An examination of the relationships between attention/deficit hyperactivity disorder symptoms and functional connectivity over time

Luke J Norman,Gustavo Sudre,Wendy Sharp,Marine Bouyssi-Kobar,Philip Shaw

doi:10.1038/s41386-021-00958-y

Abstract

Previous cross-sectional work has demonstrated resting-state connectivity abnormalities in children and adolescents with attention/deficit hyperactivity disorder (ADHD) relative to typically developing controls. However, it is unclear to what extent these neural abnormalities confer risk for later symptoms of the disorder, or represent the downstream effects of symptoms on functional connectivity. Here, we studied 167 children and adolescents (mean age at baseline = 10.74 years (SD = 2.54); mean age at follow-up = 13.3 years (SD = 2.48); 56 females) with varying levels of ADHD symptoms, all of whom underwent resting-state functional magnetic resonance imaging and ADHD symptom assessments on two occasions during development. Resting-state functional connectivity was quantified using eigenvector centrality mapping. Using voxelwise cross-lag modeling, we found that less connectivity at baseline within right inferior frontal gyrus was associated with more follow-up symptoms of inattention (significant at an uncorrected cluster-forming threshold of p ≤ 0.001 and a cluster-level familywise error corrected threshold of p < 0.05). Findings suggest that previously reported cross-sectional abnormalities in functional connectivity within inferior frontal gyrus in patients with ADHD may represent a longitudinal risk factor for the disorder, in line with efforts to target this region with novel therapeutic methods.

Highlights

Attention deficit/hyperactivity disorder (ADHD) is a childhoodonset neurodevelopmental disorder characterized by symptoms of age-inappropriate inattention and hyperactivity/impulsivity [1]
The current study sought to clarify the relationships over time between symptoms of ADHD and functional brain connectivity
We observed a large degree of interindividual variability in symptom change with age, which was associated with individual differences over time in the functional connectivity of an inferior frontal region commonly implicated in the disorder [19, 20, 24, 59]

Summary

Introduction

Attention deficit/hyperactivity disorder (ADHD) is a childhoodonset neurodevelopmental disorder characterized by symptoms of age-inappropriate inattention and hyperactivity/impulsivity [1]. It affects around 5–10% of children and has a significant negative impact on mental health, family functioning, and educational attainment [1,2,3,4]. Current models often assume that these functional brain abnormalities underlie ADHD symptoms, and form part of the mechanistic pathway between genetic and environmental risk and symptoms of the disorder [19,20,21]. Existing work has used primarily cross-sectional case–control designs, and it is possible that functional brain abnormalities are secondary consequences of ADHD symptoms [4, 22, 23]. Distinguishing brain abnormalities that play etiological roles in the onset, maintenance, or worsening of ADHD symptoms from those that are secondary consequences or epiphenomenal correlates of the disorder is important in light of ongoing efforts to find potential targets for novel, biomarker-driven interventions in ADHD [24]

Methods

Findings

Conclusion