The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents.

BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.

Connections Between the Middle Frontal Gyrus and the Dorsoventral Attention Network Are Associated With the Development of Attentional Symptoms.

BACKGROUND: The right middle frontal gyrus (MFG) has been proposed as a convergence site for the dorsal attention network (DAN) and ventral attention network (VAN), regulating both networks and enabling flexible modulation of attention. However, it is unclear whether the connections between the right MFG and these networks can predict changes in attention-deficit/hyperactivity disorder (ADHD) symptoms. METHODS: This study used data from the Children School Functions and Brain Development project (N = 713, 56.2% boys). Resting-state functional magnetic resonance imaging was employed to analyze the connections of the right MFG with the DAN/VAN; connectome-based predictive modeling was applied for longitudinal prediction, and ADHD polygenic risk scores were used for genetic analysis. RESULTS: ADHD symptoms were associated with the connections between the right MFG and DAN subregion, including the frontal eye field, as well as the VAN subregions, namely the inferior parietal lobule and inferior frontal gyrus. Furthermore, these connections of the right MFG with the frontal eye field, the inferior parietal lobule, and the inferior frontal gyrus could significantly predict changes in ADHD symptoms over 1 year and mediate the prediction of ADHD symptom changes by polygenic risk scores for ADHD. Finally, the validation samples confirmed that the functional connectivity between the right MFG and the frontal eye field/inferior parietal lobule in patients with ADHD was significantly weaker than that in typically developing control participants, and this difference disappeared after medication. CONCLUSIONS: The connection of the right MFG with the DAN and VAN can serve as a predictive indicator for changes in ADHD symptoms over the following year, while also mediating the prediction of ADHD symptom changes by a polygenic risk score for ADHD. These findings hold promise as potential biomarkers for early identification of children who are at risk of developing ADHD.

Human genetics of face recognition: discovery of MCTP2 mutations in humans with face blindness (congenital prosopagnosia).

Face recognition is important for both visual and social cognition. While prosopagnosia or face blindness has been known for seven decades and face-specific neurons for half a century, the molecular genetic mechanism is not clear. Here we report results after 17 years of research with classic genetics and modern genomics. From a large family with 18 congenital prosopagnosia (CP) members with obvious difficulties in face recognition in daily life, we uncovered a fully cosegregating private mutation in the MCTP2 gene which encodes a calcium binding transmembrane protein expressed in the brain. After screening through cohorts of 6589, we found more CPs and their families, allowing detection of more CP associated mutations in MCTP2. Face recognition differences were detected between 14 carriers with the frameshift mutation S80fs in MCTP2 and 19 noncarrying volunteers. Six families including one with 10 members showed the S80fs-CP correlation. Functional magnetic resonance imaging found association of impaired recognition of individual faces by MCTP2 mutant CPs with reduced repetition suppression to repeated facial identities in the right fusiform face area. Our results have revealed genetic predisposition of MCTP2 mutations in CP, 76 years after the initial report of prosopagnosia and 47 years after the report of the first CP. This is the first time a gene required for a higher form of visual social cognition was found in humans.

Association of emotional and behavioral problems with the development of the substantia nigra, subthalamic nucleus, and red nucleus volumes and asymmetries from childhood to adolescence: A longitudinal cohort study.

The substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) have been widely studied as important biomarkers of degenerative diseases. However, how they develop in childhood and adolescence and are affected by emotional behavior has not been studied thus far. This population-based longitudinal cohort study used data from a representative sample followed two to five times. Emotional and behavioral problems were assessed with the Strengths and Difficulties Questionnaire (SDQ). Linear mixed models were used to map developmental trajectories and behavioral regulation. Using an innovative automated image segmentation technique, we quantified the volumes and asymmetries of the SN, STN and RN with 1226 MRI scans of a large longitudinal sample of 667 subjects aged 6-15 years and mapped their developmental trajectories. The results showed that the absolute and relative volumes of the bilateral SN and right STN showed linear increases, while the absolute volume of the right RN and relative volume of the bilateral RN decreased linearly, these effects were not affected by gender. Hyperactivity/inattention weakened the increase in SN volume and reduced the absolute volume of the STN, conduct problems impeded the RN volume from decreasing, and emotional symptoms changed the direction of SN lateralization. This longitudinal cohort study mapped the developmental trajectories of SN, STN, and RN volumes and asymmetries from childhood to adolescence, and found the association of emotional symptoms, conduct problems, and hyperactivity/inattention with these trajectories, providing guidance for preventing and intervening in cognitive and emotional behavioral problems.

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.

Longitudinal development of the human white matter structural connectome and its association with brain transcriptomic and cellular architecture.

From childhood to adolescence, the spatiotemporal development pattern of the human brain white matter connectome and its underlying transcriptomic and cellular mechanisms remain largely unknown. With a longitudinal diffusion MRI cohort of 604 participants, we map the developmental trajectory of the white matter connectome from global to regional levels and identify that most brain network properties followed a linear developmental trajectory. Importantly, connectome-transcriptomic analysis reveals that the spatial development pattern of white matter connectome is potentially regulated by the transcriptomic architecture, with positively correlated genes involve in ion transport- and development-related pathways expressed in excitatory and inhibitory neurons, and negatively correlated genes enriches in synapse- and development-related pathways expressed in astrocytes, inhibitory neurons and microglia. Additionally, the macroscale developmental pattern is also associated with myelin content and thicknesses of specific laminas. These findings offer insights into the underlying genetics and neural mechanisms of macroscale white matter connectome development from childhood to adolescence.

Reduced volume of the left cerebellar lobule VIIb and its increased connectivity within the cerebellum predict more general psychopathology one year later via worse cognitive flexibility in children.

Predicting the risk for general psychopathology (the p factor) requires the examination of multiple factors ranging from brain to cognitive skills. While an increasing number of findings have reported the roles of the cerebral cortex and executive functions, it is much less clear whether and how the cerebellum and cognitive flexibility (a core component of executive function) may be associated with the risk for general psychopathology. Based on the data from more than 400 children aged 6-12 in the Children School Functions and Brain Development (CBD) Project, this study examined whether the left cerebellar lobule VIIb and its connectivity within the cerebellum may prospectively predict the risk for general psychopathology one year later and whether cognitive flexibility may mediate such predictions in school-age children. The reduced gray matter volume in the left cerebellar lobule VIIb and the increased connectivity of this region to the left cerebellar lobule VI prospectively predicted the risk for general psychopathology and was partially mediated by worse cognitive flexibility. Deficits in cognitive flexibility may play an important role in linking cerebellar structure and function to the risk for general psychopathology.

Functional connectome through the human life span.

The functional connectome of the human brain represents the fundamental network architecture of functional interdependence in brain activity, but its normative growth trajectory across the life course remains unknown. Here, we aggregate the largest, quality-controlled multimodal neuroimaging dataset from 119 global sites, including 33,809 task-free fMRI and structural MRI scans from 32,328 individuals ranging in age from 32 postmenstrual weeks to 80 years. Lifespan growth charts of the connectome are quantified at the whole cortex, system, and regional levels using generalized additive models for location, scale, and shape. We report critical inflection points in the non-linear growth trajectories of the whole-brain functional connectome, particularly peaking in the fourth decade of life. Having established the first fine-grained, lifespan-spanning suite of system-level brain atlases, we generate person-specific parcellation maps and further show distinct maturation timelines for functional segregation within different subsystems. We identify a spatiotemporal gradient axis that governs the life-course growth of regional connectivity, transitioning from primary sensory cortices to higher-order association regions. Using the connectome-based normative model, we demonstrate substantial individual heterogeneities at the network level in patients with autism spectrum disorder and patients with major depressive disorder. Our findings shed light on the life-course evolution of the functional connectome and serve as a normative reference for quantifying individual variation in patients with neurological and psychiatric disorders.

Theta Signal Transfer from Parietal to Prefrontal Cortex Ignites Conscious Awareness of Implicit Knowledge during Sequence Learning.

Unconscious acquisition of sequence structure from experienced events can lead to explicit awareness of the pattern through extended practice. Although the implicit-to-explicit transition has been extensively studied in humans using the serial reaction time (SRT) task, the subtle neural activity supporting this transition remains unclear. Here, we investigated whether frequency-specific neural signal transfer contributes to this transition. A total of 208 participants (107 females) learned a sequence pattern through a multisession SRT task, allowing us to observe the transitions. Session-by-session measures of participants' awareness for sequence knowledge were conducted during the SRT task to identify the session when the transition occurred. By analyzing time course RT data using switchpoint modeling, we identified an increase in learning benefit specifically at the transition session. Electroencephalogram (EEG)/magnetoencephalogram (MEG) recordings revealed increased theta power in parietal (precuneus) regions one session before the transition (pretransition) and a prefrontal (superior frontal gyrus; SFG) one at the transition session. Phase transfer entropy (PTE) analysis confirmed that directional theta transfer from precuneus → SFG occurred at the pretransition session and its strength positively predicted learning improvement at the subsequent transition session. Furthermore, repetitive transcranial magnetic stimulation (TMS) modulated precuneus theta power and altered transfer strength from precuneus to SFG, resulting in changes in both transition rate and learning benefit at that specific point of transition. Our brain-stimulation evidence supports a role for parietal → prefrontal theta signal transfer in igniting conscious awareness of implicitly acquired knowledge.SIGNIFICANCE STATEMENT There exists a pervasive phenomenon wherein individuals unconsciously acquire sequence patterns from their environment, gradually becoming aware of the underlying regularities through repeated practice. While previous studies have established the robustness of this implicit-to-explicit transition in humans, the refined neural mechanisms facilitating conscious access to implicit knowledge remain poorly understood. Here, we demonstrate that prefrontal activity, known to be crucial for conscious awareness, is triggered by neural signal transfer originating from the posterior brain region, specifically the precuneus. By employing brain stimulation techniques, we establish a causal link between neural signal transfer and the occurrence of awareness. Our findings unveil a mechanism by which implicit knowledge becomes consciously accessible in human cognition.

Emotional and behavioral problems change the development of cerebellar gray matter volume, thickness, and surface area from childhood to adolescence: A longitudinal cohort study.

AIMS: Increasing evidence indicates that major neurodevelopmental disorders have potential links to abnormal cerebellar development. However, the developmental trajectories of cerebellar subregions from childhood to adolescence are lacking, and it is not clear how emotional and behavioral problems affect them. We aim to map the developmental trajectories of gray matter volume (GMV), cortical thickness (CT), and surface area (SA) in cerebellar subregions from childhood to adolescence and examine how emotional and behavioral problems change the cerebellar development trajectory in a longitudinal cohort study. METHOD: This population-based longitudinal cohort study used data on a representative sample of 695 children. Emotional and behavioral problems were assessed at baseline and at three annual follow-ups with the Strengths and Difficulties Questionnaire (SDQ). RESULTS: Using an innovative automated image segmentation technique, we quantified the GMV, CT, and SA of the whole cerebellum and 24 subdivisions (lobules I-VI, VIIB, VIIIA&B, and IX-X plus crus I-II) with 1319 MRI scans from a large longitudinal sample of 695 subjects aged 6-15 years and mapped their developmental trajectories. We also examined sex differences and found that boys showed more linear growth, while girls showed more nonlinear growth. Boys and girls showed nonlinear growth in the cerebellar subregions; however, girls reached the peak earlier than boys. Further analysis found that emotional and behavioral problems modulated cerebellar development. Specifically, emotional symptoms impede the expansion of the SA of the cerebellar cortex, and no gender differences; conduct problems lead to inadequate cerebellar GMV development only in girls, but not boys; hyperactivity/inattention delays the development of cerebellar GMV and SA, with left cerebellar GMV, right VIIIA GMV and SA in boys and left V GMV and SA in girls; peer problems disrupt CT growth and SA expansion, resulting in delayed GMV development, with bilateral IV, right X CT in boys and right Crus I GMV, left V SA in girls; and prosocial behavior problems impede the expansion of the SA and lead to excessive CT growth, with bilateral IV, V, right VI CT, left cerebellum SA in boys and right Crus I GMV in girls. CONCLUSIONS: This study maps the developmental trajectories of GMV, CT, and SA in cerebellar subregions from childhood to adolescence. In addition, we provide the first evidence for how emotional and behavioral problems affect the dynamic development of GMV, CT, and SA in the cerebellum, which provides an important basis and guidance for the prevention and intervention of cognitive and emotional behavioral problems in the future.

High-altitude exposure duration dependent global and regional gray matter volume decrease in healthy immigrants: a cross-sectional study.

BACKGROUND: The correlation between brain injury and high-altitude (HA) exposure duration (Dur_HA) as well as peripheral oxygen saturation (SpO2) remains unclear. PURPOSE: To evaluate the global and regional brain volume differences between HA immigrants and sea-level residents, and the relationship between brain volume with Dur_HA and SpO2. MATERIAL AND METHODS: Structural magnetic resonance imaging (MRI) scans were acquired in 33 healthy male HA immigrants (HA group) and 33 matched sea-level male residents (SL group). Differences in global gray matter volume (GMV), white matter volume (WMV), brain parenchyma volume (BV), total intracranial volume (TIV), and the volume-fraction (the ratio of GMV/TIV, WMV/TIV, BV/TIV) were assessed. Regional gray matter differences were investigated using voxel-based morphology analysis. The volume of clusters with GM loss were calculated as the volume of volume of interest (V_VOI). Student's t-test and partial correlation were adopted for statistic calculation. RESULTS: Compared to the SL group, the HA immigrants had larger WMV (P = 0.015), smaller ratio of GMV/WMV (P = 0.022), and regional gray matter loss in bilateral basal ganglion, limbic system, midbrain, and vermis (cluster size >100 voxels, family-wise error corrected at P = 0.01). The global GMV, BV, and V_VOI confined to vermis had negative correlations with the Dur_HA (r = -0.369, P = 0.049; r = -0.380, P = 0.042; and r = -0.471, P = 0.010. Neither global nor regional brain volume correlated with SpO2. CONCLUSION: Global and regional brain are affected by long-term HA exposure, and global and regional gray matter have a time-dependent volume loss.

Learning to read may help promote attention by increasing the volume of the left middle frontal gyrus and enhancing its connectivity to the ventral attention network.

Attention and reading are essential skills for successful schooling and in adult life. While previous studies have documented that attention development supports reading acquisition, whether and how learning to read may improve attention among school-age children and the brain structural and functional development that may be involved remain unknown. In this prospective longitudinal study, we examined bidirectional and longitudinal predictions between attention and reading development and the neural mediators of attention and reading development among school-age children using cross-lagged panel modeling. The results showed that better baseline reading performance significantly predicted better attention performance one year later after controlling for baseline attention performance. In contrast, after controlling for baseline reading performance, attention did not significantly predict reading performance one year later, while more attention problems also significantly predicted worse reading performance. Both the increasing gray matter volume of the left middle frontal gyrus and the increasing connectivity between the left middle frontal gyrus and the ventral attention network mediated the above significant longitudinal predictions. This study, directly revealed that reading skills may predict the development of important cognitive functions, such as attention, in school-age children. Therefore, learning to read is not only a challenge for school-age children but is also an important way to optimize attention and brain development.

Increasing diversity in connectomics with the Chinese Human Connectome Project.

Cultural differences and biological diversity play important roles in shaping human brain structure and function. To date, most large-scale multimodal neuroimaging datasets have been obtained primarily from people living in Western countries, omitting the crucial contrast with populations living in other regions. The Chinese Human Connectome Project (CHCP) aims to address these resource and knowledge gaps by acquiring imaging, genetic and behavioral data from a large sample of participants living in an Eastern culture. The CHCP collected multimodal neuroimaging data from healthy Chinese adults using a protocol comparable to that of the Human Connectome Project. Comparisons between the CHCP and Human Connectome Project revealed both commonalities and distinctions in brain structure, function and connectivity. The corresponding large-scale brain parcellations were highly reproducible across the two datasets, with the language processing task showing the largest differences. The CHCP dataset is publicly available in an effort to facilitate transcultural and cross-ethnic brain-mind studies.

Development of functional connectome gradients during childhood and adolescence.

Connectome mapping studies have documented a principal primary-to-transmodal gradient in the adult brain network, capturing a functional spectrum that ranges from perception and action to abstract cognition. However, how this gradient pattern develops and whether its development is linked to cognitive growth, topological reorganization, and gene expression profiles remain largely unknown. Using longitudinal resting-state functional magnetic resonance imaging data from 305 children (aged 6-14 years), we describe substantial changes in the primary-to-transmodal gradient between childhood and adolescence, including emergence as the principal gradient, expansion of global topography, and focal tuning in primary and default-mode regions. These gradient changes are mediated by developmental changes in network integration and segregation, and are associated with abstract processing functions such as working memory and expression levels of calcium ion regulated exocytosis and synaptic transmission-related genes. Our findings have implications for understanding connectome maturation principles in normal development and developmental disorders.

Learning to read Chinese promotes two cortico-subcortical pathways: The development of thalamo-occipital and fronto-striatal circuits.

Learning to read may result in network reorganization in the developing brain. The thalamus and striatum are two important subcortical structures involved in learning to read. It remains unclear whether the thalamus and striatum may form two independent cortico-subcortical reading pathways during reading acquisition. In this prospective longitudinal study, we aimed to identify whether there may be two independent cortico-subcortical reading pathways involving the thalamus and striatum and to examine the longitudinal predictions between these two cortico-subcortical pathways and reading development in school-age children using cross-lagged panel modeling. A total of 334 children aged 6-12 years completed two reading assessments and resting functional imaging scans at approximately 12-month intervals. The results showed that there were two independent cortico-subcortical pathways, the thalamo-occipital and fronto-striatal circuits. The former may be part of a visual pathway and was predicted longitudinally by reading ability, and the prediction was stronger in children in lower grades and weaker in children in higher grades. The latter may be part of a cognitive pathway related to attention, memory, and reasoning, which was bidirectionally predicted with reading ability, and the predictive effect gradually increasing with reading development. These results extend previous findings on the relationship between functional connectivity and reading competence in children, highlighting the dynamic relationships between the thalamo-occipital and fronto-striatal circuits and reading acquisition.

Functional connectivity alteration of the deprived auditory regions with cognitive networks in deaf and inattentive adolescents.

Adolescents with early profound deafness may present with distractibility and inattentiveness. The brain mechanisms underlying these attention impairments remain unclear. We performed resting-state functional magnetic resonance imaging to investigate the functional connectivity of the superior temporal and transverse temporal gyri in 25 inattentive adolescents with bilateral prelingual profound deafness, and compared the results with those of 27 age-matched normal controls. Pearson and Spearman's rho correlation analyses were used to investigate the correlations of altered functional connectivity with the clinical parameters, including the duration of hearing loss sign language, and hearing aid usage. Compared with normal controls, prelingual profound deafness demonstrated mainly decreased resting-state functional connectivity between the deprived auditory regions and several other brain functional networks, including the attention control, language comprehension, default-mode, and sensorimotor networks. Moreover, we also found enhanced resting-state functional connectivity between the deprived auditory cortex and salience network. These results indicate a negative impact of early hearing loss on the attentional and other high cognitive networks, and the use of sign language and hearing aids normalized the participants' connectivity between the primary auditory cortex and attention networks, which is crucial for the early intervention and clinical care of deaf adolescents.

Dissociating value-based neurocomputation from subsequent selection-related activations in human decision-making.

Human decision-making requires the brain to fulfill neural computation of benefit and risk and therewith a selection between options. It remains unclear how value-based neural computation and subsequent brain activity evolve to achieve a final decision and which process is modulated by irrational factors. We adopted a sequential risk-taking task that asked participants to successively decide whether to open a box with potential reward/punishment in an eight-box trial, or not to open. With time-resolved multivariate pattern analyses, we decoded electroencephalography and magnetoencephalography responses to two successive low- and high-risk boxes before open-box action. Referencing the specificity of decoding-accuracy peak to a first-stage processing completion, we set it as the demarcation and dissociated the neural time course of decision-making into valuation and selection stages. The behavioral hierarchical drift diffusion modeling confirmed different information processing in two stages, that is, the valuation stage was related to the drift rate of evidence accumulation, while the selection stage was related to the nondecision time spent in response-producing. We further observed that medial orbitofrontal cortex participated in the valuation stage, while superior frontal gyrus engaged in the selection stage of irrational open-box decisions. Afterward, we revealed that irrational factors influenced decision-making through the selection stage rather than the valuation stage.

The SACT Template: A Human Brain Diffusion Tensor Template for School-age Children.

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).

Progressive Stabilization of Brain Network Dynamics during Childhood and Adolescence.

Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.