Understanding Vulnerability and Adaptation in Early Brain Development using Network Neuroscience

Abstract

Early adversity influences brain development and emerging behavioral phenotypes relevant for psychiatric disorders. Understanding the effects of adversity before and after conception on brain development has implications for contextualizing current public health crises and pervasive health inequities. The use of functional magnetic resonance imaging (fMRI) to study the brain at rest has shifted understanding of brain functioning and organization in the earliest periods of life. Here we review applications of this technique to examine effects of early life stress (ELS) on neurodevelopment in infancy, and highlight targets for future research. Building on the foundation of existing work in this area will require tackling significant challenges, including greater inclusion of often marginalized segments of society, and conducting larger, properly powered studies.

Keywords: brain development; early life stress; functional brain networks; prenatal stress; resting state functional connectivity MRI.

Figure 1.. Reproducible Resting State Network Topology at the Group and Individual Level.

This figure, modified from [7], illustrates high resolution human functional neural network topology. Data used in these analyses were from the Midnight Scan Club, a study using a unique acquisition protocol involving extended sampling times for resting state functional magnetic resonance imaging (fMRI) data to facilitate reliable estimation of functional network topology at the individual level [7]. Community detection (Infomap) was utilized as a data driven way to identify highly interconnected functional systems across the brain. Panel (A) depicts an average whole brain vertex-to-vertex correlation matrix from ten highly sampled individuals, and (B) a highly sampled individual. Importantly, the individual networks highlight the vast heterogeneity of topologies within individuals, a characteristic that can be leveraged in a similar way to characterize individual network features in infants and toddlers for an array of scientific inquires. Networks identified in both images are labelled based on known functions in the literature. The list of networks included are the default mode network (DMN), the lateral and medial visual networks (lVIS and mVIS respectively), the frontal parietal network (FPN), the dorsal attention network (DAN), the ventral attention network (VAN), the premotor network (PrMN), the cingulo-opercular network (CON), the salience network (SAL), hand, face, and leg somatomotor networks (hSMN, fSMN, and lSMN respectively), the context network (CONT), the parietal memory network (PaMN), the auditory network (AUD), the posterior medial temporal network (pMTL), and the anterior medial temporal network (aMTL).

Figure 2.. Cumulative and Interactive Effects of the Preconceptional, Gestational, and Postnatal Environment on Early Neurodevelopment.

Diverse preconceptional and gestational sources of adversity have potential to influence embryonic and fetal neurodevelopmental processes through stress-sensitive aspects of maternal–placental–fetal (MPF) biology. These influences include aspects of maternal life history, current environment, psychological and biological state, physical health, and current behaviors. Variability in the maternal state and environment prior to and during gestation can be carried over into the postnatal environment (as indicated by the shaded blue area continuing across to the postnatal period), creating cumulative and interactive effects between the pre- and postnatal environment. Alterations in neurodevelopment due to prenatal exposures also have potential to alter sensitivity to postnatal environmental influences (i.e., differential susceptibility). Differential susceptibility is depicted as hinging on the fulcrum of the neonatal brain and being tipped in a specific direction by the postnatal environment to indicate that specific combinations of neurobiological phenotypes and environmental conditions will have implications for ongoing development. This is consistent with a view of early environmental influences as altering potential for resilience to, or risk for, psychiatric disorders in a non-deterministic manner, and in interaction with the future environment. Abbreviations: PTSD, Post-traumatic stress disorder; SES, socioeconomic status.

Figure I.. Timeline of Rapid Progression of Prenatal Neurodevelopmental Processes.

Brain development proceeds rapidly during the embryonic and fetal period. Stress-sensitive aspects of maternal–placental–fetal (MPF) biology play an obligatory role in guiding neurodevelopmental processes, providing ample opportunity for environmental conditions to influence the trajectory of development. Brain regions with high concentrations of glucocorticoid receptors and known roles in susceptibility for psychiatric disorders, including the amygdala, begin to develop during the first trimester of pregnancy. See also [96] for further details and relevant citations. Abbreviations: GA, Gestational age.