Frontiers in Neuroinformatics

The Hierarchical Gaussian Filter (HGF) is a hierarchical Bayesian model of learning under uncertainty and volatility, with a widely used MATLAB implementation. We present HGFX 1.0.0, a Python/JAX toolbox whose primary objective is validated behavioral and numerical compatibility with a frozen HGF Toolbox 8.2.0 reference, while removing MATLAB as a user-runtime dependency. Reimplementation is treated as a validation problem rather than source translation: configuration semantics, parameter transforms, forward trajectories, observation likelihoods, objectives, fitting and statistical surfaces, simulation workflows, official demo behavior, model selection, and backend agreement are compared against the pinned oracle under predeclared tolerances. Two official MATLAB demo workflows reproduce the reference at frozen trajectory tolerances, including a regime in which classic HGF encounters negative posterior precision while eHGF completes successfully. In paired model-selection validation, all 36 BIC winners agree between MATLAB and HGFX. Physical NVIDIA GPU applicability was confirmed on two Tesla T4 devices, with a maximum CPU-versus-GPU final-objective difference of 1.42e-14 against a frozen 1e-7 criterion. Historical parameter recovery results that did not meet predeclared criteria, together with exact MATLAB/HGFX limitation matches, are preserved and are not reclassified as scientific success. A prospectively gated comparison with pyhgf 0.3.2 shows binary64-scale agreement on mapped perceptual trajectories in one authorized three-level binary-HGF cell, while participant-response negative log-likelihood is retained as not directly comparable. HGFX therefore provides a MATLAB-independent Python implementation with an explicit evidence model that separates direct parity, matched reference limitations, backend applicability, and future performance claims.

Mean-field models are extensively used in large-scale brain simulations because they provide a wieldy description of population dynamics while preserving key features of neural activity. Despite their widespread adoption, no common and reproducible methodology currently exists to systematically derive and validate mean-field models starting from biologically grounded single neuron dynamics. As a result, implementations are often ad hoc, difficult to reproduce and rarely reusable. Here we introduce BRIDGE, a modular, open-source Python pipeline that enables the bottom-up reconstruction, analysis, validation, and simulation of mean-field models from single neurons. The framework integrates single neurons modelling, network simulations, extraction of population statistics, parameters analysis, quantitative comparisons between spiking neural networks and corresponding mean-field representations, and simulation of network of mean-fields. Its flexible architecture allows users to incorporate different neuron models and to generate region-specific or state-dependent mean-field formulations. BRIDGE provides a reproducible foundation for developing biologically informed mean-field models suitable for large-scale and whole-brain simulations, supporting the transition from generic homogeneous population models toward region-specific ones. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/742067v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1124404org.highwire.dtl.DTLVardef@2f8b2aorg.highwire.dtl.DTLVardef@1598f37org.highwire.dtl.DTLVardef@c9814b_HPS_FORMAT_FIGEXP M_FIG C_FIG

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.

Neuroimaging research focusing on subcortical brain regions showed that they play a role in a wide range of cognitive functions and associated their structural alterations to various psychiatric disorders. Methods to analyse such structures were developed to observe changes, not simply in terms of volumes, but in terms of surfaces, which are able to detect subtle and local changes in shape and geometrical configuration. Such advanced analyses have however been largely restricted to command line environments with relatively limited access to Python users or researchers with low technical expertise. We present SubCortexMesh as a user-friendly toolbox which covers automated surface estimation from popular subcortical volume segmentations (FreeSurfer and the Functional Magnetic Resonance Imaging of the Brain Software Library (FSL)), computes shape-related vertex-wise metrics (thickness, surface area and curvature) for whole cohorts and includes statistical analyses. This is all done inside Python, automatically computing all subjects of a given preprocessed directory, with the explicit intent to minimise steps and manual coding required from the users. SubCortexMesh includes statistical tools which allow conventional random field theory-based cluster analyses on native subject metrics, standardised within common surface templates, thus containing a whole workflow necessary to run an up-to-date shape-wise subcortical analyses in one package.

Simplified spiking neuron models such as the Adaptive Exponential Integrate-and-Fire (AdEx) model reproduce the firing behaviour of diverse neuron types at a fraction of the cost of biophysically detailed models, making them attractive for large-scale brain simulation. Fitting their parameters to recordings, however, still relies on derivative-free search such as grid search or evolutionary algorithms, because the discrete spike-and-reset mechanism renders these models non-differentiable. Surrogate gradients, used in deep spiking networks, replace the spike derivative with a smooth approximation on the backward pass. Whether they also enable efficient gradient-based parameter estimation for single simplified neurons is untested. We implement a differentiable AdEx model with a surrogate-gradient variant in the Jaxley framework. The implementation is on par with target-compiled C++ Brian2 code while remaining end-to-end differentiable, vmap-batchable and GPU/TPU-portable. It is 200 times faster than Brian2's default runtime mode. Across a recovery-radius benchmark of 2,700 paired runs, gradient-based fitting never matched a gradient-free Nelder-Mead baseline. At sub- threshold levels, gradient descent instead beats Nelder-Mead. The obstacle is therefore the spike mechanism and the loss geometry it induces, not gradient descent itself.

Independent component analysis (ICA) is widely used to remove artefacts from EEG and TMS-EEG recordings, but the components that correspond to artefacts are usually identified by manual inspection, which is subjective and difficult to reproduce. Existing automated classifiers are either designed for ordinary EEG and do not target the artefacts specific to concurrent transcranial magnetic stimulation, or are built on EEGLAB, so none is available for FieldTrip-based pipelines. We present TEFAR, a lightweight, configurable framework for semi-automatic artefact-component classification that applies the same detectors to ordinary EEG and TMS-EEG. TEFAR is built on FieldTrip and requires no additional MATLAB toolboxes. Each artefact class (line noise, blinks, lateral eye movements, cranial muscle, cardiac activity, and the TMS decay and recharge artefacts) is identified from the spectral, spatial, or temporal signature that its components are known to express. Detection thresholds use robust statistics (the median and the median absolute deviation rather than the mean and standard deviation), so that a single dominant artefact component cannot raise the threshold that is meant to detect it. In 30 ground-truth simulations, TEFAR reached a specificity of 1.000 and a sensitivity of 0.96-0.97 for both profiles. An application of TEFAR to real EEG and TMS-EEG recordings is the next step and will be reported separately.

As multisite and multi-study data aggregation becomes increasingly common for improving statistical power and sample diversity, robust harmonization methods are needed to address biases introduced by batch variation, particularly in neuroimaging research. Although a variety of harmonization approaches are available, the lack of systematic guidance for diagnosing batch effects and selecting appropriate methods remains a major challenge. To address this gap, we introduce ComBatFamQC, a comprehensive R package designed to streamline batch-effect diagnosis, harmonization, and post-harmonization analysis. ComBatFamQC integrates a user-friendly Shiny app for interactive batch-effect diagnostics, state-of-the-art harmonization methods from the ComBat family, including ComBat, longitudinal ComBat, ComBat-GAM, and CovBat, and tools for downstream analysis after harmonization. The package provides qualitative visualizations, statistical tests for batch-effect assessment, and a consistent interface that supports both in-sample and out-of-sample harmonization through the Shiny app, the R console, or the command line. In addition, it includes functions for post-harmonization analyses to facilitate downstream modeling. Its modular design also supports the systematic incorporation of future harmonization methods and expanded downstream analysis capabilities.

Recurrent neural networks (RNNs) provide a central tool in neuroscience to optimize cognitive tasks and reconstruct dynamical systems. Around these two paradigms, many RNN model variants have been tailored to capture specific computations of the brain. In practice, however, this methodological diversity remains difficult to exploit, because different paradigms and model variants are mostly implemented in idiosyncratic, study-specific code. Here we introduce NeuralRNN, an open-source Python framework that unifies these paradigms and model variants in a general-purpose pipeline. NeuralRNN brings task optimization, dynamical system reconstruction, and biological constraints into a single objective interface. It also provides an integrated and extensible model library spanning generic, structure-constrained, gain-modulated, and gated RNNs. Furthermore, data, models, and training are constructed through a shared automated pipeline and are equipped with a suite of tools for dynamical systems analysis. Together, NeuralRNN lowers the barrier to implementing, comparing, and extending RNN methods in neuroscience.

Electroencephalography (EEG) is fundamental to cognitive neuroscience as it provides a direct measure of human neural activities with millisecond precision. Its noninvasive nature allows for the study of brain function across diverse age groups and experimental contexts--from newborns to adults, and from tightly controlled laboratory environments to more naturalistic real-world settings. However, EEG signals--especially those recorded from infants--are highly prone to noise and arti-facts, posing significant challenges for data analysis. To address these issues, we present APICE-Py (Automated Preprocessing for Infants Continuous EEG), an open-source preprocessing pipeline originally designed as a matlab toolbox for infant EEG and now re-implemented in Python to support scalable and flexible analysis across developmental and adult datasets. APICE-Py is built upon three core principles: (i) adaptive artifact detection on continuous data using data-driven thresholds rather than fixed cutoffs; (ii) hierarchical artifact correction, combining short-segment correction via Principal Component Analysis (PCA) with broader segment and continuous data correction using Spherical Spline Interpolation (SSI); and (iii)transparent reporting, providing comprehensive quality logs and decision-tracking to ensure reproducibility and informed analysis. We summarize the underlying algorithms, release an implementation compatible with common EEG formats, and demonstrate its use on three datasets spanning neonates, 5-month-old infants, and child-parent hyperscanned data, acquired using high-density wet electrodes and mobile gel-based EEG systems. When benchmarked against the original MATLAB implementation, APICE-Py achieved comparable levels of data quality and trial retention. While the original pipeline was developed for early developmental EEG (e.g., infants), we show that the pipeline further extends its applicability to both children and adult datasets, enabling robust preprocessing across a broad age range. Moreover, it supports data acquired using a variety of EEG configurations and experimental settings, highlighting its flexibility across age groups, hardware systems, and paradigms. The APICE-Py source code and documentation are freely available at https://github.com/neurokidslab/apice-py.

Purpose: Attenuation correction (AC) of PET images is essential for accurate quantification. Brain PET studies comprising simultaneous EEG (PETEEG) may suffer from metal artifacts in CT images (CTEEG), or improper correction when electrodes are not present in the CT (CT0). As these influences are not well-characterized, we aim to compare metal artifact reduction (MAR) techniques for CTEEG images, and evaluate differences between attenuated-corrected PETEEG using CT0 and CTEEG with MAR, synthetically placed electrodes (CTEEG-synth) and extended Hounsfield unit (HU) range. Methods: 19 healthy participants underwent two total-body PET/CT scans with [18F]FDG, with and without 32 EEG scalp electrodes, respectively. We evaluated five MARs to reduce streaks caused by the EEG electrodes in the CTEEG. Finally, CT0, CTEEG with (CTEEG-iMAR-Ext) and without extended HU range (CTEEG-iMAR) and CTEEG-synth were used to perform attenuation correction of PETEEG. We compared our results to PET0/CT0 scan using relative differences. Results: CTEEG and CTEEG-iMAR showed the smallest differences to CT0. PETEEG/CTEEG-iMAR-Ext exhibited the lowest differences to PET0/CT0 (average bias across all regions of -0.46%), followed by similar performance of PETEEG/CTEEG-iMAR (-0.73%) and PETEEG/CTEEG (-0.76%). Conversely, PETEEG/CT0 demonstrated the largest average differences (-1.81%), with values reaching -2.71% in the parietal lobe. These differences were consistent across subjects, yielding significant effects in most of the brain (pFWE < 0.05). CTEEG-synth performed not as good as CTEEG (-1.21%). Conclusions: CTEEG with extended HU range is most suitable for attenuation correction of PETEEG images, with MAR correction offering little additional improvement.

Deep learning models for electroencephalography (EEG) pathology detection achieve competitive accuracy but offer limited interpretability. In this paper, we introduce concept bottleneck models (CBMs) for EEG pathology detection which use clinical EEG biomarkers computed analytically from the signal as a bottleneck to be used for prediction. Those concepts include band power, spectral ratios, alpha peak frequency and amplitude, hemispheric asymmetry and phase locking values. With the backbone based on shallow convolutional neural network (CNN), we compare a black box baseline with two variants of CBMs. The hybrid variant is a classifier receives a residual projection of the backbone features. The pure variant is a CBM where the classifier receives only the predicted concepts. Models are evaluated on abnormality detection and dementia classification followed by concept prediction quality and leakage analysis. Both CBMs approach the baseline on TUAB (82.7-82.9% vs 83.6%) and are 2-5 percentage points lower on CAUEEG (57.9-60.5% vs 62.7%). The pure CBM exhibits concept fidelity concern where the predicted concepts deviate from their ground truth values. Replacing them with their true values causes severe cost on accuracy by 26 and 22 points on TUAB and CAUEEG. The concept fidelity concern is mitigated by increasing the weight of the concept loss to match the ground truth concepts. the mitigation comes with small accuracy cost on TUAB but a relatively larger cost on CAUEEG. The code of the experiments and full logs are available at https://www.github.com/mhmdrdwn/cbm.

Brain cell morphology plays a crucial role in function and pathology. Biophysical models of diffusion MRI (dMRI) quantify cell morphology in vivo, enabling the design of novel biomarkers. These models represent cells by simplified geometries, such as spheres and randomly oriented cylinders, for which analytical signal expressions exist. However, dMRI signals are sensitive to morphological features, such as branching, tapering, undulation, beading, and protrusions, unaccounted for in most models, as they often render analytical solutions impossible. Simulations of the dMRI signal in synthetically generated cells offer a powerful tool to explore how microstructural morphology impacts the dMRI signal. Nevertheless, no tool to generate digital replicas of brain cells is available openly. To address this gap, we introduce the OCTOPUS toolbox, which generates cells featuring all geometrical features described above. OCTOPUS, provided via the Python interface OCTOpool, enables accessible, efficient creation of cells with complex geometries. We recreated histologically reconstructed neuronal and glial cells, including pyramidal, GABAergic and glutamatergic neurons, and astro- and microglia. To illustrate the plausibility of OCTOPUS-generated cells, we reproduced established properties of dMRI signals from brain tissue, such as the signatures of short-range disorder, branching and protrusions, and a high-b-value power law. By comparing the geometries and dMRI signals of generated and original cells, we found different growth strategies adequate for more isotropic and more anisotropic cells. We anticipate that realistic cell substrates created by OCTOPUS will help validate biophysical models, design dMRI sequences sensitive to fine-grained cell morphology beyond analytical models, and generate realistic numerical substrates of brain tissue.

A major goal of the BRAIN Initiative Cell Atlas Network (BICAN) is to create a suite of foundational reference cell atlases and associated standards for human and non-human primate brains. Central to this goal is the creation of cross-species harmonized cellular taxonomies and structural parcellations with formal ontologies that can be mapped into 3D reference frameworks bridging neuroimaging and cellular and histological resolutions. We describe here an iterative approach, focused initially on the basal ganglia, to co-create structural and cellular ontologies in human, macaque and marmoset brains, including a Harmonized Ontology of Mammalian Brain Anatomy (HOMBA), and to map and refine structural parcellations into neuroimaging-based common coordinate frameworks. These references provide the framework for documenting and mapping all experimental sampling in BICAN, allowing analyses of cellular and molecular variation as a function of topographic position, and enabling comparisons of cellular, molecular and neuroimaging-based functional variation within and between primate species. HighlightsO_LIA hierarchical Harmonized Ontology of Mammalian Brain Anatomy (HOMBA) covering 2348 structures C_LIO_LIHOMBA-annotated 3D common coordinate frameworks (CCFs) of the basal ganglia across species C_LIO_LIHistologically informed 3D parcellation/atlas of 280 human subcortical structures indexed by HOMBA C_LIO_LIMapping and integration of structural, cellular and functional data with HOMBA and CCFs C_LI

Large-scale biophysically-detailed models of the brain are instrumental in unraveling how cellular, synaptic, and circuit-level mechanisms contribute to neural dynamics. Such models are built around large populations of single-neuron models whose morphologies must preserve physiological variability to reproduce integrative properties and firing patterns observed experimentally. Experimental reconstruction of morphologies is a time-consuming and resource-intensive process, unlikely to supply them at the required scale. Several data-driven methods for morphology synthesis have been developed, which nonetheless rely on extensive datasets for parameter estimation. To address this limitation, we developed NeuWalk, to our knowledge the first public Python library for morphology synthesis based on branching-and-annihilating, biased-and-correlated random walks. It estimates branching and annihilation rates from Sholl intersections and, optionally, bifurcation counts, while also ensuring their replication in synthetic morphologies; user-specified combinations of biases, implementing somatofugality, self-avoidance, spatial competition, and branching-angle control, sculpt morphological patterns characteristic of each neuron class. We then validated the method on mitral and middle tufted cells of the olfactory bulb, semilunar and pyramidal cells of the anterior piriform cortex, and neocortical pyramidal neurons: means and variances of Sholl intersections, bifurcation counts, and total dendritic length were statistically indistinguishable between synthetic and natural morphologies, with the single exception of its variance in apical dendrites of piriform cortex pyramidal neurons. As Sholl intersections and bifurcation counts are commonly reported in the literature, and biases can be inferred from published images or qualitative descriptions, NeuWalk requires no immediate access to experimental reconstructions, striking a trade-off between data-driven parameterization and empiricism without sacrificing morphological accuracy.

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.

Electromyography (EMG) is fundamental to clinical assessment, rehabilitation, neuromuscular research, and human-machine interfaces. Despite decades of use, no widely adopted standard exists for organizing and sharing EMG data, limiting reusability and large-scale data aggregation. We present EMG-BIDS, an extension to the Brain Imaging Data Structure (BIDS) that standardizes the organization of EMG recordings. EMG-BIDS addresses challenges unique to EMG, including diverse electrode types (surface or intramuscular, single channel to high-density arrays), heterogeneous electrode placements across anatomical locations, montages (e.g., monopolar or bipolar sensor designs), and the critical need for transparent documentation of sensor positioning. The specification introduces hierarchical coordinate systems that link local electrode grids to anatomical landmarks, enabling precise and reproducible placement documentation. EMG-BIDS is now part of BIDS as of version 1.11.0, supported by existing tools, including MNE-BIDS and EEGLAB. We demonstrate the specification through public datasets, including high-density surface EMG recordings. EMG-BIDS provides the foundation for FAIR (Findable, Accessible, Interoperable, Reusable) EMG data sharing, enabling meta-analyses, multi-site studies, and machine learning applications that require standardized, well-documented datasets.

The cynomolgus macaque is a widely used primate model in neuroscience, yet existing brain atlas resources remain limited in resolution and lack a standardized framework for integrating structural, molecular, and connectivity data within a common reference space. Here we present CynoBrain, a high-resolution multi-modal brain atlas constructed from population-averaged MRI data at 9.4 Tesla, yielding a 75 micron isotropic template with significant improvement in resolution. A co-registered whole-brain autofluorescence template resolves cytoarchitectural boundaries not visible in MRI template. Three major parcellation schemes, D99 143-area, M132 105-area, and SARM are incorporated in CynoBrain space. Spatial transcriptomic based laminar definition, reconstructed from 2D sections into volumetric common space, provides a six-layer cortical segmentation spanning the whole cortex. As a demonstration of the integrative capability of this framework, 2D retrograde tracing data is reconstructed and mapped to the Cynobrain space, enabling volumetric compilation of 2D macaque brain mapping data across subjects. An online interactive platform was constructed to allow full access to Cynobrain, establishing it as a scalable, open platform for cross-modal data integration for primate neuroscience. Overall, CynoBrain is a unified framework for cross-modal data integration for macaque brain mapping with high-resolution, multiple atlases and transcriptomic based laminar definition.

Dynamic positron emission tomography (PET) with long axial field-of-view (LAFOV) scanners enables multi-organ imaging and kinetic quantification beyond static (late-phase) imaging; however, the long times typically required for dynamic acquisitions remain clinically impractical. This study evaluates a deep learning (DL) framework to enable abbreviated dynamic PET acquisitions, comparing single-time-window (STW, early dynamic data only) and dual-time-window (DTW, early dynamic data plus a late 5-min static frame) protocols with early dynamic scan durations of 5-30 min and dose levels ranging from 360 MBq to 18 MBq. Seventeen 60-min dynamic [18F]FDG datasets were first motion-corrected using a staggered FALCON pipeline and then used to train and test a spatiotemporal DL model for autoregressive frame prediction. Performance was assessed across the full quantitative workflow, from DL-predicted frames and time-activity curves to organ-based kinetic modeling and voxel-wise parametric imaging in multiple tissues and two patient cohorts. DTW protocols consistently outperformed STW, better preserving late-phase kinetics. For a 15-min early dynamic scan, adding a late 5-min scan reduced mean absolute Ki difference from 23% (STW) to 17% (DTW) in the liver and from 26% to 15% in the thalamus. DTW + DL further reduced errors to [&le;]10% in the liver, thalamus, and breast lesion, and 16% in muscle. Our recommended protocol, 15-min early dynamic scan plus a 5-min late scan with DL, remained robust to up to a 5-fold dose reduction (~74 MBq). Overall, these findings support DL-enabled abbreviated, low-dose dynamic LAFOV PET as a clinically feasible approach for accurate kinetic quantification

Deep brain stimulation (DBS) is a well-established therapy for various neurological disorders. Clinical outcomes of DBS depend on electrode placement and stimulation programming, with growing evidence suggesting that targeting specific sites and networks can improve therapeutic efficacy. This targeting can be facilitated using high-accuracy, multi-modal biophysical models. In this article, we present the open-source platform OSS-DBS v2 that enables researchers and clinicians to build such biophys- ical models. Building upon previous work, the new version combines automated volume conductor generation, accurate and efficient electric field modelling and stimulation-driven neural simulations. OSS-DBS v2 provides an extensive library of intracranial electrodes, which can be modelled simul- taneously to test complex stimulation paradigms. Its application programming interface facilitates integration of external data workflows, such as impedance measurements. Furthermore, an integration with the Lead-DBS toolbox offered a straightforward graphical user interface for stimulation volume and pathway activation modelling, further complemented by an optimization framework. OSS-DBS v2 relies entirely on open-source software, supports all major operating systems and is designed for efficient execution on consumer-grade hardware.

Backgroundsingle-cell and spatial omic techniques have enabled the investigation of cell type specific alterations in biologically complex tissues. In an effort to map cell taxonomies, large atlas-based studies and multi-laboratory consortia have created sets of annotated cell types. However, application of atlas- or database-level knowledge to individual studies is often resource-limited and computational demands scale with the size of both query and reference datasets. ResultsHere, we report a statistical framework for rapid label transfer using summary statistics and user-defined hyperparameters. Semi-Automated Hand Annotation (SAHA)1 allows the user to investigate magnitude, directionality, and statistical significance of matches between unnamed query clusters and reference cell types using either marker-based or marker-free methodologies. By pre-loading the package with summary statistics from the Allen Brain Cell Atlas of the mouse brain, the SAHA R package is capable of rapid cell type comparisons that closely mimic cell typing by integration-based annotation strategies. Furthermore, this flexible package is capable of comparisons across omic modalities, cluster resolutions, and annotations from any study where summary statistics are available. We demonstrate this flexibility by using multiple single-nuclei studies of the mouse cerebellum, mouse cerebral cortex, human cerebral cortex, human peripheral blood mononuclear cells, and one mouse spatial transcriptomic assay. Importantly, this method avoids privacy concerns as it does not require the sharing or deposition of raw data in a web-based tool. ConclusionsAs a result, SAHA offers a non-deterministic annotation reporting structure with automated html reports and summary statistics for transparency in cell typing decisions. Taken together, this scalable framework implemented as a package in R affords increased biological insight into the annotation of single-cell and spatial datasets. SHORT SUMMARYAcri and colleagues present rapid cell type annotation without the need for dataset integration. This paper outlines the utility of the package, SAHA, in annotating neurological datasets.