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The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study’s core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition protocol for all 27 HBCD Study recruitment sites to measure brain structure, function, microstructure, and metabolites. Acquisition parameters of individual modalities have been matched across MRI scanner platforms for harmonized acquisitions and state-of-the-art technologies are employed to enable faster and motion-robust imaging. Here, we provide an overview of the HBCD MRI protocol, including decisions of individual modalities and preliminary data. The result will be an unparalleled resource for examining early neurodevelopment which enables the larger scientific community to assess normative trajectories from birth through childhood and to examine the genetic, biological, and environmental factors that help shape the developing brain.

Resting brain activity has been widely used as an index of brain development in neuroscience and clinical research. However, it remains unclear whether early differences in resting brain activity have meaningful implications for predicting long-term cognitive outcomes. Using data from the Bucharest Early Intervention Project (Zeanah et al., 2003), we examined the impact of institutional rearing and the consequences of early foster care intervention on 18-year IQ. We found that higher resting theta electroencephalogram (EEG) power, reflecting atypical neurodevelopment, across three assessments from 22 to 42 months predicted lower full-scale IQ at 18 years, providing the first evidence that brain activity in early childhood predicts cognitive outcomes into adulthood. In addition, both institutional rearing and later (vs. earlier) foster care intervention predicted higher resting theta power in early childhood, which in turn predicted lower IQ at 18 years. These findings demonstrate that experientially-induced changes in brain activity early in life have profound impact on long-term cognitive development, highlighting the importance of early intervention for promoting healthy development among children living in disadvantaged environments.

Women experience dramatic physiological changes during pregnancy, including changes in the production of the “stress hormone,” cortisol. Evidence has been mixed regarding whether hair cortisol concentration (HCC) can be used to accurately capture the trajectory of cortisol during this period and whether factors related to psychosocial stress are related to HCC in pregnant and postpartum women. In the current study, we collected hair samples from 85 individuals during the peripartum period (with collection occasions in pregnancy [12–37 weeks], at 3–8 weeks postpartum, and at 5–8 months postpartum) from which we derived 783 monthly observations of HCC. In addition, at each assessment individuals reported their current depressive symptoms and experiences of recent psychosocial adversity. Using piecewise mixed effects modeling, we identified significant increases in HCC across pregnancy (approximately a 2-fold rise) followed by significant decreases in HCC postpartum. Beyond these effects, however, there was substantial within-individual variability in HCC. Disaggregating between- from within-individual associations of depressive symptoms and adversity with HCC, we found that within-individual fluctuations in adversity were positively coupled with levels of HCC. Overall, the current findings suggest that measurement of cortisol in human hair captures its trajectory from conception through six months postpartum, including prenatal increases and gradual recovery of typical levels following childbirth. In addition to the overall severity of psychosocial adversity, change in women's experiences of adversity during the peripartum period merit attention.

Although decades of research have shown associations between early caregiving adversity, stress physiology and limbic brain volume (e.g., amygdala, hippocampus), the developmental trajectories of these phenotypes are not well characterized. In the current study, we used an accelerated longitudinal design to assess the development of stress physiology, amygdala, and hippocampal volume following early institutional care. Previously Institutionalized (PI; N = 93) and comparison (COMP; N = 161) youth (ages 4–20 years old) completed 1–3 waves of data collection, each spaced approximately 2 years apart, for diurnal cortisol (N = 239) and structural MRI (N = 156). We observed a developmental shift in morning cortisol in the PI group, with blunted levels in childhood and heightened levels in late adolescence. PI history was associated with reduced hippocampal volume and reduced growth rate of the amygdala, resulting in smaller volumes by adolescence. Amygdala and hippocampal volumes were also prospectively associated with future morning cortisol in both groups. These results indicate that adversity-related physiological and neural phenotypes are not stationary during development but instead exhibit dynamic and interdependent changes from early childhood to early adulthood.

Stressful experiences are linked to neurodevelopment. There is growing interest in the role of stress in the connectivity between the amygdala and medial prefrontal cortex (mPFC), a circuit that subserves automatic emotion regulation. However, the specific timing and mechanisms that underlie the association between stress and amygdala–mPFC connectivity are unclear. Many factors, including variations in fetal exposure to maternal stress, appear to affect early developing brain circuitry. However, few studies have examined the associations of stress and amygdala–mPFC connectivity in early life, when the brain is most plastic and sensitive to environmental influence. In this longitudinal pilot study, we characterized the association between prenatal stress and amygdala–mPFC connectivity in young infants (approximately age 5 weeks). A final sample of 33 women who provided data on preconception and prenatal stress during their pregnancy returned with their offspring for a magnetic resonance imaging scan session, which enabled us to characterize amygdala–mPFC structural and functional connectivity as a function of prenatal stress. Increased prenatal stress was associated with decreased functional connectivity and increased structural connectivity between the amygdala and mPFC. These results provide insight into the influence of prenatal maternal stress on the early development of this critical regulatory circuitry.

Deviations in neurodevelopment may underlie the association between lower childhood socioeconomic status and difficulties in cognitive and socioemotional domains. Most previous investigations of the association between childhood socioeconomic status and brain morphology have used cross-sectional designs with samples that span wide age ranges, occluding effects specific to adolescence. Sex differences in the association between socioeconomic status and neurodevelopment may emerge or intensify during adolescence. In a sample representative of the San Francisco Bay Area, we used whole-brain tensor-based morphometry to examine sex differences in the cross-sectional association between variation in family income-to-needs ratio (INR) and cortical and subcortical gray and white matter volume during early adolescence (ages 9–13 years; N = 147), as well as in the longitudinal association between INR and change in volume from early to later adolescence (ages 11–16 years, N = 109). Biological sex interacted with INR to explain variation in volume in several areas cross-sectionally and longitudinally. Effects were primarily in cortical gray matter areas, including regions of the association cortex and sensorimotor processing areas. Effect sizes tended to be larger in boys than in girls. Biological sex may be an important variable to consider in analyses of the effects of family income on structural neurodevelopment during adolescence.

Children from lower-SES families exhibit smaller hippocampal volume than do their higher-SES peers. Few studies, however, have compared hippocampal developmental trajectories as a function of SES. Thus, it is unclear whether initial rank-order stability is preserved, or whether volumes diverge/converge over the course of adolescence. In a sample of 101 girls ages 10–24 years, we examined the longitudinal association between family income and parental education, proxies for SES, and changes in hippocampal volume. Hippocampal volume was obtained using MRI; using mixed modeling, we examined the effects of income and education on hippocampal volume across age. As expected, changes in volume were non-linear across development. Further, trajectories diverged in mid-adolescence, with lower-income girls exhibiting reductions in hippocampal volume. Maximal income-related differences were observed at 18 years, and trajectories converged thereafter. This interaction remained significant when accounting for maternal hippocampal volume, suggesting a unique contribution of environment over potential heritable differences. In contrast, the association between parental education and offspring hippocampal volume appeared to be stable across adolescence, with higher levels of parental education predicting consistently larger hippocampal volume. These findings constitute preliminary evidence that girls from lower-income homes exhibit unique trajectories of hippocampal growth, with differences most evident in late adolescence. Keywords: Adolescence, Adversity, Environmental influences, Family factors, Socioeconomic status

Several studies have shown that young children who have experienced early caregiving adversity (e.g. previously institutionalization (PI)) exhibit flattened diurnal cortisol slopes; however, less is known about how these patterns might differ between children and adolescents, since the transition between childhood and adolescence is a time of purported plasticity in the hypothalamic-pituitary-adrenal (HPA) axis. PI youth experience a massive improvement in caregiving environment once adopted into families; therefore we anticipated that a developmental increase in HPA axis plasticity during adolescence might additionally allow for an enhanced enrichment effect by the adoptive family. In a cross-sectional sample of 197 youths (PI and Comparison; 4–15 years old) we observed age-related group differences in diurnal slope. First replicating previous findings, PI children exhibited flattened diurnal slope. This group difference, however, was not observed in adolescents. Moderation analyses showed that pubertal development, increased time with family, and early adoption contributed to the steeper diurnal cortisol slope in PI adolescents. These findings add support to existing theories positing that the transition between middle childhood and adolescence may mark an additional sensitive period for diurnal cortisol patterning, allowing PI youth to benefit from the enriched environment provided by adoptive parents during this period of development. Keywords: Childhood, Adolescence, Stress, Enrichment, Early adversity

The way caregivers think of their infants and young children may impact caregiving behavior. One way to assess caregivers’ thoughts of their young children is to prompt them to describe the child's personality. Popular methods to analyzing valenced language include the use of software approaches, which have limitations in scoring and application. The present investigation offers an alternative scoring system for the emotional tone of words and phrases relevant to descriptions of infants and children. Using a database of personality descriptions provided by pregnant people and parents to describe their child's personality, we asked experts in infant mental health and related disciplines (N = 51) to rate the words/phrases with regard to the emotional tone or connotation of the descriptive words provided (e.g., positive, neutral, or negative). Experts (i.e., participants) were individuals with self-reported expertise in infants and young children via their profession. Participants were recruited via email to known infant and early childhood mental health practicians and researchers and through participant referral. A total of 496 unique words or phrases were rated by the experts, and in order to reduce participant burden, experts were randomly assigned approximately half of the words. From these ratings, we computed a continuous measure of average valence score across all raters and a categorical variable representing expert consensus (i.e., if ≥80 % of experts agreed it was positive or negative it was assigned that category, otherwise it was assigned neutral). As such, the data provided include caregiver adjectives used to describe their young children, expert ratings of the emotional tone of the provided description, average emotional tone for each word, and expert consensus for each word.

This work demonstrates the successful long-term transfection in vivo of a DNA plasmid vector in rat visual cortex neurons using the magnetofection technique. The transfection rates reached values of up to 97% of the neurons after 30days, comparable to those achieved by viral vectors. Immunohistochemical treatment with anti-EGFP antibodies enhanced the detection of the EYFP-channelrhodopsin expression throughout the dendritic trees and cell bodies. These results show that magnetic nanoparticles offer highly efficient and enduring in vivo high-rate transfection in identified neurons of an adult mammalian brain and suggest that the magnetotechnique facilitates the introduction of large functional genetic material like channelrhodopsin with safe non-viral vectors using minimally invasive approaches., From the Clinical Editor: Gene therapy may be one of the treatment modalities for neurological diseases in the future. The use of viral transfection remains a concern due to restrictions to the size limit of the genetic material able to be packed, as well as safety issues. In this work, the authors evaluated magnetoplexes as an alternative vehicle. The results showed very promising data in that these nanoparticles could offer high transfection efficiency., (Copyright © 2015 Elsevier Inc. All rights reserved.)