The effects of neural modulation on phonatory function in laryngeal dystonia

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Project Summary This application will provide the Principal Investigator, Dr. Teresa Kimberley, with protected time and support to (1) accelerate a successful record of mentoring junior investigators; (2) provide research training to mentees engaged in patient-oriented communication disorder research; (3) enhance training in assessing voice production and; (4) advance the translation of Dr. Kimberley's ongoing research on laryngeal dystonia. Dystonia is a group of devastating neurological movement disorders that can affect any body region. There is no cure or disease-modifying treatment and the pathophysiology of the disorder remains largely unknown. The most common dystonia affecting the vocal fold muscles is adductor laryngeal dystonia (AdLD). People with AdLD suffer from a strangled voice and speech interruption due to involuntary spasms of the thyroarytenoid (TA) muscles. The long- term goal of this award is to elucidate the pathophysiology of laryngeal dystonia and to develop sensitive testing and novel interventions to treat the disease. The proposed project builds upon Dr. Kimberley's cutting-edge work of developing a novel and valid transcranial magnetic stimulation (TMS) methodology to assess the cortical excitability of the laryngeal motor cortical area. Recent findings have shown an atypical pattern of brain activation and decreased intracortical inhibition in people with AdLD. The hypothesis is that a 5-day inhibitory rTMS protocol targeted to the left laryngeal motor area associated with the TA muscles will increase intracortical inhibition and improve phonatory function in people with AdLD. Individuals with AdLD will participate in a randomized, double-blinded, sham-controlled, preliminary trial. The primary tests will include assessments of phonatory function (Aim 1) and TMS-measured neurophysiology (Aim 2). Factors associated with positive response to the intervention will also be explored (Aim 3). This project offers a unique opportunity for mentees to train in clinical and translational research that is at the intersection of corticobulbar neurophysiology, non- invasive neuromodulation, and clinical assessment of voice disorders. The rich resources at Massachusetts General Hospital, MGH Institute of Health Professions, and Spaulding Rehabilitation Hospital provide an outstanding scientific environment to train the next generation of researchers in an interdisciplinary approach to communication disorders research. This project has the potential to positively impact people with AdLD by expanding treatment options, improving quality of life and reducing healthcare burden for people with this disorder. The knowledge gained from the proposed study will extend to future research to optimize neuromodulatory interventions, explore rTMS as an adjunct therapy to current treatments, and to determine if rTMS can be translated to other voice disorders or types of focal dystonia.