PROJECT SUMMARY / ABSTRACT Laryngeal dystonia (LD) and voice tremor (VT) are hyperkinetic neurological disorders that significantly impair voice and speech production and negatively impact the patient’s quality of life, extending beyond speech motor alterations and often causing occupational disability and life-long social isolation. The standards of clinical care of LD and VT are not established; that is, the differential diagnostic criteria remain vague, leading to a high rate of misdiagnosis, whereas treatment is largely limited to temporary symptom management with botulinum toxin injections into the affected laryngeal muscles. One of the major causes of suboptimal clinical care of these patients is the limited understanding of their distinct clinical characteristics and neural pathophysiology. We propose a multi-institutional, cross-disciplinary Center research program that will focus on the delineation of unique clinical and pathophysiological features of LD and VT in order to establish the fundamental framework for the enhanced clinical management of these disorders, including their accurate diagnosis and disorder-specific therapies. The Center research goals will be accomplished through collaborative clinical research studies at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, University of California San Francisco, and University of Utah, which will include three Center Projects, a Scientific Core that incorporates the Clinical Research and Data Science components, and an Administrative Core that provides an overall organizational infrastructure to the Center activities. The overall Specific Aims of this Center will be (1) Characterization of clinical phenotypes of LD and VT; (2) Understanding disorder-specific neural pathophysiology in LD and VT; (3) Deep brain stimulation in LD and VT, and (4) Machine-learning platforms for differential diagnosis of LD and VT. We expect that our cross-disciplinary and collaborative Center, encompassing the expertise in otolaryngology, speech-language pathology, neurology, neurosurgery, brain and larynx imaging, invasive neurophysiology, and clinical neuroscience and applying complementary multimodal methodologies across these fields, will have a significant positive impact on developing new knowledge about the links between symptomatology and pathophysiology of LD and VT, which will help define the new standards of enhanced clinical care of these disorders.

PROJECT NARRATIVE The overall goals of this Center are to (1) identify integrated features of clinical, behavioral and neural characteristics that reflect overlapping and distinct pathophysiology of laryngeal dystonia and voice tremor, and (2) develop predictive analytics for differential diagnosis of these disorders. This research is relevant to public health because it is expected to advance the understanding of the disorder pathophysiology and help define new approaches for their clinical management. Thus, the proposed research is relevant to NIH’s mission that pertains to developing fundamental knowledge that will help reduce the burdens of human disability.