Longitudinal associations between language network characteristics in the infant brain and school-age reading abilities are mediated by early-developing phonological skills.

Reading acquisition is a prolonged learning process relying on language development starting in utero. Behavioral longitudinal studies reveal prospective associations between infant language abilities and preschool/kindergarten phonological development that relates to subsequent reading performance. While recent pediatric neuroimaging work has begun to characterize the neural network underlying language development in infants, how this neural network scaffolds long-term language and reading acquisition remains unknown. We addressed this question in a 7-year longitudinal study from infancy to school-age. Seventy-six infants completed resting-state fMRI scanning, and underwent standardized language assessments in kindergarten. Of this larger cohort, forty-one were further assessed on their emergent word reading abilities after receiving formal reading instructions. Hierarchical clustering analyses identified a modular infant language network in which functional connectivity (FC) of the inferior frontal module prospectively correlated with kindergarten-age phonological skills and emergent word reading abilities. These correlations were obtained when controlling for infant age at scan, nonverbal IQ and parental education. Furthermore, kindergarten-age phonological skills mediated the relationship between infant FC and school-age reading abilities, implying a critical mid-way milestone for long-term reading development from infancy. Overall, our findings illuminate the neurobiological mechanisms by which infant language capacities could scaffold long-term reading acquisition.

Longitudinal associations between language network characteristics in the infant brain and school-age reading abilities are mediated by early-developing phonological skills.

Reading acquisition is a prolonged learning process relying on language development starting in utero. Behavioral longitudinal studies reveal prospective associations between infant language abilities and preschool/kindergarten phonological development that relates to subsequent reading performance. While recent pediatric neuroimaging work has begun to characterize the neural network underlying language development in infants, how this neural network scaffolds long-term language and reading acquisition remains unknown. We addressed this question in a 7-year longitudinal study from infancy to school-age. Seventy-six infants completed resting-state fMRI scanning, and underwent standardized language assessments in kindergarten. Of this larger cohort, forty-one were further assessed on their emergent word reading abilities after receiving formal reading instructions. Hierarchical clustering analyses identified a modular infant language network in which functional connectivity (FC) of the inferior frontal module prospectively correlated with kindergarten-age phonological skills and emergent word reading abilities. These correlations were obtained when controlling for infant age at scan, nonverbal IQ and parental education. Furthermore, kindergarten-age phonological skills mediated the relationship between infant FC and school-age reading abilities, implying a critical mid-way milestone for long-term reading development from infancy. Overall, our findings illuminate the neurobiological mechanisms by which infant language capacities could scaffold long-term reading acquisition.

Development of segregation and integration of functional connectomes during the first 1,000 days.

The first 1,000 days of human life lay the foundation for brain development and later cognitive growth. However, the developmental rules of the functional connectome during this critical period remain unclear. Using high-resolution, longitudinal, task-free functional magnetic resonance imaging data from 930 scans of 665 infants aged 28 postmenstrual weeks to 3 years, we report the early maturational process of connectome segregation and integration. We show the dominant development of local connections alongside a few global connections, the shift of brain hubs from primary regions to high-order association cortices, the developmental divergence of network segregation and integration along the anterior-posterior axis, the prediction of neurocognitive outcomes, and their associations with gene expression signatures of microstructural development and neuronal metabolic pathways. These findings advance our understanding of the principles of connectome remodeling during early life and its neurobiological underpinnings and have implications for studying typical and atypical development.

Electroconvulsive Therapy Regulates Brain Connectome Dynamics in Patients With Major Depressive Disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for patients with major depressive disorder (MDD), but its underlying neural mechanisms remain largely unknown. The aim of this study was to identify changes in brain connectome dynamics after ECT in MDD and to explore their associations with treatment outcome. METHODS: We collected longitudinal resting-state functional magnetic resonance imaging data from 80 patients with MDD (50 with suicidal ideation [MDD-SI] and 30 without [MDD-NSI]) before and after ECT and 37 age- and sex-matched healthy control participants. A multilayer network model was used to assess modular switching over time in functional connectomes. Support vector regression was used to assess whether pre-ECT network dynamics could predict treatment response in terms of symptom severity. RESULTS: At baseline, patients with MDD had lower global modularity and higher modular variability in functional connectomes than control participants. Network modularity increased and network variability decreased after ECT in patients with MDD, predominantly in the default mode and somatomotor networks. Moreover, ECT was associated with decreased modular variability in the left dorsal anterior cingulate cortex of MDD-SI but not MDD-NSI patients, and pre-ECT modular variability significantly predicted symptom improvement in the MDD-SI group but not in the MDD-NSI group. CONCLUSIONS: We highlight ECT-induced changes in MDD brain network dynamics and their predictive value for treatment outcome, particularly in patients with SI. This study advances our understanding of the neural mechanisms of ECT from a dynamic brain network perspective and suggests potential prognostic biomarkers for predicting ECT efficacy in patients with MDD.

Development of sensorimotor-visual connectome gradient at birth predicts neurocognitive outcomes at 2 years of age.

Functional connectome gradients represent fundamental organizing principles of the brain. Here, we report the development of the connectome gradients in preterm and term babies aged 31-42 postmenstrual weeks using task-free functional MRI and its association with postnatal cognitive growth. We show that the principal sensorimotor-to-visual gradient is present during the late preterm period and continuously evolves toward a term-like pattern. The global measurements of this gradient, characterized by explanation ratio, gradient range, and gradient variation, increased with age (p < 0.05, corrected). Focal gradient development mainly occurs in the sensorimotor, lateral, and medial parietal regions, and visual regions (p < 0.05, corrected). The connectome gradient at birth predicts cognitive and language outcomes at 2-year follow-up (p < 0.005). These results are replicated using an independent dataset from the Developing Human Connectome Project. Our findings highlight early emergent rules of the brain connectome gradient and their implications for later cognitive growth.

Structural connectome architecture shapes the maturation of cortical morphology from childhood to adolescence.

Cortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence.