Early-life stress exposure and large-scale covariance brain networks in extremely preterm-born infants

The stressful extrauterine environment following premature birth likely has far-reaching and persistent adverse consequences. The effects of early “third-trimester” ex utero stress on large-scale brain networks’ covariance patterns may provide a potential avenue to understand how early-life stress following premature birth increases risk or resilience. We evaluated the impact of early-life stress exposure (e.g., quantification of invasive procedures) on maturational covariance networks (MCNs) between 30 and 40 weeks of gestational age in 180 extremely preterm-born infants (<28 weeks of gestation; 43.3% female). We constructed MCNs using covariance of gray matter volumes between key nodes of three large-scale brain networks: the default mode network (DMN), executive control network (ECN), and salience network (SN). Maturational coupling was quantified by summating the number of within- and between-network connections. Infants exposed to high stress showed significantly higher SN but lower DMN maturational coupling, accompanied by DMN-SN decoupling. Within the SN, the insula, amygdala, and subthalamic nucleus all showed higher maturational covariance at the nodal level. In contrast, within the DMN, the hippocampus, parahippocampal gyrus, and fusiform showed lower coupling following stress. The decoupling between DMN-SN was observed between the insula/anterior cingulate cortex and posterior parahippocampal gyrus. Early-life stress showed longitudinal network-specific maturational covariance patterns, leading to a reprioritization of developmental trajectories of the SN at the cost of the DMN. These alterations may enhance the ability to cope with adverse stimuli in the short term but simultaneously render preterm-born individuals at a higher risk for stress-related psychopathology later in life.