Deep Brain Stimulation in Laryngeal Dystonia and Voice Tremor

The goals of this project are 1) to determine the incidence of neurological voice disorders in patients with dystonia and essential tremor undergoing deep brain stimulation (DBS), 2) investigate the neuroimaging and intracranial neurophysiology correlates of voice dysfunction in these subjects, and subsequently 3) determine the effects of DBS on voice function.

Study Overview

• Status: Recruiting
• Conditions: Dystonia; Tremor; Spasmodic Dysphonia; Laryngeal Dystonia
• Intervention / Treatment: Procedure: Deep Brain Stimulation

Detailed Description

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 research 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. The investigators will use simultaneous electrocorticography (ECoG) and subcortical activity recording in dystonia and tremor patients who are awake and speaking during DBS implantation surgery. The results of this research 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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristina Simonyan, MD, PhD; Phone Number: 617-573-6016; Email: simonyan_lab@meei.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital, University of California San Francisco, University of Utah
      • Contact: Kristina Simonyan, MD, PhD; Phone Number: 617-573-6016; Email: simonyan_lab@meei.harvard.edu
      • Principal Investigator: Julie Barkmeier-Kraemer, PhD
      • Principal Investigator: Shervin Rahimpour, MD
      • Principal Investigator: Ian Bledsoe, MD, MS
      • Principal Investigator: Jeremy Greenlee, MD
      • Principal Investigator: Farid Hamzei-Sichani, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion

1. Clinical indications to proceed with DBS implantation, as determined by the clinical multidisciplinary movement disorders board, including: a) definitive diagnosis of essential tremor or dystonia, b) medically refractory disease, c) adequate performance on neuropsychological evaluation as determined by a licensed clinical neuropsychologist.
2. The ability to comply with test directions, complete pre-operative task training, and provide informed consent.
3. Age 18-80 years.

Exclusion

1. Inability to understand or perform the task outlined in the protocol during a pre-surgery training session. 2. Significant hearing loss.

3. Cortical venous anatomy that could potentially obstruct ECoG electrode placement, as determined by the surgeon, visualized on pre-op MRI or during surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electrophysiological signal data collection; Patients diagnosed with dystonia or tremor who are recommended for DBS surgery. Electrophysiological data will be collected at the time of DBS surgery.	Procedure: Deep Brain Stimulation; Clinically indicated DBS treatment for dystonia or tremor with simultaneous research electrocorticography (ECoG).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations between brain signals and intraoperative voice and speech production performance.	Analysis of intraoperative recordings from deep basal ganglia structures and cortical regions relevant to voice and speech control.	5 years
Changes in standard clinical outcome for dystonia patients	Quantitative measures of voice and motor changes following deep brain stimulation surgery using standard clinical criterion of Burk-Fahn-Marsden Dystonia Rating Scale where higher score means a worse outcome.	5 years
Changes in standard clinical outcome for tremor patients	Quantitative measures of voice and motor changes following deep brain stimulation surgery using standard clinical criterion of Fahn-Tolosa-Marin Tremor Rating Scale where higher score means a worse outcome.	5 years

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Collaborators: Massachusetts General Hospital; University of California, San Francisco; University of Utah
• Investigators: Study Director: Kristina Simonyan, MD, PhD, Massachusetts Eye and Ear

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: November 27, 2021
• First Submitted That Met QC Criteria: November 27, 2021
• First Posted (Actual): December 8, 2021

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Movement Disorders; Dyskinesias; Laryngeal Diseases; Voice Disorders; Dystonia; Dystonic Disorders; Tremor; Dysphonia
• Other Study ID Numbers: 2021P003236

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No