Dopamine Function in Developmental Stuttering
This study will use positron emission tomography (PET) to examine the role of the chemical messenger dopamine in stuttering. It will measure and compare the number of dopamine receptors and the amount of dopamine released in the brains of stutterers with that of normal volunteers. The results may provide information about how drugs that block dopamine's effect might work to enable fluent speech.
Healthy normal volunteers and people with developmental stuttering between the ages of 18 and 55 may be eligible for this study. Candidates will be screened with a medical history and possibly a physical examination and laboratory tests.
Participants will have a hearing test and cognitive function tests to measure speech, language, memory and visual skills. In addition, they will undergo the following procedures:
- PET scanning to measure brain blood flow and dopamine distribution in the brain. PET uses radioactive materials to show cellular activity in specific tissues of the body. Before starting the procedure, a thin plastic tube (intravenous, or IV line) is placed in a vein in each arm of the subject and a special plastic mask is molded to the face. (The mask is used to insure that the position of the head does not change during the scan.) For the scan, the subject lies on a bed that is positioned into the scanner. A preliminary "transmission" scan is done to make necessary measurements and adjustments. Following this scan, 10 injections of radioactive water are given through an IV line. During these injections, the subject performs a series of speech tasks-such as singing, telling a story, or reciting nursery rhymes-that will elicit either fluent speech or stuttering. A special camera detects the radiation emitted and produces images of brain blood flow during stuttering and normal speech. Next, raclopride (a radioactive material that attaches to dopamine receptors on the cell surface) is given through an IV line and more pictures of the brain are taken. Fifty minutes after the raclopride injection, amphetamine-a drug that increases brain dopamine levels-is injected through the other IV line and more pictures are taken to show dopamine distribution in the brain. Fifty minutes after the amphetamine infusion, the IV lines are removed.
- Magnetic resonance imaging (MRI) of the brain to complement and interpret information from the PET scans. MRI uses a strong magnetic field and radio waves to show structural changes in tissues. The subject lies on a table surrounded by a metal cylinder (the scanner). During the procedure, which may take from 20 minutes to 2 hours, subjects may be asked to perform simple tasks, such as speaking or moving their arms. They can speak with a staff member via an intercom at all times during the procedure and can be moved out of the machine any time they request.
Participants may be asked to return for up to two scanning sessions within a year. For these scans, only 1 injection of radioactive water will be given.
|Official Title:||Assessment of Pre- and Post-Synaptic Dopamine Function in Developmental Stuttering Using 11C-Raclopride and Positron Emission Tomography|
|Study Start Date:||October 2001|
|Estimated Study Completion Date:||October 2010|
Clinical responses to dopamine (DA) antagonists from patients with developmental stuttering suggest that the pathophysiology of this disorder may involve an abnormality of central DA systems. This hypothesis has never been tested using methods that measure both pre- and postsynaptic dopaminergic mechanisms within the CNS. A new PET technique permits evaluation of these mechanisms in human subjects. 11C raclopride, a relatively selective D2 receptor antagonist, is used to estimate postsynaptic DA receptor binding potential following establishment of equilibrium conditions. A low dose bolus of amphetamine is then used to release DA from the presynaptic neuron and displace the ligand from postsynaptic binding sites, in order to estimate the size of the releasable presynaptic DA pool. We propose to use this technique in individuals with developmental stuttering and control subjects to test the hypothesis that stuttering is due to dopaminergic hyperactivity within the CNS. The cause of this hyperactivity is hypothesized to be due to an increase in either the postsynaptic binding potential or the size of the releasable presynaptic dopamine vesicular pool (in which case postsynaptic receptors may be down regulated). Our studies should help conjoin and modify this pathophysiological model. If low dose amphetamine can be used to demonstrate a difference between people who stutter and controls, a second study will be conducted to see if stuttering behavior per se has a measurable effect on DA release that differs from the effect of similar speech tasks in control subjects. Lastly, in a third study, DA releasability will be measured in those recovered from stuttering and those not affected by stuttering but are part of families who have many members that stutter. The culmination of these studies is to attempt isolation of a DA marker that can be used as a phenotyping tool in genetic studies of stuttering.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00024960
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|