Cortical inhibition in attention deficit hyperactivity disorder: new insights from the electroencephalographic response to transcranial magnetic stimulation.

Attention deficit hyperactivity disorder is one of the most frequent neuropsychiatric disorders in childhood. Transcranial magnetic stimulation studies based on muscle responses (motor-evoked potentials) suggested that reduced motor inhibition contributes to hyperactivity, a core symptom of the disease. Here we employed the N100 component of the electroencephalographic response to transcranial magnetic stimulation as a novel marker for a direct assessment of cortical inhibitory processes, which has not been examined in attention deficit hyperactivity disorder so far. We further investigated to what extent affected children were able to regulate motor cortical inhibition, and whether effects of age on the electroencephalographic response to transcranial magnetic stimulation were compatible with either a delay in brain maturation or a qualitatively different development. N100 amplitude evoked by transcranial magnetic stimulation and its age-dependent development were assessed in 20 children with attention deficit hyperactivity disorder and 19 healthy control children (8-14 years) by 64-channel electroencephalography. Amplitude and latency of the N100 component were compared at rest, during response preparation in a forewarned motor reaction time task and during movement execution. The amplitude of the N100 component at rest was significantly lower and its latency tended to be shorter in children with attention deficit hyperactivity disorder. Only in controls, N100 amplitude to transcranial magnetic stimulation was reduced by response preparation. During movement execution, N100 amplitude decreased while motor evoked potential amplitudes showed facilitation, indicating that the electroencephalographic response to transcranial magnetic stimulation provides further information on cortical excitability independent of motor evoked potential amplitudes and spinal influences. Children with attention deficit hyperactivity disorder showed a smaller N100 amplitude reduction during movement execution compared with control children. The N100 amplitude evoked by transcranial magnetic stimulation decreased with increasing age in both groups. The N100 reduction in children with attention deficit hyperactivity disorder at all ages suggests a qualitative difference rather than delayed development of cortical inhibition in this disease. Findings further suggest that top-down control of motor cortical inhibition is reduced in children with attention deficit hyperactivity disorder. We conclude that evoked potentials in response to transcranial magnetic stimulation are a promising new marker of cortical inhibition in attention deficit hyperactivity disorder during childhood.