Retaining Adolescent and Young Adult Participants in Research During a Pandemic: Best Practices From Two Large-Scale Developmental Neuroimaging Studies (NCANDA and ABCD)

The novel coronavirus pandemic that emerged in late 2019 (COVID-19) has created challenges not previously experienced in human research. This paper discusses two large-scale NIH-funded multi-site longitudinal studies of adolescents and young adults – the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) and the Adolescent Brain Cognitive Development (ABCD) Study – and valuable approaches to learn about adaptive processes for conducting developmentally sensitive research with neuroimaging and neurocognitive testing across consortia during a global pandemic. We focus on challenges experienced during the pandemic and modifications that may guide other projects, such as implementing adapted protocols that protect the safety of participants and research staff, and addressing assessment challenges through the use of strategies such as remote and mobile assessments. Given the pandemic’s disproportionate impacts on participants typically underrepresented in research, we describe efforts to retain these individuals. The pandemic provides an opportunity to develop adaptive processes that can facilitate future studies’ ability to mobilize effectively and rapidly

A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania

Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n=22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI=0.12, 1.10; p=0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p<0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n=48; 2 cm, compared to 1 cm in the placebo group; 95% CI=0.20, 1.70; p=0.01; p for interaction by age group=0.01). Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. CLINICALTRIALS.GOV IDENTIFIER: NCT00145184

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 was higher than that 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

Defining semantic space and degree of association using brainwaves: An ERP investigation of alcohol expectancies

The current study investigated the cognitive organization of alcohol expectancies using event-related potentials (ERPs). Building on previous behavioral and ERP paradigms, the goal of the current study was to quantify the relationship among alcohol expectancies using ERP indices of salience, congruence, and cognitive distance. The ERP components being evaluated fit perfectly into the alcohol expectancy theory and research; however, implementing specific paradigms to reliably measure individual differences in alcohol expectancies using ERPs has proven to be more elusive than originally thought. This study utilized established cognitive modeling techniques coupled with ERP responses to linguistic stimuli. In essence, this study provides an implicit measure of how particular types of words, in the context of alcohol, are categorized and integrated into individuals\u27 expectancy frameworks. The study looked at two specific ERP components, the P300 and the N400, that have been shown to be sensitive to expectancy violations. In a sentence processing task the P300 was predicted to be related to individuals\u27 alcohol expectancies and in a word pair task the N400 was predicted to index these expectancies. Results indicated that the P300 and N400 were both related to alcohol expectancies in the sentence task and the N400 was related to alcohol expectancies in the word pair task. While the results supported parts of the hypotheses, they were not unequivocal endorsements of the hypothesized relationships, perhaps highlighting the countervailing forces of salience and expectancy congruence. Furthermore, there were unexpected differences between males and females in the sample that interacted with the effect of expectancy on ERPs. In sum, prior research has highlighted individuals\u27 expectations about alcohol as a mediator of biopsychosocial risk for alcohol use disorders (Goldman, 2002), and the results of this study provide a model for how ERP measures of expectancy could capture an aspect of individuals\u27 risk based on reactions to expectancy related stimul