Monitoring cortical excitability during repetitive transcranial magnetic stimulation in children with ADHD: a single-blind, sham-controlled TMS-EEG study

PLoS One. 2012;7(11):e50073. doi: 10.1371/journal.pone.0050073. Epub 2012 Nov 21.


Background: Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children.

Objective: TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available.

Methods: In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition.

Results: TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation.

Conclusion: The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Brain
  • Case-Control Studies
  • Child
  • Electroencephalography
  • Electromyography
  • Evoked Potentials, Motor*
  • Female
  • Humans
  • Male
  • Motor Cortex / physiology
  • Motor Cortex / physiopathology*
  • Placebos
  • Reaction Time
  • Single-Blind Method
  • Transcranial Magnetic Stimulation*


  • Placebos

Grants and funding

The study was supported by the Medical Faculty at the Goethe University, Frankfurt/Main via a grant (Young Scientists Program) to SB as well as by the Interdisciplinary Center for Neurosciences Frankfurt; Plasticity via magnetic brain stimulation: cellular mechanism – modeling – modulation via a grant to JR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.