Childhood violence exposure, but not social deprivation, was associated with reduced adolescent resting-state neural network density

Association of Childhood Violence Exposure With Adolescent Neural Network Density. Leigh G. Goetschius et al. JAMA Netw Open. 2020;3(9):e2017850, September 23, 2020. doi:10.1001/jamanetworkopen.2020.17850

Key Points

Question  Are violence exposure and social deprivation associated with person-specific patterns (heterogeneity) of adolescent resting-state functional connectivity?

Findings  In this cohort study of 175 adolescents, childhood violence exposure, but not social deprivation, was associated with reduced adolescent resting-state density of the salience and default mode networks. A data-driven algorithm, blinded to childhood adversity, identified youth with heightened violence exposure based on resting-state connectivity patterns.

Meaning  Childhood violence exposure appears to be associated with adolescent functional connectivity heterogeneity, which may reflect person-specific neural plasticity and should be considered in neuroscience-based interventions.

Abstract

Importance  Adverse childhood experiences are a public health issue with negative sequelae that persist throughout life. Current theories suggest that adverse childhood experiences reflect underlying dimensions (eg, violence exposure and social deprivation) with distinct neural mechanisms; however, research findings have been inconsistent, likely owing to variability in how the environment interacts with the brain.

Objective  To examine whether dimensional exposure to childhood adversity is associated with person-specific patterns in adolescent resting-state functional connectivity (rsFC), defined as synchronized activity across brain regions when not engaged in a task.

Design, Setting, and Participants  A sparse network approach in a large sample with substantial representation of understudied, underserved African American youth was used to conduct an observational, population-based longitudinal cohort study. A total of 183 adolescents aged 15 to 17 years from Detroit, Michigan; Toledo, Ohio; and Chicago, Illinois, who participated in the Fragile Families and Child Wellbeing Study were eligible for inclusion. Environmental data from birth to adolescence were collected via telephone and in-person interviews, and neuroimaging data collected at a university lab. The study was conducted from February 1, 1998, to April 26, 2017, and data analysis was performed from January 3, 2019, to May 22, 2020.

Exposures  Composite variables representing violence exposure and social deprivation created from primary caregiver reports on children at ages 3, 5, and 9 years.

Main Outcomes and Measures  Resting-state functional connectivity person-specific network metrics (data-driven subgroup membership, density, and node degree) focused on connectivity among a priori regions of interest in 2 resting-state networks (salience network and default mode) assessed with functional magnetic resonance imaging.

Results  Of the 183 eligible adolescents, 175 individuals (98 girls [56%]) were included in the analysis; mean (SD) age was 15.88 (0.53) years and 127 participants (73%) were African American. Adolescents with high violence exposure were 3.06 times more likely (95% CI, 1.17-8.92) to be in a subgroup characterized by high heterogeneity (few shared connections) and low network density (sparsity). Childhood violence exposure, but not social deprivation, was associated with reduced rsFC density (β = −0.25; 95% CI, −0.41 to −0.05; P = .005), with fewer salience network connections (β = −0.26; 95% CI, −0.43 to −0.08; P = .005) and salience network-default mode connections (β = −0.20; 95% CI, −0.38 to −0.03; P = .02). Violence exposure was associated with node degree of right anterior insula (β = −0.29; 95% CI, −0.47 to −0.12; P = .001) and left inferior parietal lobule (β = −0.26; 95% CI, −0.44 to −0.09; P = .003).

Conclusions and Relevance  The findings of this study suggest that childhood violence exposure is associated with adolescent neural network sparsity. A community-detection algorithm, blinded to child adversity, grouped youth exposed to heightened violence based only on patterns of rsFC. The findings may have implications for understanding how dimensions of adverse childhood experiences impact individualized neural development.

Discussion

Results from a predominantly understudied and underserved sample with high rates of poverty suggest that childhood violence exposure, but not social deprivation, is associated with adolescent neural circuitry. Data-driven analyses identified a subset of adolescents with heterogeneous patterns of connectivity (ie, few shared and many individual connections) in 2 key neural networks associated with salience detection, attention, and social-cognitive processes (ie, the SN and DMN).^7,8 This subgroup of adolescents was exposed to more violence in childhood than the other subgroup, whose patterns of neural connectivity were relatively more homogeneous (ie, had many connections in common), suggesting that violence exposure may lead to more person-specific alterations in neural circuitry. Beyond subgroups, network density within the SN and between the SN and DMN was sparse for adolescents with high violence exposure, likely due to few connections involving the right insula and the left IPL. These factors could not be accounted for by social deprivation, in-scanner motion, race, sex, pubertal development, current life stress, or maternal marital status or educational level at the time of the participant’s birth.

Findings regarding the neural network subgroups are noteworthy because the community detection algorithm within GIMME detected rsFC patterns in the brain from exposures that occurred at least 6 years earlier. Moreover, high childhood violence exposure in the subgroup characterized by neural heterogeneity likely reflects the person-specific outcomes of early adversity on the brain and suggests that research on the developmental sequelae of adverse childhood experiences should consider individual differences in neural compensatory responses to stress.¹⁷ Although it is important to replicate these findings in other samples, S-GIMME has reliably classified subgroups in empirical data,^40,45 and there is evidence from simulations that modeling connections at the subgroup level, in addition to the group level, improves the validity and reliability of results.⁴⁰

Considering the sample as a whole, results also suggest that violence exposure is associated with blunted connectivity within the SN and between the SN and DMN. As expected, the observed reduced SN density in adolescents with heightened childhood violence exposure differs from typical developmental patterns that show stronger rsFC within SN nodes and increased density of connections with hub regions, such as the anterior insula, as the brain matures.^8,16 It is difficult, however, to align the present findings with previous work that reported increased SN rsFC in trauma-exposed youth^9,10 because those samples were small, used different metrics of connectivity, and had different sample compositions. Moreover, the present sample was likely experiencing chronic adversity, and research from animal models of chronic stress proposes that, over time, the body’s stress response (eg, hypothalamic pituitary adrenal axis reactivity) becomes blunted or habituated to typical stressors.⁴⁷ Previous research on hypothalamic pituitary adrenal axis reactivity in this sample revealed a blunted cortisol response in adolescents with heightened childhood violence exposure,²⁸ and work in other high-risk samples showed blunted activation of the amygdala, an SN node, to threatening stimuli.^48,49 The present study expands this notion to the function of threat detection neural circuits, and future research should examine whether this is compensatory or even adaptive.

Beyond density, childhood violence exposure was associated with reduced node degree of the right anterior insula and left IPL. These results are consistent with the extant literature because the right anterior insula in the SN facilitates shifting between the DMN and central executive network,⁵⁰ which contributes to higher-level executive function.⁸ Moreover, early life stress has been linked to insular connectivity within the SN,⁹ DMN (specifically, the left IPL, which plays a role in working memory⁵¹), and other neural ROIs.⁵² These results also show differences in the way that the anterior insula is integrated within and between neural networks in youth exposed to violence in their homes and neighborhoods using longitudinal data from a population-based sample.

This study represents a person-specific approach to the neuroscientific investigation of the sequelae of early adversity. Past research on early adversity and rsFC assumed that the same connectivity patterns characterize all, or a majority of participants, but if this assumption is violated (as is likely the case in studies of diverse populations and biopsychosocial phenomena), then results may not accurately describe any individual.^18,53 The presence of group- and subgroup-level connections in the present study suggests that there is some consistency in the connections within and between the SN and DMN, aligning with an assumption of homogeneity that is prevalent in rsFC research, but the large number of individual-level connections, especially in adolescents with high levels of early violence exposure, show that there was also notable heterogeneity that required person-specific analyses to accurately reflect rsFC, encouraging future research using person-specific modeling approaches.

All significant findings concerned violence exposure, and there were no detected associations between social deprivation and rsFC. This set of results could indicate that social deprivation has a less salient influence on patterns of spontaneous neural fluctuations. Some studies have identified links between social deprivation and functional connectivity, but they concerned extreme, nonnormative deprivation (eg, previous institutionalization).^21,54 This deprivation may be qualitatively different from deprivation operationalized in the present study, and may operate through different mechanisms. In addition, because a hypothesis-driven approach to node selection was taken in this study, it is possible that deprivation is associated with rsFC of SN or DMN nodes not measured here, with other networks (eg, central executive), or in different populations (eg, with extreme or heightened variability of deprivation). It is also tenable that there are other dimensions of adversity that would have differential associations with rsFC (eg, those linked to emotionality), which future research should explore. Nonetheless, these findings present evidence for dimensional frameworks of adversity^5,55 because there were distinct neural correlates for violence exposure.

Limitations

This study had limitations. Based on the demographic characteristics of the sample (eg, 73% African American, born in Midwestern cities), it is not clear whether findings will generalize beyond low-income, urban, African American youth; nonetheless, the present work is important because these populations are often underrepresented in neuroimaging research and underserved by the medical community.¹² Resting-state functional MRI was collected on only a single occasion in adolescence; thus, it is unclear whether connectivity patterns reflect stable or changing neural features. In addition, it is not possible to know the direction of association (eg, whether neural differences predate exposure to adversity). Violence exposure and social deprivation composites were derived from parent reports. Exposures between the FFCWS collection waves at ages 9 and 15 years could not be accounted for in this study. Owing to changes in the FFCWS questionnaire at year 15, current adversity could not be controlled using the composite scores created for earlier ages.⁵ To compensate, a life stress scale was used as a covariate; however, that confounding variable did not impact associations. The ecologic pattern of poverty-related adversity is complex; thus, there are unmeasured variables that may explain these associations or contribute to cascades of risk (eg, parental psychopathologic factors).