Abstract We introduce a brain-constrained neurocomputational model designed to simulate higher cognitive functions of the human brain, implemented using NEST, a widely used open-source simulator optimised for high-performance spiking neural network simulations. Previously implemented in the custom-built C-based Felix simulation library, transitioning the model to NEST enhances accessibility, reproducibility, and computational efficiency. At the cellular level, the model comprises spiking excitatory neurons and local inhibitory neurons, whereas at the network level, it replicates the structural and functional organisation of 12 cortical regions spanning frontal, temporal, and occipital cortices, along with their associated inter-area connectivity. Additionally, global inhibition mechanisms and neuronal noise are integrated. Learning in the model follows biologically plausible Hebbian plasticity principles, incorporating both long-term potentiation and long-term depression. To validate the NEST implementation, we replicated previous simulation findings obtained with the Felix-based model. The new implementation successfully reproduced the same topographical distribution of cell assemblies following associative learning of object and action words within action and perception systems, replicating a range of previous neuroimaging results. Although the NEST model produced larger cell assemblies than Felix, the overall topographical patterns remained similar, indicating preservation of fundamental network characteristics. Moreover, the transition to NEST significantly enhanced computational efficiency, reducing simulation runtime nearly sixfold compared to Felix. This improvement in computational speed is crucial for expanding the model to include additional cortical regions, such as extending to the right hemisphere, which necessitates increased computational resources.

Integrated Structural Analysis of Trunk Function Assessment After Stroke- New Evaluation Model Based on Multiscale Factor Analysis and Rasch Analysis.

Taxonomic classification alone fails to capture the ecological and functional diversity of vaginal microbiomes, particularly those dominated by Gardnerella species. Using the expanded VIRGO2 gene catalog, we developed the vaginal inference of subspecies and typing algorithm (VISTA), a novel ortholog-based framework that defined metagenomic subspecies and 25 metagenomic community state types (mgCSTs), including six distinct Gardnerella-dominated profiles. The mgCSTs exhibit marked differences in species composition, functional gene content, transcriptional activity, and host immune responses. These findings reveal that Gardnerella predominance does not uniformly equate to dysbiosis and underscore the importance of functional context in shaping host-microbiome interactions. VISTA provides scalable classifiers and an interactive application to support mechanistic studies of vaginal microbiome function and its implications for reproductive health.IMPORTANCEThe vaginal microbiome plays a central role in reproductive and gynecologic health, yet its functional diversity and ecological organization remain poorly understood. Traditional 16S rRNA approaches provide only a partial view of this complexity, overlooking the strain-level variation that often determines microbial behavior and host outcomes. By applying metagenomic sequencing and scalable computational modeling, we developed the vaginal inference of subspecies and typing algorithm, a framework that defines gene-based subspecies and community state types across diverse populations. These classifications reveal new insights into the genomic and ecological foundations of vaginal community structure and offer a standardized resource for comparative and translational microbiome research. This work establishes the foundation for functionally informed diagnostics and precision interventions targeting women's reproductive health.

We identified in two awake surgery cases a postoperative double dissociation between phonological and graphemic output buffer deficits. Using lesion-symptom mapping from ischaemic mini-strokes and preoperative tractography, we demonstrated that the phonological (resp. graphemic) disorder fitted with ventral (resp. dorsal) damage to the AF. Further studies are needed to confirm our hypothesis of a ventro-dorsal functional organization within the AF for phonological versus graphemic processing.

DNA damage repair is essential for maintaining genomic integrity, thereby preventing diseases like cancer. Traditionally, radioresistance has been linked to the ability of cells to repair DNA double-strand breaks (DSBs) accurately. Recent research emphasizes the critical role of spatial chromatin organization and its dynamic reorganization in regulating repair and gene expression. In this study, we have employed single-molecule localization microscopy (SMLM) and Python-based mathematical methods of statistics and topology to locally analyze the spatial organization of γH2AX and 53BP1 foci in 15N-ion irradiated normal human dermal fibroblasts (NHDF) and highly radioresistant U87 glioblastoma cells over extended post-irradiation (PI) periods with nanoscale resolution. Our findings reveal that U87 cancer cells fail to regulate chromatin changes at DSB sites during and after repair. Specifically, Ripley's statistics and cluster analysis showed that both NHDF and U87 cells exhibit smaller, denser, and better separated γH2AX nano-foci surrounded by 53BP1 nano-foci. Mathematical topology approaches, including persistent homology, revealed that γH2AX nano-foci (clusters) have lower topological similarity compared to the more conserved 53BP1 nano-foci during the 24-hour repair period. These findings support the non-random, functional spatial organization of DSB repair (nano)foci and demonstrate its preservation in cancer cells. However, principal component analysis of persistent images showed that γH2AX- and 53BP1 nano-foci in normal fibroblasts exhibit stable, closed cycles, while U87 cells display chaotic, open shifts in topology in the 2D latent space. Combined with DSB repair kinetics measurements, this observation indicates that although U87 cells rejoin DSBs similar to normal cells, they experience more pronounced, dysregulated chromatin alterations during repair, ultimately failing to restore it to its pre-irradiation state. These alterations correlate with topologically more variable DSB sites, slower (more challenging) repair focus formation but faster repair once foci are established, compared to NHDF cells. More disorganized repair and persistent topological alterations likely contribute to genetic instability of cancer cells after irradiation and the development of radioresistant clones, posing challenges for effective radiotherapy.

As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite its popularity among recreational users and distinct pharmacodynamics, the neural correlates of 2C-B remain unexplored. Using 7 T resting-state functional MRI in 22 healthy volunteers, we mapped out the acute effects of matched doses of 20 mg 2C-B, 15 mg psilocybin and placebo across spatiotemporal benchmarks of functional brain organisation. In a within-subjects, double-blind, placebo-controlled crossover design, we evaluated the neuropharmacological and neurobehavioural correlates of an array of connectivity measures - including static (sFC) and global connectivity (gFC), dynamic connectivity variability (dFC), and spontaneous brain complexity. Compared to placebo, 2C-B and psilocybin selectively reduced intranetwork sFC, while broadly increasing between-network and subcortical-cortical connectivity. Compared to psilocybin, 2C-B exhibited less pronounced reductions in between-network dFC but elicited elevations in transmodal sFC. Both compounds yielded spatially divergent increases in gFC yet produced similar increases in brain complexity. Using PET density modelling, the spatial distribution of neural effects aligned with documented differences in monoaminergic transporter and serotonergic receptor binding affinity beyond 5-HT2A, highlighting the role of pharmacology in shaping functional dynamics. Lastly, we show behavioural markers of psychedelic effects are reflected by the decoupling of the transmodal axis of functional brain organisation. Together, our findings highlight 2C-B as a useful new addition to the study of psychedelic neuroscience and may motivate new pharmacotherapy strategies.

Sleep loss significantly disrupts cognitive and emotional functioning, yet the neural consequences of different types of sleep deprivation remain unclear. In a within-subject resting-state fMRI study, we examined how acute total sleep deprivation (TSD) and chronic sleep restriction (CSR) alter intrinsic functional brain organization in 28 healthy adults scanned under three conditions: rested wakefulness (RW), after one night of TSD, and after five nights of CSR.To quantify network-level disruption, we applied graph-theoretical analyses, including a novel within-subject adaptation of the Hub Disruption Index and Covariate-Constrained Manifold Learning (CCML), an unsupervised embedding technique sensitive to subject-level covariates. Moreover, we assessed subjective sleep quality, sleepiness, and circadian traits. Both TSD and CSR were associated with a consistent reorganization of graph topology relative to RW. Furthermore, direct comparisons revealed that TSD and CSR affect different brain hubs. Regional changes in degree, closeness, and clustering coefficients were most prominent in subsystems of the default mode network, frontoparietal network, and cerebellum. These differences were also captured in CCML embeddings, supporting the hypothesis that acute and chronic sleep deprivation exert divergent effects on brain connectivity. Findings were robust across graph thresholds, brain atlases, and nodal metrics. Moreover, these results were further supported by subjective measures - sleepiness was associated with reduced network integration in RW, and circadian phenotype emerged as a key determinant of individual sensitivity to sleep loss. Our results show that TSD and CSR induce divergent alterations in brain functional organization, offering new insights into their neural impact.

A shared hippocampal hub for anxiety and memory contrasts with depression-specific circuitry: A high-resolution 7T fMRI study.

On biological and artificial consciousness: A case for biological computationalism.

Triplet longitudinal masked autoencoder for predicting individualized functional connectome development during infancy.

Mind wandering and its relationship with sustained attention and executive functions in preschoolers.

Rhizostomeae (Scyphozoa) jellyfishes are widespread in neritic waters and include species of commercial importance in Asia. This group comprises jellyfish taxa that host endosymbiotic dinoflagellates of the family Symbiodiniaceae, which provide autotrophic benefits. Despite their value, limited molecular data for Japanese rhizostome taxa has hinder accurate taxonomic classification and interpretation of novel traits. This study combines molecular methods to provide the most complete understanding of molecular phylogenetic relations of Rhizostomeae jellyfishes while assessing the number of Symbiodiniaceae taxa that can be hosted in each species at the medusa level through a new method developed herein for tandem amplification of symbionts and host, validated with microscopy. We also evaluate which rhizostomes produce cassiosomes and whether Symbiodiniaceae are found in the core. Phylogenetic analysis of host mitochondrial (16S rRNA, COI) and nuclear (28S) gene regions of 18 medusae from five genera revealed: (1) Mastigias in Japanese waters corresponds to M. albipunctata ; (2) Cassiopea from Kagoshima likely represents an undescribed species, though Cassiopea xamachana may have been introduced; (3) Two cepheid species - Cephea cephea and Netrostoma setouchianum - occur in Japan; (4) Rhopilema esculentum , a commonly harvested species, is endemic to western Japan. Symbiotic Symbiodiniaceae ITS2 analysis identified three dominant genera ( Symbiodinium , Cladocopium , and Durusdinium ). More than one genus among these was found to be hosted in samples of the genera Mastigias and Cassiopea , indicating plasticity in symbiont association at both the taxon and individual medusa level. Microscopy confirmed cassiosome production exclusively in species examined of the suborder Kolpophorae: Cassiopea sp., N. setouchianum , and M. albipunctata , though absent in a juvenile M. albipunctata sample. Conversely, R. esculentum hosts Symbiodiniaceae but appears to lack the ability to produce cassiosomes. Overall, findings support the distinctive evolution of Symbiodiniaceae–Rhizostomeae symbiosis, the monophyly of the suborder Kolpophorae, and the synapomorphy of cassiosome production in Kolpophorae with onset likely influenced by developmental stage. Broader taxon sampling, especially within Dactyliophorae, will provide further clues on the functional evolution and cellular organization underlying photoendosymbiosis and cassiosome production in these medusozoans.

Mixed-selective organization of reach and grasp in the primate fronto-parietal network.

High-frequency oscillations (HFOs) were discovered more than 20 years ago, and since then they have been studied intensively in the context of epilepsy. HFOs encompass a broad spectrum of oscillations, typically ranging from 80 Hz to several kHz, that include both normal and pathological oscillations, documented in people with epilepsy and animal models. HFOs have drawn considerable attention due to their prominent roles in epileptogenesis, ictogenesis, and functional organization of epileptic tissue. We provide historical background on HFOs in epilepsy and summarize the current state of knowledge, synthesizing clinical and basic science content from the Third International Workshop on HFOs in Epilepsy. Over the years, the field has evolved from single-center analysis of HFOs on invasive electroencephalographic recordings to recent multicenter studies and meta-analysis, which have tempered the conviction or hope that HFOs are uniform, "one event fits all," stand-alone biomarkers. Instead, association of HFOs with other electrophysiological phenomena such as interictal spikes, seizures, and signal features like entropy have highlighted new ways to identify epileptogenic tissue. Advances in recording and analytical tools have significantly expanded their potential applications in both clinical and basic science settings. Several recent publications focus on how scalp HFOs can illuminate disease propensity, severity, and therapy responses. Moreover, it was recently discovered that HFOs are also present in experimental models of Alzheimer's disease, and research is ongoing regarding their relations to the HFOs found in epilepsy. Together, these developments highlight that HFOs represent an evolving research area, with significant inroads made over the years. Yet, key gaps in knowledge remain, and we propose five benchmark areas that warrant future research and advancement.

Objective. In the course of their professional activities, heads of pathological anatomy organizations are faced with the need to resolve problematic issues of a clinical and organizational nature. The wide range of tasks being resolved by the pathological anatomy service (PAS) determines the importance of maintaining its close ties with the clinic, creating structures that combine educational, scientific, and diagnostic areas, as well as the significance of centralizing these structures. A steady trend over the past two decades has been the development of high technologies, which increases the automation of various processes and optimizes the work of both individual laboratories and healthcare institutions as a whole. One of the tools that increases the effectiveness of PAS tasks is the introduction of information systems into routine activities. It is important to analyze the state of the pathomorphological service in terms of trends and methods for improving its efficiency and informatization, as well as to identify problematic issues and ways to solve them. The aim of the study is to characterize the peculiarities of functioning of pathology and anatomy departments and bureaus of the Ministry of Health of the Russian Federation, the status of oncological morbidity, and to determine the current directions of PAS development. Methodology. The material was based on the documents regulating the activities of pathology and anatomy departments and bureaus of the Ministry of Health of the Russian Federation, as well as scientific publications on the organization and problems of functioning of departments of this profile, indexed in the Russian National Library and the Scientific Electronic Library. The content analysis method was used, which allowed us to analyze text arrays (normative-legal documents) and products of communicative correspondence with subsequent substantive interpretation to identify facts and trends of the reviewed documents. Results. Despite the existing regulatory documents governing the functioning of PAS, the ongoing process of computerization of pathological anatomy departments in recent years still lacks clear legislative justification. One of the persistent trends in recent years is the continuing shortage of personnel and material and technical resources in pathological anatomy departments. At the same time, there has been an increase in the number of ante-mortem pathological examinations of biopsy (surgical) material (+8.2% compared to 2022), of which the share of material of the highest degree of complexity (categories IV and V) amounted to more than 54.2%. One effective solution to this problem is the digital transformation of this area, aimed at automating various processes and optimizing the work of healthcare institutions. The introduction of medical and laboratory information systems makes it possible to increase the number of tests, reduce the time required to perform them, create an archive to reduce the number of repeat tests, and, in general, reduce the administrative burden on staff. Modern healthcare technologies make it possible to expand the capabilities of medical institutions by creating a unified information space with the ability to quickly transfer test results to attending physicians and consultants, improve the quality of medical documentation, and simplify the creation of reporting documents. Conclusions. The PAS is under serious pressure due to chronic staff shortages and the moral and physical obsolescence of equipment, against the backdrop of an annual increase in the amount of biopsy material. The increase in the number of pathological studies of surgical material is largely due to the expansion of oncological diagnostics. At the same time, the incidence of malignant neoplasms in the Russian Federation remains high, despite preventive measures and improvements in the effectiveness of cancer treatment. The trend toward increased detection of malignant neoplasms has continued in recent years and is due to both an increase in life expectancy and improved access to imaging methods in the post-COVID era. One effective way to improve the quality of antemortem (biopsy) examinations and speed up diagnosis is to computerize the pathological anatomy service.

The notochord is the defining characteristic of the phylum Chordata, distinguishing this taxonomic group and determining the vertebrate body plan. This review presents current data on the evolutionary origin, molecular mechanisms of morphogenesis, and structural and functional organization of the notochord. Hypotheses regarding dorsoventral inversion and aboral dorsalization are discussed. The role of the gene regulatory network (TBXT, Wnt/PCP, Hedgehog) in the processes of convergent extension and cell vacuolization is described in detail. Particular attention is given to the postnatal fate of the notochord in humans, specifically its transformation into the nucleus pulposus of the intervertebral disc. The role of resident Tie2+ and GD2+ progenitor cells in disc homeostasis and their potential for regenerative medicine, as well as the significance of notochordal markers in chordoma diagnosis, are discussed.

Emerging evidence from both human and preclinical research indicates that cannabis use during pregnancy can influence offspring neurodevelopmental outcomes. Δ9-Tetrahydrocannabinol (THC), the psychoactive compound in cannabis, permeates the placental barrier and modulates the endocannabinoid system, a critical regulator of neurodevelopmental processes. Although converging findings suggest that prenatal cannabis exposure (PCE) is associated with adverse cognitive and mental health outcomes in offspring, the neurobiological mechanisms underlying these associations—particularly in terms of large-scale functional brain network organization—remain poorly understood. In this large-scale cross-sectional study, we leveraged baseline data from the ongoing longitudinal Adolescent Brain Cognitive Development (ABCD) Study, which enrolled 11,875 children across 22 research sites. We examined the effects of PCE, occurring both before and after maternal awareness of pregnancy, on offspring psychopathology and cognitive performance. Resting-state functional MRI data were analyzed using the NeuroMark framework, enabling the identification of individualized intrinsic connectivity networks (ICNs) and estimation of functional network connectivity (FNC) among them. Associations between prenatal exposure, behavioral outcomes, and functional connectivity were assessed using linear mixed-effects models, controlling for a comprehensive set of familial, pregnancy-related, and child-specific covariates. Among 10,836 children (female/male = 5,194/5,642; mean age = 9.96 ± 0.62 years), 754 (6.96%) were prenatally exposed to cannabis. Compared with non-exposed peers, exposed children exhibited higher levels of psychopathology and poorer cognitive performance, except composite fluid cognition (Cohen’sd= − 0.1393 ~ 0.2451, false discovery rate [FDR]–correctedp < .05), consistent with prior reports linking PCE to adverse developmental outcomes. Importantly, prenatal exposure was associated with alterations in FNC that significantly overlapped with neurofunctional correlates of both mental health symptoms (positive correlations betweent-statistics,r = 0.0641 ~ 0.5993, FDR-correctedp < .05) and cognitive performance (negative correlations,r= − 0.5438 ~ − 0.6665, FDR-correctedp < .05). These findings provide novel evidence that PCE is associated with altered large-scale brain network connectivity, which in turn relates to both cognitive and mental health outcomes in late childhood. The overlapping neurofunctional correlates of exposure and behavioral outcomes suggest that THC’s interaction with the endocannabinoid system may disrupt the maturation of functional brain networks, providing a potential mechanistic link between prenatal exposure and neurodevelopmental vulnerability.

The intrinsic organization underlying the central cognitive role of the prefrontal cortex (PFC) is poorly understood. We approached organization by profiling the activity and spatial location of >24,000 neurons recorded in awake mice. High-resolution activity maps of the PFC did not align with cytoarchitecturally defined subregions. Instead, spontaneous activity and tuning to choice during a behavioral task were both related to intra-PFC hierarchy, suggesting that connectivity, rather than cytoarchitecture, shapes the PFC's activity landscape. Low-rate, regular spontaneous firing was a hallmark of both the PFC and high hierarchy. Surprisingly, choice tuning was overrepresented in units displaying high spontaneous firing rates, linking connectivity-based hierarchy to distinct functional properties in separate neuronal populations. Our data-driven approach provides a scalable roadmap to explore functional organizations in diverse brain regions and species, opening avenues to obtain an integrated view of activity, structure and function in the brain.

Abstract Functional connectivity (FC) patterns in the human brain form a reproducible, individual-specific “fingerprint” that allows reliable identification of the same participant across scans acquired over different sessions. While brain fingerprinting is robust across healthy individuals and neuroimaging modalities, little is known about whether the fingerprinting principle extends beyond the brain. Here, we used multiple functional magnetic resonance imaging (fMRI) datasets acquired at different sites to examine whether a fingerprint can be revealed from FCs of the cervical region of the human spinal cord. Our results demonstrate that the functional organisation of this region also exhibits individual-specific properties, suggesting the potential existence of a spine-print within the same acquisition session. Although the spine-print scores are not directly comparable to those observed in the brain, this discrepancy may in part reflect the intrinsic limitations of imaging this region with fMRI, where where the signals are more susceptible to noise and effective resolution relative to structure size, and tSNR are markedly lower than in the brain.This study provides the first evidence of a spinal cord connectivity fingerprint, underscoring the importance of considering a more comprehensive view of the entire central nervous system. Eventually, these spine-specific signatures could contribute to identifying individualized biomarkers of neuronal connectivity, with potential clinical applications in neurology and neurosurgery.

Objective.Precise segmentation and quantification of nerve morphology from imaging data are critical for designing effective and selective peripheral nerve stimulation (PNS) therapies. However, prior studies on nerve morphology segmentation suffer from important limitations in both accuracy and efficiency. This study introduces a deep learning approach for robust and automated three-dimensional (3D) segmentation of human vagus nerve fascicles and epineurium from high-resolution micro-computed tomography (microCT) images.Methods.We developed a multi-class 3D U-Net to segment fascicles and epineurium that incorporates a novel anatomy-aware loss function to ensure that predictions respect nerve topology. We trained and tested the network using subject-level five-fold cross-validation with 100 microCT volumes (11.4μm isotropic resolution) from cervical and thoracic vagus nerves stained with phosphotungstic acid from five subjects. We benchmarked the 3D U-Net's performance against a two-dimensional (2D) U-Net using both standard and anatomy-specific segmentation metrics.Results.Our 3D U-Net generated high-quality segmentations (average Dice similarity coefficient: 0.93). Compared to a 2D U-Net, our 3D U-Net yielded significantly better volumetric overlap, boundary delineation, and fascicle instance detection. The 3D approach reduced anatomical errors (topological and morphological implausibility) by 2.5-fold, provided more consistent inter-slice boundaries, and improved detection of fascicle splits/merges by nearly 6-fold.Significance.Our automated 3D segmentation pipeline provides anatomically accurate 3D maps of peripheral neural morphology from microCT data. The automation allows for high throughput, and the substantial improvement in segmentation quality and anatomical fidelity enhances the reliability of morphological analysis, vagal pathway mapping, and the implementation of realistic computational models. These advancements provide a foundation for understanding the functional organization of the vagus and other peripheral nerves and optimizing PNS therapies.