Widespread Positive Direct and Indirect Effects of Regular Physical Activity on the Developing Functional Connectome in Early Adolescence.

Adolescence is a period of profound but incompletely understood changes in the brain's neural circuitry (the connectome), which is vulnerable to risk factors such as unhealthy weight, but may be protected by positive factors such as regular physical activity. In 5955 children (median age = 120 months; 50.86% females) from the Adolescent Brain Cognitive Development (ABCD) cohort, we investigated direct and indirect (through impact on body mass index [BMI]) effects of physical activity on resting-state networks, the backbone of the functional connectome that ubiquitously affects cognitive function. We estimated significant positive effects of regular physical activity on network connectivity, efficiency, robustness and stability (P ≤ 0.01), and on local topologies of attention, somatomotor, frontoparietal, limbic, and default-mode networks (P < 0.05), which support extensive processes, from memory and executive control to emotional processing. In contrast, we estimated widespread negative BMI effects in the same network properties and brain regions (P < 0.05). Additional mediation analyses suggested that physical activity could also modulate network topologies leading to better control of food intake, appetite and satiety, and ultimately lower BMI. Thus, regular physical activity may have extensive positive effects on the development of the functional connectome, and may be critical for improving the detrimental effects of unhealthy weight on cognitive health.

Functional testing, coronary artery calcifications, and outcomes in Hodgkin lymphoma survivors treated with chest radiation.

BACKGROUND: Consensus guidelines recommend periodic screening for coronary artery disease (CAD) in Hodgkin lymphoma (HL) survivors treated with radiation therapy (RT) to the chest. However, the prognostic utility of screening strategies in this population remains unclear. We evaluated the association between functional testing, coronary artery calcifications (CAC), and guideline-based risk assessment and major adverse cardiovascular events (MACE) in HL survivors treated with RT. METHODS: We retrospectively studied HL survivors treated with RT who underwent functional testing between 2003 and 2020 and chest computed tomography (CT) within 12 months of each other at our center. CAC was assessed semi-quantitatively from CT images. Cardiovascular risk was estimated using the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. Diagnostic test characteristics were calculated using major adverse cardiac events (MACE) during follow-up as the gold standard. RESULTS: The study included 159 patients (median age at functional testing 48 years, median age at HL diagnosis 27 years, 62.9% female). Abnormal functional testing had the highest specificity (94.2% (95% CI 88.4%-97.6%)) and positive likelihood ratio (4.55 (95% CI 1.86-11.13)) while CAC had the highest sensitivity (63.2% (95% CI 46.0%-78.2%)) and lowest negative likelihood ratio (0.52 (95% CI 0.34-0.80)). Specificity for ACC/AHA risk assessment was also high (88.5% (95% CI 81.1%-93.7%)). Over 3.3 years of follow-up, abnormal functional testing (adjusted subdistribution hazard ratio (SHR) 5.10, 95% CI 2.41 - 10.78, p < 0.001) and CAC (adjusted SHR 3.58, 95% CI 1.35 - 9.47, p = 0.010) were both significantly associated with MACE. CONCLUSIONS: In HL survivors treated with RT, both abnormal functional testing and ACC/AHA risk assessment had high specificity for subsequent MACE, but CAC had higher sensitivity. Further research is needed to inform CAD screening and primary prevention strategies in this population.

Parental religiosity is associated with changes in youth functional network organization and cognitive performance in early adolescence.

Parental religious beliefs and practices (religiosity) may have profound effects on youth, especially in neurodevelopmentally complex periods such as adolescence. In n = 5566 children (median age = 120.0 months; 52.1% females; 71.2% with religious affiliation) from the Adolescent Brain Cognitive Development study, relationships between parental religiosity and non-religious beliefs on family values (data on youth beliefs were not available), topological properties of youth resting-state brain networks, and executive function, inhibitory control, and cognitive flexibility were investigated. Lower caregiver education and family income were associated with stronger parental beliefs (p < 0.01). Strength of both belief types was correlated with lower efficiency, community structure, and robustness of frontoparietal control, temporoparietal, and dorsal attention networks (p < 0.05), and lower Matrix Reasoning scores. Stronger religious beliefs were negatively associated (directly and indirectly) with multiscale properties of salience and default-mode networks, and lower Flanker and Dimensional Card Sort scores, but positively associated with properties of the precuneus. Overall, these effects were small (Cohen's d ~ 0.2 to ~ 0.4). Overlapping neuromodulatory and cognitive effects of parental beliefs suggest that early adolescents may perceive religious beliefs partly as context-independent rules on expected behavior. However, religious beliefs may also differentially affect cognitive flexibility, attention, and inhibitory control and their neural substrates.

Big Data-Driven Brain Parcellation from fMRI: Impact of Cohort Heterogeneity on Functional Connectivity Maps.

Ongoing large-scale human brain studies are generating complex neuroimaging data from thousands of individuals that can be leveraged to derive data-driven, anatomically accurate brain parcellations. However, despite their promise and many strengths, these data are highly heterogeneous, a characteristic that may affect the anatomical accuracy and generalization of the template but has received relatively little attention. Using multiple similarity measures and thresholding approaches, this study investigated the topological intra- and inter-individual variability of restingstate (rs) functional edge maps (often used for brain parcellation), estimated from rs-fMRI connectivity in n = 5878 children from the Adolescent Brain Cognitive Development (ABCD) study. Findings from this initial investigation indicate that choosing a subject- vs cohort-based threshold for estimating edge maps from connectivity matrices does not significantly impact the map topology. In contrast, the choice of similarity measure and non-linear relationship between similarity and edge map sparsity may have a significant impact on map classification and the generation of parcellation atlases. Multi-level classification revealed multiple clusters with a potentially complex mapping onto biological variables beyond simple demographics.Clinical Relevance- Case-control neuroimaging studies should use domain-specific (e.g., demographics-specific) atlases for parcellating the brain, to improve accuracy and rigor of cohort comparisons. To be generalizable, such atlases need to be derived from large datasets, which are inherently heterogeneous. In a cohort of 5878 children (age ~9-10 years), this study systematically assessed the impact of heterogeneity and similarity of edge maps, which are derived from rs-fMRI connectivity and typically used to generate parcellation atlases.