Human Brain Mapping最新文献

{"title":"Inside a Programmer's Brain: Dissociating Code and Language Comprehension Networks Using a Novel fMRI-ESM Protocol.","authors":"Victor Cepero-Escribano, Patricia León-Cabrera, Anna Gasa-Roqué, Xavier Otazu, Alejandro Fernandez-Coello, Pablo Naval-Baudin, Àngels Camins, Immaculada Rico, Andreu Gabarros, Antoni Rodriguez-Fornells, Xim Cerda-Company","doi":"10.1002/hbm.70634","DOIUrl":"https://doi.org/10.1002/hbm.70634","url":null,"abstract":"<p><p>Code comprehension and natural language share structural similarities but engage partially distinct neural systems. While language predominantly recruits the classical perisylvian language network, code comprehension has been linked to the multiple-demand system, associated with mathematical thinking and problem solving. We report the case of a professional software engineer with an IDH-mutant astrocytoma in the left middle frontal gyrus, a region where these networks converge. To address the potential risk of impairing computer programming abilities during surgery, we implemented a personalized protocol combining fMRI and intraoperative electrical stimulation mapping (ESM), extending the standard language assessment with a Code comprehension task. Intraoperative mapping identified sites in the left inferior frontal cortex that were functionally relevant to the Code comprehension task but were not identified during standard object-naming mapping. Complete tumor resection was achieved while preserving these critical regions, with the patient showing intact post-operative language and programming performances. This single case study suggests that individualized Code comprehension mapping may identify functionally relevant sites not detected by standard object-naming mapping, supporting the potential clinical value of tailored fMRI-ESM protocols for preserving higher-order cognitive functions in neurosurgical patients.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 15","pages":"e70634"},"PeriodicalIF":4.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Imaging of Hippocampal Layers Using VASO and BOLD on the Next Generation (NexGen) 7T Scanner","authors":"Suvi Häkkinen,&nbsp;Alexander Beckett,&nbsp;Erica Walker,&nbsp;Laurentius Huber,&nbsp;David A. Feinberg","doi":"10.1002/hbm.70660","DOIUrl":"https://doi.org/10.1002/hbm.70660","url":null,"abstract":"<p>Spatial accuracy and venous biases are a central concern in mesoscale fMRI, with subcortical brain regions facing additional challenges due to lower sensitivity, high physiological noise, and complicated vasculature. Here, we optimized CBV VASO on the NexGen 7T scanner for layer-specific investigations of the human hippocampus. Both VASO and BOLD (from the same acquisition) detected significant hippocampal activation during an established autobiographical memory task. At the macroscale, activation patterns converged, showing pronounced memory task activation in the anterior hippocampus and consistent engagement across the frontoparietal neocortex. At the laminar scale, however, differences in depth-dependent profiles emerged within the subiculum: BOLD exhibited a pronounced bias toward the inner layers, consistent with the known venous drainage pattern in the subfield. Finally, the optimized effective TR of 3.2 s allowed exploratory study of retrieval stages and neocortical functional connectivity, which both supported hippocampal anterior–posterior dissociation using either VASO or BOLD. Thus, hippocampal fMRI allows mapping layer function with high accuracy and can provide deeper insights into a number of neuropsychological phenomena and disorders.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 15","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hbm.70660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lobular and Voxel-Wise Genetic Influences on Cerebellar Gray Matter Volume and Associations With Social and Trait Anxiety in Twins","authors":"Tugce Yildiz-Ahola,&nbsp;Granit Kastrati,&nbsp;Peter Fransson,&nbsp;Fredrik Åhs,&nbsp;Tomas Furmark,&nbsp;Amirhossein Manzouri,&nbsp;Dagmar Timmann,&nbsp;Kristoffer N. T. Månsson,&nbsp;Jörgen Rosén","doi":"10.1002/hbm.70655","DOIUrl":"10.1002/hbm.70655","url":null,"abstract":"<p>The cerebellum supports motor, cognitive, and affective functions, but the spatial pattern of genetic influence on its morphology and its relevance to anxiety traits remains unclear. Using structural MRI data from monozygotic and dizygotic twins (298 participants), we estimated additive genetic and environmental contributions to cerebellar gray matter volume at lobular and voxel scales. Monozygotic twins showed higher intra-pair correlations than dizygotic twins across cerebellar regions, indicating genetic influence with marked spatial heterogeneity: effects were strongest in posterior and vermal lobules (notably lobule IX, Crus I/II, and vermis VII–VIII) and more moderate in anterior motor-related lobules; cerebellar white matter also showed strong genetic influence. Voxel-wise mapping confirmed this pattern and revealed within-lobule heterogeneity not captured by lobular averaging, with additive genetic factors explaining ~45% of voxel-level variance and minimal shared environmental effects. Social (measured via the Liebowitz Social Anxiety Scale-Self Report; LSAS-SR) and trait (State–Trait Anxiety Inventory; STAI-T) anxiety were substantially heritable, whereas phenotypic, genetic, and unique environmental correlations with cerebellar volumes were small and did not survive multiple-comparisons correction. These results show that genetic influence on cerebellar structure is strongly spatially heterogeneous and scale-dependent, whereas associations between cerebellar gray matter volume and anxiety severity are weak in this non-clinical adult sample.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individualised Structural and Functional Frontostriatal Connectivity Mapping in Adult ADHD","authors":"Tuija Tolonen,&nbsp;Matti Laine,&nbsp;Kimmo Alho,&nbsp;Sami Leppämäki,&nbsp;Pekka Tani,&nbsp;Anniina Koski,&nbsp;Juha Salmi,&nbsp;Timo Roine","doi":"10.1002/hbm.70652","DOIUrl":"10.1002/hbm.70652","url":null,"abstract":"<p>Abundant research from early neurocognitive models to recent mega-analyses has highlighted the central role of frontostriatal circuits in attention deficit hyperactivity disorder (ADHD). However, it remains unclear which specific aspects of functionally organised frontostriatal loops are affected by ADHD and how these disruptions differ across individuals in light of the disorder's marked heterogeneity. We investigated frontostriatal connectivity in individualised circuits in 40 adults with ADHD and 36 neurotypical controls using a multimodal dataset that included diffusion-weighted magnetic resonance imaging (MRI), as well as functional MRI during working memory updating, resting state, and a naturalistic attention task. Compared with the neurotypical controls, the adults with ADHD exhibited reduced structural connectivity strength in a tract originating from left orbital prefrontal areas. However, structural results did not reproduce in control analyses using different thresholds in individual formation of regions of interest. Functional data revealed weaker connectivity in the ADHD group during verbal and visuospatial working memory tasks in circuits connecting the striatum with the dorsolateral prefrontal cortex, motor regions, and orbitofrontal cortex, while no group differences were found during resting state or the naturalistic task. Comparisons with atlas-based analyses highlighted the precision of individualised connectivity mapping. Together, these findings suggest that frontostriatal functional connectivity aberrancies in ADHD are driven by striatum-dependent cognitive processes such as working memory, and that precise mapping of frontostriatal pathways can be achieved through individualised connectivity mapping.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Dynamics Underlying Reaching Movements Under Uncertainty","authors":"Nan Liu,&nbsp;Adam Zabicki,&nbsp;Gereon R. Fink,&nbsp;Paola Mengotti,&nbsp;Simone Vossel","doi":"10.1002/hbm.70643","DOIUrl":"10.1002/hbm.70643","url":null,"abstract":"<p>Motor responses are influenced by inferred predictability, but it remains unclear how uncertainty, or its inverse, precision, is encoded within motor control networks. In this study, we combined computational modeling of reaching movement response speed with functional magnetic resonance imaging (fMRI). We used a cueing paradigm with changing cue predictability (~50%, ~70%, and ~90%) to test how predictive inference about left/right reaching responses affected cortical activity and network connectivity in 28 healthy young adults. Behavioral results showed that the response speed differences between invalid and valid cueing increased with a higher model-derived probability that the cue will be valid. The fMRI results revealed that activity in the bilateral intraparietal sulcus (IPS), the caudal part of dorsal premotor cortex (cPMd), and the cerebellum increased with higher uncertainty during valid trials. Moreover, the activation in the premotor cortex, bilateral inferior parietal lobe (IPL), IPS, and temporoparietal cortex was enhanced when reaching to invalidly cued targets (i.e., during motor reprogramming). Dynamic causal modeling revealed that uncertainty increased the connectivity from left to right IPS, from left IPS to cPMd, and from cPMd to primary motor cortex (M1) during valid trials. Motor reprogramming during invalid trials increased the coupling between bilateral IPL and strengthened pathways from IPL to M1 and from IPS to PMd, while decreasing connectivity from right to left IPS. These findings provide the first evidence of uncertainty-dependent network dynamics during reaching movements in the human brain and shed light on distinct neural mechanisms underlying precision-dependent motor control and motor reprogramming, with potential implications for psychiatric and neurological disorders characterized by aberrant precision control.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Static and Dynamic Resting-State fMRI Connectivity Show Frequency-Resolved Associations With Intracranial EEG Connectivity","authors":"Tahereh Rashnavadi,&nbsp;Kristina Sabaroedin,&nbsp;William Wilson,&nbsp;Daniel J. Pittman,&nbsp;Paolo Federico,&nbsp;Pierre Levan","doi":"10.1002/hbm.70646","DOIUrl":"10.1002/hbm.70646","url":null,"abstract":"<p>Resting-state functional connectivity (FC) derived from functional MRI (fMRI) is widely used to characterize brain functional organization, yet its electrophysiological basis remains incompletely understood. Here, we investigated how electrophysiological connectivity relates to both static and dynamic fMRI connectivity using simultaneous intracranial EEG (icEEG)–fMRI recordings from 48 adults with focal epilepsy. Linear mixed-effects models were applied to sampled electrode-pair connections to examine frequency-resolved associations between band-limited icEEG connectivity and corresponding fMRI FC within non-epileptogenic brain regions. Time-averaged icEEG connectivity was robustly associated with spatial variation in static fMRI connectivity across sampled connections and frequency bands, with strongest effects in the beta and low-gamma ranges. At the window level, dynamic fMRI connectivity showed significant positive associations with window-specific icEEG FC deviations in the alpha, beta, and low-gamma bands. Exploratory spatial stratification suggested that cross-modal coupling varied across clinically sampled frontal, temporal, and insular region pairs, and the main findings remained robust after motion-control analyses. Together, these findings indicate that resting-state fMRI connectivity is associated with both average electrophysiological coupling across sampled connections and window-level fluctuations in electrophysiological connectivity, with the strongest primary band-wise evidence observed in the alpha, beta, and low-gamma ranges.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Functional-Metabolic Synergy in the Healthy Brain: Multivariate Integration of Dynamic [18F]FDG-PET and Resting-State fMRI","authors":"Claudia Tarricone,&nbsp;Giulia Vallini,&nbsp;Giorgia Baron,&nbsp;Massimiliano Facca,&nbsp;Erica Silvestri,&nbsp;Tommaso Volpi,&nbsp;Andrei G. Vlassenko,&nbsp;Manu S. Goyal,&nbsp;Alessandra Bertoldo","doi":"10.1002/hbm.70651","DOIUrl":"10.1002/hbm.70651","url":null,"abstract":"<p>Despite accounting for only 2% of body weight, the human brain requires significant amounts of glucose, even at rest, underscoring the importance of functional-metabolic relationships. Previous studies revealed moderate associations between resting-state fMRI functional connectivity (FC) and local metabolism via [¹⁸F]FDG-PET, yet much remains to be understood, particularly regarding their coupling between functional and metabolic networks. To this end, we employed multivariate Partial Least Squares Correlation (PLSC) to investigate the functional-metabolic relationship at both nodal and network levels. From dynamic [¹⁸F]FDG-PET data we estimated parameters describing glucose metabolism—delivery rate (<i>K</i>₁), phosphorylation rate (<i>k</i>₃), and fractional uptake (<i>K</i>_i)—and generated within-individual metabolic connectivity (MC) networks. FC was derived from fMRI data filtered into two frequency bands and summarized as region-wise strength to capture nodal characteristics. Our findings revealed that glucose delivery is linked with FC strength, particularly when fMRI signal frequencies include greater hemodynamic contributions. Even stronger functional-metabolic coupling occurs at the network level in the low-frequency fMRI band, with higher MC between sensory/attention and transmodal networks supporting stronger FC within sensory/attention areas. By leveraging PLSC, this work deepens our understanding of the functional-metabolic synergy in the healthy brain, providing new insights into its organization.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orbitofrontal and Medial Frontal Gray Matter Volumes Are Associated With Hyperactivity Traits in 2548 Nonclinical Adults","authors":"Handityo Aulia Putra,&nbsp;Kaechang Park","doi":"10.1002/hbm.70647","DOIUrl":"10.1002/hbm.70647","url":null,"abstract":"<p>Attention-deficit/hyperactivity disorder (ADHD) traits vary continuously across the general population, yet whether the frontal structural correlates established in clinical ADHD extend to trait variation in nonclinical adults is unknown. Based on meta-analytic evidence, we hypothesized that orbitofrontal gray matter volumes would be negatively associated with hyperactivity traits in 2548 nonclinical Japanese adults (1488 males, 1060 females; aged 23–76 years) who underwent structural MRI and completed the Adult ADHD Self-Report Scale. Regional gray matter volumes of 61 bilateral-averaged regions were tested against inattention, hyperactive motor, and hyperactive verbal trait subscales using partial correlations controlling for age and sex, with false discovery rate (FDR) correction. Five associations survived correction, all linking smaller orbital or medial frontal volumes to higher hyperactivity: medial frontal cortex with hyperactive motor and hyperactive verbal traits, and anterior orbital gyrus, lateral orbital gyrus, and orbital inferior frontal gyrus with hyperactive verbal traits (<i>r</i> = −0.070 to −0.078). The effect sizes were within the range reported for clinical ADHD by the ENIGMA consortium, and secondary analyses found no evidence that bilateral averaging concealed an additional hemisphere-specific association. The findings were robust across sensitivity and permutation analyses. Inattention showed no FDR-significant associations, with Bayesian and equivalence analyses supporting near-null effects at the benchmarked magnitude for most regions. Brain volumes did not improve individual-level prediction of trait scores. These findings identify small orbitofrontal and medial frontal volume associations with hyperactivity along the adult ADHD trait continuum and provide a foundational nonclinical baseline for clinical and transdiagnostic studies of ADHD traits.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth of White Matter Signal Aberrations and Cortical Changes in Men and Women: A 9-Year Multiple-Time-Point Longitudinal MRI Study in Older Adults","authors":"Asta K. Håberg,&nbsp;Line S. Reitlo,&nbsp;Torgil R. Vangberg","doi":"10.1002/hbm.70639","DOIUrl":"10.1002/hbm.70639","url":null,"abstract":"<p>In aging, white matter hyperintensities (WMH) or white matter signal aberrations (WMSA), a proxy for cerebral small vessel disease, are the most common age-related finding on brain MRI scans, with women reported to have a greater burden. Previous studies found that WMH/WMSA were linked to lower cortical volume and thickness. However, no study has investigated the connection between WMSA and both cortical thickness and area using multiple assessments over 9 years. We hypothesized that increasing WMSA was associated with a decrease in both cortical thickness and area over time, compounding the age-typical decrease, and that the effect was more pronounced in women than men. Our cohort consisted of 104 older adults from the general population, born between 1936 and 1942, scanned at the same 3T scanner at baseline (mean age 72.4 years), and followed up at 1-, 3-, 5, and 9 years. We analyzed the 3D MPRAGE scans in FreeSurfer's longitudinal pipeline and extracted the volume of WMSA, cortical thickness and area, grey matter-white matter intensity ratio, plus hippocampal and intracranial volume. Linear mixed-effects models included the interaction between sex and WMSA on cortical thickness and area, and hippocampal volume. We also performed sex-specific analyses. Finally, complete case and sensitivity analyses with known confounders were run. In both men and women, baseline WMSA volume was 3.6 cm³ (95% CI, 2.1–6.2), followed by an average annual growth rate of 7.2% (95% CI, 6.1–8.3). Increasing WMSA over time was associated with accelerated cortical thinning. In men, the association between WMSA and cortical thinning was more pronounced and present in more lobes than in women, despite similar WMSA volume and growth in both sexes. In the lobes with accelerated cortical thinning, increasing WMSA was also associated with an increase in cortical area present only in men. The sex-specific analyses revealed even more pronounced differences in the relationships between WMSA growth and cortical features over time. The changes in cortex associated with WMSA volume were superimposed on the changes related to aging in both sexes. Change in WMSA over time was not directly associated with change in hippocampal volume. Complete case and sensitivity analyses supported the main findings. Thus, contrary to our hypothesis, WMSA change over 9 years was connected to greater cortical thinning alongside a surprising increase in cortical area in men, despite men and women having similar WMSA volume and growth. Our results underscore the presence of marked sex differences in cortical plasticity in the aging brain in the presence of WMSA. WMSA, the most common age-related proxy for small vessel disease, contributed significantly and above that related to aging, to cortical changes, more so in men than women.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149074544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charting the Normal Development of Structural Brain Connectivity in Utero Using Diffusion MRI","authors":"Davood Karimi,&nbsp;Bo Li,&nbsp;Athena Taymourtash,&nbsp;Camilo Jaimes,&nbsp;P. Ellen Grant,&nbsp;Simon K. Warfield","doi":"10.1002/hbm.70609","DOIUrl":"https://doi.org/10.1002/hbm.70609","url":null,"abstract":"<p>Understanding the structural connectivity of the human brain during fetal life is critical for uncovering the early foundations of neural function and vulnerability to developmental disorders. Diffusion-weighted MRI (dMRI) enables non-invasive mapping of white matter pathways and construction of the brain's structural connectome, but its application to the fetal brain has been limited by data scarcity and technical difficulties in analyzing fetal dMRI data. Here, we present the largest study to date of in utero brain connectivity, analyzing high-quality dMRI data from 198 fetuses between 22 and 37 gestational weeks from the Developing Human Connectome Project. We employed advanced fetal-specific tools for brain segmentation and parcellation, and used ensemble tractography to encourage more complete reconstruction of various white matter tracts. For connection weighting, we relied on the notion of fiber bundle capacity. We reconstructed individual structural connectomes and characterized the developmental trajectories. Graph-theoretical analysis revealed consistent increases in integration and segregation metrics over gestation, while bootstrapping confirmed the robustness of nodal and edge-wise developmental patterns. Furthermore, we proposed a novel method for constructing age–specific connectome templates based on aggregation of individual subject connectomes. The new method follows an optimization-based approach to ensure that the connectome templates closely represent individual subject connectomes, are temporally consistent, and proportionally preserve short and long connections. Our analysis shows that this approach is superior to spatial alignment and averaging of the data in image space, with the resulting connectome templates supporting accurate prediction of the gestational age of individual fetuses (mean error = <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mn>0.90</mn>\u0000 <mo>±</mo>\u0000 <mn>0.81</mn>\u0000 </mrow>\u0000 <annotation>$$ 0.90pm 0.81 $$</annotation>\u0000 </semantics></math> weeks). In summary, this study provides robust normative benchmarks for fetal brain structural connectivity and demonstrates that connectome-based measures capture meaningful developmental signatures, offering a framework for future studies of early brain development.</p>","PeriodicalId":13019,"journal":{"name":"Human Brain Mapping","volume":"47 14","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hbm.70609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}