Biomarker Validation in Motor System Physiology in Attention Deficit Hyperactivity Disorder

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.

Timeline

Start

2020-09-01

Primary completion

2026-02-09

Completion

2026-07-01

Publications

• Background Doherty AC, Huddleston DA, Horn PS, Ratner N, Simpson BN, Schorry EK, Aschbacher-Smith L, Prada CE, Gilbert DL. Motor Function and Physiology in Youth With Neurofibromatosis Type 1. Pediatr Neurol. 2023 Jun;143:34-43. doi: 10.1016/j.pediatrneurol.2023.02.014. Epub 2023 Mar 3.
• Background Luo Y, Adamek JH, Crocetti D, Mostofsky SH, Ewen JB. Dissociation in Neural Correlates of Hyperactive/Impulsive vs. Inattentive Symptoms in Attention-Deficit/Hyperactivity Disorder. Front Neurosci. 2022 Jun 22;16:893239. doi: 10.3389/fnins.2022.893239. eCollection 2022.
• Background Luo Y, Chen C, Adamek JH, Crocetti D, Mostofsky SH, Ewen JB. Altered cortical activation associated with mirror overflow driven by non-dominant hand movement in attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jan 10;112:110433. doi: 10.1016/j.pnpbp.2021.110433. Epub 2021 Aug 27.
• Background Chen C, Rosch KS, Seymour KE, Crocetti D, Mahone EM, Mostofsky SH. Sex Effects on Mirror Overflow during Finger Tapping in Children with ADHD. J Int Neuropsychol Soc. 2022 Apr;28(4):371-381. doi: 10.1017/S1355617721000576. Epub 2021 May 17.
• Background Nikolaidis A, He X, Pekar J, Rosch K, Mostofsky SH. Frontal corticostriatal functional connectivity reveals task positive and negative network dysregulation in relation to ADHD, sex, and inhibitory control. Dev Cogn Neurosci. 2022 Apr;54:101101. doi: 10.1016/j.dcn.2022.101101. Epub 2022 Mar 23.
• Background Thapaliya G, Carnell S, Mostofsky SH, Rosch KS. Neurobehavioral phenotypes of delay discounting and cognitive control in child attention-deficit/hyperactivity disorder and obesity: Shared or distinct? Pediatr Obes. 2023 Apr;18(4):e13001. doi: 10.1111/ijpo.13001. Epub 2023 Jan 18.

Drugs

Indications