The Role of Cerebellum in Speech

NCT03972202 | Active Not Recruiting FDA Device

• 2 other identifiers: 19-271461R01DC017091-01A1
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 3

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.

Conditions

Cerebellar Ataxia; Dysarthria; Healthy

Keywords

dysarthria; ataxia; cerebellum; cerebellar; adult; speaking; language; TMS; MRI; speech

Outcome Measures

Primary Outcomes (3)

• Speech-motor response percent compensation

  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.

  Baseline

• Dysarthria symptoms

  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.

  Baseline

• Voxel-based morphometry (VBM)

  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.

  Baseline

Study Arms (3)

Patients with cerebellar ataxia (CA)

EXPERIMENTAL

Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI)

Diagnostic Test: MRI; Behavioral: Speech-motor behavioral testing

Matched controls

ACTIVE COMPARATOR

Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI)

Diagnostic Test: MRI; Behavioral: Speech-motor behavioral testing

Additional healthy volunteers

EXPERIMENTAL

Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI) Transcranial magnetic stimulation (TMS)

Diagnostic Test: MRI; Device: TMS; Behavioral: Speech-motor behavioral testing

Interventions

MRI DIAGNOSTIC_TEST

Brain MRI will be performed (no contrast) to correlate brain anatomy/function with behavioral testing.

Also known as: Magnetic Resonance Imaging

Additional healthy volunteers; Matched controls; Patients with cerebellar ataxia (CA)

TMS DEVICE

Repetitive TMS will be applied to transiently disrupt cerebellar speech pathways.

Also known as: Transcranial Magnetic Stimulation, Repetitive TMS, rTMS

Additional healthy volunteers

Speech-motor behavioral testing BEHAVIORAL

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.

Additional healthy volunteers; Matched controls; Patients with cerebellar ataxia (CA)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of California, Berkeley: collaborator
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (3)

University of California, Berkeley

Berkeley, California, 94720, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Wisconsin--Madison

Madison, Wisconsin, 53705, United States

Location

Related Publications (19)

• Chang EF, Niziolek CA, Knight RT, Nagarajan SS, Houde JF. Human cortical sensorimotor network underlying feedback control of vocal pitch. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2653-8. doi: 10.1073/pnas.1216827110. Epub 2013 Jan 23.

  PMID: 23345447 BACKGROUND

• Hinkley LB, Marco EJ, Brown EG, Bukshpun P, Gold J, Hill S, Findlay AM, Jeremy RJ, Wakahiro ML, Barkovich AJ, Mukherjee P, Sherr EH, Nagarajan SS. The Contribution of the Corpus Callosum to Language Lateralization. J Neurosci. 2016 Apr 20;36(16):4522-33. doi: 10.1523/JNEUROSCI.3850-14.2016.

  PMID: 27098695 BACKGROUND

• Kort NS, Cuesta P, Houde JF, Nagarajan SS. Bihemispheric network dynamics coordinating vocal feedback control. Hum Brain Mapp. 2016 Apr;37(4):1474-85. doi: 10.1002/hbm.23114. Epub 2016 Feb 25.

  PMID: 26917046 BACKGROUND

• Ranasinghe KG, Gill JS, Kothare H, Beagle AJ, Mizuiri D, Honma SM, Gorno-Tempini ML, Miller BL, Vossel KA, Nagarajan SS, Houde JF. Abnormal vocal behavior predicts executive and memory deficits in Alzheimer's disease. Neurobiol Aging. 2017 Apr;52:71-80. doi: 10.1016/j.neurobiolaging.2016.12.020. Epub 2017 Jan 3.

  PMID: 28131013 BACKGROUND

• Moberget T, Gullesen EH, Andersson S, Ivry RB, Endestad T. Generalized role for the cerebellum in encoding internal models: evidence from semantic processing. J Neurosci. 2014 Feb 19;34(8):2871-8. doi: 10.1523/JNEUROSCI.2264-13.2014.

  PMID: 24553928 BACKGROUND

• Sokolov AA, Miall RC, Ivry RB. The Cerebellum: Adaptive Prediction for Movement and Cognition. Trends Cogn Sci. 2017 May;21(5):313-332. doi: 10.1016/j.tics.2017.02.005. Epub 2017 Apr 3.

  PMID: 28385461 BACKGROUND

• Koch G, Oliveri M, Torriero S, Salerno S, Lo Gerfo E, Caltagirone C. Repetitive TMS of cerebellum interferes with millisecond time processing. Exp Brain Res. 2007 May;179(2):291-9. doi: 10.1007/s00221-006-0791-1. Epub 2006 Dec 5.

  PMID: 17146647 BACKGROUND

• Jenkinson N, Miall RC. Disruption of saccadic adaptation with repetitive transcranial magnetic stimulation of the posterior cerebellum in humans. Cerebellum. 2010 Dec;9(4):548-55. doi: 10.1007/s12311-010-0193-6.

  PMID: 20665254 BACKGROUND

• Parrell B, Agnew Z, Nagarajan S, Houde J, Ivry RB. Impaired Feedforward Control and Enhanced Feedback Control of Speech in Patients with Cerebellar Degeneration. J Neurosci. 2017 Sep 20;37(38):9249-9258. doi: 10.1523/JNEUROSCI.3363-16.2017. Epub 2017 Aug 23.

  PMID: 28842410 BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.

  PMID: 19833552 BACKGROUND

• Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

  PMID: 15664172 BACKGROUND

• Oberman L, Edwards D, Eldaief M, Pascual-Leone A. Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. J Clin Neurophysiol. 2011 Feb;28(1):67-74. doi: 10.1097/WNP.0b013e318205135f.

  PMID: 21221011 BACKGROUND

• Tarapore PE, Picht T, Bulubas L, Shin Y, Kulchytska N, Meyer B, Berger MS, Nagarajan SS, Krieg SM. Safety and tolerability of navigated TMS for preoperative mapping in neurosurgical patients. Clin Neurophysiol. 2016 Mar;127(3):1895-900. doi: 10.1016/j.clinph.2015.11.042. Epub 2015 Dec 11.

  PMID: 26762952 BACKGROUND

• Tarapore PE, Picht T, Bulubas L, Shin Y, Kulchytska N, Meyer B, Nagarajan SS, Krieg SM. Safety and tolerability of navigated TMS in healthy volunteers. Clin Neurophysiol. 2016 Mar;127(3):1916-8. doi: 10.1016/j.clinph.2015.11.043. Epub 2015 Dec 11. No abstract available.

  PMID: 26762949 BACKGROUND

• Wassermann EM. Side effects of repetitive transcranial magnetic stimulation. Depress Anxiety. 2000;12(3):124-9. doi: 10.1002/1520-6394(2000)12:33.0.CO;2-E.

  PMID: 11126186 BACKGROUND

• Tarapore PE, Findlay AM, Honma SM, Mizuiri D, Houde JF, Berger MS, Nagarajan SS. Language mapping with navigated repetitive TMS: proof of technique and validation. Neuroimage. 2013 Nov 15;82:260-72. doi: 10.1016/j.neuroimage.2013.05.018. Epub 2013 May 20.

  PMID: 23702420 BACKGROUND

• Tarapore PE, Tate MC, Findlay AM, Honma SM, Mizuiri D, Berger MS, Nagarajan SS. Preoperative multimodal motor mapping: a comparison of magnetoencephalography imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation. J Neurosurg. 2012 Aug;117(2):354-62. doi: 10.3171/2012.5.JNS112124. Epub 2012 Jun 15.

  PMID: 22702484 BACKGROUND

MeSH Terms

Conditions

Cerebellar Ataxia; Dysarthria; Ataxia; Speech; Language

Interventions

Magnetic Resonance Imaging; Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Articulation Disorders; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Verbal Behavior; Communication; Behavior

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Magnetic Field Therapy; Therapeutics

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: June 3, 2019
• Study Start: September 15, 2019
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)