Motor Physiology Transcranial Magnetic Stimulation–Based Biomarkers and Associated Neurocognitive Profiles in Attention‐Deficit/Hyperactivity Disorder

ABSTRACT Purpose Attention‐deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental condition for which current diagnostic approaches rely on symptom‐based classifications that do not capture underlying neurobiology. This study examined whether transcranial magnetic stimulation (TMS) measures of motor cortex physiology could identify biologically meaningful ADHD subtypes and their associated neurocognitive profiles. Methods A sample of 176 children ages 8–12 years (82 ADHD; 94 neurotypical controls) completed clinical assessments, cognitive and motor tasks, and TMS protocols. Three TMS metrics, resting motor threshold (RMT) and task‐related up‐modulation (TRUM) during response execution and inhibition, were used in hierarchical cluster analyses. Results Results identified three primary ADHD clusters, each defined by distinct neurocognitive profiles. Despite comparable ADHD symptom severity across clusters, differences emerged in cognitive, motor, and behavioral domains. ADHD‐1 (low RMT, low TRUM) showed slower reaction times, suggesting inefficient motor initiation. ADHD‐2 (high RMT, intermediate TRUM) exhibited the greatest impairments in working memory, motor control, and attention, consistent with deficits in executive functioning. ADHD‐3 (intermediate RMT, high TRUM) demonstrated elevated oppositional symptoms, indicating increased behavioral dysregulation. Conclusion These findings provide proof‐of‐concept that TMS‐derived measurements can parse heterogeneity within ADHD beyond traditional clinical symptom measures. RMT and TRUM appear to capture complementary aspects of cortical excitability and dynamic modulation, offering potential biomarkers for ADHD subtyping. This approach may support future precision medicine efforts by linking neurophysiological mechanisms to targeted interventions.