The overgrowth of structure-function coupling level in premature brain during infancy

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Abstract Submission 

Rong Wang¹, Jing Yu¹, Tianyu Fang¹, Yue Zhang¹, Qiuyun Fan¹, Yuanyuan Chen¹

¹Academy of Medical Engineering and Translational Medicine, Medical School of Tianjin University, Tianjin, China

Rong Wang  
Academy of Medical Engineering and Translational Medicine, Medical School of Tianjin University
Tianjin, China

Jing Yu  
Academy of Medical Engineering and Translational Medicine, Medical School of Tianjin University
Tianjin, China

Tianyu Fang  
Academy of Medical Engineering and Translational Medicine, Medical School of Tianjin University
Tianjin, China

Yue Zhang  
Academy of Medical Engineering and Translational Medicine, Medical School of Tianjin University
Tianjin, China

Qiuyun Fan  
Academy of Medical Engineering and Translational Medicine, Medical School of Tianjin University
Tianjin, China

Yuanyuan Chen  
Academy of Medical Engineering and Translational Medicine, Medical School of Tianjin University
Tianjin, China

There are plenty of literatures about the two parallel development of infant brain during infancy, brain structure and brain function, but not about their coupling together with development, which also have been indicated to be very coupled in adult brain. In this study, we explore the concurrent development of brain structure and function in infants, a process known to be closely interlinked in adults. We are aimed to explore how the brain structure function couple during infancy, develop with age and alter with prematurity.

All data were acquired from the Developing Human Connectome Project(Hughes, Winchman et al. 2017). This study included 436 full-term infants (202 females; mean gestational age at birth: 39.9±1.27 weeks; mean PMA at scan:41.14±1.71 weeks) and 174 preterm infants (78 females, mean gestational age at birth: 32.24±3.44 weeks), out of which 63 preterm infants underwent two scans (PMA of 1th scan at birth: 34.49±1.77 weeks; PMA at 2th scan at term-equivalent age: 40.96±2.10 weeks). Cognitive assessments were collected at approximately 18 months of age using the Bayley Scale of Infant Development third edition (BSID-III). Image preprocessing was done including distortion correction, motion correction, scrubbing, interpolation, filtering, nuisance regression of spectrally matched motion parameters plus signals within CSF, white-matter, and grey-matter tissues. The UNC neonatal brain template as well as the AAL-aligned brain parcellation with 90 nodes were used to define the final space, and to construct the structural and functional connectome. Functional connectivity matrixes were calculated based on Fisher-Z transformed correlation. Structural connectivity matrixes were obtained from the fiber bundle density between two regions. The structural and functional connectivity coupling index was calculated for each brain regions individually, based on a multilinear regression model. The regression model incorporated multiple cortical connectivity including Euclidean distance, shortest path length and communicability, which were obtained from the sparse structural connectivity matrix and used to predict functional connectivity for the connectivity profile at each region. And the R-square value of the regression model was considered as the coupling index between regional structure and function.

The brain structure-function coupling at the whole brin level showed significant group difference between the preterm at birth, the preterm at TEA and the full-term group (see Figure 1a). The preterm group showed a lower coupling level at birth and followed with a great growth at TEA, which was even higher than the coupling level of full-term group and consistent across all sub systems (Figure 1b). However, the spatial pattern of coupling index for two groups showed quite similar, with higher level for unimodal cortex and lower level for transmodal cortex.
The developmental dynamics with PMA showed a rapid increase for both whole brain and reginal coupling index in full-term group but not in preterm at TEA group (Figure 2a and 2b). Highlighted regions were located within unimodal networks (Figure 2c). Finally, the coupling index for both groups showed significant association with cognitive outcomes at 19 months age, controlling covariables like gestational age at birth, PMA at scan, gender and motion parameters (Figure 2 d and e). Noteworthy, negative association for preterm and positive association for full-term between coupling index and cognitive score were identified.

The immaturity of brain is very sensitive and vulnerable to the explosive environment inputs. The preterm infant brain possesses low level of structure-function coupling at birth and goes through an overgrowth to the term equivalent age. This overgrowth of brain structure-function coupling for preterm infants was verified to be negative correlated with the 19-month-old cognition outcome.

Normal Brain Development: Fetus to Adolescence ¹

Connectivity (eg. functional, effective, structural) ²

fMRI Connectivity and Network Modeling

FUNCTIONAL MRI

Multivariate

Other - Brain development; Structural and functional coupling; DTI; Infant;