Neuroinformatics
○ Springer Science and Business Media LLC
Preprints posted in the last 30 days, ranked by how well they match Neuroinformatics's content profile, based on 46 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.
Dudschig, C.; Sonntag, S.; Mackenzie, I. G.
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EegFun.jl is an open-source package for electroencephalography (EEG) analysis implemented in the Julia programming language. EegFun.jl provides a flexible framework for EEG research, covering data import from standard file formats, filtering and re-referencing, Independent Component Analysis (ICA) for artifact detection/correction, epoch extraction, and ERP averaging and visualisation. The Julia language provides the readability of a high-level scripting environment together with execution speeds comparable to compiled code. EegFun.jl combines interactive data visualization with high-performance execution, making large-scale analyses both efficient and easy. Here, we provide a brief overview and introductory tutorial of the core stages of the EEG analysis workflow to illustrate the packages capabilities. The package is freely available under the MIT license.
Ort, J.; Witzig, V. S.; Bak, A.; Heckelmann, J.; Roeb, A.-K.; Hamou, H.; Höllig, A.; Weber, Y.; Clusmann, H.; Delev, D.; Koch, H.
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Micro-electrode array (MEA) recordings are widely used to characterize functional connectivity in neural cultures and have gained traction for the analysis of human brain slices. However, the impact of graph construction methodology on the resulting network topology has not been systematically quantified. Here, we benchmark three methods - shared spiking activity, Pearson cross-correlation, and the spike time tiling coefficient (STTC) - across 37 recordings from human cortical slice cultures classified into low, moderate, and high activity groups. We show that method choice alone produces large topological differences (Cohens d = 0.86-1.14 for clustering coefficient, d > 1.0 for node count), while higher-order features such as modularity remain stable. Each method exhibits a distinct sensitivity profile: shared spiking detects activity-dependent changes primarily through network size, correlation uniquely captures clustering differences, and STTC combines strong biological sensitivity with negligible parameter dependence across lag windows (all d < 0.1). Within shared spiking, z-score normalization dominates all other parameter choices (d > 1.0 versus bin size effects of d < 0.23), functioning as an implicit analytical null model that fundamentally reshapes the edge set rather than merely rescaling weights. Inter-method edge overlap is low (Jaccard index 0.08-0.45) and activity dependent, demonstrating that these methods identify substantially different connections from identical data. Our results reveal that methodological choices including construction method, threshold, and normalization introduce hidden degrees of freedom with effect sizes comparable to the biological signals being measured. We provide practical recommendations for parameter selection, reporting, and cross-method validation in MEA-based network neuroscience. Author SummaryWhen we record electrical activity from brain tissue using grids of electrodes, we can ask how different sites influence one another and map the tissue as a network of connections. Thanks to novel culturing methods, this approach is increasingly used to study human brain slices. However, deciding what is "connected" is not well defined. Researchers use several different methods, and it has never been clear how much this choice shapes the network they end up describing. Here we compared three widely used methods on 37 recordings from human cortical slices spanning a range of activity levels. We found that the method alone can change the apparent structure of the network as much as real biological differences do. The methods frequently disagreed about which connections exist and some technical choices, including normalization techniques, had surprisingly large effects. Because these hidden choices can rival the biological signal, we provide this benchmarking work with practical recommendations for selecting, reporting, and cross-checking methods, so that network studies of brain tissue become more transparent, comparable, and reproducible.
Mohammad, U.; Parani, P.; Saeed, F.
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Background and Objective Epileptic seizure prediction is a critical challenge requiring the discrimination of subtle preictal physiological changes from interictal brain activity. While deep learning has shown promise in this domain, existing models often face limitations due to small EEG datasets, high computational costs for training from scratch, and a lack of patient-independent generalizability. In this paper, we present a novel framework for EEG-based seizure prediction that leverages pre-trained Vision Transformers (ViTs) through custom architectural modifications and optimized re-training strategies. Methods Our primary contributions include: [bullet]CVIT-ESP: A family of vision transformer architectures that replaces standard patch embedding layers with custom N-dimensional CNN stages to refine EEG representations. [bullet] ESPFormer: A lightweight, custom-designed transformer specifically engineered to mitigate overfitting on limited-scale EEG datasets. We identified optimal fine-tuning combinations for transformer blocks by devising a heuristic search-space reduction strategy, significantly reducing the training complexity. We validated our methods using the patient-independent MLSPred-Bench, involving 12 diverse benchmarks with varying seizure prediction horizons. Results Results demonstrate a clear progression in performance: while prior ResNet and vanilla Transformer models achieved an AUC-ROC of 69.0%, our CVIT-ESP architectures achieved the highest performance with a maximum average AUC of 76.4%. Conclusions These findings suggest that adapting pre-trained ViTs with domain-specific CNN front-ends and strategic fine-tuning offers a robust, generalizable, and resource-efficient path forward for clinical seizure prediction systems. Our code is available at: https://github.com/pcdslab/CVitEsp and https://github.com/pcdslab/ESPFormer
Gerin-Lajoie, A.; Frigon, E.-M.; Adame-Gonzalez, W.; Dadar, M.; Boire, D.; Maranzano, J.
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Background: Brain banks usually provide small tissue blocks fixed by immersion in neutral-buffered formalin (NBF). While still underexploited for research, gross anatomy laboratories could provide full brains fixed by perfusion with solutions better suited for gross anatomy dissection. However, the chemicals in these solutions might have a different impact on histology protocols for cell quantification than in NBF-fixed brains. The main goal of this study is to compare the effects on the number and size of labeled neurons of the primary motor cortex (PMC) of mouse brains fixed with three different solutions: (1) NBF, typical of brain banks, (2) a saturated salt solution (SSS), and (3) an alcohol-formaldehyde solution (AFS), both used in human anatomy laboratories. Methods: 27 C57BL/6J mouse brains were perfused with the NBF (N=9), SSS (N=9) or AFS (N=9), then cut in 40-m slices and processed with immunohistochemistry to target neurons. Various quantitative variables were assessed manually and automatically on photomicrographs of 3 regions of interest (ROIs) of the PMC per specimen, namely the total and individual neuronal profile areas, number and diameters. The effects of the three fixatives on these variables were compared using ANOVA or Kruskal-Wallis, depending on the distribution. For measures on individual cells, a generalized linear mixed model was applied. Dice coefficients and correlations were applied to evaluate the agreement of the manual and automatic methods. Results: There was no significant difference between the brains fixed by the three fixatives for the total and individual cell areas, the total cell count and the cell diameters. The values obtained from manual and automatic measures had an overall good agreement (Dice coefficients > 0.79). Conclusion: It was found that the SSS and AFS had similar impacts on the quantitative variables in the tissue as the NBF. These results are promising for neuroscientists interested in using brains from anatomy laboratories for quantitative research on neurons from the PMC.
Herz, N.; Cao, R.; Qiu, S.
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Intracranial electroencephalography (iEEG) provides an unprecedented opportunity to directly record neural activity and causally perturb the human brain through electrical stimulation. Yet, the increasingly collaborative nature and complexity of modern iEEG studies pose substantial challenges for experimental control, data quality, and standardization. Unlike most experimental modalities, human iEEG data are acquired within dynamic clinical environments, where patient condition, recording quality, hardware configuration, and experimental protocols may vary across recording sessions and collaborating sites. The resulting heterogeneity creates opportunities for technical and procedural failures that often remain undetected until downstream analyses, when corrective action is no longer possible. Here, we present a framework for standardized session-level quality assurance in human iEEG research and provide an open-source implementation compatible with Brain Imaging Data Structure (BIDS)-organized datasets. The framework defines four complementary domains of quality assessment crucial for human iEEG studies: protocol fidelity, behavioral integrity, stimulation validation, and signal quality. These domains integrate electrophysiological recordings, behavioral event logs, and stimulation metadata to verify data completeness, confirm participant engagement, validate stimulation delivery, and identify potentially compromised recording channels. Automated quality metrics and standardized diagnostic visualizations are generated following each testing session, enabling rapid identification of technical and procedural failures while corrective action is still possible. By providing a standardized approach to session-level quality assurance, the framework improves data integrity, enhances reproducibility, facilitates analyst training, and supports harmonized data collection across laboratories and clinical sites.
Zaitsev, V.; Wei, C.-S.
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AO_SCPLOWBSTRACTC_SCPLOWElectroencephalography (EEG) is a promising tool for automated detection of mild cognitive impairment (MCI) and dementia, but comparisons across studies are limited by inconsistent datasets and evaluation protocols. This study benchmarks ten deep learning models across four resting-state EEG datasets and eight binary classification tasks using a unified preprocessing pipeline and five-fold subject-wise cross-validation. Each experiment was repeated ten times. SCCNet obtained the highest mean subject-level accuracy, sensitivity, and F1 score, while ShallowConvNet achieved the highest mean segment-level accuracy, specificity, and precision. Subject-level aggregation improved mean accuracy for all evaluated models, and performance varied substantially across datasets and diagnostic tasks. Higher computational cost did not consistently correspond to better classification performance, with several compact architectures remaining competitive with substantially larger models. The results provide a reproducible reference for comparing EEG-based dementia classification models under consistent subject-independent evaluation conditions.
Kerezoudis, P.; Jensen, M.; Klassen, B.; Worrell, G.; Ince, N.; Van Gompel, J.; Miller, K. J.
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IntroductionThe insula is an increasingly important target for functional neurosurgery given its involvement in a range of neurological and neuropsychiatric disorders, including epilepsy and chronic pain. As this practice evolves, optimal targeting will require standardized outcome measures that relate electrode or laser trajectory to postprocedural outcome. Traditional whole- brain registration approaches fail to capture the substantial person-to-person variability in insular gyral configuration, including the relative internal rotation of the insular gyri with respect to standard stereotactic space. ObjectiveWe propose and validate a stereotactic coordinate system based on local anatomical landmarks to facilitate surgical planning and standardized outcome assessment within the insular cortex. MethodsOur approach transforms brain MRI first into standard AC-PC space, and then into an insular-specific space defined by five anatomical landmarks: four points along the central sulcus of the insula and one point at the middle cerebral artery (MCA) bifurcation (at the limen insulae). The system calculates two angles - {theta} (axial) and {varphi} (sagittal) - between the AC-PC line and the insular axis, and the brain volume undergoes sequential rotation through these angles followed by translation to place the coordinate systems origin along the insular axis. ResultsIn a sample of 32 patients, the angle between the AC-PC line and the insular axis ranged from -17{degrees} to 17{degrees} in the axial plane ({theta}) and 31{degrees} to 69{degrees} in the sagittal plane ({varphi}). In the resulting coordinate system, the insular axis defines z = 0 and the MCA turning point defines y = 0. We developed a custom, open-access MATLAB graphical interface that allows intuitive implementation of this system for both surgical planning and postoperative analysis; implanted electrodes, laser fiber position, and ablation geometry can each be localized within this common space. As a demonstration of its utility for pooling data across subjects, we applied the transformation to a previously acquired intracranial electrophysiology dataset and found that anatomically consistent, effector-specific motor representations emerged across 18 subjects once electrode positions were expressed in insular-specific coordinates. ConclusionAs stereotactic surgery for insular targets becomes more common with expanding scientific inquiry, an insular-specific coordinate system may facilitate operative planning and functional mapping, and may help standardize outcome assessment across patients and institutions. SIGNIFICANCE STATEMENTThe insular cortex represents an increasingly important surgical target for therapeutic interventions, yet substantial person-to-person anatomical variability hampers standardized targeting and outcome comparison. The insula is simultaneously the subject of expanding scientific inquiry -- into interoception, pain, autonomic regulation, salience processing, and sensorimotor representation -- much of it now pursued through intracranial recording and stimulation in humans, where cohorts are small, electrode sampling is idiosyncratic, and progress therefore depends on pooling data across patients in a frame that respects insular gyral architecture. We present "Insulotaxy," a stereotactic coordinate system built from consistent, easily identifiable local anatomical landmarks that accounts for the insulas unique rotational relationship to standard brain coordinates. An open-source MATLAB tool transforms imaging into insular-specific coordinates, facilitating surgical planning for ablation and electrode placement while enabling standardized outcome reporting across institutions. By providing locally anchored, anatomically aligned coordinates rather than relying on whole-brain registration, this framework addresses a practical gap in functional neurosurgery and lays a foundation for pooling clinical and electrophysiological data as insular interventions become more prevalent.
Delicado-Moll, R. M.; Guillamon, A.; Teruel, A. E.; Vich, C.
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Determining the amount of information a neuron receives per unit of time is key to understanding brain connectivity and how neural networks encode and transmit information. In particular, estimating this information flow by distinguishing between excitatory and inhibitory synaptic contributions is critical to understanding neural network function, as maintaining the excitation-inhibition (E/I) balance regulates neuronal excitability and circuit stability, whereas its disruption can lead to a plethora of brain disorders, including neurodegenerative and psychiatric conditions. However, because synaptic conductances cannot be measured directly, inverse methods are required to infer them from the membrane potential --a readily measurable quantity. Although partial solutions have been proposed, accurately estimating these conductances remains a significant challenge due to the complexity and diversity of the inputs. This is particularly true in the spiking regime, where neurons actively fire. In this work, we introduce a novel computational strategy that combines two critical metrics extracted from the time course of the membrane potential recording: the amplitude of the spike and the interspike interval. By using these quantities, the proposed method enables the accurate separation of excitatory and inhibitory contributions, yielding highly favorable results in the spiking regime. Author summaryQuantifying the continuous stream of inputs a neuron receives is key to understanding brain connectivity. Inside the brain, individual cells must maintain a tight balance between excitation and inhibition (E/I) to process information correctly, as any disruption in this equilibrium can impair its functionality. However, directly measuring the underlying excitatory and inhibitory synaptic conductances is technically challenging, and existing mathematical tools often fail when neurons enter their active firing regime. In this work, we introduce a novel computational strategy designed to extract and separate these time-varying conductances directly from the neurons spiking activity. By dynamically tracking just two accessible metrics - the amplitude of the spikes and the time intervals between them - our algorithm estimates both conductance profiles with high precision. Furthermore, we demonstrate that this procedure is highly robust against realistic experimental noise and data variability, providing an accessible framework that does not require complex hardware or an unfeasible number of repetitive experimental trials. By tracking changes in the E/I ratio of the synaptic input, this method provides an efficient approach to detecting pathological imbalances and understanding how local connectivity shapes cellular functionality.
Gallitto, G.; Englert, R.; Kincses, B.; Kotikalapudi, R.; Li, J.; Hoffschlag, K.; Ali, S.; Bingel, U.; Spisak, T.
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Traditional fMRI studies rely on predefined task paradigms, where fixed stimulus designs limit the flexibility with which brain-stimulus relationships can be explored. Here, we introduce Reinforcement Learning via Brain Feedback (RLBF), a framework and open-source software package for adaptive stimulus optimization using real-time fMRI. RLBF reverses the conventional direction of inference by using neural responses to guide the exploration of stimulus spaces through reinforcement learning, enabling optimization of predefined brain targets such as regional activity or multivariate neural signatures. The accompanying Python-based software provides a modular framework integrating real-time fMRI data processing, reinforcement learning agents, adaptive stimulus generation, simulation-based testing, and experiment monitoring. Its flexible architecture allows researchers to customize preprocessing pipelines, reward functions, stimulus spaces, and RL strategies for diverse closed-loop neuroimaging applications. We validate the framework in a proof-of-concept study (N=10), demonstrating real-time optimization of a simple visual stimulus space by adapting checkerboard contrast and frequency to maximize primary visual cortex (V1) responses within a single 10-minute fMRI session. RLBF provides an extensible foundation for brain-guided stimulus optimization and enables new approaches for investigating neural specificity, individualized brain-stimulus relationships, and adaptive experimental design.
Han, L.; Yang, X.; Zheng, T.; Yang, Q.; Qin, Y.; Chen, L.; Wei, Q.; Hong, B.; Zhang, X.; Xiong, R.; Gu, Y.; Poo, M.-m.; Xu, B.; Li, C.; Zhang, T.
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Brain-computer interface (BCI) research relies on multistage computational pipelines, but progress has been slowed by fragmented data formats, heterogeneous decoder implementations and hardware-specific deployment toolchains. Here, we introduce BCIJelly, a unified ecosystem that standardizes 18 BCI datasets into AI-ready inputs and integrates 15 benchmark decoders, 80 reusable modules, automated architecture search (AAS) and hardware-aware neuromorphic deployment. Our AAS constructs task-specific decoders without manual design and extends into a large language model (LLM)-driven closed-loop mode supporting single-task, multitask and cross-species decoder design. A single-command pipeline compiles trained decoders for neuromorphic hardware, reducing power consumption by 30 to 50 times while preserving decoding performance. An interactive visualization software enables code-free exploration of neural recordings and decoding outputs. BCIJelly is validated across five BCI paradigms (motor, visual, speech, emotion and auditory) in humans, macaques and mice, providing an extensible ecosystem connecting data standardization, decoder development, systematic evaluation and hardware-aware deployment for BCI research.
Gorenshtein, A.; Omar, M.; Jia, E. L.; Adiniaev, Y.; Daniel, O.; Kruskal, J.; Ahmed, M.; Brook, O. R.; Klang, E.; Barash, Y.
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Objective: Published P300-speller fusion schemes fix prior trust regardless of trial reliability; we tested whether a reliability estimate improves on it. Methods: We reanalyzed 3,373 archived P300-speller selections from 47 people with ALS (BigP3BCI). A fair, matched-search-space comparison, tuning both a fixed weight and an adaptive policy out-of-fold, was evaluated across 22 evaluable language-model priors up to 46.7B parameters. Two representative priors, GPT-2 and a classical 5-gram, additionally received detailed naive and mechanistic analyses. Results: No prior's 95% CI favored adaptive fusion under the fair comparison, despite unexploited oracle headroom at every scale. Under GPT-2, the naive comparison was significantly worse for adaptive fusion; both anchors converged to a degenerate or near-degenerate fair-comparison solution. For the representative anchors, three further controllers failed to convert that headroom into benefit; the fixed-fused posterior's output probability outperformed the best controller for flagging errors (2.8- to 3.8-fold enrichment). Conclusion: A tuned fixed weight is a difficult-to-beat default across the tested scale range; reliability estimation gave no deployable adaptive advantage. Significance: Adaptive weighting should be validated against a fairly tuned baseline across model families and scales; in this dataset, the fused output's confidence identified high-risk selections better than the tested purpose-built ranker.
Eliscu, R.; Kang, G.; Schupp, P. G.; Brody, D. J.; Hariharan, N.; Shamsian, S.; Oldham, M. C.
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Genome-wide coexpression analysis of intact tissue samples is a powerful approach for identifying reproducible signatures of cell types and states, since it can survey vast numbers of individuals, cells, and transcripts. However, it can be difficult to optimize gene coexpression network construction and compare results from independent analyses. To address these challenges, we developed OMICON (theomicon.ucsf.edu) for research on human brain gene coexpression networks. OMICON contains gene expression data from >17K normal and neoplastic human brain samples with standardized metadata. Systematic analysis of independent datasets identified >250K gene coexpression modules, which were characterized and compared via enrichment analysis with >40K gene sets. All modules are discoverable via an advanced search engine that can filter by genes, metadata, and enrichment results. Analyses can also be browsed with an interactive workflow visualization tool, and users can communicate within OMICON using @mention functionality to support communal research on human brain gene coexpression networks.
Mukherjee, S.; Templeton, K. A.; Schiff, S. J.; Monga, V.
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Objective: Accurate volumetric analysis of the brain and cerebrospinal fluid (CSF) is essential for monitoring hydrocephalus, a significant pediatric neurological condition. While computed tomography (CT) provides high-quality volumetric assessment, its associated ionizing radiation poses risks, especially for children. Low-field magnetic resonance imaging (LF-MRI) offers a safer and more accessible alternative, particularly in resource-constrained settings. However, its lower resolution and increased susceptibility to structural distortions make accurate segmentation challenging. This study aims to demonstrate that reliable volumetric measurements can be obtained from LF-MRI that are comparable to CT, enabling safer and more frequent monitoring of infants with hydrocephalus. Approach: We propose EnSegNet-Cross, a cross-modality, enhancement-aware segmentation network for brain volume analysis using LF-MRI. The framework leverages high-fidelity CT data during training but requires only LF-MRI during inference. At the core of the framework is a novel cross-modal topological penalty designed to minimize discrepancies between predicted LF-MRI and CT structures. A central contribution is the integration of a three-dimensional topological loss based on persistent homology, which penalizes topological discrepancies in CSF regions, specifically CSF holes formed by enclosed brain parenchyma, between CT and LF-MRI segmentations. Incorporating these structural priors facilitates generalization across heterogeneous clinical cases while eliminating the need for CT data during inference, resulting in more anatomically coherent and topologically faithful segmentations. Main Results: On a curated cohort of infants with hydrocephalus who had paired LF-MRI and CT scans, including cases with infectious and non-infectious causes, EnSegNet-Cross consistently outperformed state-of-the-art machine learning alternatives. It achieved the highest Dice score of 0.8532 plus/minus 0.03 and Volume Score of 0.9318 plus/minus 0.03. The method also demonstrated robust performance in challenging cases with confounding factors, achieving a Dice score of 0.8340 plus/minus 0.03 and a Volume Score of 0.9111 plus/minus 0.05. By leveraging CT-derived topological priors, EnSegNet-Cross successfully handled anatomically complex scenarios in which conventional models failed. Significance: EnSegNet-Cross provides a reliable and interpretable solution for brain and CSF segmentation, particularly in complex cases of hydrocephalus. This study demonstrates that high-fidelity volumetric estimates can be achieved using only LF-MRI, facilitating frequent, radiation-free monitoring. By bridging the fidelity gap between low-quality LF-MRI and high-resolution CT through clinically grounded enhancement and topological supervision, EnSegNet-Cross offers a robust clinical tool for brain volumetric analysis in infants with hydrocephalus using LF-MRI.
Rajesh, S.; Sharma, D.; Venugopal, R.; Sasidharan, A.; Malipeddi, S.; Chowdhury, P.; P. N., R.
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Aging affects individuals at varying biological rates, prompting the development of the Brain Age Index (BAI) to quantify neurobiological health relative to chronological age and disease risk. While structural MRI has dominated brain age prediction, its high cost, immobility, and low temporal resolution restrict its clinical scalability and responsiveness to transient neurophysiological changes. Electroencephalography (EEG) offers a highly scalable, portable, and temporally precise alternative capable of capturing dynamic brain states. However, the transition of EEG-based models to clinical biomarkers is impeded by methodological limitations, including small or biased datasets, inconsistent preprocessing pipelines, and a distinct lack of interpretable machine learning approaches. To address these persistent challenges, this paper presents a comprehensive, open-source, end-to-end pipeline for large-scale EEG-based brain age modeling. Developed using the Temple University Hospital EEG Corpus (TUEG) the largest publicly available resting-state EEG dataset. The pipeline encompasses rigorous data engineering, reproducible preprocessing, and robust feature extraction. Following quality control and subject-level dataset partitioning to definitively prevent data leakage, exactly 41,181 recordings were successfully retained. Two independent feature sets were extracted: the Catch22 time-series characteristics and a comprehensive set of spectral, aperiodic, and non-linear dynamics from the CCS toolbox. The methodology evaluates seven regression models, optimized via Optuna for hyperparameter tuning, and integrates SHAP (SHapley Additive exPlanations) for transparent feature importance analysis. By making this infrastructure publicly available, this work lowers the barrier to entry for large-cohort studies, fostering reproducible development and clinical validation of dynamic brain age biomarkers.
Djioua, M.
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This study presents improvements to the Hodgkin-Huxley (HH) models of ionic conductance and action potential generation. Sodium and potassium conductances are expressed by a single analytical formula describing the impulse response of a convolution of exponential distributions within a short-memory integration space. Treating transmembrane ion transit duration as a random variable, conductance profiles are interpreted as realizations of the probability density functions governing ionic movements. Applying the central limit theorem, the lognormal distribution emerges as the asymptotic profile of ionic conductances, constituting a fundamental primitive for such biosignals. A temporal state-transition paradigm describes the action potential waveform through four successive membrane potential transitions. Applied to electrophysiological recordings from lamprey reticulospinal neurons, this framework enables indirect estimation of key physiological quantities, including depolarization threshold, Nernst potentials, and net ion fluxes across the membrane. These advances open new perspectives for parameter estimation from experimental data and neuronal network simulation.
Lazar, A. A.; Shukla, S.; Zhou, Y.
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Drosophila connectomic datasets provide increasingly comprehensive maps of neuronal morphology and synaptic connectivity, offering an unprecedented opportunity to explore the structural organization of its neural circuits. This calls for designing automated tools to interact with connectomic datasets at scale for efficiently exploring structural features embedded in the vast amount of data. Yet the central challenge remains the understanding of the functional logic of neural circuits. In order to understand how elements of the functional logic may emerge from this structural organization, it is critical to (i) characterize the objects in the natural environment in which brain circuits operate, and (ii) formulate how brain circuits represent and process the defined objects in the natural environment. To develop and demonstrate a methodology for these requirements, we focus on the Drosophila looming-evoked escape pathway. We modeled the trajectory of looming objects that are on a collision course (direct-hits) or pass-by the fly (near-misses): their projected images on the retina can be characterized by the solid angle (angular size) and elevation. We then analyzed the pathway's morphology across the OpticLobe, Hemibrain, and FlyWire connectome datasets. By abstracting their sub-neuronal structure and retinotopic organization, we constructed an executable circuit model that maps each structural element to a processing block. We demonstrate that this model separates direct hits from near misses well before the angular size could tell them apart. To accelerate the connectomic analysis step, we developed a Python toolset with an agentic, code-free workspace interface called NeuroGraphBench (NGB). NGB provides four composable morphology-analysis primitives and an AI agent that composes them to interactively respond to natural-language queries aided by visualization on an interactive 3D canvas. Thus, NGB automates tedious and repetitive tasks to enable faster and scalable connectomic exploration, keeping human reasoning, instead of writing code, at the center of an open-ended research inquiry.
Jain, Y.; Desai, B.; Qaurooni, D.; Bhavsar, A.; Kienle, P.; Pouch, A. M.; ONeill, K.; Apte, S.; Herr, B. W.; Fisher, S. A.; Börner, K.
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Over the last five years, over 13,000 tissue datasets with 200+ million cells from 20 consortia have been spatially registered into the Human Reference Atlas (HRA) common coordinate framework (CCF). The shared 3D spatial and semantic reference system enables exploration of datasets in the context of all other data across organs, assay types, and spatial scales. However, manual registration of individual samples remains resource intensive, posing feasibility challenges exacerbated by the proliferation of samples, assays, and atlasing efforts. This paper presents two approaches to scale up HRA construction: (1) projecting data across biomedical reference atlas systems and (2) using millitomes to bulk register tissue blocks into a reference organ. Both methods use the AutoMated Alignment and Projection (AMAP) pipeline to align 3D mesh models using point cloud registration. We demonstrate the evolving HRA-aligned atlas ecosystem for 6 models from the SPARC Program (heart), Gut Cell Atlas (large intestine), 500-subject consensus kidneys, and the Julich Brain Atlas. Additionally, we used AMAP to project 7 millitome models across 5 organs onto the HRA ecosystem, integrating 300+ tissue extraction sites. AMAP enables scalable tissue registration of data across atlas ecosystems enabling the construction of detailed reference maps of the human body.
Khan, M. H.; Marin-Pardo, O.; Chakraborty, S.; Lee, K.; Lee, S. Y.; Raman, N.; Iglesias, J. E.; Liew, S.-L.
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Accurate stroke lesion segmentation is essential for large-scale neuroimaging studies, yet manual delineation remains labor-intensive, and existing automated methods often struggle to generalize across imaging protocols and stages of recovery. We developed MAESTRO, a deep learning framework for automated lesion segmentation across the stroke recovery continuum using T1-weighted (T1) MRI alone. We hypothesized that combining a transformer-based architecture with an image augmentation strategy would improve segmentation accuracy and robustness under heterogeneous imaging conditions. T1 MRI scans and expert-traced lesion masks from 955 stroke participants across 33 international cohorts were used to train and evaluate MAESTRO within the open-source nnU-Net framework. Performance was evaluated on a held-out test set using spatial and volumetric agreement metrics. An exploratory human-in-the-loop (HITL) evaluation compared correction of MAESTRO-generated segmentations with manual tracing from scratch. MAESTRO achieved the strongest performance across several evaluated model configurations, providing the most accurate lesion localization and lesion volume estimates (median Dice = 0.686; Pearson r = 0.861; ICC = 0.792). Segmentation performance was sensitive to lesion size and stroke chronicity but remained robust across diverse imaging conditions. Additionally, using a HITL workflow to correct MAESTRO segmentations reduced annotation time by 47.4% compared to manual tracing while improving accuracy relative to both automated and manual workflows. MAESTRO is publicly available to enable robust, automated stroke lesion segmentation from T1 MRI. When combined with human review and correction, MAESTRO offers a practical approach for generating standardized, high-quality lesion annotations, helping reduce a major practical barrier to large-scale stroke imaging studies.
Schirmacher, J.; Maurer, M. C.; Metsch, J. M.; Ploesch, S.; Chereda, H.; Blumenthal, D. B.; Hauschild, A.-C.
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Motivation: Graph Neural Networks (GNNs) have gained increasing interest in the biomedical domain, as the integration of prior knowledge and deep neural networks has the potential to enhance insights into molecular processes and disease mechanisms. However, a comprehensive and systematic assessment of model architectures, data modalities, graph structures, and their performance for graph signal classification in the biomedical domain is yet to be performed. In order to close this gap, we conducted a benchmarking study on multiple GNNs on a Protein-Protein Interaction (PPI) network for Kidney Renal Clear Cell Carcinoma and Breast cancer subtype prediction, performing an in-depth investigation of architectures, incorporating skip connections and various data modalities. Results: While none of the GNNs outperforms the structure-agnostic Multi-Layer Perceptron baseline, all of them can handle bimodal data (gene methylation and expression) and offer the ability to gain explainability based on PPIs. We offer practical guidelines for applying GNNs to graph signal processing tasks specifically for cancer classification. Depending on the underlying dataset and PPI structure employed, models on different data modalities outperform others. Overall, we suggest using ChebNet, which tends to outperform the Graph Convolutional Network and the Graph Attention Network in cancer subtype prediction. We recommend using GNN architectures that employ a simple flattening readout layer, as they provide better classification performance and faster training time than those with global average pooling. Additionally, we tested residual connections, but they had only an insignificant impact on classification performance.
Moshe, Y. H.; Sharma, M.; Dahan, A.; Gvirts, H.
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Despite the growing use of functional near-infrared spectroscopy (fNIRS) hyperscanning to record brain activity simultaneously from interacting individuals in naturalistic settings, most analyses quantify functional connectivity separately for each channel pair. The resulting collection of pairwise estimates is difficult to integrate into a network-level characterization of intra- and inter-brain organization. Here, we present an open, configuration-driven Python toolkit that transforms preprocessed fNIRS hyperscanning time series into functional connectivity graphs. The toolkit constructs a bipartite inter-brain network for each dyad and separate intra-brain networks for each participant, computes node- and graph-level measures, and exports adjacency matrices, edge lists, analysis-ready summary tables, reproducibility metadata, and standardized visualizations. Dataset-specific parameters, including directory structure, participant naming, channel selection, epoch extraction, and edge-retention criteria, are defined in a human-readable YAML configuration file, enabling the same workflow to accommodate differently organized datasets without changes to the source code. We illustrate the pipeline using a representative recording from a mother-infant fNIRS hyperscanning dataset and present the resulting network outputs. The toolkit provides a reproducible framework for moving from pairwise functional connectivity estimates to network-level analyses of dyadic and individual brain organization.