Importance Severe early life neglect is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in white matter pathways that underlie emotional and cognitive development are unknown. Objective To examine associations between early life neglect, early intervention, and microstructural integrity of white matter pathways in middle childhood. Design, setting, and participants The Bucharest Early Intervention Project is a randomized clinical trial of high quality foster care as an intervention for institutionally reared children in Bucharest, Romania. During infancy, children were randomly selected to remain in an institution or to be placed into foster care. Developmental trajectories of these children were compared to a group of socio-demographically matched children reared in biological families at baseline and several points throughout development. At around eight years of age, 69 of the original 136 children underwent structural MRI scans. Intervention(s) for Clinical Trials Institutionally reared children were randomized into high quality foster homes in Bucharest, Romania. Main Outcome Measure(s) Four estimates of white matter integrity (Fractional Anisotropy, and Mean, Radial, and Axial Diffusivity) for 48 white matter tracts throughout the brain were obtained through Diffusion Tensor Imaging. Results Significant associations emerged between early life neglect and microstructural integrity of the body of the corpus callosum and tracts involved in limbic circuitry (fornix crus, cingulum), fronto-striatal circuitry (anterior and superior corona radiata, external capsule) and sensory processing (medial lemniscus, retrolenticular internal capsule). Follow up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care. Conclusions and Relevance Results suggest that removal from conditions of severe early life neglect and entry into a high quality family environment can support more normative trajectories of white matter growth. Findings have implications for public health and policy efforts designed to promote normative brain development among vulnerable children. Trial Registration clinicaltrials.gov Identifier: NCT00747396

Objectives Although US state laws shape population health and health equity, few studies have examined how state laws affect the health of marginalized racial/ethnic groups (eg, Black, Indigenous, and Latinx populations) and racial/ethnic health inequities. A team of public health researchers and legal scholars with expertise in racial equity used systematic policy surveillance methods to develop a comprehensive database of state laws that are explicitly or implicitly related to structural racism, with the goal of evaluating their effect on health outcomes among marginalized racial/ethnic groups. Methods Legal scholars used primary and secondary sources to identify state laws related to structural racism pertaining to 10 legal domains and developed a coding scheme that assigned a numeric code representing a mutually exclusive category for each salient feature of each law using a subset of randomly selected states. Legal scholars systematically applied this coding scheme to laws in all 50 US states and the District of Columbia from 2010 through 2013. Results We identified 843 state laws linked to structural racism. Most states had in place laws that disproportionately discriminate against marginalized racial/ethnic groups and had not enacted laws that prevent the unjust treatment of individuals from marginalized racial/ethnic populations from 2010 to 2013. Conclusions By providing comprehensive, detailed data on structural racism–related state laws in all 50 states and the District of Columbia over time, our database will provide public health researchers, social scientists, policy makers, and advocates with rigorous evidence to assess states’ racial equity climates and evaluate and address their effect on racial/ethnic health inequities in the United States.

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Adolescence is a period of profound but incompletely understood changes in the brain’s neural circuitry (the connectome), which is vulnerable to risk factors such as unhealthy weight, but may be protected by positive factors such as regular physical activity. In 5955 children (median age = 120 months; 50.86% females) from the Adolescent Brain Cognitive Development (ABCD) cohort, we investigated direct and indirect (through impact on body mass index [BMI]) effects of physical activity on resting-state networks, the backbone of the functional connectome that ubiquitously affects cognitive function. We estimated significant positive effects of regular physical activity on network connectivity, efficiency, robustness and stability (P ≤ 0.01), and on local topologies of attention, somatomotor, frontoparietal, limbic, and default-mode networks (P < 0.05), which support extensive processes, from memory and executive control to emotional processing. In contrast, we estimated widespread negative BMI effects in the same network properties and brain regions (P < 0.05). Additional mediation analyses suggested that physical activity could also modulate network topologies leading to better control of food intake, appetite and satiety, and ultimately lower BMI. Thus, regular physical activity may have extensive positive effects on the development of the functional connectome, and may be critical for improving the detrimental effects of unhealthy weight on cognitive health.

Modulations of neuronal network interactions by seizure precursors are only partially understood and difficult to measure, in part due to inherent intra- and inter-patient seizure heterogeneity and EEG variability. This study investigated preictal neuromodulations associated with seizures originating in the temporal and/or frontal lobes, using information theoretic parameters estimated from awake scalp EEGs in two frequency ranges, ≤100 Hz and >100 Hz, respectively. Seizure-related activity at high frequencies has not been extensively estimated in awake scalp EEGs. Based on the statistical similarity of preictal and ictal information parameters, preictal network interactions appeared to be specifically modulated at frequencies >100 Hz, but not at lower frequencies. The dynamics of these parameters varied distinctly according to the origin of seizure onset (temporal versus frontal). Although preliminary, and based on a small patient sample for which the potential heterogeneity of multiple anticonvulsive medications was difficult to control, these results suggest that preictal modulations may be estimated from high-frequency scalp EEGs using directional information measures with high specificity to ictal events, and may thus be promising for improving seizure prediction.

caterina@mit.edu.

Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross-frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1–3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross-frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross-alpha coupling was estimated in this group compared to the other two groups at 96 months, suggesting impaired suppression of alpha–theta and alpha–delta activity, which has been associated with neuropsychiatric disorders. Age at foster care placement had a significant positive modulatory effect on alpha and beta trajectories and their mutual coupling, although by 96 months these trajectories remained distinct from those of never-institutionalized children. Overall, these findings suggest that early psychosocial neglect may profoundly impact neural maturation, particularly the evolution of neural oscillations and their interactions across a broad frequency range. These differences may result in widespread deficits across multiple cognitive domains.

Distal femoral valgus deformity occurred in 30% of patients with distal diaphyseal fractures and in 12% overall. We advocate long-term monitoring of patients with femoral plate fixation, particularly those in whom the plate is placed ≤20 mm from the distal femoral physis.