Study of Attention Deficit/Hyperactivity Disorder Using Transcranial Magnetic Stimulation

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.