Differentiation of frontolimbic functional connectivity from birth to early adulthood links with adversity exposure and cognition.

Abstract

Frontolimbic circuits connecting the frontal cortex with the amygdala and the hippocampus are critical for emotion and learning. These connections undergo major changes throughout childhood and adolescence, yet the principles guiding their maturation remain unclear. Analyzing large developmental cohorts, we show that fronto-hippocampus connectivity develops rapidly in early childhood and stabilizes thereafter. In contrast, fronto-amygdala connectivity becomes progressively differentiated from fronto-hippocampus connectivity, with development most pronounced during adolescence. This entailed hippocampus and amygdala respectively becoming preferentially tethered to association-related regions and sensorimotor-related regions. Greater adversity exposure was associated with more differentiated fronto-amygdala connectivity for a given age. Higher cognitive ability was associated with less differentiated fronto-hippocampus connectivity. These findings suggest that frontolimbic connectivity development follows a principle of differentiation, with circuit-specific timing and sensitivity to stress and learning. This work provides a foundation for understanding typical and atypical frontolimbic circuitry development from birth to emerging adulthood.