Towards an Understanding of the Mechanism of Action of Methylphenidate in ADHD

Approximately 1-in-20 children worldwide have Attention Deficit Hyperactivity Disorder (ADHD), a condition associated with disabling inattention, hyperactivity and impulsivity. These problems can manifest as poor inhibitory control (e.g., difficulty holding back impulsive actions) and atypical reward processing (e.g., failing to learn from adverse outcomes). Poorly treated ADHD is associated with negative academic and socioeconomic consequences. This project aims to ultimately improve clinical management of children with ADHD. Methylphenidate, a stimulant medication, is used as the first-option pharmacological treatment for ADHD and often successfully reduces problem behaviour. Although Methylphenidate can be extremely effective, it does not work for every child. There is currently no 'objective' way (e.g., blood test or brain scan) to measure if a child is genuinely responding to Methylphenidate. Instead, clinicians must rely on reports from parents and teachers, an approach that is problematic and that often leads to delays in optimising ADHD treatment. The absence of a biological test to quantify Methylphenidate response is primarily because we do not understand exactly how Methylphenidate changes behaviours to produce the known beneficial effects. This lack of knowledge is despite the very common use of this medication. This project will investigate the specific brain processes that are affected by Methylphenidate by recording brain activity and behaviour in children with ADHD (who have already been prescribed Methylphenidate as part of their clinical care) when they are on and off this medication. Brain activity will be recorded using two separate approaches, which are both non-invasive and routinely used in Trinity College Institute of Neuroscience: electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Brain activity data will be collected while children with ADHD are performing two computer-game like tasks. One task measures the child's ability to hold back impulsive actions (inhibition) and the other assesses how they learn from positive and negative outcomes (reward processing). The data from the two tasks, the EEG recording and the fMRI scan will be analysed using advanced computer-modelling approaches to determine exactly how Methylphenidate changes behaviour. This project is important because if we can understand the brain mechanisms affected by Methylphenidate, we can ultimately develop a computerised measure that will allow clinicians to predict whether a child is going to respond to this treatment or not. Such a measure would allow clinicians to treat ADHD more effectively and would result in children with ADHD experiencing faster relief from symptoms.

NCT Number	NCT05600881
Lead Sponsor	University of Dublin, Trinity College Collaborators: St. James's Hospital, Ireland
Conditions	Attention Deficit Hyperactivity Disorder
Enrollment	35 participants
Start Date	2023-06
Primary Completion	2026-06 (estimated)
Study Completion	2026-09 (estimated)
Updated on ClinicalTrials.gov	2023-05-15