Exploring Neural Heterogeneity in Inattention and Hyperactivity

Abstract

Inattention and hyperactivity are cardinal symptoms of Attention Deficit Hyperactivity Disorder (ADHD). These characteristics have also been observed across a range of other neurodevelopmental conditions, such as autism and dyspraxia, suggesting that they might best be studied across diagnostic categories. Here, we evaluated the associations between inattention and hyperactivity behaviours and features of the structural brain network (connectome) in a large transdiagnostic sample of children (Centre for Attention, Learning, and Memory; n = 383). In our sample, we found that a single latent factor explains 77.6% of variance in scores across multiple questionnaires measuring inattention and hyperactivity. Partial Least-Squares (PLS) regression revealed that variability in this latent factor could not be explained by a linear component representing nodewise properties of connectomes. We then investigated the type and extent of neural heterogeneity in a subset of our sample with clinically-elevated levels of inattention and hyperactivity. Multidimensional scaling combined with k-means clustering revealed two neural subtypes in children with elevated levels of inattention and hyperactivity (n = 232), differentiated primarily by nodal communicability--a measure which demarcates the extent to which neural signals propagate through specific brain regions. These different clusters had indistinguishable behavioural profiles, which included high levels of inattention and hyperactivity. However, one of the clusters scored higher on multiple cognitive assessment measures of executive function. We conclude that inattention and hyperactivity are so common in children with neurodevelopmental difficulties because they emerge from multiple different trajectories of brain development. In our own data, we can identify two of these possible trajectories, which are reflected by measures of structural brain network topology and cognition. Research HighlightsO_LIWe investigated variability in structural brain network organisation and its relationship with cognition and behaviour in a sample of 383 children. C_LIO_LIWe did not find linear components of brain structure that explained continuous variations in inattention and hyperactivity across this heterogeneous sample. C_LIO_LIFollowing this, we explored different attributes of brain organisation in children with particularly elevated levels of inattention and hyperactivity (n = 232). C_LIO_LIAmong highly inattentive and hyperactive children, we found two profiles of structural brain organisation ( neurotypes), which were differentiated primarily by the communicability of nodes in frontal and occipital brain areas. C_LIO_LIThese subgroups did not differ on additional measures of behaviour. However, the lower-nodal-communicability group demonstrated weaker performance on cognitive assessments of executive function and visuospatial processing. C_LIO_LIWe discuss the implications that these findings have for our understanding of variability in neurodevelopmental difficulties and related conditions, such as ADHD C_LI