Characterizing the Effect of Premature Birth on Adolescent Brain Network Organization
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Date
2021-11
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Abstract
Premature birth is associated with negative health outcomes (e.g. neurocognitive deficits) from infancy into adulthood. Recent work using functional connectivity during rest in infants suggests that premature birth disrupts the broad-scale organization of the brain. In adults, individual differences in functional connectivity correlate with behavioral and personality measures in controls and can dissociate disease states. Further, our previous work showed that these individual differences in functional connectivity are observed even in full-term neonates scanned within the first few weeks of life. However, it remains unclear how premature birth can alter broadscale network organization later in life. Here, we characterize and compare broad network organization between adolescents born premature (N=22; mean age at scan: 13.9 years) and age-matched adolescents born full-term (N=28; mean age at scan: 13.8 years). We calculated each individual's connectome (voxel-to-voxel correlations of resting-state fMRI data) and used k-means clustering to parcellate the brain into broad-scale networks. Using a leave-one-subject-out procedure, we left out one subject's data, calculated the average connectome among the rest of the subjects, defined networks based on k-means clustering of that group connectome, and assigned each voxel of the left-out subject's data to a cluster based on which cluster's centroid best matched the connectivity profile of that voxel. Therefore, we generated independent networks for each individual that were based on that individual's own nuanced connectome data. We first assessed the optimal k solution for each group (from k=2 to 25 clusters). Based on the fit to data and stability (two common ways to assess optimal k solutions), we found that k=7 and k=12 solutions were optimal for both groups. We then compared the network solutions between the premature and control groups, and found that while both groups had symmetrical and contiguous networks, the limbic network showed the least overlap between the preterm and full-term adolescents. We also compared these solutions to networks previously generated in adults (using similar clustering methods) and found that while both groups had good overlap with the adult networks, only the premature group had a network resembling the adult limbic network. Ongoing investigations include classifying an individual as preterm vs. full-term based on only their connectome (based largely on the network differences we observed in preterm vs. full-term adolescents). Overall, our work suggests that by adolescence, the broad-scale organization of the brain is quite adult-like, reliably dissociating into 7 major networks across the brain. However, we also find evidence of continued maturation of especially the limbic network; but this network is actually more adult-like in preterm adolescents than adolescents born full-term, suggesting that precocious development of this network may play a role in adverse neurocognitive outcomes associated with preterm birth.
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developmental neuroscience, brain organization, clustering, brain network, network organization