Dopamine Function in Developmental Stuttering
Condition: Developmental Stuttering
MeSH terms: Stuttering
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Keywords: Speech; Motor Control; Phenotype; Dysfluency; Fluency; Stuttering; Healthy Volunteer; HV; Normal Control