Objective Diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD), the most prevalent neurodevelopmental condition, relies on subjective symptom ratings rather than objective brain-based measures. Using Transcranial Magnetic Stimulation (TMS), we have found that children with ADHD show reduced task-related-up-modulation (TRUM) of motor cortex excitability from baseline “rest” to active selection/inhibition of motor responses. We aimed to replicate and extend those findings to determine whether ADHD-associated reductions in TRUM are associated with particular action states. Methods In 71 8-12-year-old children (34 ADHD, 53% male; 37 TD, 54% male), we used TMS to evaluate left motor cortex (M1) excitability, measured as right first dorsal interosseus motor evoked potential amplitudes (MEPs) during 3 trial types from a racecar Slater-Hammel Stop-Signal Reaction Task: “Anticipate” @250 milliseconds (ms), “Prepare” @650 ms; and “Inhibit” @150 ms after the dynamic stop cue. Diagnosis and Task effects on TRUM were estimated using mixed models, repeated measures regression. Results Across all trial types, TRUM (MEP amplitudes) was 33% reduced in ADHD (p = 0.075). There was a highly significant Diagnosis*Task interaction (p < 0.001). Post hoc, pairwise analyses revealed a significant Diagnosis-effect only for Inhibition trials (p = 0.025). There was a significant effect of Task on TRUM (Inhibit>Prepare>Anticipate; p<0.001); however, this seemed driven by state differences within TD children (all p<0.001). Conclusion In children with ADHD, there is diminished and less specific TRUM of motor cortex during a response inhibition task. This supports reduced TRUM during response inhibition as a potential neurophysiological biomarker for ADHD. Research funded by NIH/NIMH.

Donald Gilbert
Cincinnati Children's Hospital Medical Center
United States

Paul Horn
Cincinnati Children's Hospital Medical Center
United States

David Huddleston
Cincinnati Children's Hospital Medical Center
United States

Steve Wu
Cincinnati Children's Hospital Medical Center
United States

Karlee Migneault
Cincinnati Children's Hospital Medical Center
United States

Deana Crocetti
Kennedy Krieger Institute
United States

Stewart Mostofsky
Kennedy Krieger Institute
United States