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Understanding Disorder-specific Neural Pathophysiology in Laryngeal Dystonia and Voice Tremor

Early Phase 1
Recruiting
Conditions
Spasmodic Dysphonia
Laryngeal Dystonia
Tremor
Interventions
Other: Brain imaging
Drug: Laryngeal sensory block with topical bupivacaine
Registration Number
NCT05216770
Lead Sponsor
Massachusetts Eye and Ear Infirmary
Brief Summary

The researchers will examine functional neural correlates that differentiate between laryngeal dystonia and voice tremor and contribute to disorder-specific pathophysiology using a cross-disciplinary approach of multimodal brain imaging.

Detailed Description

Laryngeal dysphonia (LD) and Voice Tremor (VT) are neurological voice disorders that impair speech production. The characteristic feature of LD (i.e., occurring during speaking but not laughing or crying) and the lack of physical laryngeal abnormalities suggests that LD is likely a disorder affecting the task-specific control of phonation by the central nervous system (CNS). Similarly, VT is often observed without any clear peripheral laryngeal etiology, also suggesting a central origin but distinct from that affected in LD. The overall goal of this project is to characterize the common and distinct features of CNS pathophysiology in the neurological voice disorders, LD and VT. The act of speech is a dynamic process, including initial glottal movement, voice onset, and compensatory responses to sensory feedback fluctuations during sustained phonation. Identifying specific functional impairments in LD and VT requires a clear understanding of when in the process of phonation, as well as where in the CNS, aberrant activity occurs. Due to their poor temporal resolution, prior neuroimaging studies have not been able to address the question of when abnormal CNS activation occurs relative to specific phonation events. As a result, critical clues about the underlying etiologies in these disorders have likely been missed. A multimodal brain imaging will asses CNS abnormalities associated with LD and VT, specifically 1) Spatial and temporal CNS pathophysiology during speech and other vocal tasks; 2) Sensorimotor modulations on CNS pathophysiology; and 3) Motor learning and CNS pathophysiology. Future treatments for LD and VT can be developed by targeting CNS pathophysiological mechanisms identified in this project.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
165
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Auditory feedback processing in laryngeal dystonia and voice tremorBrain imagingThe role of auditory feedback processing on task-induced speech sensorimotor activity will be examined using MEG imaging during perturbing pitch or formants of auditory feedback, unpredictably during speech production, and examining the behavioral and neural correlates of the resulting within-trial compensation responses.
Spatial and temporal CNS pathophysiology of laryngeal dystonia and voice tremorBrain imagingSimultaneous fMRI with EEG and MEG imaging will be used to examine neural dynamics during phonation.
Sensorimotor modulations of laryngeal dystonia and voice tremor with bupivacaineLaryngeal sensory block with topical bupivacaineTopical laryngeal block (1 ml of 0.75% bupivacaine solution) will be used to modulate somatosensory feedback from the laryngeal mucosa during speech production and examine associated changes in brain activity.
Motor learning and CNS pathophysiology of laryngeal dystonia and voice tremorBrain imagingImplicit learning of the production of motor sequences will be examined during simultaneous fMRI/EEG and MEG imaging. Sensorimotor adaptation of speech production during MEG imaging will be examined during perturbing pitch or formants of auditory feedback consistently during speech production and examining the behavioral and neural correlates of the resulting across-trial adaptation responses.
Placebo effects in laryngeal dystonia and voice tremorLaryngeal sensory block with topical bupivacaine1 ml of saline placebo matching to 1 ml of 0.75% bupivacaine solution will be used for a comparison with the topical laryngeal block to modulate somatosensory feedback from the laryngeal mucosa during speech production and examine associated changes in brain activity.
Primary Outcome Measures
NameTimeMethod
Effects of sensorimotor brain modulation on voice function in laryngeal dystonia5 years

Quantitative measures of symptoms will be determined using Burk-Fahn-Marsden Dystonia Rating Scale where higher score means a worse outcome, following sensorimotor feedback modulation in patients with laryngeal dystonia

Effects of sensorimotor brain modulation on voice function in voice tremor5 years

Quantitative measures of symptoms will be determined using Fahn-Tolosa-Marin Rating Scale where higher score means a worse outcome, following sensorimotor feedback modulation in patients with voice tremor

Functional MRI, MEG and EEG signal changes in laryngeal dystonia compared to voice tremor5 years

Qualitative analysis of brain regions with disorder-specific increases and decreases of spatial (functional MRI) and temporal (MEG and EEG) signals will be determined in patients with laryngeal dystonia compared to patients with voice tremor

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Massachusetts Eye and Ear and University of California San Francisco

🇺🇸

Boston, Massachusetts, United States

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