PROJECT SUMMARY / ABSTRACT
Laryngeal dystonia (LD) is a neurological disorder that selectively affects speech production due to
involuntary spasms in the laryngeal muscles. As speech communication is a vital part of our daily existence,
LD symptoms have a pervasive effect on the quality of life of the affected individual, often extending beyond
speech motor deficits and causing significant occupational disability, psychiatric comorbidities, long-lasting
stress, and social isolation. Despite the chronic, debilitating impact of LD, its clinical management remains
challenging. The current treatment of LD is mostly limited to the temporary relief of voice symptoms with
repeated injections of botulinum toxin into the laryngeal muscles, which, however, are not effective in all
patients. Thus, there is an urgent clinical need to develop next-generation therapeutic interventions that are
informed by LD-specific pathophysiology for their most effective outcome in the majority of patients. Our long-
term goal is to determine the causes and pathophysiology of LD and to establish enhanced diagnostics and
treatment of this disorder. The overall objective of this study is to conduct a randomized, double-blind, sham-
controlled, parallel design, phase 1 clinical trial to assess the feasibility and efficacy of a neurofeedback brain-
computer interface (BCI) paradigm in LD patients that acts upon and modulates the disorder pathophysiology.
Our central hypothesis is that the disorder-specific neural patterns, which are distinctly associated with
symptomatic speech vs. asymptomatic whisper, maybe successfully targeted and modulated with
neurofeedback BCI intervention for rehabilitation of speech production in LD patients. Our central hypothesis
will be tested by pursuing two specific aims: (1) develop neural signatures of task-characteristic activity during
symptomatic and asymptomatic speech motor behaviors in LD patients, and (2) assess the feasibility and
efficacy of neurofeedback BCI therapeutic intervention in LD patients. The rationale for the proposed studies is
that delineation of task-specific neural signatures in LD will establish a robust scientific foundation for their
utilization as a feasible pathophysiological target of novel BCI therapeutic intervention. This research is
significant because it is expected to have a meaningful translational impact by informing the conduct of the
next phase of the clinical trial in LD patients and thus directly contribute to closing the critically existing gap in
the clinical management of this disorder. The research proposed in this application is innovative because it
uses a controlled experimental design and advanced methodologies to target disorder-specific central
pathophysiology of LD for the development of new non-invasive treatment for these patients.
