Recent work suggests that thousands of individuals are required in multivariate brain-behaviour analyses to obtain consistently replicable results. Some believe, however, that smaller sample sizes may be sufficient if specific subpopulations are targeted. We investigate how sample size and cohort composition influence the replicability of Canonical Correlation Analysis (CCA) results using the UK Biobank (N = 40,514). We apply CCA to diffusion-weighted magnetic resonance imaging (dMRI) phenotypes and cognitive assessment test scores. We define four participant cohorts based on clinical profile and find that, across all cohorts, sample sizes of ≈500 are needed to obtain replicable canonical correlations and variable loadings. The most targeted cohort (comprising individuals with a history of psychoactive substance use) requires much fewer samples to achieve similar or greater correlations than the other cohorts. Our findings support the idea that moderate sample sizes from targeted cohorts can be sufficient for obtaining replicable brain-behaviour associations.

Diffusion MRI fiber tractography is sensitive to noise and artifacts in diffusion-weighted images, and these challenges can propagate into fiber-orientation estimation and the tractography process. In this “Did You Know” communication, we synthesize evidence that state-of-the-art preprocessing improves tractography anatomical fidelity and test-retest reproducibility compared to minimally processed data. We summarize best-practice preprocessing – including denoising, motion and eddy current correction, EPI distortion correction, and Gibbs ringing removal – along with additional and emerging steps, and highlight integrated, publicly available pipelines that implement these methods in standardized, containerized workflows. We also outline practical acquisition and data-handling considerations that maximize the benefits of modern processing, providing a foundation for reliable tractography-based studies of the brain.

Visual attention is often described as the selection of locations in retinal or body-centered space, yet behavior also requires selection within objects. A new study identifies posterior inferotemporal cortex as a ventro-temporal node for object-centered spatial representation.

White matter tracts form the structural backbone of large-scale brain networks, yet their relation to functional organization remains poorly defined. Although major pathways are well characterized anatomically, their relationship to distributed cognitive systems has not been systematically established. Here, we constructed a population-level white matter tract termination atlas and projected tract endpoints onto the cortical surface to characterize their spatial organization. We integrated this atlas with large-scale meta-analytic decoding to derive functional profiles for individual tracts. Functional decoding revealed that white matter tracts exhibited distinct and biologically interpretable cognitive signatures. Hierarchical clustering of these profiles further showed that tracts organize into coherent ensembles defined by shared functional associations. These tract ensembles recapitulated canonical intrinsic brain networks across multiple cortical atlases, including a notable ensemble that demonstrated alignment with the default mode, salience, and frontoparietal control networks, corresponding to the core architecture of the triple-network model of cognitive control. This finding identified a candidate structural backbone linking distributed functional systems implicated across neuropsychiatric conditions. Together, these results demonstrate that white matter architecture is organized according to large-scale functional principles and establish a tract-to-network framework for linking structural connectivity to cognition.

Tractography is a key component of efforts to map brain connectivity. As a rapidly-evolving field of neuroscience, current tractography methods are diverse, often varying across research laboratories and different software pipelines. Therefore, it suffers from a lack of standardization leading to inconsistencies in results, which can limit reproducibility, and affect the robustness needed for research and clinical applications of these methods. Variability in data acquisition procedures, inconsistencies in spatial referencing schemes and implementations, and anatomical heterogeneity —at the individual level, across the lifespan, and across species— hinders comparative analyses. Additionally, the lack of consensus on best practices complicates the development of robust automated quality control pipelines and limits the clinical translation of tractography-based procedures. Establishing standardized protocols for acquisition, preprocessing, and tractography reconstruction are critical towards enabling reliable tract-specific analyses, facilitating cross-study harmonization, and supporting replicable large-scale population studies. The present article provides an overview of the current challenges in tractography standardization and identifies the key aspects that require standardization for reliable, reproducible, and robust tractography.

Polarization-sensitive optical coherence tomography (PS-OCT) is a label-free imaging technique that exploits birefringence to visualize myelinated axons at micrometer resolution. However, serial PS-OCT imaging has been limited to small volumes, including tissue blocks from larger species, owing to constraints in acquisition speed, system stability, and data processing. These limitations have prevented its application to whole-brain mapping in large mammals. Here we present a scalable PS-OCT acquisition system and computational pipeline for whole-brain imaging in the rhesus macaque. The framework integrates high-throughput serial imaging with automated reconstruction and processing, enabling volumetric imaging at micrometer-scale resolution across decimeter-scale brain volumes. Using this approach, we acquired two complete macaque brains at a voxel size of 5.5 × 5.5 × 3.4 μm and an effective resolution of approximately 10 × 10 × 5.5 μm, generating multi-terabyte datasets consisting of multiple contrasts including fiber orientation information. The datasets and associated processing tools are made publicly available. This platform establishes a method for large-scale, high-resolution mapping of white matter architecture in primate brains. The resulting datasets provide a reference for validating MRI models and support the development of neurotechnological applications, including deep brain stimulation, where accurate characterization of axonal organization is required.

Insights, or "Aha!" moments, are a crucial aspect of idea generation in creative cognition. While functional neuroimaging studies have identified brain regions involved in these insights, their white matter substrate remains unexplored. This study employed diffusion tensor imaging (DTI) to investigate how white matter microstructure—measured by fractional anisotropy (FA) and mean diffusivity (MD)—relates to individuals’ tendency to solve Compound Remote Associates problems through insight versus step-by-step analytical reasoning. After controlling for age and gender, left-hemisphere omnibus tests (Stouffer’s Z and FDR) showed significant FA associations for left dorsal tracts composites (i.e., Arcuate Fasciculus, Posterior Arcuate Fasciculus, and Superior Longitudinal Fasciculus III), while MD tracts composites trended but were not FDR-significant (p= 0.032 q= 0.081). Findings point to a left-lateralized dorsal substrate of insight. These findings suggest that insight may benefit from more diffuse connectivity patterns, allowing for broader semantic activation and cognitive flexibility. Our study provides novel evidence for distinct structural connectivity patterns associated with different idea-generation approaches, contributing to a more comprehensive understanding of the neural architecture supporting creative cognition.

The first year of formal schooling is a year of foundational reading and math learning, and individual differences emerging within this single year predict academic achievement decades later. Yet, how brain changes throughout this critical year relate to individual differences in reading and math learning remains uncharacterized. In this pre-registered study ( https://osf.io/97ybe ), we acquired monthly both behavioral assessments of reading- and math-learning, and diffusion-weighted MRI scans to measure white matter microstructure, across the first-grade year. Behavioral learning trajectories follow either a sigmoid for reading or an inverted-U for math. Month-to-month microstructural changes in the right middle longitudinal fasciculus predicted corresponding changes in math performance, but not in reading. Findings highlight white matter microstructure as a dynamic substrate of early math learning, and reveal a more general principle: rapid changes in white-matter microstructure during the foundational learning window may be associated with distinct academic domains. Funding:R01 HD114489.

White matter tracts (WMTs) are the brain's structural foundation for information transfer, underlying essential cognitive and behavioral functions. While diffusion MRI and tractography enable non-invasive mapping of these pathways, automated segmentation often lacks generalizability across diverse data sources. We conducted a systematic, cross-dataset evaluation of four state-of-the-art deep learning architectures, benchmarking their performance across independent datasets with varying acquisition protocols and populations. CNN-based models such as TractSeg achieved the highest within-domain accuracy, but performance dropped sharply under domain shift, most severely when we applied adult-trained models to pediatric data. To address this degradation, we introduce Ensemble White Matter Tract Segmentation (EWMTS), which combines complementary models to partially recover accuracy under domain shift, although performance still falls short of within-domain levels. By openly releasing this benchmark and a reproducible processing pipeline, we provide the neuroimaging community with a framework to develop and benchmark segmentation models across the heterogeneity of real-world neuroimaging data.

Recent work suggests that thousands of individuals are required in multivariate brain-behaviour analyses to obtain consistently replicable results. Some believe, however, that smaller sample sizes may be sufficient if specific subpopulations are targeted. We investigated how sample size and cohort composition influence the replicability of Canonical Correlation Analysis (CCA) results using the UK Biobank (N=40,514). We applied CCA to diffusion-weighted magnetic resonance imaging (dMRI) phenotypes and cognitive assessment test scores. We defined four participant cohorts based on clinical profile and found that, across all cohorts, sample sizes of around 500 were needed to obtain replicable canonical correlations and variable loadings. The most targeted cohort required much fewer samples to achieve similar or greater correlations than the other cohorts. Variable loadings were consistent between sample sizes of ~500 to thousands, suggesting that sample sizes in the order of hundreds may be sufficient for obtaining reliable CCA results.

Longitudinal measurements of brain structure and function are critical for understanding how humans change over time. Traditional longitudinal approaches sample sparsely across large windows of time to estimate coarse, long-term brain changes. This review showcases insights from dense longitudinal neuroimaging (DLN), an emerging approach that samples densely across relatively short windows of time to precisely estimate individual trajectories of brain change. DLN measures multiple samples from individuals throughout critical periods of rapid change. It allows precise estimates of nonlinear trajectories to advance a mechanistic understanding of brain change. Novel findings from this approach are improving our understanding of human cognition, such as the role of the motor system in visual development and learning.

Mapping brain connectivity in primates remains a major challenge due to difficulties in resolving microscopic white matter architecture, while maintaining whole-brain coverage. Increasing imaging spatial resolution is key for disambiguating fiber configurations within smaller anatomical volumes. Here, we present developments that allow high-resolution diffusion MRI of the macaque brain, both in vivo and ex vivo, using one of the world's highest-field human MRI scanners operating at 10.5 Tesla. Our approach achieves data of highest reported resolutions for this field strength and scanner type, (750 μm)3 in vivo and (400 μm)3 ex vivo, with diffusion weighting up to b = 6000 s/mm2. We detail methodological advances in data acquisition, image reconstruction, processing and whole-brain tractography that overcome critical challenges associated with ultra-high-field imaging. This work establishes a new benchmark for high-resolution neuroimaging at 10.5T, paving the way for comparable human studies and enabling analyses of brain connectivity across species and tissue states at unprecedented detail. The dataset, along with all processing pipelines, containerised workflows, and reusable web services, is openly shared to support reproducibility and future integration with microscopy for studying white matter microstructure and connections at the mesoscale. ### Competing Interest Statement The authors have declared no competing interest. NIH Common Fund, UM1NS132207 European Research Council, 101000969 Sir Henry

IntroductionThe effectiveness of research and innovation often relies on the diversity or heterogeneity of datasets that are Findable, Accessible, Interoperable and Reusable (FAIR). However, the global landscape of brain data is yet to achieve desired levels of diversity that can facilitate generalisable outputs. Brain datasets from low-and middle-income countries of Africa are still missing in the global open science ecosystem. This can mean that decades of brain research and innovation may not be generalisable to populations in Africa.MethodsThis research combined experiential learning or experiential research with a survey questionnaire. The experiential research involved deriving insights from direct, hands-on experiences of collecting African Brain data in view of making it FAIR. This was a critical process of action, reflection, and learning from doing data collection. A questionnaire was then used to validate the findings from the experiential research and provide wider contexts for these findings.ResultsThe experiential research revealed major challenges to FAIR African brain data that can be categorised as socio-cultural, economic, technical, ethical and legal challenges. It also highlighted opportunities for growth that include capacity development, development of technical infrastructure, funding as well as policy and regulatory changes. The questionnaire then showed that the wider African neuroscience community believes that these challenges can be ranked in order of priority as follows: Technical, economic, socio-cultural and ethical and legal challenges.ConclusionWe conclude that African researchers need to work together as a community to address these challenges in a way to maximise efforts and to build a thriving FAIR brain data ecosystem that is socially acceptable, ethically responsible, technically robust and legally compliant.

Replication and the reported crises impacting many fields of research have become a focal point for the sciences. This has led to reforms in publishing, methodological design and reporting, and increased numbers of experimental replications coordinated across many laboratories. While replication is rightly considered an indispensable tool of science, financial resources and researchers’ time are quite limited. In this perspective, we examine different values and attitudes that scientists can consider when deciding whether to replicate a finding and how. We offer a conceptual framework for assessing the usefulness of various replication tools, such as preregistration.

We describe a Magnetic Resonance Imaging (MRI) dataset from individuals from the African nation of Nigeria. The dataset contains pseudonymized structural MRI (T1w, T2w, FLAIR) data of clinical quality. Dataset contains data from 36 images from healthy control subjects, 32 images from individuals diagnosed with age-related dementia and 20 from individuals with Parkinson's disease. There is currently a paucity of data from the African continent. Given the potential for Africa to contribute to the global neuroscience community, this first MRI dataset represents both an opportunity and benchmark for future studies to share data from the African continent.

The human brain’s long-range axonal connections are the scaffolding for communication across functionally distinct areas. Yet knowledge of the human brain’s wiring diagram remains limited, largely due to longstanding technological challenges. Recent innovations in microscopy may now enable mapping human brain connectivity at the mesoscale (groups of neurons and their axons). In this review we describe the challenges of generating the wiring diagrams of the human brain, avenues forward, and reasons why such an effort is so important. We argue for building a human mesoscale connectome via a multimodal, multi-species, axon-centric approach, focusing on where axons begin and end to reconstruct connectivity across spatial resolutions. Finally, we consider the utility of a potential exemplar connectome for both clinical applications and research.

This study demonstrates the effectiveness of integrating cloud computing platforms with Course-based Undergraduate Research Experiences (CUREs) to broaden access to neuroscience education. Over four consecutive spring semesters (2021–2024), a total of 42 undergraduate students at Lawrence Technological University participated in computational neuroscience CUREs using brainlife.io, a cloud-computing platform. Students conducted anatomical and functional brain imaging analyses on openly available datasets, testing original hypotheses about brain structure variations. The program evolved from initial data processing to hypothesis-driven research exploring the influence of age, gender, and pathology on brain structures. By combining open science and big data within a user-friendly cloud environment, the CURE model provided hands-on, problem-based learning to students with limited prior knowledge. This approach addressed key limitations of traditional undergraduate research experiences, including scalability, early exposure, and inclusivity. Students consistently worked with MRI datasets, focusing on volumetric analysis of brain structures, and developed scientific communication skills by presenting findings at annual research days. The success of this program demonstrates its potential to democratize neuroscience education, enabling advanced research without extensive laboratory facilities or prior experience, and promoting original undergraduate research using real-world datasets.

Diffusion MRI provides a non-invasive probe of local fibre bundles and long-range anatomical connections to characterise the structural connectome. One way to achieve very high spatial resolution diffusion MRI data for connectivity investigations is to scan ex-vivo brains over many hours or days, ideally at ultra-high field strength to boost signal levels. However, conventional diffusion MRI acquisition techniques do not generally deliver good data quality for the challenging conditions of ex-vivo tissue, characterised by reduced diffusivities and relaxation times when compared to in vivo. In this work, we investigate the potential of the diffusion-weighted steady-state free precession (DW-SSFP) sequence for ex vivo diffusion imaging of the macaque brain using a 10.5 T human MRI scanner with a conventional ( G max = 70 mT/m ) gradient set. SNR-efficiency optimisations incorporating experimental relaxation times demonstrate that the DW-SSFP sequence is predicted to achieve improved or similar SNR efficiency compared to a diffusion-weighted spin- and stimulated-echo sequence. Importantly, DW-SSFP can achieve this with the additional benefit of negligible geometric distortions, unlike conventional diffusion MRI using an echo-planar imaging readout. Using optimised DW-SSFP sequence parameters, we propose a protocol at 0.4 mm isotropic resolution using a two-shell multi-orientation protocol (effective b-values of 3200 s/mm2 and 5600 s/mm2). We fit the data using Tensor, Ball and 3-Sticks and Constrained Spherical Deconvolution signal representations. The results demonstrate high-quality diffusivity estimates across the entire brain with the ability to resolve multiple fibre populations in challenging crossing-fibre regions. The data will be made fully open source and multimodal as part of the Center for Mesoscale Connectomics, providing a resource for future connectivity investigations.