A three-wave longitudinal study of subcortical-cortical resting-state connectivity in adolescence: Testing age- and puberty-related changes

Abstract

Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward-driven behavior. Although reward-driven behavior is supported by subcortical-medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting-state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three-wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self-reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age-related strengthening of subcortico-subcortical and cortico-cortical connectivity. Subcortical-cortical connectivity, such as, between the nucleus accumbens-frontal medial cortex, and the caudate-dorsal anterior cingulate cortex, however, weakened across age. Model-based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical-cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes.

Keywords: adolescence; functional connectivity; longitudinal; pubertal development; resting-state.

Figure 1

The four cortical midline structures and five subcortical regions of interest [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Pubertal Development Scale (PDS) score across age in years. Plot indicates fitted lines of PDS from a generalized additive mixed model for males (blue) and females (red) separately on top of the raw longitudinal data [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Average full‐correlation matrices (uncorrected Pearson's r) between all regions of interest for time point 1, time point 2, and time point 3 [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Spaghetti plots indicating a significant fitted line of age on top of the raw longitudinal data for (a) cortico‐cortical connections (b) and subcortical–cortical connections (c,d). Location of region of interest (ROI) is indicated schematically as dots, visualized with the BrainNet viewer (Xia, Wang, & He, 2013, http://www.nitrc.org/projects/bnv/). Green lines between ROIs indicate age‐related increases, and red lines indicate age‐related decreases. If there was a sex difference in functional connectivity development, males are plotted in blue and females in red in spaghetti plots (only the case for hippocampus–amygdala connectivity) [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Spaghetti plots indicating a significant fitted line of pubertal development on top of the raw longitudinal data for males (left panel) and females (right panel). Location of region of interest (ROI) is indicated schematically as dots, visualized with the BrainNet viewer (Xia et al., 2013, http://www.nitrc.org/projects/bnv/). Green lines between ROIs indicate Pubertal Development Scale (PDS)‐related increases, and red lines indicate PDS‐related decreases [Color figure can be viewed at http://wileyonlinelibrary.com]