Protocol Number: 08-N-0181

Title:

Role of Neurotransmission and Functional CNS Networks in Spasmodic Dysphonia

Number:

08-N-0181

Summary:

This study will examine how the brain controls speech in patients with spasmodic dysphonia, a voice disorder that involves involuntary spasms of muscles in the larynx (voice box), causing breaks in speech. Although the causes of spasmodic dysphonia are unknown, recent studies found changes in brain function in patients with the disorder that may play a role in its development.

People between 21 and 80 years of age with adductor spasmodic dysphonia may be eligible for this study. Candidates are screened with the following procedures:

Medical history and physical examination.

Nasolaryngoscopy to examine the larynx. For this test, the inside of the subject's nose is sprayed with a decongestant and a small, flexible tube called a nasolaryngoscope is passed through the nose to the back of the throat to allow examination of the larynx. The subject may be asked to talk, sing, whistle and say prolonged vowels during the procedure. The nasolaryngoscope is connected to a camera that records the movement of the vocal cords during these tasks.

Voice and speech recording to measure the type and severity of voice disorder. Subjects are asked questions about their voice disorder and their voice is recorded while they repeat sentences and sounds.

Participants undergo positron emission tomography (PET) and magnetic resonance imaging (MRI) of the brain, as follows:

PET: A catheter is placed in a vein in the subject's arm to inject a radioactive substance called a tracer that is detected by the PET scanner and provides information on brain function. [11C]flumazenil is used in one scanning session and [11C]raclopride is used in another. For the scan, the subject lies on a bed that slides in and out of the doughnut-shaped scanner, wearing a custom-molded mask to support the head and prevent it from moving during the scan. For the first scan the subject lies quietly for 60 minutes. For the second scan, the subject lies quietly for 50 minutes and is then asked to say sentences during another 50 minutes. The amount of radiation received in this study equals to a uniform whole-body exposure of 0.9 rem, which is within the dose guideline established by the NIH Radiation Safety Committee for research subjects. The guideline is an effective dose of 5 rem received per year.

MRI: This procedure uses a strong magnetic field and radio waves instead of X-rays to obtain images of the brain. The subject lies on a table that slides into the scanner, a narrow metal cylinder, wearing ear plugs to muffle loud knocking sounds that occur during the scan. Images of the brain structure are obtained while the subject lies still in the machine for 10 minutes. This is followed by functional MRI (fMRI) for 60 minutes, in which pictures are taken while the subject speaks, showing changes in brain regions that are involved in speech production.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Healthy research volunteers and adult patients with ADSD will be eligible for the study.

1. Adult patients will have clinically documented ADSD established by voice and speech testing and fiberoptic nasolaryngoscopy.

Patients will be required to have:

-Intermittent uncontrolled voice breaks in vowels, liquids (r & l), semivowels (w & y) during speech in ADSD (at least 3 voice breaks), or

-Less prominent symptoms during whisper, singing, falsetto, or shout;

-Normal voice and vocal fold movement during protective laryngeal functions and emotional phonation, such as cough, laughter, cry.

2. Controls will be healthy subjects with a negative history of laryngeal, neurological, or psychiatric problems.

3. All participants will be from 21 to 80 years old.

EXCLUSION CRITERIA:

1. Subjects who are incapable of giving an informed consent.

2. Pregnant or breastfeeding women until a time when they are no longer pregnant or breastfeeding.

3. Subjects with past or present medical history of (a) neurological problems, such as stroke, movement disorders (other than SD in the patient group), brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence; (b) psychiatric problems, such as schizophrenia, major and/or bipolar depression, obsessive-compulsive disorder; (c) laryngeal problems, such as vocal fold paralysis, paresis, vocal fold nodules and polyps, carcinoma, chronic laryngitis.

4. Patients who are currently taking medications known to affect GABA and dopamine receptor binding. Occasionally, patients report receiving such medication, although dopaminergic and GABA agonist/antagonists are not typically prescribed in these patients.

5. Patients who received treatment with botulinum toxin injections into the laryngeal muscles within the past 4-6 months.

6. Patients with vocal tremor or muscle tension dysphonia.

7. Subjects who have tattoos with contraindications to MRI, ferromagnetic objects in their bodies (e.g., implanted stimulators, surgical clips, prosthesis, artificial heart valve, etc.) that cannot be removed for the purpose of study participation.

8. Subjects who received previous radiation exposure greater than 4.0 rem per year.

Special Instructions:

Currently Not Provided

Keywords:

Spasmodic Dysphonia

Dystonia

Basal Ganglia

PET Imaging

fMRI

Recruitment Keyword(s):

Spasmodic Dysphonia

Voice Disorder

Healthy Volunteer

HV

Condition(s):

Spasmodic Dysphonia

Focal Dystonia

Investigational Drug(s):

11[C]flumazenil

[11C]raclopride

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Neurological Disorders and Stroke

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Albin RL, Young AB, Penney JB.The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989 Oct;12(10):366-75.

Alexander GE, Crutcher MD.Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990 Jul;13(7):266-71.

Ali SO, Thomassen M, Schulz GM, Hosey LA, Varga M, Ludlow CL, Braun AR.Alterations in CNS activity induced by botulinum toxin treatment in spasmodic dysphonia: an H215O PET study. J Speech Lang Hear Res. 2006 Oct;49(5):1127-46.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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