The human brain is highly dynamic, supporting a remarkable range of cognitive abilities that emerge over the course of development. While flexible and dynamic coordination between different neural systems is firmly established for children, our understanding of brain functional organization in early life has been built largely on the implicit assumption that functional connectivity (FC) is static. Understanding the nature of dynamic neural interactions during development is a critical issue for cognitive neuroscience, with implications for neurodevelopmental pathologies that involve anomalies in brain connectivity. In this work, we delineate FC dynamics of neurocognitive networks in a sample of 146 youth from varied sociodemographic backgrounds. We apply independent component analysis, sliding time window correlation, and k-means clustering to resting-state fMRI data. Our analyses revealed six FC states that re-occur over time and that complement, but significantly extend, measures of static connectivity averaged across the experiment. Moreover, the occurrence and amount of time spent in specific FC states are related to the content of self-generated thought during the scan. We also found age-related increases in temporal variability of FC among neurocognitive networks. In addition, some connections are more variable over time than are others, including those between inferior parietal lobe and precuneus. These regions contribute to multiple large-scale systems and likely play a role in adaptive processes in early life. Taken together, these findings lay the groundwork for understanding how variation in the developing chronnectome is related to risk for neurodevelopmental disorders. Understanding how brain systems reconfigure with development should provide insight into the ontogeny of complex, flexible cognitive processes in adulthood.

Socioeconomic disadvantage (SED) experienced in early life is linked to a range of risk behaviors and diseases. Neuroimaging research indicates that this association is mediated by functional changes in corticostriatal reward systems that modulate goal-directed behavior, reward evaluation, and affective processing. Existing research has focused largely on adults and within-household measures as an index of SED, despite evidence that broader community-level SED (e.g., neighborhood poverty levels) has significant and sometimes distinct effects on development and health outcomes. Here, we test effects of both household- and community-level SED on resting-state functional connectivity (rsFC) of the ventral striatum (VS) in 100 racially and economically diverse children and adolescents (ages 6-17). We observed unique effects of household income and community SED on VS circuitry such that higher community SED was associated with reduced rsFC between the VS and an anterior region of the medial prefrontal cortex (mPFC), whereas lower household income was associated with increased rsFC between the VS and the cerebellum, inferior temporal lobe, and lateral prefrontal cortex. Lower VS-mPFC rsFC was also associated with higher self-reported anxiety symptomology, and rsFC mediated the link between community SED and anxiety. These results indicate unique effects of community-level SED on corticostriatal reward circuitry that can be detected in early life, which carries implications for future interventions and targeted therapies. In addition, our findings raise intriguing questions about the distinct pathways through which specific sources of SED can affect brain and emotional development.

BackgroundMost children who are exposed to threat-related adversity (e.g., violence, abuse, neglect) are resilient - that is, they show stable trajectories of healthy psychological development. Despite this, most research on neurodevelopmental changes following adversity has focused on the neural correlates of negative outcomes, such as psychopathology. The neural correlates of trait resilience in pediatric populations are unknown, and it is unclear whether they are distinct from those related to adversity exposure and the absence of negative outcomes (e.g., depressive symptomology).MethodsThis functional magnetic resonance imaging (fMRI) study reports on a diverse sample of 55 children and adolescents (ages 6–17 years) recruited from a range of stressful environments (e.g., lower income, threat-related adversity exposure). Participants completed a multi-echo multi-band resting-state fMRI scan and self-report measures of trait resilience and emotion-related symptomology (e.g., depressive symptoms). Resting-state data were submitted to an independent component analysis (ICA) to identify core neurocognitive networks (salience and emotion network [SEN], default mode network [DMN], central executive network [CEN]). We tested for links among trait resilience and dynamic (i.e., time-varying) as well as conventional static (i.e., averaged across the entire session) resting-state functional connectivity (rsFC) of core neurocognitive networks.ResultsYouth with higher trait resilience spent a lower fraction of time in a particular dynamic rsFC state, characterized by heightened rsFC between the anterior DMN and right CEN. Within this state, trait resilience was associated with lower rsFC of the SEN with the right CEN and anterior DMN. There were no associations among trait resilience and conventional static rsFC. Importantly, although more resilient youth reported lower depressive symptoms, the effects of resilience on rsFC were independent of depressive symptoms and adversity exposure.ConclusionsThe present study is the first to report on the neural correlates of trait resilience in youth, and offers initial insight into potential adaptive patterns of brain organization in the context of environmental stressors. Understanding the neural dynamics underlying positive adaptation to early adversity will aid in the development of interventions that focus on strengthening resilience rather than mitigating already-present psychological problems.

Fragile X Syndrome (FXS) is a common inherited cause of intellectual disability that results from a CGG repeat expansion in the FMR1 gene. Large repeat expansions trigger both transcriptional and translational suppression of Fragile X protein (FMRP) production. Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is an allelic neurodegenerative disease caused by smaller “pre-mutation” CGG repeat expansions that enhance FMR1 transcription but lead to translational inefficiency and reduced FMRP expression in animal models. Sensorimotor gating as measured by pre-pulse inhibition (PPI) is altered in both FXS patients and Fmr1 knock out (KO) mice. Similarly, FXTAS patients have demonstrated PPI deficits. Recent work suggests there may be overlapping synaptic defects between Fmr1 KO and CGG knock-in premutation mouse models (CGG KI). We therefore sought to interrogate PPI in CGG KI mice. Using a quiet PPI protocol more akin to human testing conditions, we find that Fmr1 KO animals have significantly impaired PPI. Using tis same protocol, we find CGG KI mice demonstrate an age-dependent impairment in PPI compared to wild type (WT) controls. This study describes a novel phenotype in CGG KI mice that can be used in future therapeutic development targeting premutation associated symptoms.