The VAST Research Lab is an energetic group of researchers engaged in a variety of research projects, in collaboration with partners both within and outside the University of Utah. This lab supports funded and unfunded projects addressing normal and abnormal voice, breathing and swallowing.
NIH Funded Projects
PROJECT SUMMARY / ABSTRACT: The goal of this research is to systematically investigate the contribution of the compliance levels of the aortic arch and pulmonary artery to onset of impaired function of the recurrent laryngeal branch (RLN) of the vagus nerve associated with unilateral vocal fold paralysis (UVP). The RLN provides sensorimotor innervation to the muscles that control the vocal folds within the larynx. Vocal fold function is important for protection of the airway during swallowing, the regulation of breathing, and for voice production. Individuals with UVP frequently experience choking while eating, difficulty breathing, and difficulty speaking. The majority of individuals diagnosed with UVP are older than 45 years of age. Although surgery is the most common etiology of UVP, approximately 12-42% of those diagnosed with UVP have no known cause (i.e. idiopathic). Prior work studying idiopathic onset of UVP in horses identified nerve changes and characteristics indicative of chronic compression on the RLN near the aortic arch. Our team recently identified that individuals with iUVP exhibited significantly higher aortic arch compliance than age- and gender-matched controls as a possible contributing factor in iUVP. This finding supported our hypothesis that RLN stress and strain levels associated with aortic arch dynamic diameter changes could impact RLN function. Similar patterns in pulmonary artery compliance levels were also identified in the same group of those with iUVP compared to normal controls suggesting a systemic change in vascular compliance. Given that the left RLN is most commonly associated with iUVP, we hypothesize that increased compliance levels in large- diameter blood vessels adjacent to the RLN (i.e. aortic arch and pulmonary artery) can impair RLN function due to excessive stress and strain levels that compromise the nerve's protective layers of connective tissues resulting in damaged nerve fibers. The goal of this project is to investigate the level of compliance change in the aorta associated with impaired RLN function in pigs. We will also expand imaging of the aortic arch and pulmonary artery to include the right subclavian artery to determine whether vascular compliance levels generally differ between those with iUVP compared to controls. In addition, we will compare compliance levels between a large-diameter vessel (aortic arch) and a small-diameter vessel (right subclavian artery) associated with the RLN between human subjects with iUVP and matched normal controls. Outcomes will eludicate whether the size of vessel explains the predominance of left-sided iUVP. Systematic comparison of medical, environmental, and genetic historical data between human subject groups will also enable identification of risk factors associated with hypercompliance of the vasculature. Outcomes of this project will elucidate the role of vascular hypercompliance on impaired RLN function in those with iUVP and determine co-morbidities and risk factors that could lead to prevention or alternative treatment approaches for iUVP in the future. View study details on NIH.gov
University of Utah Collaborators: Richard Wiggins, MD; Ed DiBella, PhD
Multi-Site Collaborators: Jonathan Vande Geest, PhD (University of Pittsburgh), Randal Paniello, MD (Washington University, St Louis), Andrew Bierhals, MD (Washington University, St Louis).
PROJECT SUMMARY / ABSTRACT Essential tremor is one of the most common movement disorders in the world affecting approximately 4.6% of those 65 years of age or older and approximately 2.2% of the US population, or 7 million people. Approximately 30% of these individuals exhibit a vocal tremor due to essential tremor (ET), or Essential Vocal Tremor (EVT), with the majority being female. EVT significantly impacts quality of life and does not consistently or significantly benefit from medications or medical management approaches that are currently used to treat limb tremor. The differing response to current medical treatments between those with EVT and those with ET without vocal tremor (EVT0) highlights the need for determining differing characteristics between those with EVT compared to EVT0. Individuals with EVT report increased effort during speaking and worsening of their vocal tremor during stressful activities that promote anxiety or require more concentration and effort. To date, EVT has been characterized primarily by acoustic measures of voice modulation resulting in limited understanding regarding speech structure contributions to the onset and progression of this disorder. This is in contrast to longstanding diagnostic characteristics of tremor rate and extent described in the literature for tremor affecting the arms, hands, head, or legs that can be used to distinguish between neurologic etiologies. Insight into the physiologic underpinnings of speech structures affected by tremor and their links to impaired speech production would enable insights regarding optimal clinical approaches for evaluating and managing vocal tremor. Further, determining salient physiologic characteristics associated with vocal tremor could potentially lead to clinical evaluation approaches that enable identification of the different neurogenic causes of vocal tremor (e.g. basal ganglia, cerebellar, extrapyramidal pathways). The goal of this project is to systematically evaluate and model the contribution of tremor affecting the respiratory, laryngeal, and articulatory structures to vocal tremor acoustic patterns. Outcomes of this research will significantly advance our scientific knowledge regarding the physiologic underpinnings of EVT and its correspondence to impaired communication function. Further, outcomes will advance current clinical evaluation and treatment methods and enable future investigation of unique physiologic characteristics across other etiologies of vocal tremor (e.g. Parkinson Disease, Dystonia) that will advance current and future treatment approaches. View project details on NIH.gov
Upper airway stenosis is a condition that significantly impairs breathing and voice. Stenosis-related voice disorders can adversely impact communication, job performance, psychosocial function, and quality of life. Clinical and scientific studies have elucidated important relationships between voice function and stenosis severity and management, but many aspects of these relationships are not fully understood. The objectives of the proposed research are to develop larynx-specific MRI coils and protocols for upper airway stenosis imaging and to determine the impact of glottic and subglottic morphology on voice function in upper airway stenosis patients. Custom imaging coils and protocols will be developed and refined based on physical principles and preliminary tests. MR images in stenosis patients will be acquired pre- and post-operatively. Images will be used to create 3D geometric models for morphometric analysis and posting on an online laryngeal data repository for further research. Retrospective and prospective pre- and post-operative aerodynamic and acoustic studies of patients with upper airway stenosis will be conducted to explore relationships between preoperative voice complaints and pre/post-operative voice changes. Excised larynx and synthetic vocal fold laboratory experiments using 3D-printed airways with adjustable stenoses, in conjunction with complementary computational simulations of phonatory flow-structure-acoustic interactions, will be used to explore fundamental physical relationships between stenosis geometry and changes in flow patterns, vocal fold vibration, and acoustics. Anticipated outcomes include larynx imaging coil prototypes and protocols suitable for the needs of clinical laryngeal imaging evaluations and scientific research, detailed geometric three-dimensional models of the upper airway in healthy and stenosis populations, and deeper insight into the sources of dysphonia in stenosis patients and into the aerodynamic and acoustical changes associated with upper airway stenosis. The ultimate aim is to develop tools and understanding that will lead to improved voice outcomes for patients with upper airway stenosis. View project details on NIH.gov
PROJECT SUMMARY/ABSTRACT Over 40 million children and adults in the US suffer from chronic pulmonary diseases including asthma, chronic bronchitis and obstructive pulmonary disease. Asthma alone accounts for 25 million cases, with prevalence increasing by 10% each decade. Combination inhaled corticosteroids (ICs) are the treatment of choice for the long-term management of breathing symptoms. Regrettably, ICs are also associated with voice disorders in up to 50% of cases. These disorders become chronic, impair communication, and have significant adverse occupational, financial, and psychosocial consequences. Given the prevalence of voice disorders associated with combination ICs since chlorofluorocarbon-propelled inhalers were banned in 2008, compelling clinical evidence necessitates a new research initiative to address this critical threat to public health. The long-term goal of this research program is to prevent and cure voice disorders associated with combination ICs across the lifespan. Children placed on inhalers face lifelong, possibly permanent communication impairment. Determining the pathophysiology of IC-related voice disorders is the critical next step to developing new voice-sparing asthma drugs. It is essential to determine the pathophysiology of voice disorders associated with combination ICs, to treat, reverse, and prevent these voice changes. This project accomplishes these objectives in 3 hypothesis-driven aims. Aim 1 determines structural laryngeal biomarkers of IC use associated with voice disorders in children and adults with the 2 most common phenotypes of asthma (high TH2 allergic and low TH2 primarily eosinophilic). Aim 2 quantifies voice disorder onset and reversibility for ICs versus sham using an in vivo animal model. Aim 3 examines the pathogenesis of IC-related voice disorders via examination of cytokines associated with inflammation (IL-1β, IL-6, TNF-α) from animal true vocal folds and human false vocal folds. Collectively, these aims define the pathophysiology associated with IC-related voice disorders, laying the foundation for voice disorder cure and prevention in this population. This translational project will have immediate and significant clinical implications, making a powerful and sustained impact in the field of communication disorders. View project details on NIH.gov
PROJECT SUMMARY / ABSTRACT Loss of voice control, which is critical for conveying effective spoken communication, is often a significant feature in patients with movement disorders, such as dystonia and essential tremor. Voice dysfunction, however, has been overshadowed clinically by a focus on limb motor symptoms. For example, deep brain stimulation (DBS) effectively reduces limb dystonia and tremor in these patients, but the modulation of voice symptoms by DBS has been vastly understudied. It is assumed that the production and modulation of voice are regulated by the basal ganglia-thalamo-cortical network in a loop architecture that is common to all motor behaviors. There is, however, little empirical data to inform our specific understanding of how voice function is encoded in basal ganglia-thalamo-cortical interactions. The overall goal of this Project is to use a combination of invasive and non-invasive human neuroscience to improve our understanding of the incidence and neural correlates of neurological voice disorders (laryngeal dystonia and voice tremor) in patients with isolated dystonia and essential tremor undergoing DBS surgery. We will use simultaneous electrocorticography (ECoG) and subcortical activity recording in dystonia and tremor patients who are awake and speaking during DBS implantation surgery. We will supplement these data with non- invasive, multimodal scalp magneto/electroencephalography (M/EEG) and functional MRI (fMRI) recordings before DBS surgery and longitudinal M/EEG recordings within one year after surgery to enhance our understanding of DBS-induced neural network modulation relevant to voice motor symptoms in dystonia and tremor patients. This work will be facilitated by the fact that all participating Center sites already use the same equipment and techniques for DBS implantation and will follow standardized experimental protocols. The disorder-specific intracranial neurophysiological signatures will be correlated with non-invasive imaging findings, stimulation location defined connectivity maps, and voice outcomes. The results of this Project will inform the development of strategies for closed-loop brain stimulation specifically to treat neurological voice dysfunction that can be tested in a subsequent clinical trial. View project details on NIH.gov
Project Summary Systematically improving upon current voice therapy outcomes is problematic as the specific clinician actions (i.e., ingredients) responsible for improved patient functioning (i.e., targets) are unknown. For example, Comparative Effectiveness Research (CER) can show that therapy A works better than therapy B on global outcome X. But why did therapy A provide better outcomes? Why did some patients in therapy B significantly improve with the “worse” program; and some patients in therapy A remain unchanged with the “better” program? A theory-based system is needed to scientifically identify a program’s ingredients associated with improved outcomes across patients. And standard labels are needed to make the identified active ingredients generalizable across therapy programs. Therefore, this project will use a theory-driven framework for describing the ingredients/targets of rehabilitation treatments—called the Rehabilitation Treatment Specification System (RTSS)—and standard voice-specific terminology/definitions—called the RTSS-Voice— to standardly describe (Aim 1) and compare (Aim 2) variations in treatment across 9 well-known and diverse voice therapies. Also, we will create/test an implementation toolkit to facilitate RTSS-Voice adoption in clinical care across 5 Voice Centers (Aim 3). It is hypothesized that the RTSS and RTSS-Voice will characterize all therapies without needing revisions (Aim 1) and identify ingredients/targets that are unique to one therapy and/or common across multiple therapies (Aim2). And since the RTSS-Voice will help clinicians think about their treatment more specifically and in relation to 9 evidence-based therapies, we hypothesize adoption will be associated with improved outcomes at all 5 Voice Centers. The resulting list of mutually exclusive ingredient/targets across therapy programs will obviously improve the state of CER by enabling the identification/comparison of active ingredients across therapy programs; instead of the current practice of studying/comparing entire programs. Clinical adoption will result in large datasets with standard ingredients linked to outcomes, which will facilitate innovative hypotheses and interpretable datamining/machine learning to realistically improve voice therapy effectiveness. This work is likely to generalize to other Centers due to the involvement of >20 influential clinicians and the implementation toolkit. View project details on NIH.gov
Essential voice tremor (EVT) affects over 40% of individuals with essential tremor (ET), one of the most common movement disorders characterized primarily by upper limb tremor. EVT is a significant problem because it profoundly disturbs communication and quality of life. The few available pharmacological treatments, such as propranolol and botulinum toxin injections, have limited efficacy. When tremor intensifies and patients no longer respond to medication the standard management of ET is deep brain stimulation (DBS) of the ventral intermedius nucleus (VIM) of the thalamus. The few available studies suggest that VIM DBS can be an effective treatment for suppression of EVT in addition to upper limb tremor. However, most studies are limited to subjective categorical (0-4) severity ratings and the few studies that have used acoustic voice analysis to quantify EVT have examined a small number of patients. Also, based on theory and few case studies, the placement of a DBS lead in specific thalamic locations could affect both hand and head regions and consequently suppress EVT and upper limb tremor. In summary, to establish VIM DBS as a treatment for EVT, there is a need to determine the optimal thalamic location for neurostimulation that will mediate upper limb and voice tremor suppression. This requires precise quantification of voice tremor changes in a large and well-established cohort. Here, our multidisciplinary group, proposes to address the current knowledge gaps and determine if VIM DBS is an effective treatment of EVT. In the next five years, we will leverage our ability to recruit 140 ET patients undergoing VIM DBS treatment to test the central hypothesis that neurostimulation applied onto specific thalamic neurocircuitry will suppress EVT and limb tremor. In Aim 1, we will use sensitive acoustic analyses to precisely quantify the effectiveness of DBS on EVT and advance our current understanding which is based on perceptual analysis. We will test the hypothesis (H1) that bilateral thalamic DBS will suppress voice tremor only in EVT patients. In Aim 2, based on our strong preliminary data, we propose to examine the association between voice tremor with axial tremor and fall risk. We will test the hypothesis (H2) that voice tremor suppression will be associated with reduced axial tremor and reduced fall risk. In Aim 3, we will use cutting-edge neuroimaging techniques to determine the effect of the volume of tissue activated (VTA) locations and related neurocircuitry on EVT suppression. This proposition is based on our preliminary data that stimulation of the non-decussating dentato-rubral-thalamo-tract (nDRTT) associated with reduced EVT. We will test the following two hypotheses: H3.a. - Bilateral stimulation of the nDRTT will be associated with EVT suppression. H3.b. - VTAs located in thalamic areas that affect both the hand and head (medially in the thalamus) will induce a greater suppression of EVT. The outcomes of this R01 will be clinically impactful and improve current treatment of ET because they will identify thalamic targets that optimize EVT suppression and determine if this EVT suppression is a marker for reduced fall risk in ET.
Contact Us
Julie Barkmeier-Kraemer, PhD
Professor, Department of Otolaryngology, Head & Neck Surgery
Adjunct Faculty, Department of Communication Sciences & Disorders
Email: JulieB.Kraemer@hsc.utah.edu
Phone: 801-585-7143
To Contact the VAST Lab: 801-213-7317
Imaging & Neurosciences Building
729 Arapeen Drive
Salt Lake City, UT 84108