The Limbic System in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Longitudinal Structural Magnetic Resonance Imaging Analysis.

Background: During childhood and adolescence, attention-deficit/hyperactivity disorder (ADHD) is associated with changes in symptoms and brain structures, but the link between brain structure and function remains unclear. The limbic system, often termed the "emotional network," plays an important role in a number of neurodevelopmental disorders, yet this brain network remains largely unexplored in ADHD. Investigating the developmental trajectories of key limbic system structures during childhood and adolescence will provide novel insights into the neurobiological underpinnings of ADHD. Methods: Structural magnetic resonance imaging data (380 scans), emotional regulation (Affective Reactivity Index), and ADHD symptom severity (Conners 3 ADHD Index) were measured at up to 3 time points between 9 and 14 years of age in a sample of children and adolescents with ADHD (n = 57) and control children (n = 109). Results: Compared with the control group, the ADHD group had lower volume of the amygdala (left: ß standardized [ß_std] = -0.38; right: ß_std = -0.34), hippocampus (left: ß_std = -0.44; right: ß_std = -0.34), cingulate gyrus (left: ß_std = -0.42; right: ß_std = -0.32), and orbitofrontal cortex (right: ß_std = -0.33) across development (9-14 years). There were no significant group-by-age interactions in any of the limbic system structures. Exploratory analysis found a significant Conners 3 ADHD Index-by-age interaction effect on the volume of the left mammillary body (ß_std = 0.17) in the ADHD group across the 3 study time points. Conclusions: Children and adolescents with ADHD displayed lower volume and atypical development in limbic system structures. Furthermore, atypical limbic system development was associated with increased symptom severity, highlighting a potential neurobiological correlate of ADHD severity.

Connectome-based predictive modelling of cognitive reserve using task-based functional connectivity.

Cognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task-based fMRI data that could then be applied to independent resting-state data. Connectome-based predictive modelling with leave-one-out cross-validation was applied to predict a residual measure of cognitive reserve using task-based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). This model generated summary measures of connectivity strength that accurately predicted a residual measure of cognitive reserve in unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio-behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting-state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network-strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task-based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task-based functional connectivity can be applied to independent resting-state data.

White matter microstructure in children and adolescents with ADHD.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Advances in diffusion magnetic resonance imaging (MRI) acquisition sequences and analytic techniques have led to growing body of evidence that abnormal white matter microstructure is a core pathophysiological feature of ADHD. This systematic review provides a qualitative assessment of research investigating microstructural organisation of white matter amongst children and adolescents with ADHD. This review included 46 studies in total, encompassing multiple diffusion MRI imaging techniques and analytic approaches, including whole-brain, region of interest and connectomic analyses. Whole-brain and region of interest analyses described atypical organisation of white matter microstructure in several white matter tracts: most notably in frontostriatal tracts, corpus callosum, superior longitudinal fasciculus, cingulum bundle, thalamic radiations, internal capsule and corona radiata. Connectomic analyses, including graph theory approaches, demonstrated global underconnectivity in connections between functionally specialised networks. Although some studies reported significant correlations between atypical white matter microstructure and ADHD symptoms or other behavioural measures there was no clear pattern of results. Interestingly however, many of the findings of disrupted white matter microstructure were in neural networks associated with key neuropsychological functions that are atypical in ADHD. Limitations to the extant research are outlined in this review and future studies in this area should carefully consider factors such as sample size, sex balance, head motion and medication status.