Anomalous Motor System Physiology in Attention Deficit Hyperactivity Disorder: Biomarker Validation and Modeling Domains of Function
Donald Gilbert, MD, MS, FAAN, FAAP
Summary
Attention-Deficit/Hyperactivity Disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder in childhood. Children with ADHD struggle in school due to problems with attention and high levels of impulsivity and hyperactivity. They are at substantially increased risk for long-term difficulties into adulthood, including academic underachievement, substance abuse, and criminal behavior. The diagnosis of ADHD, which is based on subjective ratings by parents and teachers, likely results from multiple different, overlapping differences in circuits of the brain responsible for attention and impulse control. However, we do not have any scientific or clinical tests that allow us to understand these circuits. In an effort to improve ADHD outcomes, we have used a technology called Transcranial Magnetic Stimulation (TMS) to identify highly reliable measurements of brain function. We have identified two very promising measures that are abnormal in children with ADHD and, importantly, also predict the severity of ADHD behaviors. The goal of this project is to determine if these two TMS measurements could be used to help better guide ADHD treatment. To do this, we will perform three investigations in 8 to 12 year old children to determine: 1) test-retest reliability; 2) pharmacologic responsiveness; and 3) correlations with two domains of function relevant to ADHD: "Cognitive Control" and "Emotional Valence." Through these investigations, we aim to determine whether these two TMS brain measures are reliable and meaningful enough to be used to help improve precision of individually-targeted and effective ADHD treatments.
Description
4.2. NARRATIVE STUDY DESCRIPTION Summary This is a randomized, blinded, placebo-controlled, single-dose crossover study. The objective is to estimate, in a rigorous, unbiased manner, the effect of 10 mg methylphenidate (MPH) on two putative biomarkers of ADHD, measured using Transcranial Magnetic Stimulation (TMS). Two other aims of this larger study, quantifying test-retest reliability and linking TMS biomarkers to RDoC domains of cognitive control and emotional valence, are not directly part of the clinical trial and are fully described in the research strategy. Doctors use observations an…
Eligibility
- Age range
- 8–12 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Either gender, any race, ethnicity or socioeconomic status * Currently between 8 years 0 months and 12 years, 11 months, 30 days * Willing to answer questions about ADHD and related diagnoses * For children with ADHD prescribed stimulant medications, willing to suspend taking medications as specified in the study procedures * For children with ADHD, willing to participate in the single dose, randomized crossover study to probe acute effects of methylphenidate on biomarkers * Right hand dominant (predominately right-handed) * Able to participate in and sign an informed co…
Interventions
- DrugMethylphenidate
In ADHD participants only: blinded, randomized, placebo-controlled single dose, crossover on separate days separated by at least one week.
- DrugPlacebo
In ADHD participants only: blinded, randomized, placebo-controlled, single dose, crossover on separate days separated by at least one week.
Locations (2)
- Kennedy Krieger InstituteBaltimore, Maryland
- Cincinnati Children's Hospital Medical CenterCincinnati, Ohio