Frank Haist

The Adolescent Brain Cognitive Development (ABCD) Study^® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Children born preterm are at risk for cognitive deficits and lower academic achievement. Notably, mathematics achievement is generally most affected. Here, we investigated the cognitive functions mediating early mathematics skills and how these are impacted by preterm birth. Healthy children born preterm (gestational age at birth < 33 weeks; n = 51) and children born full term (n = 27) were tested at ages 5, 6, and 7 years with a comprehensive battery of tests. We categorized items of the TEMA-3: Test for Early Mathematics Abilities Third Edition into number skills and arithmetic skills. Using multiple mediation models, we assessed how the effect of preterm birth on mathematics skills is mediated by spatial working memory, inhibitory control, visual-motor integration, and phonological processing. Both number and arithmetic skills showed group differences, but with different developmental trajectories. The initial performance gap observed in the preterm children decreased over time for number skills but increased for arithmetic skills. Phonological processing, visual-motor integration, and inhibitory control were poorer in children born preterm. These cognitive functions, particularly phonological processing, had a mediating effect on both types of mathematics skills. These findings help define and chart the trajectory of the specific cognitive skills directly influencing math deficit phenotypes in children born very preterm. This knowledge provides guidance for targeted evaluation and treatment implementation.

Children born preterm are at risk for cognitive deficits and lower academic achievement. Notably, mathematics achievement is generally most affected. Here, we investigated the cognitive functions mediating early mathematics skills and how these are impacted by preterm birth. Healthy children born preterm (gestational age at birth < 33 weeks; n = 51) and children born full term (n = 27) were tested at ages 5, 6, and 7 years with a comprehensive battery of tests. We categorized items of the TEMA-3: Test for Early Mathematics Abilities Third Edition into number skills and arithmetic skills. Using multiple mediation models, we assessed how the effect of preterm birth on mathematics skills is mediated spatial working memory, inhibitory control, visual-motor integration, and phonological processing. Both number and arithmetic skills showed group differences, but with different developmental trajectories. The initial poorer performance observed in the preterm children decreased over time for number skills but increased for arithmetic skills. Phonological processing, visual-motor integration, and inhibitory control were poorer in children born preterm. These cognitive functions, particularly phonological processing, had a mediating effect on both types of mathematics skills. These findings help define and chart the trajectory of the specific cognitive skills directly influencing math deficit phenotypes in children born very preterm. This knowledge provides guidance for targeted evaluation and treatment implementation.

Functional magnetic resonance imaging (fMRI) using the blood oxygenation level dependent (BOLD) signal is a standard tool in human neuroscience studies. However, the BOLD signal is physiologically complex, depending on the baseline state of the brain and the balance of changes in blood flow and oxygen metabolism in response to a change in neural activity. Interpretation of the magnitude of the BOLD response is thus problematic; specifically, group differences of the BOLD response to a standard task or stimulus, or a change after administration of a drug, could be due to a change in the neural response, neurovascular coupling, or the baseline state. While changes in oxygen metabolism can serve as a biomarker of neural activity change, reflecting the energy cost of activity, oxygen metabolism cannot be estimated from BOLD measurements alone. Here we used the effects of caffeine as a test case to show that a suite of additional noninvasive measurements, requiring no manipulation of inhaled gases, makes it possible to untangle the underlying effects of caffeine on blood flow and oxygen metabolism. After caffeine administration, the BOLD response to a standard motor task was reduced, but oxygen metabolism was not reduced; rather, caffeine reduced the balance of blood flow relative to oxygen metabolism, both in the baseline state and in response to the task. The MRI methods used required only an additional 12 minutes of scanning, can be implemented on any MRI system, and painted a more complete picture of the physiological effects of caffeine. In addition to the assessment of drug effects in the human brain, these methods make it possible to resolve ambiguities of the BOLD signal in studies of development, aging, and disease. (Duplicated from first paragraph of manuscript)

Quantitative functional magnetic resonance imaging methods make it possible to measure cerebral oxygen metabolism (CMRO ₂ ) 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 CMRO ₂ 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 R ₂ *; VSEAN to estimate baseline O ₂ extraction fraction (OEF) from a measurement of venous blood R ₂ , which in combination with the baseline CBF measurement yields an estimate of baseline CMRO ₂ ; and FLAIR-GESSE to measure tissue R ₂ ′ to estimate the scaling parameter needed for calculating the change in CMRO ₂ 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 CMRO ₂ in response to a visual stimulus were in good agreement between the traditional hypercapnia calibration and calibration based on R ₂ ′ . These results support the potential of gas-free methods for quantitative physiological measurements. Synopsis: We tested noninvasive methods to measure absolute oxygen metabolism (CMRO ₂ ) in both baseline and activation states without the use of special gases: VSEAN to measure baseline O ₂ extraction fraction (OEF), and FLAIR-GESSE to measure R ₂ ′ to estimate the scaling parameter M . Primary findings were: CMRO ₂ changes to visual stimulation derived from R ₂ ′ were similar to estimates based on hypercapnia-derived M ; OEF values were in good agreement with previous PET findings; and, variation of baseline CBF/CMRO ₂ coupling across subjects does not follow activation coupling, suggesting different mechanisms may be involved. These results support the potential of gas-free methods for quantitative physiological measurements. Purpose: To demonstrate the potential for two non-invasive techniques, VSEAN and FLAIR-GESSE, for absolute measurements of CMRO ₂ during both baseline and activation states.