Cerebral Cortex

Working memory (WM) deficits are central to schizophrenia (SCZ), yet their mechanistic basis remains unclear. We combined computational modelling with genetic, transcriptomic, behavioural, and fMRI data to construct a mechanistic account of WM impairment in SCZ. Post-mortem RNA expression from prefrontal and anterior cingulate cortex (ACC) was integrated with single-cell, network, and synaptic plasticity models to show how SCZ-related changes in ion channel-encoding and plasticity-regulating genes alter sustained delay-period activity and long-term potentiation, suggesting an impairment of WM. The model predictions were supported by behavioural WM test (letter-number sequencing) results and polygenic risk scores for SCZ based on ion channel and plasticity gene sets. Mendelian randomization, together with nominally significant single-gene risk analyses, implicated specific ion channel genes, particularly CACNA1I, as putatively causal for both SCZ liability and WM deficits. fMRI N-back data supported ACC-specific delay-period impairments. These multimodal findings highlight candidate, druggable mechanisms for cognition-focused interventions in SCZ.

The basal ganglia and thalamus are key nodes in subcortico-cortical loops involved in sensory, motor, and cognitive function. In adults, posterior regions of the subcortex link to cortical sensorimotor networks and anterior regions link to association networks. Alterations in the size, strength, and selectivity of these subcortical regional network representations are implicated in several neuropsychiatric disorders, many of which originate early in development. However, the organization of these network representations at birth remains incompletely understood, limiting our ability to devise normative and atypical developmental models of subcortico-cortical interactions. Using resting-state fMRI, we characterized the size, strength, and selectivity of cortical network representations in the basal ganglia and thalamus in a set of neonates (n=261) and compared results to children (age range 9-11 years, n=69) and adults (n=120). We found that the broad anterior-posterior organization of the subcortex is present at birth, yet representations of somatomotor networks were larger at birth compared to children and adults (p<0.001). The strength and selectivity of subcortico-cortical functional connectivity (FC) exhibited interactions between age group and network (all p<0.001), such that subcortical representations of sensorimotor networks exhibited stronger FC and higher selectivity in neonates, while subcortical representations of association networks exhibited stronger FC and higher selectivity in older cohorts. In parallel, data-driven clustering revealed areas with integration of multiple networks in the neonatal subcortex. These results suggest that subcortico-cortical FC evolves over development largely in a sensorimotor-association manner and provide a baseline for normative and disordered subcortical development.

Developmental coordination disorder (DCD) is a common neurodevelopmental condition characterized by impaired motor coordination and learning, yet its neurobiological and genetic bases remain poorly understood. Here, we leverage the BXD recombinant inbred mouse panel to model the polygenic architecture of DCD and link behaviour, brain structure, and genotype. High-resolution ex vivo MRI across 14 strains revealed that DCD-like mice have modestly reduced total brain volume, with a distinct neuroanatomical profile characterized by enlarged cortical regions alongside reduced cerebellar, thalamic, and other subcortical volumes. These structural differences closely mirror findings reported in human DCD. Across strains, variation in brain structure strongly correlated with motor behaviours, with coordinated patterns linking increased cortical and decreased subcortical volumes to poorer motor coordination, while more focal associations were observed for motor learning. Multivariate analysis identified a dominant brain-behaviour axis capturing this cortical-subcortical trade-off. Quantitative trait locus (QTL) mapping revealed multiple loci influencing regional brain volumes, including a prominent locus on chromosome 12 regulating cerebellar structures, but did not identify single loci driving the main multivariate brain-behaviour relationships, consistent with a distributed genetic architecture. Together, these findings demonstrate that DCD-like motor impairments arise from coordinated alterations across distributed brain systems under polygenic control. This work establishes a translational framework linking genetic variation to brain organization and motor function, and suggests that DCD reflects the extreme of a continuous spectrum of neurobiological variation rather than a discrete condition.

While evidence suggests magnocellular deficits in the geniculostriate pathway in adults with dyslexia, neural deficits in the subcortical pathways during childhood remain unclear. Here, we used high-resolution fMRI to investigate subcortical abnormalities in Chinese children with developmental dyslexia. Fast achromatic motion stimuli and slowly drifting chromatic gratings were used to assess magnocellular (M) and parvocellular (P) functions, respectively. Relative to controls, children with dyslexia showed a selective reduction in responses to the M stimulus in the ventromedial pulvinar (vmPul) and the superficial layers of the superior colliculus (SCs), along with significantly reduced SCs-vmPul connectivity. Importantly, while vmPul responses to the M stimulus were positively associated with reading skills in healthy controls, this correlation was absent in children with dyslexia. Unlike previous findings in adults, the lateral geniculate nucleus (LGN) exhibited a non-selective reduction in responses to both stimuli, no volume reduction, and no correlation with reading ability. These findings demonstrate a selective deficit to achromatic motion processing in the colliculus-pulvinar pathway in children with dyslexia, which contributes to their reading difficulties. This early subcortical disruption differs from, and precedes, the neural deficits previously reported in the adult LGN, offering new insight into the developmental trajectory of dyslexia.

The noradrenergic locus coeruleus (LC) and the cholinergic nucleus basalis of Meynert (nBM) are key hubs of ascending neuromodulatory systems that shape large-scale brain dynamics. However, the behavioral relevance of the structural and functional connectivity between these nuclei remains poorly understood. Here, we investigated whether LC-nBM structural or functional connectivity is related to cognitive-motor dual-task performance in healthy younger and older adults. Fifty-four participants (36 older, 18 younger) underwent diffusion MRI, resting-state fMRI, and behavioral assessment using an MRI-compatible cognitive-motor dual-task paradigm. LC-nBM structural connectivity was estimated using tractography, whereas resting-state functional connectivity was quantified as Fisher z-transformed correlations between LC and nBM time series. LC-nBM structural connectivity was better explained by a quadratic rather than a linear or cubic age model, indicating non-linear age-related variation, whereas functional connectivity showed no significant age-related association. Higher LC-nBM structural connectivity was associated with greater cognitive dual-task cost, but not with motor dual-task cost or single- or dual-task reaction times. This association was not moderated by age group and was not statistically explained by attentional and executive performance as measured by the Test of Attentional Performance. These findings suggest that LC-nBM structural connectivity is selectively associated with cognitive-motor interference, potentially reflecting a neuromodulatory pathway that constrains the balance between task-specific stabilization and flexible cross-domain coordination during a cognitive-motor dual-tasking.

Declines in the cognitive inhibition that comes with aging impacts daily life and independence. It is still debated whether overactivation during cognitive inhibition tasks in older adults is due to compensation or neural noise. To address this question, we examined age-related changes in inter-subject similarity (ISS) of functional connectivity from task-based and resting-state fMRI. Using Bayesian hierarchical modeling, we identified 27 Stroop task-related regions of interest and found that ISS in these regions was significantly reduced in older adults during task performance. Furthermore, aging is associated with a loss of consistent functional connectivity patterns in frontal regions, accompanied by the emergence of a convergent compensatory mechanism within visual attention regions. Principal component analysis of individual activation deviations from the group-mean pattern showed that task performance in older adults cannot be explained by overall task-related brain activation, but rather by a specific spatial component involving suppression of the default mode network and increased activity in visual attention regions. These findings indicate that task-related brain overactivation in older adults is not due to uniform noise or uniform compensation, but rather a spatially specific pattern of functional reorganization.

The human brain processes sensory information through a hierarchical system, from primary to higher-level regions, integrating inputs across modalities to support perception and cognition. While early sensory loss triggers widespread neuroplastic changes, its impact on integration across the cortical hierarchy remains unclear. Here, we examined the cortical reorganization of individuals with early blindness and deafness using a sensory integration framework that quantifies how brain regions prioritize different sensory inputs across the hierarchy. We found that early sensory deprivation drives highly localized reorganization adjacent to the deprived primary cortical areas: extrastriate cortex in early blindness and the superior temporal cortex in early deafness. These findings were further corroborated by analysis of the functional gradients, which found reorganization within these sensory regions. Notably, the hierarchy was largely preserved across groups. However, the sensory integration framework uniquely detected reorganization in language-related regions in deaf individuals with knowledge of a visual communication system known as cued speech. The specific differences between early deaf and hearing individuals remained restricted to superior temporal cortex. Together, our findings demonstrate that early sensory deprivation drives targeted reorganization adjacent to the affected primary sensory cortex, while preserving the overall hierarchy of cortical integration.

Neonatal resting-state functional connectivity may provide early markers of later variation in Q-CHAT scores, measured dimensionally within a non-clinical population, but the large-scale systems carrying the most robust predictive signal remain unclear. Using resting-state fMRI data from 397 infants in the Developing Human Connectome Project (277 term-born, 120 preterm-born), we applied a stability-driven, ROI-constrained connectome-based predictive modeling framework to predict 18-month Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores. Significant prediction was observed in the whole cohort and in term-born infants, but did not reach statistical significance in the preterm-only group. Across the statistically significant models (whole cohort and term-born infants), the most prominent hubs were located in occipital and adjacent cortical regions, including the middle occipital gyrus, lingual gyrus, calcarine gyrus, and rolandic operculum. At the network level, the strongest predictive connections linked visual and visual-association systems with auditory networks, with additional contributions from medial motor, temporoparietal, and prefrontal systems. These findings suggest that later variation in Q-CHAT scores, is associated with neonatal large-scale functional organization, particularly in sensory and multisensory pathways. Keywords neonatal rs-fMRI; functional connectivity; Q-CHAT; connectome-based predictive modeling; preterm birth

Voluntary movement requires the central nervous system to transform and integrate visual and somatosensory information into coordinated motor outputs. Although mirrorlike neuronal activity during both action execution and observation has been extensively described in premotor, motor, and parietal cortices, it remains unknown whether the primary somatosensory cortex (S1) also participates in the action observation network. Here, we recorded single-unit activity from cytoarchitectonically defined areas 3a, 3b, 1, and 2 in macaque S1 while monkeys either executed or observed grasping movements. Approximately one-third of neurons across S1 modulated their firing during action observation, with the proportion of responsive neurons increasing from area 3 to areas 1 and 2, consistent with the hierarchical organization of somatosensory processing. Most action observation neurons showed congruent activity during action execution and observation, suggesting that these responses may reflect top-down motor-related or integrated visuomotor signals and are unlikely to be explained by visual input alone. The higher prevalence of action observation neurons in areas 1 and 2 suggests that action observation-related signals preferentially influence later stages of somatosensory processing, potentially via cortico-cortical interactions with motor and parietal regions.

Higher order association cortices like the prefrontal cortex (PFC) mature over a longer developmental window than sensory cortices, but whether genetically defined interneuron populations follow this region-wide delayed trajectory remains unclear. We compared the postnatal development of somatostatin-expressing interneurons in a higher-order cortical region (prelimbic cortex; PLC) and a sensory cortical region (somatosensory barrel cortex; S1BF) across adolescence using complementary structural, electrophysiological, and circuit analyses. We found that the maturation of SST neurons within these two cortical regions differs across time. S1BF SST neurons exhibited relatively linear maturation, whereas PLC SST neurons underwent continued dendritic remodeling, nonlinear intrinsic maturation, and age-dependent refinement of inhibitory output onto pyramidal neurons. Multivariate analyses likewise supported a more linear developmental trajectory in S1BF and a more prolonged, heterogeneous trajectory in PLC. This suggests divergent maturation of the PLC and S1BF and supports a broader, longer window of critical cellular plasticity in the PLC than in sensory cortices. Together, this reflects an extended developmental program at the level of a genetically defined inhibitory cell type. Because SST neurons are positioned to regulate pyramidal neuron output via control of dendritic integration, their delayed maturation is a crucial reflection of overall circuit function. These findings provide a cellular framework for the prolonged plasticity and developmental vulnerability known to be characteristic of adolescent prelimbic cortex. Significance statementWithin the brain, higher order association cortex remains plastic long after sensory cortex has matured, but the cellular basis for this prolonged developmental window has remained unknown. We find that developmental timing is encoded within genetically defined microcircuits. Prelimbic somatostatin circuits continue to remodel after sensory somatostatin circuits have largely stabilized through changes in cell shape, action potential firing dynamics, and inhibitory signaling. This work points to a specific prelimbic inhibitory cell type that matures more slowly, and less linearly, than its counterparts in other brain regions, and may help explain why prelimbic circuits remain vulnerable during adolescence, representing a biological substrate for extended adolescent remodeling in prelimbic cortex, and potentially the overall extensive flexibility, but also cognitive susceptibility, seen during adolescence.

Background Chemotherapy-related cognitive impairment is a well-documented concern among cancer survivors, yet the neural mechanisms underlying deficits in cognitive control remain poorly understood. This study examined group differences in brain activation during a flanker task using functional MRI (fMRI) between chemotherapy-exposed participants and healthy controls. Methods Participants (21 survivors (24.9 years old; 71.4 % female; 15 years from diagnosis) and 21 healthy controls (26.7 years old; 61.9 % female) completed a flanker task during fMRI, with congruent and incongruent conditions. Reaction time, accuracy, and Flanker scores were collected. Whole-brain group comparisons were performed for congruent, incongruent, and incongruent > congruent contrasts. Associations between the incongruent > congruent contrast and cognitive performance were examined. Results Compared to controls, the Chemo group had longer reaction times in both congruent and incongruent conditions (p < .001) and lower NIH Flanker scores (p = .01), with no differences in accuracy. They showed reduced activation in the bilateral inferior frontal gyri, supplementary motor area, and bilateral caudate, but greater activation in the right inferior temporal and cerebellar regions. The incongruent > congruent contrast correlated with increased activation in the orbitofrontal cortex, inferior temporal gyri, and fusiform gyrus with cognitive performance. Conclusions Chemotherapy-exposed participants showed cognitive control deficits and altered neural activation during a flanker task, indicating disrupted recruitment of frontoparietal and subcortical regions key for conflict processing. These findings improve understanding of neural causes of chemotherapy-related cognitive impairment and may help identify at-risk survivors and guide personalized rehabilitation.

The hippocampus-medial prefrontal cortex (mPFC) circuit is critical for spatial working memory and decision-making. Age-associated changes to these functions are attributed to alterations in this circuit, although the exact mechanisms remain unclear. These regions are connected via monosynaptic projections from the intermediate (iHC) and ventral (vHC) hippocampus to the infralimbic (IL) and prelimbic (PL) regions of the mPFC. We examined the functional connection between these regions in young (10-12 months) and aged (23-26 months) male F344 rats. High-density Neuropixels probes were used to record mPFC field potentials (fEPSPs) and single-unit responses to electrical stimulation of iHC and vHC. We observed that hippocampal stimulation evoked both short-latency (5-35 ms) monosynaptic and long-latency (35-100 ms) polysynaptic responses in PL and IL cortices. Monosynaptic responses, reflecting direct hippocampal-prefrontal synaptic transmission, had lower vHC-evoked IL fEPSP amplitude in aged rats, while other subregional HC-mPFC connections and evoked neural firing were preserved. The polysynaptic responses, reflecting local mPFC circuit recruitment, also had lower IL fEPSP amplitude in aged rats, while evoked neural firing in the polysynaptic window was diminished in both mPFC regions. Age-associated polysynaptic changes in mPFC neural responses differed by the HC stimulation site. In aged rats, iHC stimulation resulted in a lower proportion of recruited neurons, while vHC stimulation resulted in diminished evoked mPFC firing rates, compared to young rats. Our findings demonstrate that aging selectively impairs vHC-mPFC direct synaptic transmission and mPFC local responses, with infralimbic circuits showing particular vulnerability. These circuit-level deficits may contribute to age-related impairments in cognitive flexibility. Significance StatementAging impairs spatial working memory and decision making which require hippocampus-prefrontal communication. We examined the age-related changes in the functional connection of the intermediate (iHC) and ventral (vHC) hippocampus direct projection onto prelimbic (PL) and infralimbic (IL) regions of the mPFC. We found the vHC-evoked IL monosynaptic excitatory field potential amplitude was lower in aged rats, while other HC-mPFC connections were preserved. The evoked polysynaptic excitatory field potentials and single-unit responses were attenuated with age in both mPFC regions with responses differing between HC stimulation sites. These results identify subregional changes in how hippocampal inputs alter mPFC local recruitment in aging that may explain related impairments in cognitive flexibility.

The cerebellum has long been considered a late-maturing structure subordinate to neocortical development, therefore its potential role as an early driver of cortical organization remains largely unexplored. Using two large longitudinal neuroimaging cohorts of developing children together with lesion experiments in mice, we show that early cerebellar morphology may drive neocortical maturation in a regionally specific manner. These cross-species findings implicate the cerebellum as a possible regulator of neocortical organization.

The Component Process Model of Emotion conceptualizes any emotional episode (e.g., the discrete emotions of sadness, anger, fear, or interest) as being driven by the multiple appraisal components. However, both the specificity of the neural mechanisms underlying appraisal processes and the way these appraisal networks relate to the neural circuits underlying discrete emotions remain unclear. Here we investigated the neural correlates of appraisal processes and compared them with those of discrete emotions. Participants (n = 97) were scanned with functional magnetic resonance imaging (fMRI) while watching short movie clips with varying emotional contents. Intensity for 12 appraisals and 12 basic and epistemic emotions evoked by the movie clips were rated by independent participants (n = 444). The neural responses were modelled with convolved ratings of appraisals and discrete emotions. The results indicated that appraisals and discrete emotions are supported by a shared set of distributed brain regions that extend beyond typically reported emotion-related areas, encompassing perceptual, action-related, and higher-order cognitive systems. Activations were more consistent for and better explained by appraisals versus discrete emotions. Within this network, epistemic emotions elicited less consistent activations than basic emotions, particularly in limbic regions. Our results highlight the functional organization of appraisals and discrete emotions under dynamic and complex conditions and indicate that appraisal theories better explain neural responses than discrete emotion models.

Whether language and mathematics rely on shared or distinct neural representations remains an unresolved question in cognitive neuroscience. Here we combine latent features from a large language model (LLM) with vertex-wise encoding models to examine cross-domain generalization between language and mathematics. Thirty-two participants performed sentence comprehension and calculation tasks during fMRI, and encoding models were trained using features embedded in a common latent space. Cross-domain prediction identified cortical regions associated with partially shared representations, most prominently the left 55b, while control analyses suggested that these effects could not be fully explained by low-level visual processing or simple task-general factors. Task-specificity contrasts revealed stronger language-related prediction in the left anterior superior temporal and angular gyri and math-related prediction in the left precentral and intraparietal sulci. Model-weight analyses further showed that shared and domain-specific prediction patterns were reflected in distinct weight profiles across cortical regions. Connectivity analyses showed task-dependent functional coupling between cross-domain regions and language- or math-related networks. Together, these findings suggest that language and mathematics involve partially shared neural representations alongside domain-specific cortical organization, helping reconcile previous contrasting views on their neural basis.

Human social perception relies on multiple visual signals, including object-directed actions and emotional facial expressions. It remains unclear whether responses to these signals converge within action-observation regions and whether apparent convergence depends on the spatial scale of analysis. We scanned 39 healthy human adults during two block-design fMRI tasks, hand action observations contrasted with paper-tube controls, and emotional expression observations contrasted with neutral faces. Using independently defined meta-analytic action observation network (AON) ROIs in the inferior frontal gyrus (IFG), inferior parietal lobule (IPL), and posterior superior temporal sulcus (pSTS), we analysed responses at whole-brain, ROI-average, and AON-constrained voxelwise scales. Whole-brain overlap between the two contrasts was localised primarily to the left lateral occipitotemporal extrastriate cortex, outside the AON. At the regional ROI-average scale, the IFG showed positive responses to both contrasts, whereas the IPL and pSTS showed opposing task preferences. Crucially, regional IFG co-engagement did not imply that the same voxels responded to both contrasts. Suprathreshold voxelwise overlap within the AON was virtually absent, and individual-level analysis revealed a small but reliable posterior displacement of hand action relative to emotional face within IFG. These findings show that spatial convergence between hand and emotion observation responses depends on the scale of analysis. The same IFG region can be engaged by both stimulus domains while retaining distinct local response topographies.

The visual word form area (VWFA) is a hallmark of literacy in the human brain. Alongside reading acquisition, the functional organization of the ventral temporal cortex (VTC) undergoes substantial changes. However, it remains unclear what factors uniquely drive the emergence and continued development of the VWFA, or more broadly shaping category selectivity across the VTC. Here, we combined cross-sectional and longitudinal data from children in early childhood (3-9 years) to investigate the development of visual language selectivity. We found that after controlling for age, literacy acquisition drove increases in word selectivity of the VWFA, but not the continued development of other early-developed category selectivity. Sensitivity to spoken higher-level language information within the VWFA was also associated with reading ability. By projecting the VWFA defined at the later time point onto each childs earlier time point, we also found that the pre-VWFA showed no preferential tuning to any particular visual category. Finally, longitudinal changes within the VWFA, both increased responses to visually presented words and decreased responses to auditory control conditions, were associated with changes in functional connectivity of VWFA to high-level language regions, even after controlling for initial activity levels. Together, the current study shows a unique role for literacy acquisition and experience-dependent connectivity changes in the emergence and functional specialization of the VWFA, providing empirical evidence for the revised neuronal recycling hypothesis and connectivity hypothesis of functional brain organization.

Some aspects of human behavior and cognition depend on focal and selective cortical areas, such as the frontal eye fields or fusiform face area, while others, like semantic knowledge, are broadly distributed across the cortex. Whether higher-level cognitive functions like language can also be highly localized has been a longstanding matter of debate. Here, we provide multiple lines of evidence that receptive language in the brain is subserved by a network of discrete, focal, and uniquely language-selective areas when examining individual brains. Using precision neuroimaging, we observed highly circumscribed patches of cortex that are distinctly selective for language, uniquely consistent in their response properties during language processing, and highly reliable in their anatomical locations within individuals (though variable in location across individuals). These findings indicate that language regions in the brain are characterized by unique functional profiles and sharp boundaries, consistent with the systems neuroscience definition of true "cortical areas."

Visuo-spatial attention and semantic memory are supported by distinct, largely competing brain networks, yet they are frequently engaged together in daily life. How these networks interact during combined tasks remains unexplored. We conducted a factorial fMRI experiment in which 25 participants performed a novel task requiring visuo-spatial attention, semantic judgment, or both. Covert shifts of attention towards cued lateral location activated bilateral parietal (PEF), frontal eye fields (FEF), and anterior insula. Categorizing a word as referring to a living or non-living entity activated a lateral parietal region (LaP) between the dorsal tip of the angular gyrus and the lateral bank of the intraparietal sulcus, along with the left inferior frontal gyrus (IFG), superior temporal sulcus, inferior temporal lobe and bilateral anterior insula. Notably, the anterior insula was active in both conditions. Dynamic causal modeling showed excitatory-inhibitory parieto-frontal loops driving attention (PEF[-&gt;]FEF) and semantic processing (LaP[-&gt;]IFG) separately, but in the combined condition frontal-to-parietal feedback became excitatory, reflecting stronger integration, with the anterior insula driving overall connectivity. These findings identify LaP as a novel region supporting semantic processing of linguistic stimuli, and highlight the anterior insula as a key hub integrating attentional and semantic networks under concurrent cognitive demands. HighlightsVisuo-spatial attention and semantic memory rely on segregated parieto-frontal circuits. However, concurrent demands induce a large-scale reconfiguration centered on the left anterior insula, which acts as an integrative hub between the two networks.

Introduction Understanding the mechanisms of human neuromaturation constitutes one of the fundamental questions of neuroscience. While it is well described that large-scale brain maturation is initiated within sensorimotor brain regions and progresses to associative cortex, the underlying developmental neurobiology remains to be fully characterized. Animal models have indicated that cortical inhibitory upregulation might be a driver of neurodevelopment. To investigate the hypothesis that cortical inhibitory upregulation plays a similar role in human neuromaturation, we developed a The Virtual Brain (TVB) based computational model (TVB-Child) to explore potential mechanisms of human neurodevelopment. Material and method We created neurodevelopmental dynamic brain network models capturing neurobiological maturation by using the large-scale brain simulator TVB and fitting brain network models to developmental functional MRI (fMRI) from the Human Connectome Project-Development (HCP-D) data set with 640 subjects with an age range of 6-21 years. Age-dependent trajectories in the fMRI data set were first analyzed by combined group-ICA/Dual Regression extracting subject-specific resting-state networks (RSN). Maturational topographical and topological redistribution of these networks were analyzed by linear and non-linear regression of RSN size and degree and strength centrality. Brain network models were fitted to the fMRI functional connectivity obtained from the HCP-D data set. Hypothesizing that cortical inhibition is a driver of neuromaturation, we analyzed spatiotemporal inhibition parameter gradients in the dynamic brain network model for the hypothesized significant correlations with fMRI RSN maturational trajectories. Results While during development frontoparietal (FP) and default mode network (DMN) grew and exhibited an increase in both degree and strength centrality, becoming dominant network hubs, the attention network underwent network pruning with a decrease in size and node degree. The primary sensory network changed little. For the fitted brain network models, we obtained a high degree of reproduction with correlation coefficients between empirical and simulated functional connectivities ranging between 0.80 and 0.95. Values of the feed forward inhibition model parameter wijFFI representing the strength of regional feedforward inhibitory input exhibited the most significant increase with age within the FP and DMN networks. A less pronounced, but significant, age-dependent increase of the inhibitory parameter values were seen in attention networks and no change within primary sensory networks. Conclusion Our study shows that high order (FP, DMN), attention and primary sensory networks exhibit distinct topographical and topological maturation trajectories. Moreover, brain network modeling revealed RSN-specific age-dependent inhibition trajectories, indicating that the model is able to reproduce and thus support candidate mechanisms of neurodevelopment.