Professor Robert Whelan

Summary

This project uses precision medicine to improve treatment of childhood Attention Deficit Hyperactivity Disorder (ADHD). Methylphenidate is the first-line pharmacological treatment but there is wide individual variation in outcomes: 30% of children will have no clinically meaningful response. There is currently no validated objective, quantitative method for predicting who will ultimately respond. We propose to use neurally informed computational models derived from behaviour and electroencephalography to decompose medication effects on distinct neural mechanisms. Our industry collaborators, Cumulus Neuroscience, have developed dry-sensor electroencephalography headsets allowing users to obtain data at home. Their cloud-based software can automatically process large amounts of electroencephalographic data. We will recruit 300 medication-naive patients (ages 10-14) from ADHD services led by co-PI McGrath and our collaborators. Tasks will be gamified to maintain engagement. Interrogating this immense amount of data will be solved by using computational model parameters as inputs into machine learning algorithms. The goal will be to identify neurocognitive processes predicting who will respond clinically to methylphenidate. Two PhD students and a research assistant will be recruited. This project can significantly enhance quality of life of those with ADHD. The approach outlined here can be a new sector in the precision medicine field.

Funding Agency

Science Foundation Ireland

Programme

Frontiers for the Future

Project Type

Empirical

Summary

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 negative 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.

Funding Agency

TCD Provost Award

Programme

TCD Provost Award

Project Type

Empirical Research

Person Months

48

Summary

The goal of this project is to use mathematical models to improve our understanding of brain functioning, which can ultimately inform brain-inspired computing. The project"s goal will be achieved by applying these models to two very large neuroimaging datasets that focus on substance use and adolescent brain development.

Funding Agency

China Scholarship Council

Programme

PhD program

Project Type

Empirical Research

Person Months

48

Summary

The concept of Patient and public voice (PPV; also known as `patient and public involvement", PPI) is designed to foster a meaningful and active partnership between the public and researchers. Active involvement may take the form of consultation, collaboration or user control (Boote et al., 2015). Examples include public involvement in prioritizing research, advising on a research project, assisting in the design of a project, or in carrying out the research (e.g., INVOLVE UK:2015, www.invo.org.uk/)researchers should involve patients and the public at all stages of the research cycle (INVOLVE. Briefing notes:2012), including formulating the research question. In countries such as the United Kingdom, PPV is a requirement to obtain research support from many funders (Department of Health, 2005), is necessary for ethical approval of human research (Iliffeet al 2013) and is likely to become a standard requirement for research. While to date fellows at UCSF have had the opportunity to interact with the Memory and Aging Centre"s (MAC) Family Advisory Council (FAC), this has not been a core part of the fellowship across both sites. There is both a need and an opportunity to enhance the learning experience in this space in a cross-site fashion. In this application, we propose a two-year development project to work with a Patient and Public Voice (PPV) panel for the two sites (TCD and UCSF) of GBHI, fully aligned with GBHI"s learning and research goals. Including PPV in the Global Brain Health Institute (GBHI) fellowship experience will foster the GBHI values of equity and promote person-centred research and practice.

Funding Agency

Global Brain Health Institute (GBHI)

Summary

Our project uses a precision medicine approach to predict treatment response to stimulant medication in adolescents with ADHD. There are three novel aspects to this project relevant to this supplemental funding. First, we are developing gamified neurocognitive tasks to maintain engagement and interest of participants (essentially, applying principles from video game development to established laboratory tasks). Second, we will apply " at scale (~2,400 sessions) " sophisticated computational methods to the brain and behaviour data. Third, we are committed to making materials from this project accessible to the research community, adhering to FAIR principles. Dr Revenko is an experienced researcher with skills that perfectly match these three novel aspects, with experience in computational modeling and software development (including game development).

Funding Agency

Science Foundation Ireland

Programme

SFI Rapid Response Supplemental Grant for Displaced Researchers

Project Type

Empirical Research

Person Months

12