Cortical structural and functional coupling during development and implications for Attention Deficit Hyperactivity Disorder

Abstract

Objective: Functional connectivity is scaffolded by the structural connections of the brain. Disruptions of either structural or functional connectivity can lead to deficits in cognitive functions and increase risk for neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). To date, very little research has examined the association between structural and functional connectivity in typical development, while no studies have attempted to understand the development of structure-function coupling in children with ADHD. Methods: 175 individuals (84 typically developing children and 91 children with ADHD) participated in a longitudinal neuroimaging study with up to three waves. In total, we collected 278 observations between the ages 9 and 14 (139 each in typically developing controls and ADHD). Regional measures of structure-function coupling were calculated at each timepoint using Spearman’s rank correlation and mixed effect models were used to determine group differences and longitudinal changes in coupling over time. Results: In typically developing children, we observed increases in structure-function coupling strength across multiple higher-order cognitive and sensory regions. Overall, weaker coupling was observed in children with ADHD, mainly in prefrontal cortex, superior temporal gyrus and inferior parietal cortex. Further, children with ADHD showed an increased rate of coupling strength predominantly in the inferior frontal gyrus, superior parietal cortex, precuneus, mid cingulate, and visual cortex, compared to no corresponding change over time in typically developing controls. Conclusions: This study provides evidence of the joint maturation of structural and functional brain connections in typical development across late childhood to mid-adolescence, particularly in regions that support cognitive maturation. Findings also suggest that children with ADHD exhibit different patterns of structure-function coupling, suggesting atypical patterns of coordinated white matter and functional connectivity development predominantly in the regions overlapping with the default mode network, salience network and dorsal attention network during late childhood to mid-adolescence.

Group-common and individual-specific effects of structure-function coupling in human brain networks with graph neural networks

“…Particularly, a total of 15 participants from the HCP-D were excluded from subsequent structural connectivity analyses due to incomplete DWI data (8 participants), tissue segmentation failure (5 participants), or the identification of isolated regions after tractography (2 participants). Therefore, a total of 297 participants from HCP-YA (137 males, aged [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and 499 participants from HCP-D (237 males, aged 8-21) were analyzed in subsequent structure-function coupling analyses.…”

“…Additionally, three participants from the HCP-YA were excluded because of incomplete restingstate fMRI runs (less than 1,200 frames). Consequently, 415 participants (179 males, aged 8-21) from the HCP-D and 245 participants (114 males, aged [22][23][24][25][26][27][28][29][30][31][32][33][34][35] from the HCP-YA datasets were included in subsequent analyses.…”

“…In contrast, the highly evolutionarily conserved sensorimotor regions exhibit age-related decreases in structure-function coupling throughout adolescence 10 and the whole lifespan 13 . Moreover, higher structure-function coupling has been related to better performance in executive function 10,22 , and the abnormal pattern of the coupling is associated with a wide range of psychiatric and neurological disorders, such as major depressive disorder 26 , bipolar disorder 27 , attention deficit hyperactivity disorder 28 , and Parkinson's disease 29 .…”

“…While structure-function coupling has been extensively implicated in development, cognition, and clinical outcomes 10,13,22,27,28,30 , few studies have explicitly examined the extent to which structurefunction coupling reflects a group-common characteristic or varies across individuals. Prior studies have reported that functional connectivity is dominated by stable group and individual factors equally 31 , and structural connectivity is even less variable than functional connectivity across participants 32 , suggesting the structure-function coupling could mainly reflect group rather than individual characteristics.…”