To determine, in children with Attention Deficit/Hyperactivity Disorder (ADHD) and typically developing (TD) controls, if primary motor cortex (M1) short-interval cortical inhibition (SICI) and task-related up-modulation (TRUM) of motor evoked potentials (MEPs) correlate with each other, suggesting they capture commonly disrupted neurobiological circuits, or do not correlate, consistent with them reflecting distinct neurobiological circuits.

ADHD is a heterogeneous, behaviorally-defined diagnosis. Physiological biomarkers, if valid, might identify distinct, clinically important subgroups relating to critical areas of cognitive or emotional dysfunction. Studies using transcranial magnetic stimulation (TMS) in children recently identified that SICI and TRUM are diminished in ADHD and correlate with clinical symptoms.

A case-control study comparing TMS-evoked SICI and TRUM in 8-12 year old children with ADHD and Typically Developing (TD) controls during 1) a stop signal reaction time (SSRT) task testing cognitive control (n=43 ADHD; 40 TD) and 2) a reward cue task evaluating positive valence (n=33 ADHD; 31 TD). TRUM is ratio of the mean task (SSRT 80; Reward 105 pulses/trials) to the mean baseline (20 pulses, resting) MEP. The primary outcomes were the age-adjusted Spearman correlations between TRUM and SICI in the two tasks.

Both SSRT and Reward tasks significantly reduced SICI and induced TRUM; and both were significantly reduced in ADHD. In the response inhibition task SICI correlated modestly with TRUM (r=-0.29; p=0.01) for the entire cohort but not within diagnostic groups. In the reward cue task, SICI correlated at trend level with TRUM (r = -0.21, p = 0.09) for the entire cohort but not within diagnostic groups.

In children with ADHD, SICI correlates only modestly with TRUM across two important domains of dysfunction. Further investigation could validate SICI and TRUM as distinct biomarkers for precise treatment selection.