Reduced Ventral Tegmental Area–Hippocampal Connectivity in Children and Adolescents Exposed to Early Threat

Abstract

BackgroundPreclinical data suggest that early life stress has detrimental effects on the brain’s dopaminergic system, particularly the mesocorticolimbic pathway. Altered dopamine function is thought to contribute to the development of stress-related pathologies; yet, little is known about the impact of early stress on dopamine systems during childhood and adolescence, when stress-related disorders frequently emerge. Here, we evaluate the impact of early threat exposure (violence, abuse) on functional connectivity of putative dopaminergic midbrain regions, the ventral tegmental area (VTA) and substantia nigra (SN), giving rise to mesocorticolimbic and nigrostriatal pathways, respectively. MethodsResting-state functional magnetic resonance imaging scans were completed in 43 trauma-exposed and 43 matched comparison youth (ages 7–17). Functional connectivity of the VTA and SN were compared between groups. ResultsThe trauma group demonstrated lower functional connectivity between the VTA and hippocampus. No group differences in SN connectivity were observed. Across all participants, there were age-related decreases in connectivity of both VTA and SN with the hippocampus, suggesting that age-related attenuations in VTA-hippocampal circuitry may be exacerbated in trauma-exposed youth. Higher levels of anxiety symptomology were associated with reduced SN–nucleus accumbens connectivity. ConclusionsPrevious research suggests that VTA-hippocampal circuitry is critical for the gating of new information into long-term memory. Lower connectivity in this circuitry suggests a novel mechanism that may serve to adaptively prevent the overwriting of a previously stored trauma memory while contributing to the broad range of cognitive and emotional difficulties linked to early stress exposure.