replica to study the role of the laryngeal muscles remains a challenge. For that purpose, we designed a novel in vitro testbed to control vocal-folds pre-phonatory deformation. The testbed was used to study the vibration and the sound production of vocal-fold replicas made of (i) silicone elastomers commonly used in voice research and (ii) a gelatin-based hydrogel we recently optimized to approximate the mechanics of vocal folds during finite strains under tension, compression and shear loadings. The geometrical and mechanical parameters measured during the experiments emphasized the effect of the vocal-fold material and pre-stretch on the vibration patterns and sounds. In particular, increasing the material stiffness increases glottal flow resistance, subglottal pressure required to sustain oscillations and vibratory fundamental frequency. In addition, although the hydrogel vocal folds only oscillate at low frequencies (close to 60 Hz), the subglottal pressure they require for that purpose is realistic (within the range 0.5-2 kPa), as well as their glottal opening and contact during a vibration cycle. The results also evidence the effect of adhesion forces on vibration and sound production.

Domestic cat larynges can produce purring frequencies without neural input.

Most mammals produce vocal sounds according to the myoelastic-aerodynamic (MEAD) principle, through self-sustaining oscillation of laryngeal tissues.1,2 In contrast, cats have long been believed to produce their low-frequency purr vocalizations through a radically different mechanism involving active muscle contractions (AMC), where neurally driven electromyographic burst patterns (typically at 20-30 Hz) cause the intrinsic laryngeal muscles to actively modulate the respiratory airflow. Direct empirical evidence for this AMC mechanism is sparse.3 Here, the fundamental frequency (fo) ranges of eight domestic cats (Felis silvestris catus) were investigated in an excised larynx setup, to test the prediction of the AMC hypothesis that vibration should be impossible without neuromuscular activity, and thus unattainable in excised larynx setups, which are based on MEAD principles. Surprisingly, all eight excised larynges produced self-sustained oscillations at typical cat purring rates. Histological analysis of cat larynges revealed the presence of connective tissue masses, up to 4 mm in diameter, embedded in the vocal fold.4 This vocal fold specialization appears to allow the unusually low fo values observed in purring. While our data do not fully reject the AMC hypothesis for purring, they show that cat larynges can easily produce sounds in the purr regime with fundamental frequencies of 25 to 30 Hz without neural input or muscular contraction. This strongly suggests that the physical and physiological basis of cat purring involves the same MEAD-based mechanisms as other cat vocalizations (e.g., meows) and most other vertebrate vocalizations but is potentially augmented by AMC.