Study Objective: To learn more about ADHD and to help develop reliable diagnosis assessments.

Background: Attention Deficit Hyperactivity Disorder (ADHD) is the most common behavioral diagnosis in childhood. It incurs high medical costs and can contribute to poor academic achievement, adult mental illness, substance abuse, and criminal behavior. Standard treatments, such as stimulant medications, primarily target symptoms and long-term follow-up studies of children treated for ADHD reveal that their outcomes remain significantly worse as compared to typically developing peers. A critical obstacle to improving long-term ADHD treatment outcomes is the lack of quantitative markers, which correlate with symptoms and reveal neurobiological mechanisms in ways that could point toward more accurate prognosis and be more effective for future treatments. To this end, it is worth considering the long-standing observation that children with ADHD often demonstrate difficulties with motor control that correlate with difficulties with higher-order behavioral control.

We have addressed this barrier by taking advantage of the relationship (in developmental timing and anatomic proximity) between motor control and both cognitive and emotional control to pursue the physiology of inhibitory mechanisms in ADHD in our grant proposal. The goal of this study is to leverage these findings of impaired motor control to test, characterize, and validate pragmatic and biologically meaningful ADHD biomarkers that could lead to substantive improvements in how clinicians both selecting treatments and predicting outcomes.

Neural systems critical for development of motor control parallel those for behavioral control. As such, ADHD-associated anomalies in motor control can function as practical biomarkers for predicting treatment responses and outcomes. Our initial investigations of motor function in ADHD have yielded some promising findings. First, we have repeatedly and consistently observed that children with ADHD show excessive motor overflow, reflecting impaired inhibition of unnecessary and unwanted movements. Furthermore, physiologic assessments have revealed reduced TMS-evoked Short Interval Cortical Inhibition (SICI) as a potential biomarker for the diagnosis of ADHD, as we have found that this reduced SICI correlates not only with the severity of impairments in motor control, but also with core ADHD symptoms. We are now building on these findings to extend the evaluation of SICI into relevant functional domains of response inhibition and reward, and to clarify the dopamine (DA) and GABA neural transmission underpinnings of these findings. We anticipate that our findings will help to identify subgroups used for treatment decisions and provide a foundation for the development of novel treatment interventions, both behavioral and pharmacologic.