Leveraging the adolescent brain cognitive development study to improve behavioral prediction from neuroimaging in smaller replication samples.

Neuroimaging is a popular method to map brain structural and functional patterns to complex human traits. Recently published observations cast doubt upon these prospects, particularly for prediction of cognitive traits from structural and resting state functional magnetic resonance imaging (MRI). We leverage baseline data from thousands of children in the Adolescent Brain Cognitive DevelopmentSM Study to inform the replication sample size required with univariate and multivariate methods across different imaging modalities to detect reproducible brain-behavior associations. We demonstrate that by applying multivariate methods to high-dimensional brain imaging data, we can capture lower dimensional patterns of structural and functional brain architecture that correlate robustly with cognitive phenotypes and are reproducible with only 41 individuals in the replication sample for working memory-related functional MRI, and ~ 100 subjects for structural and resting state MRI. Even with 100 random re-samplings of 100 subjects in discovery, prediction can be adequately powered with 66 subjects in replication for multivariate prediction of cognition with working memory task functional MRI. These results point to an important role for neuroimaging in translational neurodevelopmental research and showcase how findings in large samples can inform reproducible brain-behavior associations in small sample sizes that are at the heart of many research programs and grants.

Intensity of Social Needs Case Management Services and Changes in Hospital and Emergency Department Use Among Adult Medicaid Beneficiaries.

OBJECTIVES: We identify the association between high- and low-intensity case management services on hospital and emergency department (ED) use among CommunityConnect patients. BACKGROUND: Social needs case management services vary in intensity, including the modality, workforce specialization, and maximum caseload. CommunityConnect is a social needs case management program implemented by Contra Costa Health, a county safety-net health system in California's San Francisco Bay Area. METHODS: Due to the endogeneity of high-intensity services assigned to high-risk patients, we instrument for service intensity using the number of specialist case managers hired each month of enrollment. Zero-inflated negative binomial models with 2-stage residual inclusion estimated total and avoidable hospital admissions and ED visits 12 months post-enrollment for adult Medicaid beneficiaries enrolled between August 2017 and December 2018 (n = 19,782). RESULTS: Compared with low-intensity case management, high-intensity services were associated with a reduction in the incidence rates of inpatient admissions [incidence rate ratio (IRR) = 0.341, 95% CI: 0.106-1.102; P = 0.072], ED visits (IRR = 0.608, 95% CI: 0.188-1.965; P = 0.058), and avoidable ED visits (IRR = 0.579, 95% CI: 0.179-1.872; P = 0.091). No significant association was found between service intensity and the likelihood of an event being an excess zero. CONCLUSIONS: High-intensity social needs case management may be more effective than low-intensity service at reducing health care use for individuals with non-zero use, suggesting that intensive case management may be especially helpful in supporting discharge and transitions of care.

Launching Financial Incentives for Physician Groups to Improve Equity of Care by Patient Race and Ethnicity.

Policy Points What are the facilitators and barriers of physician group participation in a performance-based financial incentive program aimed at improving equity of care by patient race and ethnicity? Launching financial incentives to improve racial equity has required extensive organizational change management for participating physician groups, including major investments to improve quality management systems. Carefully designing financial incentives to encourage equity improvement while managing unintended consequences, and considering physician groups' populations served, baseline maturity of quality management systems, and efforts to assess and address patients' social risk factors have been central to prepare physician groups for financial incentives to improve equity of care. Given the major investments required of physician groups to prepare for financial incentives that reward equity improvement, alignment of equity of care measure specifications and reporting requirements across payers could facilitate physician group engagement. Evidence about how baseline physician group capabilities, including the maturity of their quality management systems, impact equity improvement may help health plans prioritize and target their investments to advance equity of care by patient race and ethnicity. CONTEXT: Blue Cross Blue Shield of Massachusetts (BCBSMA), a large commercial health insurer, is using financial incentives to advance equity of care by patient race and ethnicity. Understanding experiences of this payer and its contracted physician groups can inform efforts elsewhere. We qualitatively assess physician groups' barriers and facilitators of planning and implementing BCBSMA's financial incentives to improve equity of ambulatory care quality by patient race and ethnicity. METHODS: Key informant interviews (n = 44) of the physician group, BCBSMA, and external stakeholders were conducted, equity initiative meetings were observed, and documents were analyzed to identify barriers and facilitators of designing and preparing for financial incentives to advance racial equity. Physician group experiences of preparing for and responding to financial incentives for equity improvement were assessed. FINDINGS: Analyses revealed 1) the central importance of valid and reliable equity performance measurement and carefully designed equity improvement incentives for physician group buy-in, 2) that prior to implementing financial incentives for equity improvement, physician groups needed to improve their quality management systems and the accuracy and completeness of patient race and ethnicity data, and 3) physician groups' populations served, baseline maturity of quality management systems, and efforts to assess and address patients' social risk factors were central to consider to plan for physician group financial incentives to improve racial equity. CONCLUSIONS: Given the major infrastructure investments and organizational change management resources required of physician groups to participate in a financial incentive program designed to reward equity improvement, alignment of equity measurement and performance requirements across payers would facilitate physician groups' engagement in efforts to improve quality of care for racial and ethnic minority patients.

Conjoint Analysis of Telemedicine Preferences for Hypertension Management Among Adult Patients.

Background: Telemedicine has been differentially utilized by different demographic groups during COVID-19, exacerbating inequities in health care. We conducted conjoint and latent class analyses to understand factors that shape patient preferences for hypertension management telemedicine appointments. Methods: We surveyed 320 adults, oversampling participants from households that earned <$50K per year (77.2%) and speak a language other than English at home (68.8%). We asked them to choose among 2 hypothetical appointments through 12 conjoint tasks measuring 6 attributes. Individual utilities for attributes were constructed using logit estimation, and latent classes were identified and compared by demographic and clinical characteristics. Results: Respondents preferred in-person visits (0.353, standard error [SE] = 0.039) and video appointments conducted through a secure patient portal (0.002, SE = 0.040). Respondents also preferred seeing a clinician with whom they have an established relationship (0.168, SE = 0.021). We found four latent classes: "in-person" (26.5% of participants) who strongly weighted in-person appointments, "cost conscious" (8.1%) who prioritized the lowest copay ($0 to $10), "expedited" (19.7%) who prioritized getting the earliest appointment possible (same/next day or at least within the next week), and "comprehensive" (45.6%) who had preferences for in-person care and telemedicine appointments through a secure portal, low copayments, and the ability to see a familiar clinician. Conclusions: Appointment preferences for hypertension management can be segmented into four groups that prioritize (1) in-person care, (2) low copayments, (3) expedited care, and (4) balanced preferences for in-person and telemedicine appointments. Evidence is needed to clarify whether aligning appointment offerings with patients' preferences can improve care quality, equity, and efficiency.

Telehealth Use, Care Continuity, and Quality: Diabetes and Hypertension Care in Community Health Centers Before and During the COVID-19 Pandemic.

BACKGROUND: Community 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. OBJECTIVE: We 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 DESIGN: This was a cohort study. PARTICIPANTS: Electronic health record data from 166 CHCs with n=20,792 patients with diabetes and/or hypertension with ≥2 encounters/year during 2019 and 2020. METHODS: Multivariable 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. RESULTS: MMCI [2019: odds ratio (OR)=1.98, marginal effect=0.69, z=165.50, P<0.001; 2020: OR=1.50, marginal effect=0.63, z=147.73, P<0.001] and telehealth use (2019: OR=1.50, marginal effect=0.85, z=122.87, P<0.001; 2020: OR=10.00, marginal effect=0.90, z=155.57, P<0.001) were associated with higher odds of A1c testing. MMCI was associated with lower systolic (ß=-2.90, P<0.001) and diastolic blood pressure (ß=-1.44, P<0.001) in 2020, and lower A1c values (2019: ß=-0.57, P=0.007; 2020: ß=-0.45, P=0.008) in both years. In 2020, telehealth use mediated 38.7% of the relationship between MMCI and A1c testing. CONCLUSIONS: Higher care continuity is associated with telehealth use and A1c testing, and lower A1c and blood pressure. Telehealth use mediates the association of care continuity and A1c testing. Care continuity may facilitate telehealth use and resilient performance on process measures.

Hospital Characteristics Associated With Clinically Integrated Network Participation.

BACKGROUND: Increased integration of physician organizations and hospitals into health systems has not necessarily improved clinical integration or patient outcomes. However, federal regulators have issued favorable opinions for clinically integrated networks (CINs) as a way to pursue coordination between hospitals and physicians. Hospital organizational affiliations, including independent practice associations (IPA), physician-hospital organizations (PHOs), and accountable care organizations (ACOs), may support CIN participation. No empirical evidence, however, exists about factors associated with CIN participation. METHODS: Data from the 2019 American Hospital Association survey (n = 4405) were analyzed to quantify hospital CIN participation. Multivariable logistic regression models were estimated to examine whether IPA, PHO, and ACO affiliations were associated with CIN participation, controlling for market factors and hospital characteristics. RESULTS: In 2019, 34.6% of hospitals participated in a CIN. Larger, not-for-profit, and metropolitan hospitals were more likely to participate in CINs. In adjusted analyses, hospitals participating in CINs were more likely to have an IPA (9.5% points, P < 0.001), a PHO (6.1% points, P < 0.001), and ACO (19.3% points, P < 0.001) compared with hospitals not participating in a CIN. CONCLUSIONS: Over one-third of hospitals participate in a CIN, despite limited evidence about their effectiveness in delivering value. Results suggest that CIN participation may be a response to integrative norms. Future work should attempt to better define CIN participation and strive to disentangle overlapping organizational participation.

Shared Decision-making Lowers Medical Expenditures and the Effect Is Amplified in Racially-Ethnically Concordant Relationships.

BACKGROUND: Racial-ethnic disparities are pervasive in health care. One mechanism that may underlie disparities is variation in shared decision-making (SDM), which encompasses high-quality clinician-patient communication, including deliberative discussions about treatment options. OBJECTIVES: To determine whether SDM has causal effects on outcomes and whether these effects are stronger within racial-ethnic concordant clinician-patient relationships. RESEARCH DESIGN: We use instrumental variables to estimate the causal effect of SDM on outcomes. SUBJECTS: A total of 60,584 patients from the 2003-2017 Integrated Public Use Microdata Series Medical Expenditure Panel Survey. Years 2018 and 2019 were excluded due to changes in the Medical Expenditure Panel Survey that omitted essential parts of the SDM index. MEASURES: Our key variable of interest is the SDM index. Outcomes included total, outpatient, and drug expenditures; physical and mental health; and the utilization of inpatient and emergency services. RESULTS: SDM lowers annual total health expenditures for all racial-ethnic groups, but this effect is only moderated among Black patients seen by Black clinicians, more than doubling in size relative to Whites. A similar SDM moderation effect also occurs for both Black patients seen by Black clinicians and Hispanic patients seen by Hispanic clinicians with regard to annual outpatient expenditures. There was no significant effect of SDM on self-reported physical or mental health. CONCLUSIONS: High-quality SDM can reduce health expenditures without negatively impacting overall physical or mental health, supporting a business case for health care organizations and systems to improve racial-ethnic clinician-patient concordance for Black and Hispanic patients.

A human neurodevelopmental model for Williams syndrome.

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.

Understanding the distributional impacts of health insurance reform: Evidence from a consumer cost-sharing program.

We examine the heterogeneous effects of reference pricing, a health insurance reform introduced by the California Public Employees' Retirement System (CalPERS), on the distribution of spending by patients and insurers. Using medical claims data for CalPERS and a comparison group not subject to reference pricing, we use the changes-in-changes approach to estimate the quantile treatment effects of the program across different medical procedures. We find that the quantile treatment effects vary across the patient spending distributions, with a range of positive and negative estimates of the QTE, depending on the medical procedure considered. However, across all procedures, the insurer's spending distributions tend to shift left, with the largest reductions occurring in the right-tail of the spending distributions. These effects are not captured by mean estimates but have important policy implications.

Association of Reference Pricing with Drug Selection and Spending.

Background In the United States, prices for therapeutically similar drugs vary widely, which has prompted efforts by public and private insurers to steer patients toward the lower-priced options. Under reference pricing, the insurer or employer establishes a maximum contribution it will make toward the price of a drug or procedure, and the patient pays the remainder. Methods We used difference-in-differences multivariable regression methods to analyze changes in prescriptions and pricing for 1302 drugs in 78 therapeutic classes in the United States, before and after implementation of reference pricing by an alliance of private employers. We assessed trends for the study group relative to those for an employee group that was not subject to reference pricing. The study included 1,122,741 prescriptions that were reimbursed during the period from 2010 through 2014. Results Implementation of reference pricing was associated with a higher percentage of prescriptions that were filled for the lowest-priced reference drug within its therapeutic class (difference in probability, 7.0 percentage points; 95% confidence interval [CI], 4.0 to 9.9), a lower average price paid per prescription (-13.9%; 95% CI, -23.8 to -2.7), and a higher rate of copayment by patients (5.2%; 95% CI, 0.2 to 10.4) than in the comparison group. During the first 18 months after implementation, spending for employers was $1.34 million lower and the amount of copayments for employees was $0.12 million higher than in the comparison group. Conclusions Implementation of reference pricing was associated with significant changes in drug selection and spending for a population of patients covered by employment-based insurance in the United States. (Funded by the Agency for Healthcare Research and Quality and the Genentech Foundation.).

Patterns of structural lateralization in cortical language areas of older adolescents.

Structural lateralization of cortical language areas has been extensively studied in the past, with the conclusion that there is a predominant left lateralization in the majority of typically developing adolescents. However, lateralization in this age group has often been examined using cortical volumetric measures, without taking into account the independence of surface area and thickness. Utilizing structural MRI data in a relatively large sample size, the lateralization of cortical volume, surface area, and thickness was analysed across regions of interest (ROIs) known to support language processing in 118 typically developing adolescents, ages 13;9 to 18;9 using a laterality index. Results showed that the laterality index scores for volume and surface area were more strongly correlated than volume and thickness. Results also showed that not all language regions were left lateralized, with some ROIs being significantly right lateralized. Results also showed that surface area and thickness did not always share direction of lateralization. Taken together these results indicate that cortical ROIs supporting language are not all strongly left lateralized in adolescents. These data also show that cortical surface area and cortical thickness need to be treated independently in future studies characterizing language and lateralization in the adolescent brain.

A multisample study of longitudinal changes in brain network architecture in 4-13-year-old children.

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.

Through Thick and Thin: a Need to Reconcile Contradictory Results on Trajectories in Human Cortical Development.

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.

The Pediatric Imaging, Neurocognition, and Genetics (PING) Data Repository.

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.

Reference Pricing, Consumer Cost-Sharing, and Insurer Spending for Advanced Imaging Tests.

BACKGROUND: Fees charged for similar imaging tests often vary dramatically within the same market, leading to wide variation in insurer spending and consumer cost-sharing. Reference pricing is an insurance design that offers good coverage to patients up to a defined contribution limit but requires the patients who select high-priced facilities to pay the remainder out of pocket. OBJECTIVES: To measure the association between implementation of reference pricing and patient choice of facility, test prices, out-of-pocket spending, and insurer spending for advanced imaging (CT and MRI) procedures. RESEARCH DESIGN: Difference-in-differences multivariable analysis of insurance claims data. Study included 4751 employees of a national grocery chain (treatment group) and 23,428 enrollees in the nation's largest private insurance plan (comparison group) that used CT or MRI tests between 2010 and 2013. MEASURES: Patient choice of facility, price paid per test, patient out-of-pocket cost-sharing, and employer spending. RESULTS: Compared with trends in prices paid by insurance enrollees not subject to reference pricing, and after adjusting for characteristics of tests and patients, implementation of reference pricing was associated with a 12.5% (95% CI, -25.0%, 2.1%) reduction in average price paid per test by the end of the second full year of the program for CT scans and a 10.5% (95% CI, -16.9%, 3.6%) for MRIs. Out-of-pocket cost-sharing by patients declined by $71,508 (13.8%). The savings accruing to employees amounted to 45.5% of total savings from reference pricing, with the remainder accruing to the employer. CONCLUSIONS: Implementation of reference pricing led to reductions in payments by both employer and employees.

Returns on Investment in California County Departments of Public Health.

OBJECTIVES: To estimate the average return on investment for the overall activities of county departments of public health in California. METHODS: I gathered the elements necessary to estimate the average return on investment for county departments of public health in California during the period 2001 to 2008-2009. These came from peer-reviewed journal articles published as part of a larger project to develop a method for determining return on investment for public health by using a health economics framework. I combined these elements by using the standard formula for computing return on investment, and performed a sensitivity analysis. Then I compared the return on investment for county departments of public health with the returns on investment generated for various aspects of medical care. RESULTS: The estimated return on investment from $1 invested in county departments of public health in California ranges from $67.07 to $88.21. CONCLUSIONS: The very large estimated return on investment for California county departments of public health relative to the return on investment for selected aspects of medical care suggests that public health is a wise investment.

Reference Pricing with Endogenous or Exogenous Payment Limits: Impacts on Insurer and Consumer Spending.

Reference pricing (RP) theories predict different outcomes when reference prices are fixed (exogenous) versus being a function of market prices (MPs) (endogenous). Exogenous RP results in MPs at both high-price and low-price firms converging towards the reference price from above and below, respectively. Endogenous RP results in MPs at both high-price and low-price firms decreasing, with low-price firms acting strategically to decrease the reference price in order to gain market share. We extend these models to a hospital context focusing on insurer and consumer payments. Under exogenous RP, insurer and consumer payments to low-price hospitals increase, and insurer payments to high-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. Under endogenous RP, insurer payments to high-price and low-price hospitals decrease, and consumer payments to low-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. We test these predictions with difference-in-differences specifications using 2008-2013 data on patients undergoing joint replacement. For 2 years following RP implementation, insurer payments to high-price and low-price hospitals moved downward, consistent with endogenous RP. However, when the reference price was not reset to account for changes in MPs, insurer payments to low-price hospitals reverted to pre-implementation levels, consistent with exogenous RP. Copyright © 2015 John Wiley & Sons, Ltd.

Age-related changes in tissue signal properties within cortical areas important for word understanding in 12- to 19-month-old infants.

Recently, our laboratory has shown that the neural mechanisms for encoding lexico-semantic information in adults operate functionally by 12-18 months of age within left frontotemporal cortices (Travis et al., 2011. Spatiotemporal neural dynamics of word understanding in 12- to 18-month-old-infants. Cereb Cortex. 8:1832-1839). However, there is minimal knowledge of the structural changes that occur within these and other cortical regions important for language development. To identify regional structural changes taking place during this important period in infant development, we examined age-related changes in tissue signal properties of gray matter (GM) and white matter (WM) intensity and contrast. T1-weighted surface-based measures were acquired from 12- to 19-month-old infants and analyzed using a general linear model. Significant age effects were observed for GM and WM intensity and contrast within bilateral inferior lateral and anterovental temporal regions, dorsomedial frontal, and superior parietal cortices. Region of interest (ROI) analyses revealed that GM and WM intensity and contrast significantly increased with age within the same left lateral temporal regions shown to generate lexico-semantic activity in infants and adults. These findings suggest that neurophysiological processes supporting linguistic and cognitive behaviors may develop before cellular and structural maturation is complete within associative cortices. These results have important implications for understanding the neurobiological mechanisms relating structural to functional brain development.

Long-term influence of normal variation in neonatal characteristics on human brain development.

It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences.

Multimodal imaging of the self-regulating developing brain.

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.