Attention deficit/hyperactivity disorder is a condition characterized by a decreased
attention span, hyperactivity, and/or impulsiveness inappropriate for a certain age.
Typically, young children have what are known as subtle neurological signs. These are
involuntary movements of one part of the body that occur while the child is making a
voluntary movement of another part of the body. This is referred to as synkinesis, or
overflow movements. These overflow movements disappear during normal development and are
usually gone by the age of 10. However, in children with ADHD these overflow movements tend
to be more intense and last long after the age of 10. This leads researchers to believe
there is an abnormality in the maturation and development of the brain areas associated with
motor activity in children with ADHD.
Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that gives information
about brain function. It is very useful when studying areas of the nervous system related to
motor activity (motor cortex, corticospinal tract, and corpus callosum). A magnetic signal
given from a special instrument held close to the patient's head stimulates a small area of
the brain that controls a few muscles (for example, the muscles that control one finger).
Doctors put electrodes (small pieces of metal taped to areas of the body) over the muscle to
measure the electrical activity the muscle produces when it makes a movement. When the
magnetic signal activates those muscles the electrodes pick up and record the electrical
activity of the movement that the muscles make in response to the magnetic signal.
Researchers will study normal children and those diagnosed with ADHD using TMS to find out
if the clinical abnormalities of ADHD are associated with a delay or abnormality in
maturation of areas of the nervous system responsible for motor activity (motor cortex and
Subtle neurological signs (synkinesis and mirror movements) are present in normal children
up until 9 or 10 years of age. In addition, speed of repetitive and sequential movements
increases from 5 to 8 years of age at which time children perform these movements at close
to adult speeds. Based on clinical studies of both normal children and of children with
corticospinal tract lesions, it has been postulated that these subtle motor signs reflect
neurodevelopmental immaturity of the intracortical and interhemispheric inhibitory systems
and that their disappearance occurs as a result of maturation.
The presence of subtle neurological signs can accurately distinguish children with
attention-deficit/hyperactivity disorder (ADHD) from healthy controls. The increased
intensity of these neurological signs in younger age groups and their persistence beyond the
age of 9 years suggest that children with ADHD may have delayed or abnormal
neuromaturational development; in particular, development of the inhibitory systems of the
motor cortex. This is in concert with the theories of cognitive abnormalities seen in these
children where behavioral studies indicate that children with ADHD have most difficulty in
executive function tests that look specifically at motor inhibition.
Transcranial magnetic stimulation (TMS) is a non-invasive tool which gives information about
cortical function. It is particularly useful in the study of the motor cortex and its
connections via the corticospinal tract and the corpus callosum. A single suprathreshold
stimulus to the motor cortex produces a motor evoked potential (MEP) and inhibition of
ongoing muscle activity in ipsilateral and contralateral target muscles. TMS studies have
demonstrated differences in both the velocity of central motor conduction, and the ability
to evoke motor inhibition when comparing adults with children under 10 years of age. These
differences suggest that cortical inhibitory and facilitatory systems undergo normal
developmental changes during the first decade of life, and that they may form the neural
substrate for the clinical developmental changes that occur in children during this same
period of time.
We propose to study children with ADHD with single and paired pulse TMS to determine if the
clinical abnormalities present in these children reflect an underlying delay or abnormality
in maturation of the inhibitory and facilitatory systems of the cortex and corticospinal
tracts. If present, these findings would give objective evidence of abnormal inhibitory
systems in attention-deficit/hyperactivity disorder; their presence (or absence) may
differentiate between the different subtypes of ADHD. Since stimulants have an ameliorative
effect on the neuropsychological functioning in these children, future studies would be able
to determine whether they have a similar effect on the motor system.
TMS is associated with a click which can have a 120 dB peak sound level at maximum
stimulator output. Studies in adults and children have shown no long-lasting or permanent
hearing loss after TMS, but there is no information regarding transient decrease in hearing
thresholds immediately after TMS as can occur after listening to music through headphones
using personal cassette recorders. As part of the main study, we will be conducting a
safety study to determine the risk for temporary hearing loss after TMS in children.
Boys and girls 9 to 13 years of age.
Right handed subjects only.
Subjects that are off stimulant medications.
Children who undergo a medication washout as a part of a different study or are on a
planned drug holigay will be allowed to enroll in the study once they have bee off the
medications for at least 10 days.
Adult men with a history of ADHD between 18 and 30 years and healthy age-matched normal
Patients with neurological disorders will be excluded. In particular, persons with a
personal or family history of seizures or epilepsy; structural cerebral disorders (e.g.
hemiplegia or other abnormalities of the corticospinal tracts). We will also exclude from
our study any persons who have a personal or family history of sensorineural loss. Person
with abnormally decreased pigmentation (albinism) will also be excluded from the study.
Patients with a chronic motor or vocal tic disorder or Tourette Syndrome. Children with
tics, not meeting DSM-III criteria for tic disorder will be allowed to enroll in the
Children with localizing neurological signs (asymmetric deep tendon reflexes (DTRs),
dysmetria, hypotonia) will also be excluded.
Children with psychiatric disorders other than oppositional defiant disorder (ODD) will be
excluded from study.
Children who have dyslexia and learning disabilities but do not have ADHD will be
Children with ADHS who are on a stimulant medication will be excluded from enrollment in
Healthy controls cannot have any of the exclusionary conditions mentioned above and, by
definition, must necessarily be free of ADHD symptoms.