Biology subjects

Sydnor, V. J.

Publications and source records attributed to Sydnor, V. J..

At least 19 recordsLinked to original sources

bioRxiv2026

Generalizable sex differences in functional brain organization follow the cortical hierarchy in youth

It remains unknown if sex differences in human functional connectivity follow a generalizable overarching principle. Here, we tested whether sex differences in functional connectivity during childhood and adolescence are organized along the sensorimotor-association (S-A) axis, a cortical hierarchy spanning unimodal sensorimotor to transmodal association cortex. We analyzed four large-scale, independent datasets of youth ages 5-23 years (total N = 3,355). Across datasets, males showed greater connectivity between functional networks, whereas females showed greater connectivity within networks, most prominently within the default mode network. More broadly, the sensorimotor and association ends of the S-A axis were more segregated in females and more integrated in males. This difference extended to macroscale cortical organization: the cortical hierarchy was expanded in females relative to males along the principal gradient of functional connectivity. Together, these findings identify the S-A axis as a generalizable organizing principle of sex differences in functional brain organization during youth.

neuroscience↗

bioRxiv2026

Algorithmic Geometry Shapes the Biological Meaning of Thalamocortical Structural Covariance

Neuroimaging studies often derive and discuss structural covariance (SC) as a representation of underlying brain circuitry that reflects coordinated maturation, anatomical connectivity, transcriptional similarity, and shared genetic influences. These associations motivate its use to study brain organization across development, aging, and disease. However, the algorithms used to derive SC networks impose constraints that may shape their biological interpretation. To understand the impact of algorithm choice, we used the thalamocortical system as an example and compared five common representations of voxelwise SC, namely, principal component analysis (PCA), independent component analysis (ICA), non-negative matrix factorization (NMF), orthogonal projective NMF (OPNMF), and \textit{k}-means clustering, in 755 participants aged 8--22 years from the Philadelphia Neurodevelopmental Cohort (PNC). SC networks derived from deformation-based morphometry (DBM) were evaluated against three complementary biological benchmarks: age-related individual differences, fractional-anisotropy (FA)-based microstructural connectivity of regionally-specific thalamocortical connections, and Allen Human Brain Atlas gene expression. Each algorithm demonstrated underlying sensitivity to differing aspects of neurobiology: PCA and OPNMF showed the strongest associations between participant-level component weights and age. NMF, OPNMF, and \textit{k}-means showed greater spatial overlap between positive cortical SC and tractography-derived projections. ICA and PCA showed stronger correspondence between thalamic and cortical gene-expression profiles across the transcriptome, whereas NMF, OPNMF, and \textit{k}-means more often identified thalamic components with relatively high core-matrix gene expression. This study emphasizes that algorithmic constraints effectively act as biological priors and decomposition methods do not provide neutral compression of the data. We conclude that it is critical to consider whether the algorithmic objective matches the representational geometry of the neurobiology being studied. Overall, our findings suggest that SC studies should select and justify algorithms according to the biological question, explicitly considering whether their constraints favour distributed gradients, overlapping regional parts, or discrete clusters. Meanwhile, interpretations of SC findings could also be informed by the specific algorithmic constraints used to derive them.

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bioRxiv2026

Insula functional connectivity development follows a canonical antero-posterior axis of organization

The insula is a heterogeneous region associated with a range of functional domains including sensory, cognitive, and emotional processing. Cytoarchitectural and functional studies have described an antero-posterior axis of insula organization. However, the insula's functional development remains sparsely described. We delineated the development of insula resting-state functional connectivity across 562 individuals (6-22 years) using generalized additive models and population value decomposition. We show insulo-cortical functional connectivity development differs across the insula: anterior subregions have predominantly decreasing connectivity across the age range examined, whereas posterior subregions have variable connectivity that aligns with the sensorimotor-association axis. Vertex-level analysis revealed that age-related trajectories followed an antero-posterior axis that aligned with estimates of insula microstructure. Our results emphasize that the development of insula connectivity is spatially heterogeneous and aligns with known cytoarchitecture. The normative insula development described here provides a foundation for investigating how emerging psychopathology may be linked to variation in insula development.

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bioRxiv2026

Task-evoked flexibility of intrinsic neural timescales is hierarchically organized, behaviorally relevant, and refined across two developmental stages

Cortical regions integrate temporal information over different timescales at rest, ranging from fast in sensorimotor regions to slow in the association cortex. Here, we study how far regions adapt these timescales to meet task demands, as well as how this \emph{timescale flexibility} is organized across the cortical hierarchy, and how it develops in humans. We quantified rest-to-task changes in intrinsic neural timescales, referred to as \emph{timescale deflections}, using fMRI data from four independent datasets totaling 1,712 participants aged 8--64 years. We found that timescales reduced under cognitive load in all four datasets, most strongly in association cortex, which partially flattened the resting-state timescale hierarchy. Individual differences in timescale deflections were organized along the sensorimotor-association (S-A) axis and tracked cognitive performance, both in adults and in youth. Next, in youth, deflections followed a two-stage developmental course: a generalized reduction throughout childhood, followed by a selective expansion in association cortex from mid-adolescence. Furthermore, the timing of these stages aligned with cortical gradients of inhibitory gene expression and intracortical myelin content, both features implicated in the opening and closing of critical periods of neural plasticity. Overall, our results demonstrate that task-evoked timescale flexibility is hierarchically organized, behaviorally and neurobiologically relevant, and refined across adolescence.

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bioRxiv2026

An Open Test--Retest Dataset of Rapid Myelin Mapping Acquisitions

Myelin supports rapid and efficient neural communication and is implicated in brain development, learning, aging, and neurological disease. Although numerous magnetic resonance imaging (MRI) approaches have been proposed to characterize myelin in vivo, they have rarely been evaluated together within the same participants and across repeated acquisitions. To address these gaps, we introduce the Myelin Imaging Reliability and ReprOducibility Resource (MIRROR), an openly available multimodal test--retest MRI dataset of diffusion MRI (dMRI), inhomogeneous magnetization transfer imaging (ihMT), quantitative susceptibility mapping (QSM), MP2RAGE, T1w/T2w ratio mapping, and transverse relaxometry in 22 healthy adults. We evaluated gray--white matter differentiation, intermetric correspondence, test--retest reliability, and participant specificity across 27 myelin-sensitive metrics. Gray--white matter differentiation was strong for dMRI derivatives, MP2RAGE-derived R1, T1w/T2w, and ihMT, while being substantially weaker for QSM measures. Intermetric spatial correlations were generally strongest within acquisition or modeling families. Test--retest reliability was generally high, particularly for dMRI-derived metrics, but was more variable among QSM-, ihMT-, and R2*-derived measures. Regional spatial profiles were also highly participant-specific, with discriminability approaching its upper bound for most metrics. All imaging data, derived maps, and processing code are openly released. MIRROR provides a benchmark for characterizing the measurement properties and practical tradeoffs of scalable myelin-sensitive MRI methods, supporting principled acquisition selection and accelerating methodological development and validation.

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bioRxiv2026

Developmental Changes in Gray Matter Microstructure and Local Brain Connectivity Support Inhibitory Control from Adolescence to Young Adulthood

Background: Adolescence is marked by improvements in inhibitory control along with brain maturational processes affecting function and structure of cortical circuitry. Preliminary evidence shows a developmental decrease of local neuronal inputs, suggesting a weakening of local connectivity supporting circuit refinement and mature behavior. Microstructural changes in gray matter, arising from processes such as synaptic pruning and myelination, may support this refinement, though it remains unknown how microstructural features interact with the reconfiguration of functional circuitry, or how this unfolds in vivo in normative development to support mature cognitive functioning. Methods: In this study, 175 participants ages 10-26 (93F; 17.32{+/-}4.82yo) completed an anti-saccade task, a developmentally-validated measure of inhibitory control, as well as a 3T MRI scan involving a multi-shell diffusion weighted imaging acquisition, multi-echo resting state fMRI, and structural (T1w, T2w) scans. We computed measures of neurite density (NDI) in gray matter using neurite orientation dispersion and density imaging, local functional connectivity with surface-based and volumetric regional homogeneity (ReHo), and intracortical myelin using T1w/T2w ratio. Generalized additive models examined non-linear age-related trends across a number of cortical and subcortical regions implicated in inhibitory control, as well as associations with anti-saccade performance. Results: We found that NDI significantly increased with age in all regions while ReHo decreased. Greater NDI was associated with more accurate anti-saccade performance and lower ReHo, which remained after residualizing NDI for T1w/T2w ratio, suggesting that microstructural reorganization beyond myelination may underlie functional specialization throughout adolescence. Lower ReHo, specifically in young adolescents, also resulted in better anti-saccade performance. Finally, an interaction between ReHo and NDI, rather than either measure alone, best predicted inhibitory control performance, such that the maturity of neurite density had the greatest effect when local connectivity was high, suggesting immaturity. Conclusions: Our results suggest that the joint maturation of microstructural elements and associated specialization of local functional circuitry interact to support the emergence of stable adult-level inhibitory control.

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bioRxiv2026

Nucleus-level thalamic organization anchors multimodal signatures of thalamocortical maturation

The human thalamus is composed of multiple nuclei that differ in structure and function. From early development onwards, these nuclei form reciprocal, nucleus-specific connections with the cerebral cortex, contributing to sensory and cognitive processing. In childhood and adolescence, a key period of neurocognitive development, these connections undergo widespread refinement, yet how developmental trajectories of thalamocortical connections vary across nuclei remains unknown. Here, we leveraged the Human Connectome Project in Development dataset (HCP-D, N = 604, age range 8-21) and segmented 10 thalamic nuclei using a segmentation approach optimized for intrathalamic contrast. Applying probabilistic tractography, we reconstructed nucleus-specific thalamocortical connections and charted their maturational profiles based on changes in fractional anisotropy (FA) using generalized additive models. We found FA to increase in thalamocortical connections, with nucleus-specific variation in temporal profiles and magnitude of age effects. Connections of core-cell-rich, sensory-projecting nuclei, such as the lateral geniculate nucleus, showed earlier maturational plateaus, whereas matrix-cell-rich, association-projecting nuclei, such as ventral anterior nucleus, showed more sustained maturation. This links maturational heterochronicity to thalamic organization of cell distribution and connectivity embedding. In parallel, functional thalamocortical connectivity decreased with age, with FA and functional connectivity age effects coupled in nucleus-connections showing prolonged maturation. Finally, concordant age effects in connectivity and nucleus volumes suggest that intra-nucleus remodeling may support refinement of structural connections while reducing thalamocortical functional synchrony. Together, our work reveals that thalamocortical maturation is anchored in the developmental and organizational heterogeneity of thalamic nuclei, offering a framework for understanding how diverse thalamic nuclei contribute to neurocognitive development.

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bioRxiv2026

White matter reflects the childhood exposome

The childhood environment is critical for brain development. However, most neuroimaging studies examine individual environmental measures (e.g., socioeconomic status) or a limited set of exposures, obscuring how the combination of complex, real-world exposures jointly influence brain development. Here we investigated how white matter shape and tissue properties are linked to the childhood exposome, a multidimensional measure capturing over 300 environmental exposures. Using multi-shell diffusion MRI from 8,183 children (ages 9-10) in the ABCD study, we quantified microstructural and macrostructural properties across 62 person-specific white matter tracts. The exposome showed widespread and highly replicable associations with both white matter microstructure and macrostructure: more advantaged environments were associated with larger tract macrostructure and lower orientation dispersion. Principal component analysis revealed that the dominant axis of exposome-white matter covariation aligns with the cortical sensorimotor-association hierarchy, such that tracts spanning this hierarchy exhibit the strongest associations with the exposome. Multivariate models demonstrated that patterns of white matter features explained 25% of the variance in the exposome in unseen individuals. Notably, white matter-based prediction of cognition was markedly reduced after accounting for the exposome ([~]82% reduction in explained variance), indicating that brain-cognition associations overlap substantially with variance captured by the exposome. These findings generalized to independent data from the Healthy Brain Network (n=869), which differs substantially from ABCD in MRI acquisition, participant selection, and childhood environments. Together, these results suggest that white matter architecture strongly reflects the childhood environment.

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bioRxiv2026

Mapping developmental patterns of intrinsic timescale

Intrinsic timescale is a commonly used measure of spontaneous neural dynamics that quantifies the temporal window of processing of neuronal populations. Intrinsic timescale displays a hierarchical cortical organization across multiple species and imaging modalities, with shorter timescales in sensorimotor cortex compared to association cortex. However, less is known about how intrinsic timescale evolves during human brain development and whether its cortical maturation patterns generalize to independent developmental samples. Here we estimate the intrinsic timescale in two independent cross-sectional datasets of youth (HCPD: n=565; HBN: n=729; age range 8-22 years) and investigate its neurodevelopmental patterns. We find that developmental patterns in the intrinsic timescale follow a hierarchical pattern that recapitulates an axis spanning sensorimotor to association cortices (S-A axis). Our analysis of an independent healthy young adult dataset (HCPYA: n=973, age range 22-37 years) underscores the specificity of these developmental findings, suggesting that the intrinsic timescale develops along the S-A axis in youth and stabilizes in adulthood. Together, these results reveal convergence between major axes of cortical organization and development, highlighting intrinsic timescale as a principled marker of hierarchical brain maturation in youth.

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bioRxiv2025

Anatomical White Matter Tracts Span the Cortical Hierarchy to Support Cognitive Diversity

Long-range white matter (WM) tracts support cognition by enabling communication between distant cortical regions, which are organized along a hierarchy defined by the sensorimotor-to-association (S-A) axis. However, it remains unknown how WM tracts are positioned within the cortical hierarchy to support cognition. Here, we show that WM tracts are differentially positioned in the cortical hierarchy to support specific cognitive functions, and that tracts spanning the hierarchy connect regions with greater cognitive diversity. Moreover, tracts situated within the same hierarchical level connect biologically similar regions, while those crossing the hierarchy bridge distinct biological milieux to support diverse cognitive functions. The placement of tracts in the cortical hierarchy also reflects developmental variation in tract microstructure and individual differences in cognition. Together, these findings provide a framework that moves beyond conventional categories of association or projection tracts and links WM tract anatomy to cortical organization, cognitive function, cortical neurobiology, and neurodevelopment. We anticipate that this cortex-anchored framework for describing WM tracts may aid the interpretation of individual differences in WM structure related to development and behavior.

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bioRxiv2025

Cross-species evidence for the refinement of intrinsic neural timescales supporting executive system maturation through adolescence

Brain functional, structural, and neurochemical maturation has been found to support the specialization of executive systems through adolescence that will lead to adult level processing. Importantly, animal models and initial EEG studies in humans indicate developmental improvements in neural processing of complex information that would be evident in changes in temporal dynamics, which are not well-understood. Intrinsic neural timescales (INTs), or the temporal windows over which neural populations integrate inputs, have been proposed to reflect circuit-level properties such as excitatory-inhibitory (E/I) balance, myelination, and functional properties supporting complex information processing such as in executive functioning. Here, we used a multimodal, cross-species approach to investigate how INTs develop across adolescence to support cognitive specialization. In parallel analyses using a large longitudinal human EEG cohort, adolescent intracranial sEEG recordings, and macaque local field potentials, we observed robust reductions in INTs through adolescence, particularly in frontal and parietal association cortices. These developmental reductions were shaped by local circuit physiology, as evidenced by associations between shorter INTs and both lower aperiodic exponents, indicative of increased E/I balance, and reduced spectral offsets, suggesting lower aggregate spiking. We also found structural contributions via developmental interactions between age and deep layer intracortical myelination which predicted shorter INTs, suggesting that long-range circuitry may play a key role in shaping spontaneous temporal dynamics. Functionally, shorter INTs in adolescence were linked to improved working memory accuracy and reduced response time variability, indicating a behavioral advantage of refined temporal integration windows through development. Together, these findings establish INTs as a conserved, biologically grounded signature of adolescent brain maturation, providing a mechanistic framework for how structural and physiological refinements reorganize temporal processing to support increasingly efficient cognitive function.

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bioRxiv2025

Benchmarking Orientation Distribution Function Estimation Methods for Tractometry in Single-Shell Diffusion Magnetic Resonance Imaging - An Evaluation of Test-Retest Reliability and Predictive Capability

Deriving white matter (WM) bundles in-vivo has thus far mainly been applied in research settings, leveraging high angular resolution, multi-shell diffusion MRI (dMRI) acquisitions that enable advanced reconstruction methods. However, these advanced acquisitions are both time-consuming and costly to acquire. The ability to reconstruct WM bundles in the massive amounts of existing single-shelled, lower angular resolution data from legacy research studies and healthcare systems would offer much broader clinical applications and population-level generalizability. While legacy scans may offer a valuable, large-scale complement to contemporary research datasets, the reliability of white matter bundles derived from these scans remains unclear. Here, we leverage a large research dataset where each 64-direction dMRI scan was acquired as two independent 32-direction runs per subject. To investigate how recently developed bundle segmentation methods generalize to this data, we evaluated the test-retest reliability of the two 32-direction scans, of WM bundle extraction across three orientation distribution function (ODF) reconstruction methods: generalized q-sampling imaging (GQI), constrained spherical deconvolution (CSD), and single-shell three-tissue CSD (SS3T). We found that the majority of WM bundles could be reliably extracted from dMRI scans that were acquired using the 32-direction, single-shell acquisition scheme. The mean dice coefficient of reconstructed WM bundles was consistently higher within-subject than between-subject for all WM bundles and ODF reconstruction methods, illustrating preservation of person-specific anatomy. Further, when using features of the bundles to predict complex reasoning assessed using a computerized cognitive battery, we observed stable prediction accuracies (r: 0.15-0.36) across the test-retest data. Among the three ODF reconstruction methods, SS3T had a good balance between sensitivity and specificity in external validation, a high intra-class correlation of extracted features, more plausible bundles, and strong predictive performance. More broadly, these results demonstrate that bundle segmentation can achieve robust performance even on lower angular resolution, single-shell dMRI, with particular advantages for ODF methods optimized for single-shell data. This highlights the considerable potential for dMRI collected in healthcare settings and legacy research datasets to accelerate and expand the scope of WM research.

neuroscience↗

bioRxiv2025

Two Axes of White Matter Development

Despite decades of neuroimaging research, how white matter develops along the length of major tracts in humans remains unknown. Here, we identify fundamental patterns of white matter maturation by examining developmental variation along major, long-range cortico-cortical tracts in youth ages 5-23 years using diffusion MRI from three large-scale, cross-sectional datasets (total N = 2,716). Across datasets, we delineate two replicable axes of human white matter development. First, we find a deep-to-superficial axis, in which superficial tract regions near the cortical surface exhibit greater age-related change than deep tract regions. Second, we demonstrate that the development of superficial tract regions aligns with the cortical hierarchy defined by the sensorimotor-association axis, with tract ends adjacent to sensorimotor cortices maturing earlier than those adjacent to association cortices. These results reveal developmental variation along tracts that conventional tract-average analyses have previously obscured, challenging the implicit assumption that white matter tracts mature uniformly along their length. Such developmental variation along tracts may have functional implications, including mitigating ephaptic coupling in densely packed deep tract regions and tuning neural synchrony through hierarchical development in superficial tract regions - ultimately refining neural transmission in youth.

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bioRxiv2025

Heterochronous laminar maturation in the human prefrontal cortex

The human prefrontal cortex (PFC) exhibits markedly protracted developmental plasticity, yet whether reductions in plasticity occur synchronously across prefrontal cortical layers is unclear. Animal studies have shown that intracortical myelin consolidates developing circuits by restricting ongoing neuronal plasticity. Here, we use longitudinal myelin-sensitive imaging collected at ultra-high field to investigate whether superficial and deep PFC layers exhibit different timeframes of malleability. We find that myelin matures earlier in deep than in superficial compartments of the cortical ribbon; this laminar divergence in maturational timing is differentially expressed across cytoarchitecturally and functionally distinct frontal regions. By integrating myelin mapping with EEG and behavioral phenotyping, we provide evidence that prefrontal myelin impacts timescales of neural activity, task learning rates, and cognitive processing speed. Heterochronous myelination across deep and superficial layers is an underrecognized mechanism through which human association cortex balances cognitively-relevant increases in circuit stability and efficiency with extended neuroplasticity.

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bioRxiv2024

A sensorimotor-association axis of thalamocortical connection development

Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence1-6. The brains capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity7-12, here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth. We first introduce, cortically annotate, and anatomically validate a new atlas of human thalamocortical connections using diffusion tractography. By applying this atlas to three independent youth datasets (ages 8-23 years; total N = 2,676), we reproducibly demonstrate that thalamocortical connections develop along a maturational gradient that aligns with the cortexs sensorimotor-association axis. Associative cortical regions with thalamic connections that take longest to mature exhibit protracted expression of neurochemical, structural, and functional markers indicative of higher circuit plasticity as well as heightened environmental sensitivity. This work highlights a central role for the thalamus in the orchestration of hierarchically organized and environmentally sensitive windows of cortical developmental malleability.

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bioRxiv2023

XCP-D: A Robust Pipeline for the post-processing of fMRI data

Functional neuroimaging is an essential tool for neuroscience research. Pre-processing pipelines produce standardized, minimally pre-processed data to support a range of potential analyses. However, post-processing is not similarly standardized. While several options for post-processing exist, they tend not to support output from disparate pre-processing pipelines, may have limited documentation, and may not follow BIDS best practices. Here we present XCP-D, which presents a solution to these issues. XCP-D is a collaborative effort between PennLINC at the University of Pennsylvania and the DCAN lab at the University at Minnesota. XCP-D uses an open development model on GitHub and incorporates continuous integration testing; it is distributed as a Docker container or Singularity image. XCP-D generates denoised BOLD images and functional derivatives from resting-state data in either NifTI or CIFTI files, following pre-processing with fMRIPrep, HCP, and ABCD-BIDS pipelines. Even prior to its official release, XCP-D has been downloaded >3,000 times from DockerHub. Together, XCP-D facilitates robust, scalable, and reproducible post-processing of fMRI data.

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bioRxiv2023

Functional Connectivity Development along the Sensorimotor-Association Axis Enhances the Cortical Hierarchy

Human cortical maturation has been posited to be organized along the sensorimotor-association (S-A) axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the S-A axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3,355; ages 5-23 years): the Philadelphia Neurodevelopmental Cohort (n = 1,207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1,126). In each dataset, the development of functional connectivity systematically varied along the S-A axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These robust and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.

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bioRxiv2023

In-vivo whole-cortex estimation of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here we non-invasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically-plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the GABA-agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 years old) and Asian (7.2 to 7.9 years old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth. SignificanceHealthy brain function requires a delicate balance of neural excitation (E) and inhibition (I). In animals, this balance - the E/I ratio - is known to decrease with the maturation of inhibitory circuitry during healthy development. However, in humans, the normative development of cortex-wide E/I ratio remains unclear. Here, we use a biophysical model and non-invasive brain scans to estimate a marker of E/I ratio. Spatial changes in our E/I ratio marker are consistent with a drug that decreases E/I ratio. We also find that our cortex-wide E/I ratio marker decreases during development. Furthermore, North American and Asian children with lower E/I ratio, especially in higher-order cortex, have better cognitive performance. Overall, E/I ratio is a potential index of healthy neurocognitive development.

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