Title: Utilising advanced neuroimaging methods to assess the reliability of candidate neural biomarkers of attention deficits in children
Funder: The Academy of Medical Sciences

Abstract: Aim: I will use advanced neuroimaging methods to study attention deficits in children in order to (i) improve understanding of the neural basis of the deficits and (ii) assess the reliability of candidate neural biomarkers that may be useful for assessing individualised interventions. This research will push the boundaries of standard assessment of attention deficits (questionnaires, task performance, and task-free electrophysiological recordings) to elucidate the neural underpinnings during an established attention demanding task, adding to theoretical models (relating alpha power to attention) and options for treatment biomarkers, via the following novel objectives. Objectives: 1.Capitalise on the spatial benefits of magnetoencephalography (MEG) over electroencephalography, recording while children with deficits perform an attention demanding task, to reveal an unprecedented picture of the neural basis of attention deficits, including focal activity and network distributed connectivity. 2.Establish the test-retest reliability of hypothesis-driven MEG-measured neural metrics 3.Relate the functional frontal-visual connectivity (from MEG) and structural connectivity (from MRI-based diffusion tractography) to each other and to task-based alpha power modulation. All novel findings will be related to ‘traditional’ markers of attention deficit /hyperactivity disorder (ADHD) including task-free theta-to-beta power ratio, continuous performance task behaviour, and behaviour questionnaires, as well as to sleep and nutrition questionnaires. I will use my expertise in analysing the neural basis of attention task-related activity, advanced MEG data-analysis methods (including software development), developing productive collaborations, and my supervising experience to realise these objectives. By focussing on individuals and retest reliability, I will produce outcomes valuable as assessment biomarkers.

Lay abstract: Paying attention, sharpening focus on one thing whilst ignoring distractions, is critical for children’s everyday function, including socially and in school. Attention problems can lead to serious consequences, including social distress and poor scholastic performance. If sustained attention problems are severe, a diagnosis of attention deficit / hyperactivity disorder (ADHD) will be made, via questionnaires and practitioner assessment. To manage symptoms, often a drug such as methylphenidate (trade name Ritalin) is taken, with reasonable success. However, the biological basis of ADHD is largely unknown. While behaviour reports and computer task performance can relate well to real-world attention deficits, neither gives us a picture of what the brain is doing when a person successfully maintains attention or fails due to inattention. Recent studies in adults (without ADHD) have provided strong evidence that a particular brain wave called ‘alpha’ and a particular front-to-back neural path both play a direct role in control of attention. However, little is known about the child (with or without ADHD) brain’s control of alpha waves or this path’s strength during attention tasks. This proposal uses state-of-the art brain imaging and advanced data processing to uncover relevant brain activity as well as how brain regions intercommunicate and the ‘highway’ path that physically connects them. The reliability of these measures one day to the next will be assessed, necessary for clinical implementation. The findings together will give us a ‘picture of the brain with attention deficits’ in a way that can be used for future treatment assessment.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL;MENTAL HEALTH