The Role of Cerebellum in Speech

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Role of Cerebellum in Speech

Conditions
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Cerebellar Ataxia, Dysarthria, Healthy

Intervention / Treatment
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* Diagnostic Test: MRI
* Device: TMS
* Behavioral: Speech-motor behavioral testing


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with cerebellar ataxia (CA)<br>Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI) | Diagnostic Test: MRI<br>* Brain MRI will be performed (no contrast) to correlate brain anatomy/function with behavioral testing.<br>* Other names: Magnetic Resonance Imaging;Behavioral: Speech-motor behavioral testing<br>* 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.<br>|
| Active Comparator: Matched controls<br>Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI) | Diagnostic Test: MRI<br>* Brain MRI will be performed (no contrast) to correlate brain anatomy/function with behavioral testing.<br>* Other names: Magnetic Resonance Imaging;Behavioral: Speech-motor behavioral testing<br>* 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.<br>|
| Experimental: Additional healthy volunteers<br>Behavioral testing including various speaking tasks Magnetic resonance imaging (MRI) Transcranial magnetic stimulation (TMS) | Diagnostic Test: MRI<br>* Brain MRI will be performed (no contrast) to correlate brain anatomy/function with behavioral testing.<br>* Other names: Magnetic Resonance Imaging;Device: TMS<br>* Repetitive TMS will be applied to transiently disrupt cerebellar speech pathways.<br>* Other names: rTMS;Behavioral: Speech-motor behavioral testing<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dysarthria, ataxia, cerebellum, cerebellar, adult, speaking, language, TMS, MRI, speech