Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains.

The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors.

Effects of prior testing lasting a full year in NCANDA adolescents: Contributions from age, sex, socioeconomic status, ethnicity, site, family history of alcohol or drug abuse, and baseline performance.

Longitudinal study provides a robust method for tracking developmental trajectories. Yet inherent problems of retesting pose challenges in distinguishing biological developmental change from prior testing experience. We examined factors potentially influencing change scores on 16 neuropsychological test composites over 1year in 568 adolescents in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) project. The twice-minus-once-tested method revealed that performance gain was mainly attributable to testing experience (practice) with little contribution from predicted developmental effects. Group mean practice slopes for 13 composites indicated that 60% to ∼100% variance was attributable to test experience; General Ability accuracy showed the least practice effect (29%). Lower baseline performance, especially in younger participants, was a strong predictor of greater gain. Contributions from age, sex, ethnicity, examination site, socioeconomic status, or family history of alcohol/substance abuse were nil to small, even where statistically significant. Recognizing that a substantial proportion of change in longitudinal testing, even over 1-year, is attributable to testing experience indicates caution against assuming that performance gain observed during periods of maturation necessarily reflects development. Estimates of testing experience, a form of learning, may be a relevant metric for detecting interim influences, such as alcohol use or traumatic episodes, on behavior.

Sharing brain mapping statistical results with the neuroimaging data model.

Only a tiny fraction of the data and metadata produced by an fMRI study is finally conveyed to the community. This lack of transparency not only hinders the reproducibility of neuroimaging results but also impairs future meta-analyses. In this work we introduce NIDM-Results, a format specification providing a machine-readable description of neuroimaging statistical results along with key image data summarising the experiment. NIDM-Results provides a unified representation of mass univariate analyses including a level of detail consistent with available best practices. This standardized representation allows authors to relay methods and results in a platform-independent regularized format that is not tied to a particular neuroimaging software package. Tools are available to export NIDM-Result graphs and associated files from the widely used SPM and FSL software packages, and the NeuroVault repository can import NIDM-Results archives. The specification is publically available at: http://nidm.nidash.org/specs/nidm-results.html.

The brain imaging data structure, a format for organizing and describing outputs of neuroimaging experiments.

The development of magnetic resonance imaging (MRI) techniques has defined modern neuroimaging. Since its inception, tens of thousands of studies using techniques such as functional MRI and diffusion weighted imaging have allowed for the non-invasive study of the brain. Despite the fact that MRI is routinely used to obtain data for neuroscience research, there has been no widely adopted standard for organizing and describing the data collected in an imaging experiment. This renders sharing and reusing data (within or between labs) difficult if not impossible and unnecessarily complicates the application of automatic pipelines and quality assurance protocols. To solve this problem, we have developed the Brain Imaging Data Structure (BIDS), a standard for organizing and describing MRI datasets. The BIDS standard uses file formats compatible with existing software, unifies the majority of practices already common in the field, and captures the metadata necessary for most common data processing operations.

Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study.

Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.

Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction.

OBJECTIVE: To investigate development of cognitive and motor functions in healthy adolescents and to explore whether hazardous drinking affects the normal developmental course of those functions. METHOD: Participants were 831 adolescents recruited across 5 United States sites of the National Consortium on Alcohol and NeuroDevelopment in Adolescence 692 met criteria for no/low alcohol exposure, and 139 exceeded drinking thresholds. Cross-sectional, baseline data were collected with computerized and traditional neuropsychological tests assessing 8 functional domains expressed as composite scores. General additive modeling evaluated factors potentially modulating performance (age, sex, ethnicity, socioeconomic status, and pubertal developmental stage). RESULTS: Older no/low-drinking participants achieved better scores than younger ones on 5 accuracy composites (general ability, abstraction, attention, emotion, and balance). Speeded responses for attention, motor speed, and general ability were sensitive to age and pubertal development. The exceeds-threshold group (accounting for age, sex, and other demographic factors) performed significantly below the no/low-drinking group on balance accuracy and on general ability, attention, episodic memory, emotion, and motor speed scores and showed evidence for faster speed at the expense of accuracy. Delay Discounting performance was consistent with poor impulse control in the younger no/low drinkers and in exceeds-threshold drinkers regardless of age. CONCLUSIONS: Higher achievement with older age and pubertal stage in general ability, abstraction, attention, emotion, and balance suggests continued functional development through adolescence, possibly supported by concurrently maturing frontal, limbic, and cerebellar brain systems. Determination of whether low scores by the exceeds-threshold group resulted from drinking or from other preexisting factors requires longitudinal study. (PsycINFO Database Record

The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA): A Multisite Study of Adolescent Development and Substance Use.

OBJECTIVE: During adolescence, neurobiological maturation occurs concurrently with social and interpersonal changes, including the initiation of alcohol and other substance use. The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) is designed to disentangle the complex relationships between onset, escalation, and desistance of alcohol use and changes in neurocognitive functioning and neuromaturation. METHOD: A sample of 831 youth, ages 12-21 years, was recruited at five sites across the United States, oversampling those at risk for alcohol use problems. Most (83%) had limited or no history of alcohol or other drug use, and a smaller portion (17%) exceeded drinking thresholds. A comprehensive assessment of biological development, family background, psychiatric symptomatology, and neuropsychological functioning-in addition to anatomical, diffusion, and functional brain magnetic resonance imaging-was completed at baseline. RESULTS: The NCANDA sample of youth is nationally representative of sex and racial/ethnic groups. More than 50% have at least one risk characteristic for subsequent heavy drinking (e.g., family history, internalizing or externalizing symptoms). As expected, those who exceeded drinking thresholds (n = 139) differ from those who did not (n = 692) on identified factors associated with early alcohol use and problems. CONCLUSIONS: NCANDA successfully recruited a large sample of adolescents and comprehensively assessed psychosocial functioning across multiple domains. Based on the sample's risk profile, NCANDA is well positioned to capture the transition into drinking and alcohol problems in a large portion of the cohort, as well as to help disentangle the associations between alcohol use, neurobiological maturation, and neurocognitive development and functioning.

Neuroinformatics Software Applications Supporting Electronic Data Capture, Management, and Sharing for the Neuroimaging Community.

Accelerating insight into the relation between brain and behavior entails conducting small and large-scale research endeavors that lead to reproducible results. Consensus is emerging between funding agencies, publishers, and the research community that data sharing is a fundamental requirement to ensure all such endeavors foster data reuse and fuel reproducible discoveries. Funding agency and publisher mandates to share data are bolstered by a growing number of data sharing efforts that demonstrate how information technologies can enable meaningful data reuse. Neuroinformatics evaluates scientific needs and develops solutions to facilitate the use of data across the cognitive and neurosciences. For example, electronic data capture and management tools designed to facilitate human neurocognitive research can decrease the setup time of studies, improve quality control, and streamline the process of harmonizing, curating, and sharing data across data repositories. In this article we outline the advantages and disadvantages of adopting software applications that support these features by reviewing the tools available and then presenting two contrasting neuroimaging study scenarios in the context of conducting a cross-sectional and a multisite longitudinal study.

Neuroanatomical domain of the foundational model of anatomy ontology.

BACKGROUND: The diverse set of human brain structure and function analysis methods represents a difficult challenge for reconciling multiple views of neuroanatomical organization. While different views of organization are expected and valid, no widely adopted approach exists to harmonize different brain labeling protocols and terminologies. Our approach uses the natural organizing framework provided by anatomical structure to correlate terminologies commonly used in neuroimaging. DESCRIPTION: The Foundational Model of Anatomy (FMA) Ontology provides a semantic framework for representing the anatomical entities and relationships that constitute the phenotypic organization of the human body. In this paper we describe recent enhancements to the neuroanatomical content of the FMA that models cytoarchitectural and morphological regions of the cerebral cortex, as well as white matter structure and connectivity. This modeling effort is driven by the need to correlate and reconcile the terms used in neuroanatomical labeling protocols. By providing an ontological framework that harmonizes multiple views of neuroanatomical organization, the FMA provides developers with reusable and computable knowledge for a range of biomedical applications. CONCLUSIONS: A requirement for facilitating the integration of basic and clinical neuroscience data from diverse sources is a well-structured ontology that can incorporate, organize, and associate neuroanatomical data. We applied the ontological framework of the FMA to align the vocabularies used by several human brain atlases, and to encode emerging knowledge about structural connectivity in the brain. We highlighted several use cases of these extensions, including ontology reuse, neuroimaging data annotation, and organizing 3D brain models.

N-CANDA data integration: anatomy of an asynchronous infrastructure for multi-site, multi-instrument longitudinal data capture.

The infrastructure for data collection implemented by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (N-CANDA) for data collection comprises several innovative features: (a) secure, asynchronous transfer and persistent storage of collected data via a revision control system; (b) two-stage import into a longitudinal database; and (c) use of a script-controlled web browser for data retrieval from a third-party, web-based neuropsychological test battery. The asynchronous operation of data transmission and import is of particular benefit, as it has allowed the consortium sites to begin data collection before the receiving database infrastructure had been deployed. Records were collected within 86 days of funding, 35 days after finalizing the collected instruments. Final instruments were added to the database import 225 days after instrument selection, with up to 173 records already collected at that time. Thus, the concepts implemented in N-CANDA's data collection system helped reduce project start-up time by several months.

Working and episodic memory in HIV infection, alcoholism, and their comorbidity: baseline and 1-year follow-up examinations.

BACKGROUND: Selective memory deficits occur in individuals with human immunodeficiency virus (HIV) infection and those with chronic alcoholism, but the potential compounded effect of these conditions is seldom considered, despite the high prevalence of alcohol use disorders in HIV infection. METHODS: Here, we examined component processes of working and episodic memory in HIV infection and chronic alcoholism (ALC) in 4 subject groups (HIV, ALC, HIV + ALC, and normal controls) at baseline and 1-year follow-up. Accuracy scores, response times, and rate of information processing were assessed with subtests of the computerized neuropsychological test battery, the MicroCog. RESULTS: Although individuals with either HIV infection or alcoholism generally performed at normal levels, individuals comorbid with HIV infection and alcoholism were impaired relative to controls and to the single diagnosis groups on selective memory processes. Immediate episodic memory was impaired, whereas working memory remained intact. Ability to retain information over time was not impaired in the clinical groups. Little performance change between groups was detected over 1 year. Results could not be explained by amount of alcohol consumed over a lifetime, CD4 cell count, AIDS diagnosis, or HAART medication. CONCLUSIONS: This study provides behavioral support for adverse synergism of HIV infection and chronic alcoholism on brain function and is consistent with neuroimaging reports of compromised hippocampal and associated memory structures related to episodic memory processes in these 2 conditions.