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Helmer, M.

Publications and source records attributed to Helmer, M..

6 recordsLinked to original sources

QuNex Recipes: Executable, Human-Readable Workflows for Reproducible Neuroimaging Research

Preprocessing and analysis of neuroimaging data are technically demanding, often requiring a combination of multiple software tools, modality-specific pipelines, and extensive parameter tuning to match dataset characteristics. These complexities make it difficult to document workflows in sufficient detail to ensure complete transparency and reproducibility. To address these challenges, we introduce QuNex recipes, a framework for defining and executing complete neuroimaging workflows - encompassing data onboarding, preprocessing, and analysis - in a transparent, machine- and human-readable format. Recipes are implemented as an integrated feature of the Quantitative Neuroimaging Environment & Toolbox (QuNex), a containerized, open-source platform for end-to-end multimodal and multi-species neuroimaging processing. The recipes framework enables seamless integration of QuNex commands with custom scripts and external tools, capturing every processing step and parameter setting. A fully reproducible study can thus be shared and replicated by providing only (a) the QuNex version used, (b) the recipe file, and (c) the data. This approach standardizes workflow specification, enhances transparency, and enables one-command replication of complex neuroimaging analyses. By providing a standardized way to describe and share workflows, recipes facilitate open exchange of best practices and reproducible methods within the neuroimaging community.

neuroscience↗

QuNex -- An Integrative Platform forReproducible Neuroimaging Analytics

Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration (1-3), particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability. To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a "turnkey" command for the reproducible deployment of custom workflows, from onboarding raw data to generating analytic features. The platform enables inter-operable integration of multi-modal, community-developed neuroimaging software through an extension framework with a software development kit (SDK) for seamless integration of community tools. Critically, it supports high-throughput, parallel processing in high-performance compute environments, either locally or in the cloud. Notably, QuNex has successfully processed over 10,000 scans across neuroimaging consortia (4), including multiple clinical datasets. Moreover, QuNex enables integration of human and non-human workflows via a cohesive translational platform. Collectively, this effort stands to significantly impact neuroimaging method integration across acquisition approaches, pipelines, datasets, computational environments, and species. Building on this platform will enable more rapid, scalable, and reproducible impact of neuroimaging technology across health and disease.

neuroscience↗

Mapping Brain-Behavior Space Relationships Along the Psychosis Spectrum

Difficulties in advancing effective patient-specific therapies for psychiatric disorders highlight a need to develop a stable neurobiologically-grounded mapping between neural and symptom variation. This gap is particularly acute for psychosis-spectrum disorders (PSD). Here, in a sample of 436 cross-diagnostic PSD patients, we derived and replicated a dimensionality-reduced symptom space across hallmark psychopathology symptoms and cognitive deficits. In turn, these symptom axes mapped onto distinct, reproducible brain maps. Critically, we found that multivariate brain-behavior mapping techniques (e.g. canonical correlation analysis) do not produce stable results. Instead, we show that a univariate brain-behavioral space (BBS) can resolve stable individualized prediction. Finally, we show a proof-of-principle framework for relating personalized BBS metrics with molecular targets via serotonin and glutamate receptor manipulations and gene expression maps. Collectively, these results highlight a stable and data-driven BBS mapping across PSD, which offers an actionable path that can be iteratively optimized for personalized clinical biomarker endpoints.

neuroscience↗

On stability of Canonical Correlation Analysis and Partial Least Squares with application to brain-behavior associations

Associations between datasets can be discovered through multivariate methods like Canonical Correlation Analysis (CCA) or Partial Least Squares (PLS). A requisite property for interpretability and generalizability of CCA/PLS solutions is stability of feature patterns driving an association. However, stability of CCA/PLS in high-dimensional datasets is questionable, as found in empirical characterizations. To study these issues in a systematic manner, we developed a generative modeling framework to simulate synthetic datasets, parameterized by dimensionality, variance structure, and association strength. We found that when sample size is relatively small, but comparable to typical studies, CCA/PLS associations are highly unstable and inaccurate; both in their magnitude and importantly in the latent pattern underlying the discovered association. We confirmed these trends across two neuroimaging modalities, functional and diffusion MRI, and in independent datasets, Human Connectome Project (n{approx}1000) and UK Biobank (n{approx}20000) and found that only the latter comprised sufficient samples for stable mappings between imaging-derived and behavioral features. We further developed a power calculator to provide sample sizes required for stability and reliability of multivariate analyses for future studies.

neuroscience↗

Generative modeling of brain maps with spatial autocorrelation

Studies of large-scale brain organization have revealed interesting relationships between spatial gradients in brain maps across multiple modalities. Evaluating the significance of these findings requires establishing statistical expectations under a null hypothesis of interest. Through generative modeling of synthetic data that instantiate a specific null hypothesis, quantitative benchmarks can be derived for arbitrarily complex statistical measures. Here, we present a generative null model, provided as an open-access software platform, that generates surrogate maps with spatial autocorrelation (SA) matched to SA of a target brain map. SA is a prominent and ubiquitous property of brain maps that violates assumptions of independence in conventional statistical tests. Our method can simulate surrogate brain maps, constrained by empirical data, that preserve the SA of cortical, subcortical, parcellated, and dense brain maps. We characterize how SA impacts p-values in pairwise brain map comparisons. Furthermore, we demonstrate how SA-preserving surrogate maps can be used in gene ontology enrichment analyses to test hypotheses of interest related to brain map topography. Our findings demonstrate the utility of SA-preserving surrogate maps for hypothesis testing in complex statistical analyses, and underscore the need to disambiguate meaningful relationships from chance associations in studies of large-scale brain organization.

neuroscience↗

Hierarchical heterogeneity across human cortex shapes large-scale neural dynamics

The large-scale organization of dynamical neural activity across cortex emerges through long-range interactions among local circuits. We hypothesized that large-scale dynamics are also shaped by heterogeneity of intrinsic local properties across cortical areas. One key axis along which microcircuit properties are specialized relates to hierarchical levels of cortical organization. We developed a large-scale dynamical circuit model of human cortex that incorporates heterogeneity of local synaptic strengths, following a hierarchical axis inferred from MRI-derived T1w/T2w mapping, and fit the model using multimodal neuroimaging data. We found that incorporating hierarchical heterogeneity substantially improves the model fit to fMRI-measured resting-state functional connectivity and captures sensory-association organization of multiple fMRI features. The model predicts hierarchically organized high-frequency spectral power, which we tested with resting-state magnetoencephalography. These findings suggest circuit-level mechanisms linking spatiotemporal levels of analysis and highlight the importance of local properties and their hierarchical specialization on the large-scale organization of human cortical dynamics.

neuroscience↗