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The Role of Cerebellum in Speech

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ClinicalTrials.gov Identifier: NCT03972202
Recruitment Status : Recruiting
First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sponsor:
Collaborators:
University of California, Berkeley
University of Wisconsin, Madison
National Institute on Deafness and Other Communication Disorders (NIDCD)
Information provided by (Responsible Party):
John Houde, University of California, San Francisco

Brief Summary:
This study will investigate the how the cerebellum is involved in speech motor learning over time and short-term corrections in patients with cerebellar ataxia and healthy controls. This will be accomplished through three approaches: behavioral studies, magnetic resonance imaging (MRI), and transcranial magnetic stimulation (TMS). During behavioral studies, participants will be asked to speak into a microphone while their voice is played back over earphones, and to do other speaking tasks. MRI will be acquired to perform a detailed analysis on brain function and anatomy related to speech and the cerebellum. In healthy controls, TMS will also be performed to temporarily disrupt the cerebellum before, during, or after the participant performs speaking tasks. Patients with cerebellar ataxia and healthy volunteers will be asked to complete behavioral studies and/or MRI; healthy volunteers may be asked to additionally participate in TMS.

Condition or disease Intervention/treatment Phase
Cerebellar Ataxia Dysarthria Healthy Diagnostic Test: MRI Device: TMS Behavioral: Speech-motor behavioral testing Not Applicable

Detailed Description:

This study will investigate the role of the cerebellum in speech, building upon prior work in understanding cerebellar function in reaching and walking. Neuroimaging and lesion studies have provided strong evidence that the cerebellum is an integral part of the speech production network, though its precise role in the control of speech remains unclear. Furthermore, damage to the cerebellum (either degenerative or focal) can lead to ataxic dysarthria, a motor speech disorder characterized, in part, by impaired articulation and severe temporal deficits. This project seeks to bridge the gap between theoretical models of cerebellar function and the speech symptoms associated with ataxic dysarthria. Two mechanisms underlie speech motor control - feedback and feedforward control. In feedback control, speakers use sensory feedback (e.g., of their own voice) to control their speech. In feedforward control, speakers use knowledge gained from their past speech productions, rather than on-line feedback, to control their speech. This study entails a systematic plan to elucidate the role of the cerebellum in feedforward and feedback control of speech. A central hypothesis is that the cerebellum is especially critical in the feedforward control of speech, but has little involvement in feedback control. To explore this hypothesis, we will obtain converging evidence from three innovative methodologies: 1) Neuropsychological studies of speech-motor responses to real-time altered auditory feedback in patients with cerebellar atrophy (CA) and matched healthy controls, 2) Parallel studies in healthy controls undergoing theta-burst transcranial magnetic stimulation to create "virtual lesions" of the cerebellum, and 3) Structural and functional studies in CA patients to examine the relationship between cerebellar lesion location, dysarthria symptoms, and feedforward and feedback control ability.

Speech provides an important opportunity to examine how well current theories of cerebellar function generalize to a novel effector (vocal tract) and sensory (auditory) domain. Its purpose for communication imposes exacting spectro-temporal constraints not seen in other motor domains. Furthermore, the distinctive balance of feedback and feedforward control in speech allows us to examine changes in both control types subsequent to cerebellar damage. Critically, this is the first work examining the link between theoretically motivated control deficits in CA patients and the speech symptoms associated with ataxic dysarthria, as well as their neural correlates.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 264 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Role of Cerebellum in Speech
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2023


Arm Intervention/treatment
Experimental: Patients with cerebellar ataxia (CA)
Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI)
Diagnostic Test: MRI
Brain MRI will be performed (no contrast) to correlate brain anatomy/function with behavioral testing.
Other Name: Magnetic Resonance Imaging

Behavioral: Speech-motor behavioral testing
Language/speaking tasks will be performed during which participants are asked to speak in response to audio/video cues; participants' responses will be recorded. For patients with cerebellar ataxia, additional diagnostic surveys may be completed.

Active Comparator: Matched controls
Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI)
Diagnostic Test: MRI
Brain MRI will be performed (no contrast) to correlate brain anatomy/function with behavioral testing.
Other Name: Magnetic Resonance Imaging

Behavioral: Speech-motor behavioral testing
Language/speaking tasks will be performed during which participants are asked to speak in response to audio/video cues; participants' responses will be recorded. For patients with cerebellar ataxia, additional diagnostic surveys may be completed.

Experimental: Additional healthy volunteers
Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI) Transcranial magnetic stimulation (TMS)
Diagnostic Test: MRI
Brain MRI will be performed (no contrast) to correlate brain anatomy/function with behavioral testing.
Other Name: Magnetic Resonance Imaging

Device: TMS
Repetitive TMS will be applied to transiently disrupt cerebellar speech pathways.
Other Names:
  • Transcranial Magnetic Stimulation
  • Repetitive TMS
  • rTMS

Behavioral: Speech-motor behavioral testing
Language/speaking tasks will be performed during which participants are asked to speak in response to audio/video cues; participants' responses will be recorded. For patients with cerebellar ataxia, additional diagnostic surveys may be completed.




Primary Outcome Measures :
  1. Speech-motor response percent compensation [ Time Frame: Baseline ]
    Percent compensation is calculated as the following ratio: -100*(change in acoustic feature produced by the subject)/(change in acoustic feature caused by auditory feedback alteration). The negative sign ensures that changes produced by the subject that oppose the auditory feedback alteration changes are counted as positive compensation. Acoustic features used to compute percent compensation depend on the experiment performed and will include pitch or formant frequencies of subjects' output speech (measured by frequency in Hz), voice onset time (measured in milliseconds), fricative consonant duration (measured in milliseconds), and formant transition time (measured in milliseconds). We will look for short-term (within-trial) and long-term (across-trial) changes in percent compensation produced by subjects in response to alterations in subjects' auditory feedback they hear while speaking.

  2. Dysarthria symptoms [ Time Frame: Baseline ]
    Ataxic dysarthria (AD) symptoms will be quantified in patients with cerebellar ataxia (CA) by licensed speech-language pathologists using the Bogenhausen Dysarthria Scales (BoDyS), a dysarthria assessment tool that has been shown to be objective, reliable, and sensitive to dysarthria subtypes 31, 60, and 61. The BoDyS test entails 33 separate component ratings, including symptoms that may be related to feedforward and feedback components of speech motor control systems.

  3. Voxel-based morphometry (VBM) [ Time Frame: Baseline ]
    VBM will be applied to explore the functional organization of the cerebellum for speech production, focusing on psychophysical measures of speech motor control as well as clinical measures of dysarthric speech symptoms.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Diagnosis of cerebellar ataxia (CA) resulting from degeneration of the cerebellum AND normal hearing abilities OR
  • Healthy volunteers with no known history of physical or neurological abnormalities AND normal speech, hearing, and reading abilities
  • For some studies, primary language of American English may be required

Exclusion criteria for healthy volunteers:

  • Neurological impairment or psychiatric illness

Exclusion criteria for participants with cerebellar ataxia (CA):

  • Neurological impairment or psychiatric illness apart from those arising from cerebellar damage

Exclusion criteria for participants with CA or for healthy volunteers participating in MRI (may still be eligible for other study procedures):

  • Any contraindication to participating in an MRI study including the following: implanted metallic parts or implanted electronic devices, including pacemakers, defibrillators, stimulators, or implant medication pump, or nonremovable piercings; aneurysm clip or other metal in the head (except mouth); claustrophobia precluding MRI

Exclusion criteria for healthy volunteers participating in TMS (may still be eligible for other study procedures):

  • Any contraindications to participating in a TMS study including the following: epilepsy, use of certain medications, heart disease, and pregnancy; scalp wounds or infections; any other contraindication discovered during screening procedures
  • Any contraindication to participating in an MRI study including the following: implanted metallic parts or implanted electronic devices, including pacemakers, defibrillators, or implant medication pump, or nonremovable piercings; claustrophobia precluding MRI

Exclusion criteria for all potential participants:

  • Pregnant or trying to become pregnant (may still be eligible for behavioral studies only)
  • History of alcohol abuse, illicit drug use or drug abuse or significant mental illness
  • Hypertensive or hypotensive condition
  • Any condition that would prevent the subject from giving voluntary informed consent
  • Enrolled or plans to enroll in an interventional trial during this study
  • Ongoing seizures that are not well controlled despite medication
  • Use of hearing aid or other device to improve hearing

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03972202


Contacts
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Contact: Coordinator for Cerebellum Speech Study 415-476-6888 cerebellumspeech@gmail.com
Contact: Anne Findlay 415-476-6888 anne.findlay@ucsf.edu

Locations
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United States, California
University of California, Berkeley Not yet recruiting
Berkeley, California, United States, 94720
Contact: Richard Ivry, Ph.D.    510-642-5292    ivry@berkeley.edu   
Principal Investigator: Richard Ivry, Ph.D.         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Anne Findlay    415-476-6888    anne.findlay@ucsf.edu   
Contact: Danielle Mizuiri    415-476-6888    danielle.mizuiri@ucsf.edu   
Principal Investigator: Srikantan Nagarajan, Ph.D.         
Principal Investigator: John Houde, Ph.D.         
United States, Wisconsin
University of Wisconsin--Madison Not yet recruiting
Madison, Wisconsin, United States, 53705
Contact: Alexa Bushinski    608-262-5776    bushinski@wisc.edu   
Principal Investigator: Ben Parrell, Ph.D.         
Sponsors and Collaborators
University of California, San Francisco
University of California, Berkeley
University of Wisconsin, Madison
National Institute on Deafness and Other Communication Disorders (NIDCD)
Investigators
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Principal Investigator: John F. Houde, Ph.D. University of California, San Francisco
Principal Investigator: Srikantan S. Nagarajan, Ph.D. University of California, San Francisco
Principal Investigator: Richard Ivry, Ph.D. University of California, Berkeley
Principal Investigator: Ben Parrell, Ph.D. University of Wisconsin, Madison

Publications:
Parrell, B., Agnew, Z., Houde, J., Nagarajan, S., & Ivry, R. (2016) Individuals with cerebellar degeneration correct for within-category variation of vowels even in the absence of auditory feedback. Talk presented at Society for Neuroscience 2016, San Diego, CA, November 2016.
Parrell, B. (2017). Evidence for reward learning in speech production. Poster presented at the 7th International Conference on Speech Motor Control, Groningen, the Netherlands, July 2017.

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Responsible Party: John Houde, Associate Professor, Otolaryngology, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03972202     History of Changes
Other Study ID Numbers: 19-27146
1R01DC017091-01A1 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2019    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by John Houde, University of California, San Francisco:
dysarthria
ataxia
cerebellum
cerebellar
adult
speaking
language
TMS
MRI
speech

Additional relevant MeSH terms:
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Ataxia
Cerebellar Ataxia
Dysarthria
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Articulation Disorders
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations