Early deprivation and white matter development: Two conceptual models in the context of an RCT

• In Event: 2-176 - Recovery from profound early psychosocial neglect 16 years after placement into institutional care

Integrative Statement

Exposure to adverse experiences in early life has profound implications for cognitive, emotional, and social development. Increasing evidence suggests that alterations in neurodevelopment play a key role in explaining poor developmental outcomes among children exposed to adversity. Here, we examine the impact of exposure to severe psychosocial deprivation in early life on patterns of white matter (WM) development in adolescence. Data come from the Bucharest Early Intervention Project (BEIP), a randomized controlled trial of foster care for children raised in deprived institutional environments. The experimental nature of the design allows for strong inferences to be drawn about the lasting effect of early deprivation on neural development.
We examine evidence for two theoretical models early deprivation and neural development. First, we have argued that deprivation constrains early forms of learning that occur in the context of caregiver interactions, leading to accelerated pruning of synaptic connections and reductions in WM connectivity throughout the brain, particularly in regions that process the types of social and cognitive inputs (e.g., fronto-parietal network) that are lacking from the early environments of children deprived of stable caregiving (McLaughlin, Sheridan, & Nelson, 2017). Second, Tottenham argues that early caregiver deprivation accelerates neural development in circuits involved in emotional processing, leading to more mature patterns of structural and functional connectivity of the amygdala and hippocampus with the prefrontal cortex (Tottenham, 2012; Callaghan & Tottenham, 2016). The first model predicts reductions in WM integrity throughout the brain, whereas the second predicts greater WM integrity specifically in fronto-limbic tracts among children exposed to deprivation.
We evaluate these predictions using diffusion tensor imaging (DTI) data collected on 116 adolescents, aged 16 years, from the BEIP study. We hypothesized that children randomized to foster care (FCG) would exhibit greater fractional anisotropy (FA) in fronto-parietal tracts (i.e., the superior longitudinal fasciculus) and reduced FA in fronto-limbic tracts (i.e., the uncinate fasciculus) compared to children randomized to care as usual (CAUG), consistent with both models of early deprivation and neural development. DTI data were analyzed using TRACULA in FreeSurfer. Global tractography was used to reconstruct known WM pathways (including the superior longitudinal fasciculus and uncinate fasciculus) and diffusion statistics were extracted at multiple cross-sections along each tract. False-discovery rate (FDR) correction was applied to correct for multiple comparisons.
Children randomized to foster care exhibited greater FA in multiple regions of the superior longitudinal fasciculus than children in the CAUG (all p<.03, FDR-corrected). Similarly, reduced axial diffusivity was observed among children in the FCG in multiple regions of the uncinate fasciculus as compared to the CAUG (all p<.02, FDR-corrected), suggesting the presence of greater axonal projections along this tract in the FCG. These findings are consistent with models arguing that early deprivation constrains WM development; we find reductions in WM integrity among children exposed to prolonged deprivation in both fronto-parietal tracts underlying cognitive control and fronto-limbic tracts involved in emotional processing. The role that these neural differences play in explaining elevations in psychopathology and difficulties with cognitive control in the BEIP sample will be discussed.

Authors

• Katie McLaughlin, Harvard University
  Presenting Author

• Margaret Sheridan, University of North Carolina at Chapel Hill
  Non-Presenting Author

• Nathan Fox, University of Maryland
  Non-Presenting Author

• Charles Zeanah, Tulane University
  Non-Presenting Author

• Charles A. Nelson, Harvard Medical School
  Non-Presenting Author