A Developmental Shift from Positive to Negative Connectivity in Human Amygdala–Prefrontal Circuitry

TLDR

Frontoamygdala circuitry is crucial for emotional regulation and its disruption is linked to anxiety disorders, yet human developmental changes in reciprocal connections remain poorly understood. The authors aimed to chart developmental changes in amygdala–prefrontal circuitry across ages 4–22 years. They used task‑based functional MRI to assess connectivity patterns across this age range. The study found that amygdala–prefrontal connectivity is positive in children under 10 but becomes negative after age 10, coinciding with reduced amygdala reactivity and suggesting that this valence shift underlies improved task performance and lower anxiety during adolescence.

Abstract

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. Although tracing studies have suggested changes in amygdala–cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala–prefrontal circuitry across the ages of 4–22 years using task-based functional magnetic resonance imaging. Results suggest positive amygdala–prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala–medial prefrontal cortex functional connectivity was significantly positive (greater than zero) among participants younger than 10 years, whereas functional connectivity was significantly negative (less than zero) among participants 10 years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.