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•Describes the ABCD study aims and design.•Covers issues surrounding estimation of meaningful associations, including population inferences, effect sizes, and control of covariates.•Outlines best practices for reproducible research and reporting of results.•Provides worked examples that illustrate the main points of the paper. The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children's health in the United States. A cohort of n = 11,880 children aged 9–10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

Quantitative functional magnetic resonance imaging methods make it possible to measure cerebral oxygen metabolism (CMRO2) in the human brain. Current methods require the subject to breathe special gas mixtures (hypercapnia and hyperoxia). We tested a noninvasive suite of methods to measure absolute CMRO2 in both baseline and dynamic activation states without the use of special gases: arterial spin labeling (ASL) to measure baseline and activation cerebral blood flow (CBF), with concurrent measurement of the blood oxygenation level dependent (BOLD) signal as a dynamic change in tissue R2*; VSEAN to estimate baseline O2 extraction fraction (OEF) from a measurement of venous blood R2, which in combination with the baseline CBF measurement yields an estimate of baseline CMRO2; and FLAIR-GESSE to measure tissue R2′ to estimate the scaling parameter needed for calculating the change in CMRO2 in response to a stimulus with the calibrated BOLD method. Here we describe results for a study sample of 17 subjects (8 female, mean age = 25.3 years, range 21–31 years). The primary findings were that OEF values measured with the VSEAN method were in good agreement with previous PET findings, while estimates of the dynamic change in CMRO2 in response to a visual stimulus were in good agreement between the traditional hypercapnia calibration and calibration based on R2′. These results support the potential of gas-free methods for quantitative physiological measurements. •Absolute CMRO2 measurements are feasible without using special gases.•OEF measurements with VSEAN are consistent with previous PET findings.•CMRO2 changes to stimuli measurements with FLAIR-GESSE are consistent with gas-based findings.

Medial temporal lobe (MTL) lesions typically produce retrograde amnesia characterized by the disproportionate loss of recently acquired memories. Temporally graded memory loss is interpreted traditionally as evidence for a consolidation process guided by the MTL. Here, using functional magnetic resonance imaging (fMRI), we show temporally graded changes in MTL activity in healthy older adults taking a famous faces remote memory test. Evidence for temporally graded change in the hippocampal formation was mixed, suggesting it may participate only in consolidation processes lasting a few years. Entorhinal cortex was associated with temporally graded changes extending up to 20 years. These findings support the basic tenets of consolidation theory and suggest that the entorhinal cortex, rather than the hippocampal formation, participates in memory consolidation over decades.

Controversy surrounds the proposal that specific human cortical regions in the ventral occipitotemporal cortex, commonly called the fusiform face area (FFA) and occipital face area (OFA), are specialized for face processing. Here, we present findings from an fMRI study of identity discrimination of faces and objects that demonstrates the FFA and OFA are equally responsive to processing stimuli at the level of individuals (i.e., individuation), be they human faces or non-face objects. The FFA and OFA were defined via a passive viewing task as regions that produced greater activation to faces relative to non-face stimuli within the middle fusiform gyrus and inferior occipital gyrus. In the individuation task, participants judged whether sequentially presented images of faces, diverse objects, or wristwatches depicted the identical or a different exemplar. All three stimulus types produced equivalent BOLD activation within the FFA and OFA; that is, there was no face-specific or face-preferential processing. Critically, individuation processing did not eliminate an object superiority effect relative to faces within a region more closely linked to object processing in the lateral occipital complex (LOC), suggesting that individuation processes are reasonably specific to the FFA and OFA. Taken together, these findings challenge the prevailing view that the FFA and OFA are face-specific processing regions, demonstrating instead that they function to individuate - i.e., identify specific individuals - within a category. These findings have significant implications for understanding the function of brain regions widely believed to play an important role in social cognition.

Cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) signal measurements make it possible to estimate steady-state changes in the cerebral metabolic rate of oxygen (CMRO2) with a calibrated BOLD method. However, extending this approach to measure the dynamics of CMRO2 requires an additional assumption: that deoxygenated cerebral blood volume (CBVdHb) follows CBF in a predictable way. A test-case for this assumption is the BOLD post-stimulus undershoot, for which one proposed explanation is a strong uncoupling of flow and blood volume with an elevated level of CBVdHb during the post-stimulus period compared to baseline due to slow blood volume recovery (Balloon Model). A challenge in testing this model is that CBVdHb differs from total blood volume, which can be measured with other techniques. In this study, the basic hypothesis of elevated CBVdHb during the undershoot was tested, based on the idea that the BOLD signal change when a subject switches from breathing a normoxic gas to breathing a hyperoxic gas is proportional to the absolute CBVdHb. In 19 subjects (8F), dual-echo BOLD responses were measured in primary visual cortex during a flickering radial checkerboard stimulus in normoxia, and the identical experiment was repeated in hyperoxia (50% O2/balance N2). The BOLD signal differences between normoxia and hyperoxia for the pre-stimulus baseline, stimulus, and post-stimulus periods were compared using an equivalent BOLD signal calculated from measured R2* changes to eliminate signal drifts. Relative to the pre-stimulus baseline, the average BOLD signal change from normoxia to hyperoxia was negative during the undershoot period (p = 0.0251), consistent with a reduction of CBVdHb and contrary to the prediction of the Balloon Model. Based on these results, the BOLD post-stimulus undershoot does not represent a case of strong uncoupling of CBVdHb and CBF, supporting the extension of current calibrated BOLD methods to estimate the dynamics of CMRO2. •The hyperoxia-BOLD effect is a way to test for elevated CBV in the BOLD undershoot.•The measured effect showed reduced blood volume in the undershoot.•Reduced blood volume during the undershoot contradicts Balloon Model predictions.•This supports extending current quantitative methods to estimate metabolism dynamics.

Age-related deficits in visual selective attention suggest that the efficiency of inhibitory processes is particularly affected by aging. To investigate whether processing inefficiencies observed in visual attention are similar in auditory attention and when shifting attention across modalities, we conducted an fMRI study with healthy young and older adults using a task that required sustained auditory and visual selective attention and cross-modal attention shifts. Older adults in this study performed as well as the younger adults, but showed age-related differences in BOLD responses. The most striking of these differences were bilateral frontal and parietal regions of significantly increased activation in older adults during both focused and shifting attention. Our data suggest that this increased activation did not reflect new recruitment, but reliance on brain regions typically used by younger adults when task demands are greater. Older adults' activation patterns suggested that even during focused attention conditions they were “shifting” attention to stimuli in the unattended modality. Increased activation during processing of both task-relevant and task-irrelevant information implies age-related loss of processing selectivity. These patterns may reflect both task-specific compensatory neural recruitment and degradation of sensory inhibition.

Background To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems. Methods A cross-sectional study was conducted utilizing the Adolescent Brain Cognitive Development℠ (ABCD) Study (n = 7613, ages 9-to-10-years-old) to determine the associations among multiple physical health factors (e.g., prenatal complications, current physical health problems). Logistic regression models controlling for age, sex, pubertal development, household income, caregiver education, race, and ethnicity evaluated relationships between perinatal factors and childhood physical health problems. Results There were significant associations between perinatal and current physical health measures. Specifically, those who had experienced perinatal complications were more likely to have medical problems by 9-to-10 years old. Importantly, sleep disturbance co-occurred with several physical health problems across domains and developmental periods. Conclusion Several perinatal health factors were associated with childhood health outcomes, highlighting the importance of understanding and potentially improving physical health in youth. Understanding the clustering of physical health problems in youth is essential to better identify which physical health problems may share underlying mechanisms. Impact Using a multivariable approach, we investigated the associations between various perinatal and current health problems amongst youth. Our study highlights current health problems, such as sleep problems at 9-to-10 years old, that are associated with a cluster of factors occurring across development (e.g., low birth weight, prenatal substance exposure, pregnancy complications, current weight status, lifetime head injury). Perinatal health problems are at large, non-modifiable (in this retrospective context), however, by identifying which are associated with current health problems, we can identify potential targets for intervention and prevention efforts.

Although the acute stroke literature indicates that cerebral blood flow (CBF) may commonly be disordered in stroke survivors, limited research has investigated whether CBF remains aberrant in the chronic phase of stroke. A directed study of CBF in stroke is needed because reduced CBF (hypoperfusion) may occur in neural regions that appear anatomically intact and may impact cognitive functioning in stroke survivors. Hypoperfusion in neurologically-involved individuals may also affect BOLD signal in FMRI studies, complicating its interpretation with this population. The current study measured CBF in three chronic stroke survivors with ischemic infarcts (greater than 1year post-stroke) to localize regions of hypoperfusion, and most critically, examine the CBF inflow curve using a methodology that has never, to our knowledge, been reported in the chronic stroke literature. CBF data acquired with a Pulsed Arterial Spin Labeling (PASL) flow-sensitive alternating inversion recovery (FAIR) technique indicated both delayed CBF inflow curve and hypoperfusion in the stroke survivors as compared to younger and elderly control participants. Among the stroke survivors, we observed regional hypoperfusion in apparently anatomically intact neural regions that are involved in cognitive functioning. These results may have profound implications for the study of behavioral deficits in chronic stroke, and particularly for studies using neuroimaging methods that rely on CBF to draw conclusions about underlying neural activity.

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder.