Developing functional network connectivity of the dorsal anterior cingulate cortex mediates externalizing psychopathology in adolescents with child neglect

Abstract

Childhood adversity has been associated with elevated risk for psychopathology. We investigated whether development of functional brain networks important for executive function (EF) could serve as potential mediators of this association. We analyzed data of 475 adolescents, a subsample of the multisite longitudinal NCANDA (National Consortium on Alcohol and Neurodevelopment in Adolescence) cohort with completed measures of childhood trauma, resting-state functional brain connectivity data, and symptoms of internalizing and externalizing psychopathology at baseline and follow-up years 1–4. Using parallel process latent growth models, we found that childhood adversity was associated with increased risk for externalizing/internalizing behaviors. We specifically investigated whether functional connectivity of the dorsal anterior cingulate cortex (dACC) to brain regions within the cingulo-opercular (CO) network, a well-known EF network that underlies control of attention and self-regulation, mediates the association between adversity and symptoms of psychopathology. We found that childhood adversity, specifically child neglect was negatively associated with functional connectivity of the dACC within the CO network, and that this connectivity mediated the association between neglect and externalizing behaviors. Our study advances a mechanistic understanding of how childhood adversity may impact the development of psychopathology, highlighting the relevance of dACC functional networks particularly for externalizing psychopathology.

Associations among negative life events, changes in cortico-limbic connectivity, and psychopathology in the ABCD Study

“…Indeed, the same circuits that are highly sensitive to stress are also implicated in a host of psychopathology outcomes in youth. For example, aberrant patterns of cortico-limbic rsFC may underlie both internalizing ( Rakesh et al, 2021 , VanTieghem and Tottenham, 2018 ) and externalizing ( Rubia, 2011 , Silveira et al, 2021 , Thijssen et al, 2020a , Thijssen et al, 2020b ) symptomatology. More specifically, connectivity between the CO network and subcortical regions has been linked to psychopathology among youth in the ABCD Study.…”

“…Taken together, prior research demonstrates that adversity is associated with individual differences in cortico-limbic circuitry that may underlie internalizing and externalizing symptomatology. However, only a few studies have integrated measures of adversity, functional connectivity, and psychopathology in order to formally investigate potential mediating effects ( Barch et al, 2018 , Callaghan et al, 2017 , Rakesh et al, 2021 , Silveira et al, 2021 ). As one example, Rakesh et al (2021) found that longitudinal increases in between-network connectivity (e.g., between the default mode network, frontoparietal network, dorsal attention network, and salience network) mediated the association between maltreatment history and adolescent depressive symptoms.…”

Large-scale functional brain networks of maladaptive childhood aggression identified by connectome-based predictive modeling

“…However, findings from the current study should also be interpreted in the context of other studies examining externalizing behaviors using machine learning and/or big data analytic approaches. For example, recent work has leveraged large datasets using related network neuroscience approaches to understand neuroetiologic pathways in children with disruptive behavior disorders 97 , 98 as well as broader externalizing behaviors 99 – 101 , which point to aberrant connectivity in frontoparietal regions and a potential broad network dysfunction similar to that observed in the current study. In addition, a recent study reported that sensorimotor network connectivity was associated with irritability in youths during a frustrating cognitive flexibility task 68 .…”

Childhood Threat Is Associated With Lower Resting-State Connectivity Within a Central Visceral Network

“…Nevertheless, our findings involved childhood threat-related differences in functional connectivity in cortico-amygdalar-hypothalamic regions that overlap with DMN and salience networks. Expanding literatures indicate that these networks, their nodes and connections between them are altered by childhood adversity ( Werff et al, 2012 ; Marusak et al, 2015 ; Hoffmann et al, 2018 ; Cheng et al, 2021 ; Huang et al, 2021 ; Rakesh et al, 2021a ; Merrick et al, 2018 ; Silveira et al, 2021 ), and that these networks are dysregulated in affective disorders ( Greicius et al, 2007 ; Seeley et al, 2007 ; Jacobs et al, 2014 , 2016 ; Iadipaolo et al, 2018 ). Thus, our findings may also reflect alterations within these large-scale networks that impact emotion regulation processes (DMN) and orientation to salient internal and external stimuli (salience) ( Menon, 2013 ).…”