Adverse childhood experiences and resting state functional connectivity of the triple brain network: a meta-analysis

Adverse childhood experiences (ACEs), which include potentially traumatic events occurring during childhood, have been found to be associated with alterations in resting-state functional connectivity (rs-FC) within large brain networks, such as the Salience (SN), Default Mode (DMN), and Central Executive (CEN) Networks. While alterations in these networks may increase vulnerability to mental health disorders, existing data are inconsistent as to the neural pathways affected and the type of connectivity pattern associated with adversity (hyper- or hypoconnectivity). These inconsistencies could be due to methodological differences across studies, to the selection of different target regions of interest (ROIs), or to the use of ROI-to-ROI approaches that could overlook broader effects at the whole-brain level. Here, we conducted a meta-analysis of rs-FC seed-to-whole brain studies using the Seed-based d Mapping software to investigate patterns of rs-FC aberrations specifically associated with ACEs. Out of 12 identified studies, eight were included in the meta-analysis, comprising 289 individuals positive for ACEs and 301 controls. The analysis showed that individuals positive for ACEs, compared to controls, present a pattern of hypoconnectivity centred within the SN, between SN and DMN integrative hubs, and between DMN and CEN. Such disruptions, potentially resulting from prolonged or excessive activity of the hypothalamus-pituitary-adrenal axis, might affect emotion regulation, fear conditioning, memory and affective learning processing, goal-directed behavior, and cognitive control, and increase vulnerability to mental health disorders. Future research should focus on more homogeneous populations and larger samples, to truly advance our understanding of the biological mechanisms underlying ACEs-related brain connectivity disruptions.