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.

Uncovering the neural control of laryngeal activity and subglottic pressure in anaesthetized rats: insights from mesencephalic regions.

To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague-Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.

Do tight nosebands have an effect on the upper airways of horses?

BACKGROUND/OBJECTIVES: The public perception relating to the welfare of horses involved with equestrian sports is associated with training methods used and the presentation of horses at events. In this context, very tight nosebands, which are intended to prevent the horse from opening its mouth, also attract a lot of attention. Various studies have evaluated the impact of tight nosebands on stress parameters, whereas the effect of tight nosebands on upper airway function is unknown. Therefore, the aim of the study was to use overground endoscopy to evaluate changes in pharyngeal and laryngeal function when a tight noseband is fitted. Moreover, the ridden horse pain ethogram (RHpE) was applied to investigate signs of discomfort (Dyson et al., 2018). STUDY DESIGN: A randomized, blinded, and prospective study was performed. METHODS: Sixteen warmblood horses consisting of twelve mares and four geldings with a mean age of 11.63 ± 3.53 years were ridden on 2 consecutive days with either loose or tight nosebands (two fingers or no space between bridge of the nose and noseband, respectively) and inserted endoscope in a random order. Videos were taken in a riding arena during a standardized exercise protocol involving beginner level tasks for 30 min in all gaits. For video analysis, freeze frames were prepared and analyzed at the beginning of the expiration phase. Pharyngeal diameter was measured using the pharynx-epiglottis ratio. Other findings (swallowing, pharyngeal collapse, soft palate movements, and secretion) were also evaluated. Moreover, the RHpE was applied. Descriptive statistics and generalized linear mixed effects models were used. Results with a p-value < 0.05 were considered statistically significant. RESULTS: While the pharynx-epiglottis ratio did not change significantly in horses ridden with loose versus tight nosebands, there was an increase in mean grade and total counts of parameters assessed in the pharyngeal region, for example, grade of secretion (1.5 [±SD 0.89] vs. 3.13 [±SD 0.96]; p = 0.0001), axial deviation of the aryepiglottic folds (0.29 [±SD 0.73] vs. 1.33 [±SD 1.44]; p = 0.01), and pharyngeal collapse (0.69 [±SD 0.87] vs. 1.88 [±SD 1.54]; p = 0.005) in horses ridden with tight nosebands. There was no RHpE score above 8 indicating musculoskeletal pain, but the RHpE scores were significantly higher in horses ridden with tight nosebands (p < 0.001). MAIN LIMITATIONS: Video quality was limited when horses showed large amounts of secretion. Another limitation was the small number of horses. CONCLUSIONS: Results add to the evidence obtained in other studies that tight nosebands do not only cause adverse reactions based on the RHpE score such as head behind the vertical or intense staring but also contribute to changes in the pharyngeal region, such as increased secretion and collapse of pharyngeal structures. This may provide further support for future decisions regarding regulations on nosebands.

What's special about human speech? A student exercise for comparing speech production between humans and chimpanzees.

Modern humans and chimpanzees share a common ancestor on the phylogenetic tree, yet chimpanzees do not spontaneously produce speech or speech sounds. The lab exercise presented in this paper was developed for undergraduate students in a course entitled "What's Special About Human Speech?" The exercise is based on acoustic analyses of the words "cup" and "papa" as spoken by Viki, a home-raised, speech-trained chimpanzee, as well as the words spoken by a human. The analyses allow students to relate differences in articulation and vocal abilities between Viki and humans to the known anatomical differences in their vocal systems. Anatomical and articulation differences between humans and Viki include (1) potential tongue movements, (2) presence or absence of laryngeal air sacs, (3) presence or absence of vocal membranes, and (4) exhalation vs inhalation during production.

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.

The domestication of the larynx: The neural crest connection.

Wolves howl and dogs bark, both are able to produce variants of either vocalization, but we see a distinct difference in usage between wild and domesticate. Other domesticates also show distinct changes to their vocal output: domestic cats retain meows, a distinctly subadult trait in wildcats. Such differences in acoustic output are well-known, but the causal mechanisms remain little-studied. Potential links between domestication and vocal output are intriguing for multiple reasons, and offer a unique opportunity to explore a prominent hypothesis in domestication research: the neural crest/domestication syndrome hypothesis. This hypothesis suggests that in the early stages of domestication, selection for tame individuals decreased neural crest cell (NCCs) proliferation and migration, which led to a downregulation of the sympathetic arousal system, and hence reduced fear and reactive aggression. NCCs are a transitory stem cell population crucial during embryonic development that tie to diverse tissue types and organ systems. One of these neural-crest derived systems is the larynx, the main vocal source in mammals. We argue that this connection between NCCs and the larynx provides a powerful test of the predictions of the neural crest/domestication syndrome hypothesis, discriminating its predictions from those of other current hypotheses concerning domestication.

Sentinels of the airways.

Epithelial cells in the larynx and trachea sense harmful cues and trigger protective reflexes.

Neuroendocrine cells initiate protective upper airway reflexes.

Airway neuroendocrine (NE) cells have been proposed to serve as specialized sensory epithelial cells that modulate respiratory behavior by communicating with nearby nerve endings. However, their functional properties and physiological roles in the healthy lung, trachea, and larynx remain largely unknown. In this work, we show that murine NE cells in these compartments have distinct biophysical properties but share sensitivity to two commonly aspirated noxious stimuli, water and acid. Moreover, we found that tracheal and laryngeal NE cells protect the airways by releasing adenosine 5'-triphosphate (ATP) to activate purinoreceptive sensory neurons that initiate swallowing and expiratory reflexes. Our work uncovers the broad molecular and biophysical diversity of NE cells across the airways and reveals mechanisms by which these specialized excitable cells serve as sentinels for activating protective responses.

Swallowing kinematics and submental muscles activation during a newly designed maneuver called Mouth Open Swallowing Maneuver: A comparative study.

The aim of this study was to design a new maneuver called the Mouth Open Swallowing Maneuver (MOSM), and to compare swallowing kinematics and submental muscles activation (SMA) between MOSM and two current approaches used in dysphagia rehabilitation. Fifty healthy volunteers were asked to perform three repetitions of dry swallowing (DS) (control task), the MOSM, the Mendelsohn Maneuver (MM), and the Tongue-Hold Maneuver (THM) during videofluoroscopic swallowing study accompanied with simultaneous SMA recording. Swallowing kinematics were measured by frame-by-frame analysis on hyolaryngeal movement using ImageJ. Swallowing with maximum hyolaryngeal movement and SMA during these tasks was used for comparative analysis. Vertical movement of the hyoid during the MOSM was significantly greater than those observed during the DS and the THM (p<0.001, p<0.001). Horizontal movement of the hyoid during DS and the THM was significantly greater than that observed during the MM (p = 0.001, p = 0.001). Vertical movement of the larynx during the MOSM was significantly greater than those observed during DS, MM, and THM (p<0.001). There was no significant difference between tasks in horizontal movement of the larynx (p = 0.785). SMA during the THM was significantly greater than that observed during MOSM (p = 0.002). No significant difference was found between other tasks in terms of SMA (p>0.05). The MOSM as a newly designed maneuver was significantly superior to other maneuvers in increasing vertical hyolaryngeal movement. The THM has as much effect on hyolaryngeal movement as the MM. In this study, the MOSM was shown to be effective in increasing hyolaryngeal movement. ClinicalTrials.gov Protocol Registration and Results System (PRS); the clinical trial registration number (NCT05579041).

The partial upward migration of the laryngeal motor cortex: A window to the human brain evolution.

The pioneer cortical electrical stimulation studies of the last century did not explicitly mark the location of the human laryngeal motor cortex (LMC), but only the "vocalization area" in the lower half of the lateral motor cortex. In the final years of 2010́s, neuroimaging studies did demonstrate two human cortical laryngeal representations, located at the opposing ends of the orofacial motor zone, therefore termed dorsal (LMCd) and ventral laryngeal motor cortex (LMCv). Since then, there has been a continuing debate regarding the origin, function and evolutionary significance of these areas. The "local duplication model" posits that the LMCd evolved by a duplication of an adjacent region of the motor cortex. The "duplication and migration model" assumes that the dorsal LMCd arose by a duplication of motor regions related to vocalization, such as the ancestry LMC, followed by a migration into the orofacial region of the motor cortex. This paper reviews the basic arguments of these viewpoints and suggests a new explanation, declaring that the LMCd in man is rather induced through the division of the unitary LMC in nonhuman primates, upward shift and relocation of its motor part due to the disproportional growth of the head, face, mouth, lips, and tongue motor areas in the ventral part of the human motor homunculus. This explanation may be called "expansion-division and relocation model".

Netrin-1 as A neural guidance protein in development and reinnervation of the larynx.

Neural guidance proteins participate in motor neuron migration, axonal projection, and muscle fiber innervation during development. One of the guidance proteins that participates in axonal pathfinding is Netrin-1. Despite the well-known role of Netrin-1 in embryogenesis of central nervous tissue, it is still unclear how the expression of this guidance protein contributes to primary innervation of the periphery, as well as reinnervation. This is especially true in the larynx where Netrin-1 is upregulated within the intrinsic laryngeal muscles after nerve injury and where blocking of Netrin-1 alters the pattern of reinnervation of the intrinsic laryngeal muscles. Despite this consistent finding, it is unknown how Netrin-1 expression contributes to guidance of the axons towards the larynx. Improved knowledge of Netrin-1's role in nerve regeneration and reinnervation post-injury in comparison to its role in primary innervation during embryological development, may provide insights in the search for therapeutics to treat nerve injury. This paper reviews the known functions of Netrin-1 during the formation of the central nervous system and during cranial nerve primary innervation. It also describes the role of Netrin-1 in the formation of the larynx and during recurrent laryngeal reinnervation following nerve injury in the adult.

Striking a (vocal) chord: musical instruments as mnemonic devices when teaching the functional anatomy of the larynx.

Mnemonic devices are memory aids that make it easier to recall information and are widely used by students studying anatomy and physiology. Simple musical instruments and toys can serve as mnemonic devices for students learning the functional anatomy of the larynx: balloons can help learners understand and recall how sound is produced; tuning pegs can help learners understand how tension affects vocal pitch; fingers on a fretboard can help learners understand how pitch is further modulated; and a common coach's whistle can demonstrate how vocal volume is controlled. Using instruments and toys engages adult learners and helps them connect complex laryngeal anatomy with previous experiences.NEW & NOTEWORTHY Musical instruments and toys can be used as mnemonic devices to help students recall and understand the functional anatomy of voice production. The mnemonics can be implemented in a variety of classrooms and are flexible and engaging.

Vocal learning-associated convergent evolution in mammalian proteins and regulatory elements.

Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

An open-source toolbox for measuring vocal tract shape from real-time magnetic resonance images.

Real-time magnetic resonance imaging (rtMRI) is a technique that provides high-contrast videographic data of human anatomy in motion. Applied to the vocal tract, it is a powerful method for capturing the dynamics of speech and other vocal behaviours by imaging structures internal to the mouth and throat. These images provide a means of studying the physiological basis for speech, singing, expressions of emotion, and swallowing that are otherwise not accessible for external observation. However, taking quantitative measurements from these images is notoriously difficult. We introduce a signal processing pipeline that produces outlines of the vocal tract from the lips to the larynx as a quantification of the dynamic morphology of the vocal tract. Our approach performs simple tissue classification, but constrained to a researcher-specified region of interest. This combination facilitates feature extraction while retaining the domain-specific expertise of a human analyst. We demonstrate that this pipeline generalises well across datasets covering behaviours such as speech, vocal size exaggeration, laughter, and whistling, as well as producing reliable outcomes across analysts, particularly among users with domain-specific expertise. With this article, we make this pipeline available for immediate use by the research community, and further suggest that it may contribute to the continued development of fully automated methods based on deep learning algorithms.

Videofluoroscopic analysis of the laryngeal movement of older adults in swallowing.

Even without diseases that cause dysphagia, physiological swallowing function declines with age, increasing the risk of aspiration. This study analyzed age-related changes in laryngeal movement in older adults. The study population consisted of 10 volunteers in their 80s and six in their 20s. A videofluoroscopic study of 3 and 10 mL barium swallows was performed laterally using a digital fluorographic. The recorded images were retrieved to a personal computer and analyzed frame-by-frame using video analysis software. The movement of the larynx during swallowing, barium's pharyngeal transit time (PTT), and laryngeal elevation delay time (LEDT) were analyzed. Results were compared between the 20s and 80s age groups using statistical analyses. The PTT was shorter in the 20s than in the 80s age group. The PTT was significantly longer in the 80s group than in the 20s for both 3 and 10 mL barium swallows. LEDT in the 80s was statistically significantly longer than that in the 20s for the 10 ml barium. No statistically significant differences were found; however, there was a tendency for the 80s group to have more types of laryngeal movement velocity peaks. In this study, LEDT was prolonged in the 80s with 10 ml barium swallowing than in the 20s. Two peak patterns of laryngeal elevation during swallowing were observed. The velocity peaks showed a two-peak pattern when the patients were in their 80s and when the barium volume was tested at 10 mL. Our results suggest that aging's effect on swallowing relates to laryngeal elevation.

The Application of Superior Laryngeal Nerve Block for Non-Cough Laryngeal Hypersensitivity.

OBJECTIVE(S): To investigate the effect of superior laryngeal nerve (SLN) block in patients with non-cough complaints relating to laryngeal who have failed conventional medical therapy. METHODS: Retrospective chart review of 46 patients who underwent SLN block for non-cough indications between July 2019 and March 2022 was performed. Demographics, comorbidities, and patient-reported outcomes were collected. The primary diagnoses for this group included: odynophagia, throat pain, cervicalgia, muscle tension dysphonia, globus sensation, hyoid bone syndrome, and Eagle syndrome. RESULTS: The cohort underwent an average of 1.24 bilateral injections (range 0-7) and 0.87 unilateral injections (range 0-4). About 35 of 46 patients reported an average of 51.0% improvement in their symptoms, with the treatment effect lasting 7.60 weeks on average. On subgroup analysis, the patients with spasmodic dysphonia, odynophagia, and hyoid bone syndrome had the best percent improvement on average (75%-77.5%). Patients with globus sensation had the lowest percent improvement on average in response to this therapy, reporting only about 25%. Five patients experienced a mild adverse reaction immediately following injection which resolved spontaneously. CONCLUSION: The use of in-office SLN block for non-cough disorders involving the larynx requires further study with larger sample sizes to better delineate the efficacy of these applications. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1765-1768, 2024.

A Tutorial on Skeletal Muscle Metabolism and the Role of Blood Lactate: Implications for Speech Production.

PURPOSE: The purpose of this tutorial is threefold: (a) present relevant exercise science literature on skeletal muscle metabolism and synthesize the limited available research on metabolism of the adult human speech musculature in an effort to elucidate the role of metabolism in speech production; (b) introduce a well-studied metabolic serum biomarker in exercise science, lactate, and the potential usefulness of investigating this metabolite, through a well-established exercise science methodology, to better understand metabolism of the musculature involved in voice production; and (c) discuss exercise physiology considerations for future voice science research that seeks to investigate blood lactate and metabolism in voice physiology in an ecologically valid manner. METHOD: This tutorial begins with relevant exercise science literature on the basic cellular processes of muscle contraction that require energy and the metabolic mechanisms that regenerate the energy required for task execution. The tutorial next synthesizes the available research investigating metabolism of the adult human speech musculature. This is followed by the authors proposing a hypothesis of speech metabolism based on the voice science literature and the application of well-studied exercise science principles of muscle physiology. The tutorial concludes with a discussion and the potential usefulness of lactate in investigations to better understand the metabolism of the musculature involved in vocal demand tasks. CONCLUSION: The role of metabolism during speech (respiratory, laryngeal, and articulatory) is an understudied yet critical aspect of speech physiology that warrants further study to better understand the metabolic systems that are used to meet vocal demands.

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.

A brainstem circuit for phonation and volume control in mice.

Mammalian vocalizations are critical for communication and are produced through the process of phonation, in which expiratory muscles force air through the tensed vocal folds of the larynx, which vibrate to produce sound. Despite the importance of phonation, the motor circuits in the brain that control it remain poorly understood. In this study, we identified a subpopulation of ~160 neuropeptide precursor Nts (neurotensin)-expressing neurons in the mouse brainstem nucleus retroambiguus (RAm) that are robustly activated during both neonatal isolation cries and adult social vocalizations. The activity of these neurons is necessary and sufficient for vocalization and bidirectionally controls sound volume. RAm Nts neurons project to all brainstem and spinal cord motor centers involved in phonation and activate laryngeal and expiratory muscles essential for phonation and volume control. Thus, RAm Nts neurons form the core of a brain circuit for making sound and controlling its volume, which are two foundations of vocal communication.