The Role of Cerebellum in Speech

Phase

N/A

Condition

Dyskinesias

Friedreich's Ataxia

Spinocerebellar Disorders

Treatment

TMS

Speech-motor behavioral testing

MRI

Clinical Study ID

NCT03972202

19-27146

1R01DC017091-01A1

Ages 18-75
All Genders
Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

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

Study Design

TMS

September 15, 2019

May 31, 2030

Study 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.

Connect with a study center

University of California, Berkeley
Berkeley, California 94720
United States
Site Not Available
University of California, San Francisco
San Francisco, California 94143
United States
Site Not Available
University of California, Berkeley
Berkeley 5327684, California 5332921 94720
United States
Site Not Available
University of California, San Francisco
San Francisco 5391959, California 5332921 94143
United States
Site Not Available
University of Wisconsin--Madison
Madison, Wisconsin 53705
United States
Site Not Available
University of Wisconsin--Madison
Madison 5261457, Wisconsin 5279468 53705
United States
Site Not Available

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