Effects of gene dosage and development on subcortical nuclei volumes in individuals with 22q11.2 copy number variations.

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in a total of 385 scans from 22qDel (n = 96, scans = 191, 53.1% female), 22qDup (n = 37, scans = 64, 45.9% female), and TD controls (n = 80, scans = 130, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the linear effects of 22q11.2 gene dosage and non-linear effects of age were characterized with generalized additive mixed models (GAMMs). Positive gene dosage effects (volume increasing with copy number) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

Effects of Gene Dosage and Development on Subcortical Nuclei Volumes in Individuals with 22q11.2 Copy Number Variations.

The 22q11.2 locus contains genes critical for brain development. Reciprocal Copy Number Variations (CNVs) at this locus impact risk for neurodevelopmental and psychiatric disorders. Both 22q11.2 deletions (22qDel) and duplications (22qDup) are associated with autism, but 22qDel uniquely elevates schizophrenia risk. Understanding brain phenotypes associated with these highly penetrant CNVs can provide insights into genetic pathways underlying neuropsychiatric disorders. Human neuroimaging and animal models indicate subcortical brain alterations in 22qDel, yet little is known about developmental differences across specific nuclei between reciprocal 22q11.2 CNV carriers and typically developing (TD) controls. We conducted a longitudinal MRI study in 22qDel (n=96, 53.1% female), 22qDup (n=37, 45.9% female), and TD controls (n=80, 51.2% female), across a wide age range (5.5-49.5 years). Volumes of the thalamus, hippocampus, amygdala, and anatomical subregions were estimated using FreeSurfer, and the effect of 22q11.2 gene dosage was examined using linear mixed models. Age-related changes were characterized with general additive mixed models (GAMMs). Positive gene dosage effects (22qDel < TD < 22qDup) were observed for total intracranial and whole hippocampus volumes, but not whole thalamus or amygdala volumes. Several amygdala subregions exhibited similar positive effects, with bi-directional effects found across thalamic nuclei. Distinct age-related trajectories were observed across the three groups. Notably, both 22qDel and 22qDup carriers exhibited flattened development of hippocampal CA2/3 subfields relative to TD controls. This study provides novel insights into the impact of 22q11.2 CNVs on subcortical brain structures and their developmental trajectories.

Adherence to 24-Hour Movement Recommendations and Health Indicators in Early Adolescence: Cross-Sectional and Longitudinal Associations in the Adolescent Brain Cognitive Development Study.

PURPOSE: Adherence to 24-hour movement guidelines of ≥60 minutes of physical activity, ≤2 hours of screen time, and 9-11 hours of sleep has been shown to benefit cognitive, physical, and psychosocial health in children and young adolescents aged 5-13 years. However, these findings have mostly been based on cross-sectional studies or relatively small samples and the associations between adherence to guidelines and brain structure remain to be evaluated. METHODS: Data from the Adolescent Brain Cognitive Development℠ (ABCD) study of 10,574 early adolescents aged 9-14 years from September 2016 to January 2021 were used to examine whether adherence to 24-hour movement guidelines benefits cognition (general cognitive ability, executive function, and learning/memory assessed by the National Institutes of Health Toolbox neurocognitive battery), body mass index, psychosocial health (internalizing, externalizing, and total problems from the parent-reported Child Behavior Checklist), and magnetic resonance imaging-derived brain morphometric measures at baseline (T1), ∼2 years later (T2), and longitudinally from T1 to T2 (T2-T1). Multivariable linear mixed models were used, with adjustments for sociodemographic confounders. Time elapsed and T1 outcome measures were also controlled for in longitudinal models. RESULTS: Better cognitive scores, fewer behavioral problems, lower adiposity levels, and greater gray matter volumes were observed in those who met both sleep and screen time recommendations compared to those who met none. Longitudinal follow-up further supports these findings; participants who met both recommendations at T1 and T2 evidenced better outcome measures than those who met none. DISCUSSION: These findings support consideration of integrated rather than isolated movement recommendations across the day in early adolescence for better cognitive, physical and psychosocial health. Although the associations between physical activity and health indicators were less consistent in this study, the significant findings from sleep and screen time demonstrate the importance of considering movement recommendations in an integrated rather than isolated manner for adolescent health. It is recommended that movement behaviors be simultaneously targeted for better developmental outcomes.

Decoding intentions of self and others from fMRI activity patterns.

Previous studies using multi-voxel pattern analysis have decoded the content of participants' delayed intentions from patterns of fMRI data. Here we investigate whether this technique can be used to decode not only participants' own intentions, but also their representation of the intentions held by other people. In other words: if Sam is thinking about Hoki, can we decode the content of Hoki's intention by scanning Sam's brain? We additionally distinguished two components of intentions: action-plans versus goals, and included novel control analyses that allowed us to distinguish intending an outcome from simply expecting it to occur or simulating its consequences. Regions of frontal, parietal, and occipital cortex contained patterns from which it was possible to decode intentions of both self and other. Furthermore, crossclasification between self and other was possible, suggesting overlap between the two. Control analyses suggested that these results reflected visuo-spatial processes by which intentions were generated in our paradigm, rather than anything special about intentions per se. There was no evidence for any representation of intentions as mental states distinct from visuospatial processes involved in generating their content and/or simulating their outcomes. These findings suggest that the brain activity patterns decoded in intention-decoding fMRI studies may reflect domain-general processes rather than being intention-specific.

Changes in cognitive flexibility and hypothesis search across human life history from childhood to adolescence to adulthood.

How was the evolution of our unique biological life history related to distinctive human developments in cognition and culture? We suggest that the extended human childhood and adolescence allows a balance between exploration and exploitation, between wider and narrower hypothesis search, and between innovation and imitation in cultural learning. In particular, different developmental periods may be associated with different learning strategies. This relation between biology and culture was probably coevolutionary and bidirectional: life-history changes allowed changes in learning, which in turn both allowed and rewarded extended life histories. In two studies, we test how easily people learn an unusual physical or social causal relation from a pattern of evidence. We track the development of this ability from early childhood through adolescence and adulthood. In the physical domain, preschoolers, counterintuitively, perform better than school-aged children, who in turn perform better than adolescents and adults. As they grow older learners are less flexible: they are less likely to adopt an initially unfamiliar hypothesis that is consistent with new evidence. Instead, learners prefer a familiar hypothesis that is less consistent with the evidence. In the social domain, both preschoolers and adolescents are actually the most flexible learners, adopting an unusual hypothesis more easily than either 6-y-olds or adults. There may be important developmental transitions in flexibility at the entry into middle childhood and in adolescence, which differ across domains.