Developmental trajectory deviation for hierarchical function system in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder is a typically neurodevelopmental disorder with intra-/inter-network dysconnectivity, indicating that characterizing its age-dependent hierarchical function system changes is crucial to understanding the disease's course. Combining hierarchical spatial gradient and partial least squares regression analysis methods, we investigated the cortical abnormalities of functional gradient in individuals with attention-deficit/hyperactivity disorder and its relationships with genic transcriptomic information. Additionally, we described the hierarchical function system development during childhood using developmental curve fitting analysis. We observed increased functional gradients in the regions within visual and dorsal attention networks, and decreased gradients distributing in the regions with limbic and default mode networks. Compared with the typical developmental age-gradient track curve, individuals with attention-deficit/hyperactivity disorder exhibited earlier turning points and smaller curve's variation ranges. Gene expression analysis showed a significantly overlapped enrichment pathways associated with nervous system development between the genes we identified and those previously reported. Above-Abnormal functional gradients and network-level averaged gradient values exhibited significant correlations with clinical inattention scores in attention-deficit/hyperactivity disorder. Overall, our findings characterized changes in hierarchical functional systems and their age-dependent relationships from both macro-neuroimaging and micro-genetic dimensions, advancing understanding of the underlying neural mechanisms behind neurodevelopmental disorders.