Development of the Brain Functional Connectome Follows Puberty-Dependent Nonlinear Trajectories

Adolescence is a developmental period that dramatically impacts body and behavior, with pubertal hormones playing an important role not only in the morphological changes in the body but also in brain structure and function. Understanding brain development during adolescence has become a priority in neuroscience because it coincides with the onset of many psychiatric and behavioral disorders. However, little is known about how puberty influences the brain functional connectome. In this study, taking a longitudinal human sample of typically developing children and adolescents (of both sexes), we demonstrate that the development of the brain functional connectome better fits pubertal status than chronological age. In particular, centrality, segregation, efficiency, and integration of the brain functional connectome increase after the onset of the pubertal markers. We found that these effects are stronger in attention and task control networks. Lastly, after controlling for this effect, we showed that functional connectivity between these networks is related to better performance in cognitive flexibility. This study points out the importance of considering longitudinal nonlinear trends when exploring developmental trajectories, and emphasizes the impact of puberty on the functional organization of the brain in adolescence. Significance Statement Understanding the brain organization along development is a crucial challenge for Neuroscience. In particular, during adolescence there is a great impact in body and cognitive functions as well as substantial incidence of mental health disruptions. Here, we tested how brain organization changes along this period based on the properties of the functional connectome in a longitudinal pediatric sample. We found a nonlinear increase in the connectivity and the brain network efficiency, particularly after the onset of puberty. These effects were more prominent in association networks. In addition, higher connectivity in those areas was associated with better performance in cognitive flexibility. These results demonstrate the importance of considering pubertal assessment as well as nonlinear trends in developmental studies.