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Cross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individual's educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to stable individual differences in reading ability or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N = 14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the cross-sectional datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning.

ObjectiveTo assess the magnitude of racial-ethnic disparities in pandemic-related social stressors and examine frontline work's moderating relationship on these stressors.Data sourcesEmployed Californians' responses to the Institute for Governmental Studies (IGS) poll from April 16-20, 2020, were analyzed. The Pandemic Stressor Scale (PSS) assessed the extent to which respondents experienced or anticipated problems resulting from the inability to pay for basic necessities, job instability, lacking paid sick leave, unavailability of childcare, and reduced wages or work hours due to COVID-19.Study designMixed-effects generalized linear models estimated (1) racial-ethnic disparities in pandemic stressors among workers during the first COVID-19 surge, adjusting for covariates, and (2) tested the interaction between race-ethnicity and frontline worker status, which includes a subset of essential workers who must perform their job on-site, to assess differential associations of frontline work by race-ethnicity.Data collectionThe IGS poll data from employed workers (n = 4795) were linked to the 2018 Centers for Disease Control and Prevention Social Vulnerability Index at the zip code level (N = 1068).Principal findingsThe average PSS score was 37.34 (SD = 30.49). Whites had the lowest PSS score (29.88, SD = 26.52), and Latinxs had the highest (50.74, SD = 32.61). In adjusted analyses, Black frontline workers reported more pandemic-related stressors than White frontline workers (PSS = 47.73 vs. 36.96, p

BackgroundCommunity health centers (CHCs) pivoted to using telehealth to deliver chronic care during the coronavirus COVID-19 pandemic. While care continuity can improve care quality and patients' experiences, it is unclear whether telehealth supported this relationship.ObjectiveWe examine the association of care continuity with diabetes and hypertension care quality in CHCs before and during COVID-19 and the mediating effect of telehealth.Research designThis was a cohort study.ParticipantsElectronic health record data from 166 CHCs with n=20,792 patients with diabetes and/or hypertension with ≥2 encounters/year during 2019 and 2020.MethodsMultivariable logistic regression models estimated the association of care continuity (Modified Modified Continuity Index; MMCI) with telehealth use and care processes. Generalized linear regression models estimated the association of MMCI and intermediate outcomes. Formal mediation analyses assessed whether telehealth mediated the association of MMCI with A1c testing during 2020.ResultsMMCI [2019: odds ratio (OR)=1.98, marginal effect=0.69, z=165.50, P

Influential investigations of postmortem human brain tissue showed regional differences in tissue properties at early phases of development, such as between prefrontal and primary sensory cortical regions. Large-scale neuroimaging studies enable characterization of age-related trajectories with much denser sampling of cortical regions, assessment ages, and demographic variables than postmortem tissue analyses, but no single imaging measure perfectly captures what is measured with histology. Using publicly available data from the Pediatric Imaging, Neurocognition, and Genetics (PING) study, including 951 participants with ages ranging from 3 to 21 years, we characterized cortical regional variability in developmental trajectories of multimodal brain imaging measures. Multivariate analyses integrated morphometric and microstructural cortical surface measures. To replicate foundational histological work showing delayed synapse elimination in middle frontal gyrus relative to primary sensory areas, we tested whether developmental trajectories differ between prefrontal and visual or auditory cortex. We extended this to a whole-cortex analysis of interregional differences, producing cortical parcellations with maximally different developmental trajectories. Consistent with the general conclusions of postmortem analyses, our imaging results suggest that prefrontal regions show a protracted period of greater developmental change; however, they also illustrate the challenges of drawing conclusions about the relative maturational phases of different brain regions.

Reference pricing (RP) is an insurance design that can be used to incentivize patients to use low-price settings. While RP is not intended to affect overall utilization, it could unintentionally reduce utilization. We examined whether utilization was reduced when a large employer adopted RP for selected elective surgeries, including inpatient joint replacement surgery and outpatient cataract surgery, colonoscopy, and arthroscopic surgery. Data included a treatment group subject to RP implementation and a comparison group that was not. We applied autoregressive integrated moving average analysis as comparison-population interrupted time-series analysis to determine whether there were procedure reductions following RP implementation. We find no evidence of short-term decreases (within 3 months of RP implementation). However, we find very modest declines of approximately 14 (20%) fewer arthroscopic knee surgeries 6 months after RP implementation and 129 (17.2%) fewer colonoscopies 8 months after RP implementation. There were no declines in the other procedures examined.

ObjectiveMusculoskeletal problems like hip and knee osteoarthritis and low-back pain are preference sensitive conditions. Patient engagement strategies (PES), such as shared decision-making and motivational interviewing, can help align patients' preferences with treatment options and potentially reduce spending. We assess the association of physician practice-level adoption of PES with utilisation and spending.DesignCross-sectional study in which patients were matched across low, moderate and high levels of PES via coarsened exact matching.SettingPrimary and secondary care in 2190 physician practices.Participants39 336 hip, 48 362 knee and 67 940 low-back patients who were Medicare beneficiaries were matched to the 2017-2018 National Survey of Healthcare Organizations and Systems.Primary and secondary outcome measuresTotal hip replacement (THR), total knee replacement (TKR), 1-2 level posterior lumbar fusion (LF), total annual spending, components of total annual spending.ResultsTotal annual spending for patients with musculoskeletal problems did not differ for practices with low versus moderate PES, low versus high PES or moderate versus high PES, but spending was significantly lower in some categories for practices with relatively higher PES adoption. For hospital-owned and health system-owned practices, the ORs of receiving LF were 0.632 (95% CI 0.396 to 1.009) for patients attributed to practices with high PES compared with patients attributed to practices with moderate PES. For independent practices, the odds of receiving THR were 1.403 (95% CI 1.035 to 1.902) for patients attributed to practices with moderate PES compared with patients attributed to practices with low PES.ConclusionsPractice-level adoption of PES for patients with musculoskeletal problems was generally not associated with total spending. PES, however, may steer patients toward evidence-based treatments. Opportunities for overall spending reduction exist as indicated by the variation in the subcomponents of total spending by PES adoption.

Introduction and Objectives: Lack of access to urologic specialists is approaching crisis levels as the number of urologists is decreasing, while the demand for urologic care is increasing. The financial implications of this have not been explored. The objective of this study is to examine the impact of access and other patient factors on cost to treat urolithiasis. We hypothesized that markers of poor access would associate with higher costs of surgical encounters for patients presenting with urolithiasis. Methods: A retrospective review of prospectively collected data from the Registry for Stones of the Kidney and Ureter (ReSKU) from September 2015 to July 2018 was conducted to investigate characteristics of surgical patients treated for urinary stone disease. Univariate analysis was performed using the Welch two-sample t-test. Multivariate analysis was performed using logistic regression. Statistical analysis was performed in R version 3.5. Results: When taking into account age, delayed presentation, procedure type, stone size >20 mm, American Society of Anesthesiologists (ASA) code, gender, race, income, distance, urologist density, body mass index, diabetes, infection, education, language, insurance, and stone complexity, patients undergoing percutaneous nephrolithotomy procedure (p

ObjectiveTo determine social factors associated with advanced stone disease (defined as unilateral stone burden >2 cm) at time of presentation to a regional stone referral center. Little is known about social determinants of urolithiasis. We hypothesize that socioeconomic factors impact kidney stone severity at intake to referral centers.MethodsA retrospective review of the prospectively collected data from the Registry for Stones of the Kidney and Ureter from 2015 to 2018 was conducted to evaluate patient characteristics predictive of having a large (>2 cm) unilateral kidney stone. Data on patient age, gender, body mass index, diabetes, race, language, education level, infection, distance, income, referring regional urologist density, American Society of Anesthesiologists score, and stone analysis were evaluated.ResultsComplete imaging and patient variable data was present in 650 of 1142 patients including 197 patients with unilateral stone burden >2 cm. On multivariate analysis, obesity, lower education level, increased distance from the referral center, and symptoms of infection predicted for unilateral stone burden greater than 2 cm. Among 191 patients with stone analysis data present, stone type, income, and urologist density predicted for unilateral stone burden greater than 2 cm.ConclusionIn addition to known biological risk factors, patients with lower education levels and from regions of lower mean income were found to be more likely to present to our tertiary care center with stone burden greater than 2 cm. More research is needed to elucidate the social and societal determinants of advanced stone disease and the impact this has on population costs for stone treatment.

The NIH Toolbox Cognition Battery (NTCB) is a brief computerized method for evaluating neuropsychological functions in children, adolescents, and adults. We examined how performance on the 2 executive function measures of cognitive flexibility and inhibitory control was related to performance on the other NTCB measures across development.Participants were 1,020 typically developing individuals between the ages of 3 and 21 from the Pediatric Imaging, Neurocognition, and Genetics Study who were divided into 5 age groups (3-6, 7-9, 10-13, 14-17, and 18-21). Scores were adjusted for sex, level of parental education, and family income.Although the correlations between the 2 executive function measures were moderate and consistent across age groups, their correlations with the other 5 cognitive measures were highest in the youngest age group and decreased across the older age groups. Exploratory factor analysis revealed that all NTCB measures loaded onto a single factor for the 3- to 6-year-olds. Across the older age groups, the executive function and processing speed measures loaded onto one factor, and the vocabulary knowledge, oral reading, and working memory measures loaded onto a second factor.These results indicate that younger children's performance on the NTCB is more intercorrelated and less differentiated, while performance on the NTCB executive function measures becomes more differentiated from performance on the other measures with development. These results support the hypothesis that executive functions become increasingly differentiated from other cognitive functions with development as the functional specialization of neural systems progresses throughout childhood and young adulthood. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Despite great interest in using magnetic resonance imaging (MRI) for studying the effects of genes on brain structure in humans, current approaches have focused almost entirely on predefined regions of interest and had limited success. Here, we used multivariate methods to define a single neuroanatomical score of how William's Syndrome (WS) brains deviate structurally from controls. The score is trained and validated on measures of T1 structural brain imaging in two WS cohorts (training, n = 38; validating, n = 60). We then associated this score with single nucleotide polymorphisms (SNPs) in the WS hemi-deleted region in five cohorts of neurologically and psychiatrically typical individuals (healthy European descendants, n = 1863). Among 110 SNPs within the 7q11.23 WS chromosomal region, we found one associated locus (p = 5e-5) located at GTF2IRD1, which has been implicated in animal models of WS. Furthermore, the genetic signals of neuroanatomical scores are highly enriched locally in the 7q11.23 compared with summary statistics based on regions of interest, such as hippocampal volumes (n = 12,596), and also globally (SNP-heritability = 0.82, se = 0.25, p = 5e-4). The role of genetic variability in GTF2IRD1 during neurodevelopment extends to healthy subjects. Our approach of learning MRI-derived phenotypes from clinical populations with well-established brain abnormalities characterized by known genetic lesions may be a powerful alternative to traditional region of interest-based studies for identifying genetic variants regulating typical brain development.

Recent advances in human neuroimaging research have revealed that white-matter connectivity can be described in terms of an integrated network, which is the basis of the human connectome. However, the developmental changes of this connectome in childhood are not well understood. This study made use of two independent longitudinal diffusion-weighted imaging data sets to characterize developmental changes in the connectome by estimating age-related changes in fractional anisotropy (FA) for reconstructed fibers (edges) between 68 cortical regions. The first sample included 237 diffusion-weighted scans of 146 typically developing children (4-13 years old, 74 females) derived from the Pediatric Longitudinal Imaging, Neurocognition, and Genetics (PLING) study. The second sample included 141 scans of 97 individuals (8-13 years old, 62 females) derived from the BrainTime project. In both data sets, we compared edges that had the most substantial age-related change in FA to edges that showed little change in FA. This allowed us to investigate if developmental changes in white matter reorganize network topology. We observed substantial increases in edges connecting peripheral and a set of highly connected hub regions, referred to as the rich club. Together with the observed topological differences between regions connecting to edges showing the smallest and largest changes in FA, this indicates that changes in white matter affect network organization, such that highly connected regions become even more strongly imbedded in the network. These findings suggest that an important process in brain development involves organizing patterns of inter-regional interactions. Hum Brain Mapp 39:157-170, 2018. © 2017 Wiley Periodicals, Inc.

This study investigates the relationship between variability in cortical surface area and thickness of the pars opercularis of the inferior frontal gyrus and motor-inhibitory performance on a stop-signal task in a longitudinal, typically developing cohort of children and adolescents. Linear mixed-effects models were used to investigate the hypotheses that (1) cortical thinning and (2) a relatively larger cortical surface area of the bilateral pars opercularis of the inferior frontal gyrus would predict better performance on the stop-signal task in a cohort of 110 children and adolescents 4-13 years of age, with one to four observations (totaling 232 observations). Cortical thickness of the bilateral opercular region was not related to inhibitory performance. However, independent of age, gender, and total cortical surface area, relatively larger cortical surface area of the bilateral opercular region of the inferior frontal gyrus was associated with better motor-inhibitory performance. Follow-up analyses showed a significant effect of surface area of the right pars opercularis, but no evidence for an effect of area of left pars opercularis, on motor-inhibitory performance. These findings are consistent with the previous work in adults showing that cortical morphology of the pars opercularis is related to inhibitory functioning. It also expands upon this literature by showing that, in contrast to earlier work highlighting the importance of cortical thickness of this region in adults, relative cortical surface area of the pars opercularis may be related to developing motor-inhibitory functions during childhood and adolescence. Relationships between cortical phenotypes and individual differences in behavioral measures may vary across the lifespan.

This paper examines the effects of the reference pricing program implemented by the California Public Employees Retirement System (CalPERS) in 2012. The program uses targeted cost-sharing to incentivize patient price shopping. We find that the program leads to a 10.3% increase in the use of low-price providers and reduces the average cost per procedure by 12.5%. We further estimate that the program reduces medical spending by $218.8 per procedure, which we estimate is approximately 53.7% of the excessive spending that is due to patient choice of higher price providers caused by insurance coverage, at the expense of a $94.3 (or 12.5%) reduction in consumer surplus. The cost savings from the reference pricing program is about two to three times as large as the reduction from implementing a high-deductible health plan, while the accompanying consumer surplus reduction is much smaller under reference pricing.

Understanding how brain development normally proceeds is a premise of understanding neurodevelopmental disorders. This has sparked a wealth of magnetic resonance imaging (MRI) studies. Unfortunately, they are in marked disagreement on how the cerebral cortex matures. While cortical thickness increases for the first 8-9 years of life have repeatedly been reported, others find continuous cortical thinning from early childhood, at least from age 3 or 4 years. We review these inconsistencies, and discuss possible reasons, including the use of different scanners, recording parameters and analysis tools, and possible effects of variables such as head motion. When tested on the same subsample, 2 popular thickness estimation methods (CIVET and FreeSurfer) both yielded a continuous thickness decrease from 3 years. Importantly, MRI-derived measures of cortical development are merely our best current approximations, hence the term "apparent cortical thickness" may be preferable. We recommend strategies for reaching consensus in the field, including multimodal neuroimaging to measure phenomena using different techniques, for example, the use of T1/T2 ratio, and data sharing to allow replication across analysis methods. As neurodevelopmental origins of early- and late-onset disease are increasingly recognized, resolving inconsistencies in brain maturation trajectories is important.

Williams Syndrome (WS) is a rare genetic disorder with unique behavioral features. Yet the rareness of WS has limited the number and type of studies that can be conducted in which inferences are made about how neuroanatomical abnormalities mediate behaviors. In this study, we extracted a WS-specific neuroanatomical profile from structural magnetic resonance imaging (MRI) measurements and tested its association with behavioral features of WS. Using a WS adult cohort (22 WS, 16 healthy controls), we modeled a sparse representation of a WS-specific neuroanatomical profile. The predictive performances are robust within the training cohort (10-fold cross-validation, AUC = 1.0) and accurately identify all WS individuals in an independent child WS cohort (seven WS, 59 children with diverse developmental status, AUC = 1.0). The WS-specific neuroanatomical profile includes measurements in the orbitofrontal cortex, superior parietal cortex, Sylvian fissures, and basal ganglia, and variability within these areas related to the underlying size of hemizygous deletion in patients with partial deletions. The profile intensity mediated the overall cognitive impairment as well as personality features related to hypersociability. Our results imply that the unique behaviors in WS were mediated through the constellation of abnormalities in cortical-subcortical circuitry consistent in child WS and adult WS. The robustness of the derived WS-specific neuroanatomical profile also demonstrates the potential utility of our approach in both clinical and research applications.

Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

Anxiety is a risk factor for many adverse neuropsychiatric and socioeconomic outcomes, and has been linked to functional and structural changes in the ventromedial prefrontal cortex (VMPFC). However, the nature of these differences, as well as how they develop in children and adolescents, remains poorly understood. More effective interventions to minimize the negative consequences of anxiety require better understanding of its neurobiology in children. Recent research suggests that structural imaging studies may benefit from clearly delineating between cortical surface area and thickness when examining these associations, as these distinct cortical phenotypes are influenced by different cellular mechanisms and genetic factors. The present study examined relationships between cortical surface area and thickness of the VMPFC and a self-report measure of anxiety (SCARED-R) in 287 youths aged 7-20 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Age and gender interactions were examined for significant associations in order to test for developmental differences. Cortical surface area and thickness were also examined simultaneously to determine whether they contribute independently to the prediction of anxiety. Anxiety was negatively associated with relative cortical surface area of the VMPFC as well as with global cortical thickness, but these associations diminished with age. The two cortical phenotypes contributed additively to the prediction of anxiety. These findings suggest that higher anxiety in children may be characterized by both delayed expansion of the VMPFC and an altered trajectory of global cortical thinning. Further longitudinal studies will be needed to confirm these findings.

Williams syndrome (WS) is a genetic condition characterized by an overly gregarious personality, including high empathetic concern for others. Although seemingly disparate from the profile of autism spectrum disorder (ASD), both are associated with deficits in social communication/cognition. Notably, the mirror neuron system (MNS) has been implicated in social dysfunction for ASD; yet, the integrity of this network and its association with social functioning in WS remains unknown. Magnetic resonance imaging (MRI) methods were used to examine the structural integrity of the MNS of adults with WS versus typically developing (TD) individuals. The Social Responsiveness Scale (SRS), a tool typically used to screen for social features of ASD, was also employed to assess the relationships between social functioning with the MNS morphology in WS participants. WS individuals showed reduced cortical surface area of MNS substrates yet relatively preserved cortical thickness as compared to TD adults. Increased cortical thickness of the inferior parietal lobule (IPL) was associated with increased deficits in social communication, social awareness, social cognition, and autistic mannerisms. However, social motivation was not related to anatomical features of the MNS. Our findings indicate that social deficits typical to both ASD and WS may be attributed to an aberrant MNS, whereas the unusual social drive marked in WS is subserved by substrates distinct from this network.

Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING).

Williams syndrome (WS) is a genetic condition characterized by a hypersocial personality and desire to form close relationships, juxtaposed with significant anxieties of nonsocial events. The neural underpinnings of anxiety in individuals with WS are currently unknown. Aberrations in the anatomical and microstructural integrity of the uncinate fasciculus (UF) have been recently implicated in social and generalized anxiety disorders. Based on these findings, we tested the hypothesis that the reported anxieties in individuals with WS share similar neuropathological correlates. Toward this end, diffusion tensor imaging (DTI) methods were employed to examine the microstructural integrity (fractional anisotropy, mean diffusivity, longitudinal diffusivity) of the UF in 18 WS and 15 typically developing adults (TD). Anxiety and sociability questionnaires were administered to determine associations with DTI indices of UF across groups. Results revealed comparable white matter integrity of the UF across groups, yet elevated subjective experience of anxiety in those with WS. Additionally, sociability and UF microstructural properties were dissociated across both groups. Whereas no relationships were found between DTI indices and anxiety in TD participants, strong negative associations were observed between these constructs in individuals with WS. Findings indicated that increased anxiety manifested by individuals with WS was associated with DTI measures of the UF and may signal structural or possibly physiological aberration involving this tract within the prefrontal-temporal network.

Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, using cortical volume, cortical thickness, and fractional anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in 332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging-genetic associations were examined by multiple linear regression, testing for influence of genotype on neuroimaging. Markers in DYX2 genes KIAA0319 and FAM65B were associated with cortical thickness in the left orbitofrontal region and global fractional anisotropy, respectively. KIAA0319 and ACOT13 were suggestively associated with overall fractional anisotropy and left pars opercularis cortical thickness, respectively. DYX3 markers showed suggestive associations with cortical thickness and volume measures in temporal regions. Notably, we did not replicate association of DYX3 markers with hippocampal measures. In summary, we performed a neuroimaging follow-up of reading-, language-, and IQ-associated DYX2 and DYX3 markers. DYX2 associations with cortical thickness may reflect variations in their role in neuronal migration. Furthermore, our findings complement gene expression and imaging studies implicating DYX3 markers in temporal regions. These studies offer insight into where and how DYX2 and DYX3 risk variants may influence neuroimaging traits. Future studies should further connect the pathways to risk variants associated with neuroimaging/neurocognitive outcomes.

The main objective of the multi-site Pediatric Imaging, Neurocognition, and Genetics (PING) study was to create a large repository of standardized measurements of behavioral and imaging phenotypes accompanied by whole genome genotyping acquired from typically-developing children varying widely in age (3 to 20 years). This cross-sectional study produced sharable data from 1493 children, and these data have been described in several publications focusing on brain and cognitive development. Researchers may gain access to these data by applying for an account on the PING portal and filing a data use agreement. Here we describe the recruiting and screening of the children and give a brief overview of the assessments performed, the imaging methods applied, the genetic data produced, and the numbers of cases for whom different data types are available. We also cite sources of more detailed information about the methods and data. Finally we describe the procedures for accessing the data and for using the PING data exploration portal.

Knowing how the human brain is shaped by migration and admixture is a critical step in studying human evolution [1, 2], as well as in preventing the bias of hidden population structure in brain research [3, 4]. Yet, the neuroanatomical differences engendered by population history are still poorly understood. Most of the inference relies on craniometric measurements, because morphology of the brain is presumed to be the neurocranium's main shaping force before bones are fused and ossified [5]. Although studies have shown that the shape variations of cranial bones are consistent with population history [6-8], it is unknown how much human ancestry information is retained by the human cortical surface. In our group's previous study, we found that area measures of cortical surface and total brain volumes of individuals of European descent in the United States correlate significantly with their ancestral geographic locations in Europe [9]. Here, we demonstrate that the three-dimensional geometry of cortical surface is highly predictive of individuals' genetic ancestry in West Africa, Europe, East Asia, and America, even though their genetic background has been shaped by multiple waves of migratory and admixture events. The geometry of the cortical surface contains richer information about ancestry than the areal variability of the cortical surface, independent of total brain volumes. Besides explaining more ancestry variance than other brain imaging measurements, the 3D geometry of the cortical surface further characterizes distinct regional patterns in the folding and gyrification of the human brain associated with each ancestral lineage.

Individuals with a diagnosis of specific language impairment (SLI) show abnormal spoken language occurring alongside normal non-verbal abilities. Behaviorally, people with SLI exhibit diverse profiles of impairment involving phonological, grammatical, syntactic, and semantic aspects of language. In this study, we used a multimodal neuroimaging technique called anatomically constrained magnetoencephalography (aMEG) to measure the dynamic functional brain organization of an adolescent with SLI. Using single-subject statistical maps of cortical activity, we compared this patient to a sibling and to a cohort of typically developing subjects during the performance of tasks designed to evoke semantic representations of concrete objects. Localized patterns of brain activity within the language impaired patient showed marked differences from the typical functional organization, with significant engagement of right hemisphere heteromodal cortical regions generally homotopic to the left hemisphere areas that usually show the greatest activity for such tasks. Functional neuroanatomical differences were evident at early sensoriperceptual processing stages and continued through later cognitive stages, observed specifically at latencies typically associated with semantic encoding operations. Our findings show with real-time temporal specificity evidence for an atypical right hemisphere specialization for the representation of concrete entities, independent of verbal motor demands. More broadly, our results demonstrate the feasibility and potential utility of using aMEG to characterize individual patient differences in the dynamic functional organization of the brain.

This study investigated the relationship between white matter microstructure and the development of morphosyntax in a spoken narrative in typically developing children (TD) and in children with high functioning autism (HFA). Autism is characterized by language and communication impairments, yet the relationship between morphosyntactic development in spontaneous discourse contexts and neural development is not well understood in either this population or typical development. Diffusion tensor imaging (DTI) was used to assess multiple parameters of diffusivity as indicators of white matter tract integrity in language-related tracts in children between 6 and 13 years of age. Children were asked to spontaneously tell a story about at time when someone made them sad, mad, or angry. The story was evaluated for morphological accuracy and syntactic complexity. Analysis of the relationship between white matter microstructure and language performance in TD children showed that diffusivity correlated with morphosyntax production in the superior longitudinal fasciculus (SLF), a fiber tract traditionally associated with language. At the anatomical level, the HFA group showed abnormal diffusivity in the right inferior longitudinal fasciculus (ILF) relative to the TD group. Within the HFA group, children with greater white matter integrity in the right ILF displayed greater morphological accuracy during their spoken narrative. Overall, the current study shows an association between white matter structure in a traditional language pathway and narrative performance in TD children. In the autism group, associations were only found in the ILF, suggesting that during real world language use, children with HFA rely less on typical pathways and more on alternative ventral pathways that possibly mediate visual elements of language.

The preschool years represent a time of expansive mental growth, with the initial expression of many psychological abilities that will continue to be refined into young adulthood. Likewise, brain development during this age is characterized by its "blossoming" nature, showing some of its most dynamic and elaborative anatomical and physiological changes. In this article, we review human brain development during the preschool years, sampling scientific evidence from a variety of sources. First, we cover neurobiological foundations of early postnatal development, explaining some of the primary mechanisms seen at a larger scale within neuroimaging studies. Next, we review evidence from both structural and functional imaging studies, which now accounts for a large portion of our current understanding of typical brain development. Within anatomical imaging, we focus on studies of developing brain morphology and tissue properties, including diffusivity of white matter fiber tracts. We also present new data on changes during the preschool years in cortical area, thickness, and volume. Physiological brain development is then reviewed, touching on influential results from several different functional imaging and recording modalities in the preschool and early school-age years, including positron emission tomography (PET), electroencephalography (EEG) and event-related potentials (ERP), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and near-infrared spectroscopy (NIRS). Here, more space is devoted to explaining some of the key methodological factors that are required for interpretation. We end with a section on multimodal and multidimensional imaging approaches, which we believe will be critical for increasing our understanding of brain development and its relationship to cognitive and behavioral growth in the preschool years and beyond.

Self-regulation refers to the ability to control behavior, cognition, and emotions, and self-regulation failure is related to a range of neuropsychiatric problems. It is poorly understood how structural maturation of the brain brings about the gradual improvement in self-regulation during childhood. In a large-scale multicenter effort, 735 children (4-21 y) underwent structural MRI for quantification of cortical thickness and surface area and diffusion tensor imaging for quantification of the quality of major fiber connections. Brain development was related to a standardized measure of cognitive control (the flanker task from the National Institutes of Health Toolbox), a critical component of self-regulation. Ability to inhibit responses and impose cognitive control increased rapidly during preteen years. Surface area of the anterior cingulate cortex accounted for a significant proportion of the variance in cognitive performance. This finding is intriguing, because characteristics of the anterior cingulum are shown to be related to impulse, attention, and executive problems in neurodevelopmental disorders, indicating a neural foundation for self-regulation abilities along a continuum from normality to pathology. The relationship was strongest in the younger children. Properties of large-fiber connections added to the picture by explaining additional variance in cognitive control. Although cognitive control was related to surface area of the anterior cingulate independently of basic processes of mental speed, the relationship between white matter quality and cognitive control could be fully accounted for by speed. The results underscore the need for integration of different aspects of brain maturation to understand the foundations of cognitive development.

Structural MRI allows unparalleled in vivo study of the anatomy of the developing human brain. For more than two decades, MRI research has revealed many new aspects of this multifaceted maturation process, significantly augmenting scientific knowledge gathered from postmortem studies. Postnatal brain development is notably protracted and involves considerable changes in cerebral cortical, subcortical, and cerebellar structures, as well as significant architectural changes in white matter fiber tracts (see [12]). Although much work has described isolated features of neuroanatomical development, it remains a critical challenge to characterize the multidimensional nature of brain anatomy, capturing different phases of development among individuals. Capitalizing on key advances in multisite, multimodal MRI, and using cross-validated nonlinear modeling, we demonstrate that developmental brain phase can be assessed with much greater precision than has been possible using other biological measures, accounting for more than 92% of the variance in age. Further, our composite metric of morphology, diffusivity, and signal intensity shows that the average difference in phase among children of the same age is only about 1 year, revealing for the first time a latent phenotype in the human brain for which maturation timing is tightly controlled.

Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing.

The need to move mental health systems toward more recovery-oriented treatment modes is well established. Progress has been made to define needed changes but evidence is lacking about the resources required to implement them. The Mental Health Services Act (MHSA) in California was designed to implement more recovery-oriented treatment modes. We use data from county funding requests and annual updates to examine how counties budgeted for recovery-oriented programs targeted to different age groups under MHSA. Findings indicate that initial per-client budgeting for Full Services Partnerships under MHSA was maintained in future cycles and counties budgeted less per client for children. With this analysis, we begin to benchmark resource allocation for programs that are intended to be recovery-oriented, which should be evaluated against appropriate outcome measures in the future to determine the degree of recovery-orientation.

In this pilot study we examined the determinants of recovery orientation among employees and influential stakeholders in a sample of 12 county departments of mental health in California. A two-level hierarchical linear model with random intercepts was estimated. Analyses show that recovery orientation has a U-shaped relationship with the age of staff/influential stakeholders and is negatively related to the difference between the desired level of adhocracy and the current level of adhocracy. Recovery orientation is positively related to the education level of staff/influential stakeholders, satisfying transformational leadership outcomes, and larger mental health budgets per capita. Policy implications are discussed.

We performed a pilot study examining the patterns of recovery from severe mental illness in a model integrated service delivery system using measures from the Milestones of Recovery Scale (MORS), a valid and reliable measure of recovery outcomes which ranges from 1 to 8 (8 levels). For purposes of presentation, we constructed an aggregate MORS (6 levels) where the levels are described as follows: (1) extreme risk; (2) unengaged, poorly self-coordinating; (3) engaged, poorly self-coordinating; (4) coping and rehabilitating; (5) early recovery, and (6) self reliant. We analyzed MORS data on individuals followed over time from The Village in Long Beach, California (658 observations). Using Markov Chains, we estimated origin-destination transition probabilities, simulating recovery outcomes for 100 months. Our models suggest that after 12 months only 8% of “extreme risk” clients remain such. Over 40% have moved to “engaged, poorly self-coordinating.” After 2 years, almost half of the initial “extreme Risk” clients are “coping/rehabilitating”, “early recovery” or “Self reliant.” Most gains occur within 2 years.