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.
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.
- INCLUSION AND EXCLUSION CRITERIA - STUTTERING AND CONTROL SUBJECTS:
Subjects must be between the ages of 18 and 55.
Subjects must be in good general health except for the primary neurological diagnosis of
Subjects may not have evidence of hypertension or cardiovascular disease, cerebrovascular
disease or hyperthyroidism.
EKG and thyroid function tests must be within normal limits.
Subjects must have no history of traumatic head injury including any head trauma that
resulted in loss of consciousness or history of substance abuse, including alcohol
Subjects will be screened for history of psychiatric illness, such as depression, anxiety
or obsessive-compulsive disorders according to DSM-IV; subjects with such diagnoses will
Subjects will be screened for a past medical history or family history of speech-language
disorders; subjects with a personal or significant family history of speech-language
disorders unrelated to the diagnoses of stuttering or aphasia will be excluded. Also those
subjects with immediate family members having a significant history of heart attack or
stroke will be excluded.
Women who are pregnant or currently breast-feeding will be excluded from this study.
Subjects with pacemakers, aneurysm clips, cochlear implants, shrapnel fragments or have a
significant history of exposure to small metallic objects, which might have become lodged
in the tissues of the head, or neck will be excluded due to the MRI.
The following criteria must be met to identify an individual who stutters:
Affected individual regards him or herself as having a stuttering disorder, reporting
instances during speech where they know exactly what they wish to say, but can not be due
to production impairment; these instances may be accompanied by a feeling of tension
somewhere within the vocal tract. Individuals may have sought treatment for their
Speech-language pathologist confirms diagnosis of stuttering disorder in affected
individuals, documenting presence of silent or sound prolongations, syllable repetitions,
word/phrase repetitions, interjections and pauses at non-linguistic loci in their speech.
Affected individuals will be at least 5% dysfluent in at least 2 of the speaking tasks
used to assess fluency.
Recovered stutterers must have a history of stuttering documented by the speech
pathologist responsible for evaluation or treatment of this individual during childhood. A
history of stuttering may alternatively be documented by a parent and at least one other
family member or friend. Recovered individuals must report that they no longer monitor
their speech on a routine basis or use speech therapy techniques while speaking.
Speech-language pathologist must judge that recovered individuals are currently free of
overt stuttering (less than 1 stuttering behavior/100 words).
Onset of stuttering in both affected individuals and recovered stutterers must have
occurred in childhood (between 3 and 10 years-of-age), unrelated to psychological or