Biology subjects

Lu, R.

Publications and source records attributed to Lu, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Maternal Folate Nutrition Programs Adult Hematopoietic Stem Cell Function Through Mitochondrial Remodeling

Folic acid fortification for the prevention of neural tube defects has been a cornerstone of public health policy for nearly three decades, but its broader consequences for other developing organ systems, particularly the hematopoietic system, are poorly studied. Hematopoietic stem cell (HSC) emergence overlaps developmentally with neural tube closure, and folate-dependent one-carbon metabolism is critical for nucleotide synthesis, cellular methylation, and redox balance, positioning folate as a candidate regulator of HSC programming. Using dietary models of maternal folate deficiency or supplementation in mice, we demonstrate that maternal folate acts as a dose-dependent developmental tuner of hematopoiesis, programming adult offspring HSC function through divergent mitochondrial and chromatin states. Maternal folate deficiency impaired adult HSC self-renewal, associated with mitochondrial defects, disrupted cristae, elevated proteotoxic stress and a stress-adapted chromatin landscape. In contrast, maternal folate supplementation enhanced HSC self-renewal accompanied by improved mitochondrial quality control and CDC42-associated organelle remodeling, and established chromatin states permissive for stem cell maintenance. Fetal HSC metabolomics identified shifts in one-carbon intermediates, pyruvate and lipid pools, suggesting that divergent fetal metabolic states provide substrate-level inputs that drive persistent and opposing chromatin programs in offspring HSCs. Our findings establish maternal folate availability as an unappreciated regulator of lifelong hematopoietic output demonstrating that a single maternal micronutrient, folate, is sufficient to program adult HSC function and regenerative capacity through persistent metabolic and mitochondrial programming.

cell biology↗

bioRxiv2026

Habitual sleep duration is associated with the cortical organisation of brain network controllability

Sleep is fundamental to adaptive brain function, yet how habitual sleep relates to the structural network properties that support flexible transitions between brain states remains poorly understood. Combining wrist-accelerometer sleep measures with diffusion MRI connectomes from 15,799 UK Biobank adults, we show that longer workday sleep is associated with higher modal controllability of somatomotor systems and lower controllability of visual cortex. This system-specific signature reproduced in a locked test set (n = 4,740) and was robust across extensive sensitivity analyses. Decomposition showed that it reflects a redistribution of structural connection weight, with greater absolute visual connectivity and a smaller somatomotor share of the whole-brain total. Weekend catch-up sleep showed no comparable association. The signature was distinct from brain-ageing patterns and, across 1,226 phenotypes, related mainly to physical activity and body composition rather than cognition. These findings link everyday sleep habits to the system-specific organisation of brain network controllability.

neuroscience↗

bioRxiv2026

Stromal control of sympathetic rewiring in metastatic lymph nodes

Metastatic lymph nodes (LNs) are dynamically remodeled tissues, but this process has been understood mainly in immune and stromal terms. We show that tumor-driven LN remodeling also involves adaptive neural rewiring. In a mouse model of nodal metastasis, sympathetic fibers, but not sensory fibers, progressively expanded during LN remodeling and tracked with metastatic progression. Fibroblastic reticular cells (FRCs) adopted a neuro-supportive program characterized by increased hepatocyte growth factor (HGF) production, while local stromal HGF acted through MET on sympathetic neurons to stimulate neurite outgrowth. Increased substrate stiffness enhanced FRC activation and HGF production, suggesting that mechanical remodeling may reinforce the neuro-supportive stromal state. Inhibition of HGF signaling or ablation of sympathetic innervation reduced LN enlargement and nodal tumor burden. These findings identify neural plasticity as a functional component of the metastatic LN niche and reveal a stromal/mechanical/neural framework that supports metastatic LN progression.

cancer biology↗

bioRxiv2026

Clonally expanded CD8 T cells in AML adopt an NK-like program distinct from canonical exhaustion

CD8 T cells are key mediators of anti-tumor immunity, yet their differentiation states and clonal architecture within the acute myeloid leukemia (AML) bone marrow microenvironment remain incompletely defined. We performed high dimensional immune profiling of bone marrow samples from 46 newly diagnosed AML patients using mass cytometry to probe the microenvironment and T cell states. We used single-cell RNA and T cell receptor (TCR) sequencing to define CD8 T cell phenotypes, transcriptional states, and clonal architecture. AML-associated CD8 T cells were skewed toward terminally differentiated effector memory cells re-expressing CD45RA (TEMRAs), while canonically exhausted T cell populations were rare. Functional studies revealed that TEMRA CD8 T cells robustly produced IFN{gamma} and TNF upon in vitro stimulation. Clonal expansion was concentrated within the TEMRA compartment. Comparison of TCR sequences with known viral epitopes identified a small subset of expanded viral-specific clonotypes, while the majority of highly expanded clonotypes had unknown specificity and may include AML-specific T cells. Differential gene expression analysis revealed shared cytotoxic effector programs during clonal expansion but diverging activation signatures: viral-specific clones upregulated canonical T cell receptor signaling genes, whereas expanded clones of unknown specificity exhibited enrichment of natural killer (NK) receptor-associated genes. These genes comprised the leukemia-associated NK-immune (LaNKi) score which was elevated in an independent AML dataset compared to pan cancer tumor infiltrating lymphocytes. These findings define the CD8 T cell differentiation landscape and clonal architecture in AML marrow at diagnosis and suggest that T cell dysfunction in AML diverges from classical activation and exhaustion paradigms.

cancer biology↗

bioRxiv2026

Somatic DDX41 mutations confer neomorphic splicing activity in the pathogenesis of myelodysplastic neoplasms

Germline mutations in the RNA helicase DDX41 are the most common genetic predisposition to myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), representing 5-7% of AML. Over 70% of patients acquire a somatic mutation at specific hotspots (R525H/G530D) in the helicase domain of DDX41 in trans, which is linked to disease progression. DDX41 has diverse cellular functions, including RNA splicing, ribosome biogenesis, R-loop resolution and inflammation. However, the mechanisms by which somatic DDX41 mutations drive MDS/AML pathogenesis are yet to be determined. Here, we systematically evaluated the function of pathogenic, missense germline and somatic DDX41 mutations. We report that DDX41 somatic mutations are gain of function alleles and fail to rescue AML cell growth, distinct from germline DDX41 mutations. DDX41 somatic mutations R525H and G530D drive widespread splicing changes in isogenic AML cell lines, consistent in genetically engineered murine bone marrow HSPCs and CD34+ cells from DDX41-mutant MDS/AML patients. Mechanistically, DDX41-R525H exhibits increased RNA binding affinity compared to wildtype, with aberrantly spliced RNA targets overlapping with enriched binding. Strikingly, aberrant splicing of SEPTIN7 is enriched exclusively in CD34+ HSPCs of patients harboring both germline and somatic DDX41 mutations but absent in samples with germline mutation alone or lacking DDX41 mutations altogether. SEPTIN7 mis-splicing introduces a premature stop codon resulting in its downregulation at the protein level. SEPTIN7 is a known regulator of cytokinesis, HSC polarity and repopulation capacity. Our results identify a novel mis-spliced candidate, SEPTIN7, whose deregulation implicates a mechanism by which the DDX41 somatic mutations promote dysplastic hematopoiesis.

cancer biology↗

bioRxiv2026

OPA1-dependent mitochondrial remodeling coordinates TCR signaling and metabolic adaptation during iNKT cell differentiation

Invariant natural killer T (iNKT) cells require mitochondrial metabolism for terminal effector development. We found iNKT cells express elevated levels of proteins regulating mitochondrial membrane dynamics, and identified Opa1, but not Drp1, as selectively required for iNKT cell differentiation. OPA1 deficiency disrupted mitochondrial cristae organization, reduced mitochondrial membrane potential, increased mitochondrial mass, and altered calcium homeostasis in iNKT cells. Bulk and single-cell transcriptomic analyses revealed impaired TCR-responsive gene expression, activation of mitochondrial stress adaptation and integrated stress response, enhanced glycolysis, and retention of immature differentiation features. SCENITH analysis demonstrated increased glycolytic dependence; LDHA became required in Opa1-deficient iNKT cells while dispensable for normal iNKT development, indicating compensatory glycolytic adaptation. EGTA in thymic organ culture partially restored NKT1 marker expression in Opa1-deficient cells. Co-deletion of Drp1 improved mitochondrial morphology, TCR signaling, stress and metabolic adaptation, and partially rescued iNKT cell differentiation, demonstrating that balanced mitochondrial dynamics coordinate mitochondrial function and terminal effector development.

immunology↗

bioRxiv2026

Cortical Hierarchy Dynamically Organizes Large-Scale Neural Propagation

Flexible behaviour depends on the continuous coordination of sensory-driven and internally guided processing, yet whether the cortical hierarchy spanning lower-order sensory to higher-order association systems dynamically organizes large-scale cortical propagation over time remains unclear. Here we combined source-resolved magnetoencephalography with Riemannian cortical-flow modelling to derive hierarchy consistency, a moment-to-moment measure of the alignment between cortical propagation and the principal sensory-to-association functional gradient. We found that large-scale cortical propagation was dynamically organized by the cortical hierarchy. Hierarchy consistency exhibited a reproducible low-frequency periodic component that defined a characteristic timescale for the continuous updating of propagation direction. This dynamic organization was coordinated by a distributed cortical switchboard spanning the default-mode, salience, control and limbic systems, and was constrained by structural connectivity and network-control architecture. It flexibly adapted to behavioural demands, with hierarchy consistency increasing across both sensorimotor and working-memory states, while its characteristic periodicity shifted in a task-dependent manner. Moreover, hierarchy-related propagation dynamics were systematically reorganized across ageing and associated with higher-order cognitive function. Together, these findings establish the cortical hierarchy as a dynamic organizing principle that continuously shapes the direction and temporal evolution of large-scale cortical propagation to support adaptive behaviour.

neuroscience↗

bioRxiv2026

Plasma titration provides a physical ruler for cross-platform proteomics

Plasma proteomics is expanding across platforms and cohorts, and integrating these data for AI demands comparability at the protein level, not merely concordant associations1,2. Affinity and MS platforms use distinct probes (antibodies, aptamers, or peptides) and signal readouts, yielding contradictory cross-platform results3,4. Without a known quantitative truth, we cannot distinguish biology from measurement distortion, leaving no gold standard for integration. Here we introduce Plasmix--a plasma reference suite with predefined male:female ratios (M, 1:0; Y, 3:1; P, 1:1; X, 1:3; F, 0:1)--and show that preserving this quantitative titration gradient, not just technical repeatability, predicts cross-platform concordance and identifies protein measurements suitable for integration. Profiling Plasmix across five platforms (Olink, SomaScan, NULISA, AAgAtlas, and MS-DIA) and 12 protocols across 17 batches, we found discordance is dominated by signal generation, not sample identity, and platforms distort signals in a protein-specific manner. Crucially, proteins retaining the titration response showed stronger agreement in an independent cohort; anchoring to the Plasmix midpoint (P) via sample-to-reference ratios reduced distortions, extending harmonizable coverage by 10-20%. Plasmix thus provides a physical ruler to benchmark accuracy, identifying genuinely integrable measurements before pooling datasets or training AI models--a critical bottleneck for plasma proteomics.

molecular biology↗

bioRxiv2026

Synthetic Longitudinal Tabular Data Generation via Copula

Synthetic data generation is increasingly used to enable data sharing and secondary analysis while protecting participant privacy, particularly for longitudinal tabular health data, where repeated measures per subject create within-subject dependence that most synthetic data methods are not designed to preserve. Existing generative methods, particularly generative adversarial network (GAN)-based approaches, can model complex distributions, but their estimated dependence structures are often difficult to interpret and their performance may be unstable or prone to overfitting in modestly sized datasets. Here we show that eCDF-copula, a statistically rooted approach using the empirical cumulative distribution function (eCDF) and copula modeling, preserves within- and between-visit dependence structure. To handle pervasive missing data, we propose a two-stage strategy combining multiple imputation with copula-based synthesis, enabling a variance decomposition that quantifies replication variability across methods. We benchmarked the proposed approach against four established methods on two longitudinal clinical datasets spanning markedly different sample sizes (n = 120 vs. n = 3, 612). eCDF-copula achieved resemblance and utility exceeding those of state-of-the-art synthetic data methods, while maintaining comparable privacy.

bioinformatics↗

bioRxiv2026

Aperiodic neural activity links electromagnetic and hemodynamic representations of domain-general cognitive demand across the cortical hierarchy

The human brain demonstrates remarkable flexibility and capacity for domain-general cognitive control, allowing us to perform diverse and complex tasks. Central to this ability is the multiple- demand (MD) network, a domain-general system that is robustly engaged during demanding tasks in fMRI studies. However, the electrophysiological signatures underlying these domain-general responses remain elusive. While recent research has implicated aperiodic neural activity as a promising candidate, the limited spatial resolution of non-invasive electrophysiology has left it unresolved how this aperiodic signal relates to demand-related activity within the MD network and whether this relationship reflects a broader organizational principle across the cortex. To address these questions, we used a multimodal fusion framework to integrate fMRI and magnetoencephalography (MEG) data acquired while participants performed a diverse set of cognitive control tasks. We found that raw MEG- fMRI correspondence was strongest in unimodal sensorimotor cortices and progressively decreased toward transmodal association cortex during cognitive control tasks, revealing a hierarchical decline in correspondence between the electromagnetic and hemodynamic signals measured by these technologies. However, the proportion of this variance that was attributable to cognitive demand and carried by aperiodic signals showed the reverse gradient, systematically increasing along the sensorimotor-association axis. In particular, in the MD network, aperiodic broadband power showed the strongest demand-specific cross-modal commonality, outperforming canonical oscillatory components. These findings reveal two opposing hierarchical gradients: overall MEG-fMRI correspondence across all electrophysiological signals decreased toward association cortex, whereas the proportion attributable to aperiodic signals associated with cognitive demand increased. Our results identify aperiodic neural activity as a key electrophysiological substrate of cognitive control and a bridge linking electromagnetic and hemodynamic representations across the cortical hierarchy.

neuroscience↗

bioRxiv2026

Thalamocortical orchestration of human theory of mind

Reasoning about others thoughts or beliefs is central to human social behavior. This ability, known as theory of mind (ToM), has been primarily attributed to cortical regions of the default network (DN). However, whether and how subcortical structures, particularly the thalamus, contribute to this high-level computation remains unknown. Here, we investigated human thalamocortical dynamics during a naturalistic ToM movie watching condition, taking a rare dual-modality approach by combining high-field 7T fMRI and intracranial stereoelectroencephalography (sEEG). Across both modalities, ToM events reliably activated the DN, whereas the thalamus lacked canonical local activation. Despite this absence of local activation, the thalamus shared ToM-related representational structure and exhibited enhanced bidirectional interactions with the DN during mentalizing across methods. Crucially, sEEG revealed that the thalamus coordinated DN activity via cross-frequency phase-amplitude coupling (PAC), whereby thalamic low-frequency phase unidirectionally modulated DN high-frequency activity. Furthermore, the strength of thalamic-DN PAC predicted both the activity magnitude and the representational quality of ToM-related information within the dorsomedial DN subsystem. Together, these findings identify the human thalamus as a regulatory hub that gates DN computations during ToM without exhibiting observable localized activity, revealing a previously unrecognized mechanism by which thalamic dynamics coordinate high-level social cognition in humans.

neuroscience↗

bioRxiv2026

Structural and functional insights into the role of Cysteine-Rich Receptor-Like Kinase 18 (CRK18) in Arabidopsis

Plants perceive and integrate diverse environmental signals through receptor kinase (RK) networks at the plasma membrane. Within this, Cysteine-Rich Receptor-Like Kinases (CRKs) constitute a large but not well-understood subfamily characterised by extracellular domains (ECDs) enriched in cysteine residues. CRKs have been implicated in plant responses to biotic and abiotic stress, as well as in developmental processes. Additionally, several CRKs have been proposed to act as redox sensors. Here, we investigate the homodimerization mechanism of Arabidopsis CRK18 and its regulation by redox conditions. By modulating pH and redox state, we assessed the stability and binding dynamics of the CRK18 ECD and its cysteine mutants. We also tested the plasma membrane localisation of all the cysteine mutants involved in the predicted disulfide bonds, and only CRK18C227A, C228A-ECD resembled the plasma membrane localization of wild-type CRK18. We combine co-immunoprecipitation, Forster resonance energy transfer-fluorescence lifetime imaging microscopy and microscale thermophoresis to quantify CRK18 self-association in planta and in vitro. Furthermore, we place CRK18 dimerization in a broader signalling context by identifying CRK18 interaction partners and CRK18-dependent signalling outputs. Using Arabidopsis CRK18 overexpression lines, we perform (phospho)proteomic and immunoprecipitation-mass spectrometry (IP-MS) analyses to map CRK18-centred signalling networks associated with stress-related responses. The constitutive activation of the CRK18 kinase domain and its interaction with many putative (cell wall) glycan-sensing RKs, including PERK15, suggest a regulatory role for CRK18. The absence of significant changes in the proteome and phosphoproteome of CRK18 overexpression lines in the absence of any trigger, and its restricted mobility after elicitation, suggest that CRK18 requires a stimulus for activation and possibly induces membrane microdomain reorganisation. This is in line with the infection assay with the nematode Heterodera schachtii, which causes modification and targeted damage to plant cell walls during infection, revealing that CRK18 acts as negative regulator of this process.

biochemistry↗

bioRxiv2026

Eyewire II - A connectomic resource for resolving cell types and circuits of the mouse retina

Comprehensive wiring diagrams from electron microscopy (EM) are a powerful tool to understand the inner workings of the brain. The retina is an easily accessible part of the brain that performs complex visual computations. Its thin, layered structure offers a unique opportunity to decipher neural cell types and map their connectivity. A major obstacle has been the limited size of existing retinal EM datasets, which could not resolve rare cell types and neurons with large dendritic arbors. Here, we describe Eyewire II, a large-scale EM dataset covering nearly 1 mm2 of the adult mouse retina - roughly 10-100 times larger than previous retinal EM volumes. Human proofreading of an automated reconstruction has so far yielded more than 8, 000 bipolar cells, 13, 000 amacrine cells, and 4, 000 retinal ganglion cells. Automated detection is complete for synaptic ribbons and in progress for conventional synapses. Prior to EM imaging, visual responses to diverse stimuli - including natural movies - were recorded in a subset of neurons using two-photon Ca2+ imaging, enabling direct alignment of morphological and functional cell type identity. To enable high-throughput, automatic cell typing, we devised a human-in-the-loop approach that combines deep learning with human expert annotations. As a proof-of-principle, we show that morphological features of reconstructed bipolar cells are sufficient to recover all 15 known bipolar cell types with regular, non-overlapping mosaics. Together, these data and tools establish Eyewire II as a shared resource for the field of retina research. Already now, more than 30 laboratories worldwide are contributing proofreading, expert annotations, and software tools, advancing Eyewire II towards a complete cell type catalog and synaptic wiring diagram of a mammalian retina.

neuroscience↗

bioRxiv2026

Serum proteomic atlas reveals distinct molecular signatures of lupus nephritis activity, chronicity, and treatment response

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE), features heterogeneous renal pathology and reliance on invasive biopsies for diagnosis, prognosis, and treatment selection. Current peripheral clinical markers inadequately capture disease activity and progression. Here, we performed comprehensive serum proteomic profiling of over 5,000 proteins in the large, longitudinal Accelerating Medicines Partnership Rheumatoid Arthritis/SLE cohort of 270 LN patients and 63 healthy controls. Machine learning identified distinct molecular signatures that classified LN versus controls, differentiated histological classes, and delineated activity- and chronicity-associated pathways, including inflammatory cytokine, PI3K/AKT, TGFb, and complement/coagulation pathways. An increase in VSIG4, CD27, HAVCR1, and LAIR1 consistently emerged as top biomarkers across multiple clinical contexts, and early decreases in these markers at 3 months were associated with complete treatment response at 1 year. By resolving coordinated serum protein modules linked to key inflammatory, PI3K/AKT, TGFb, and complement pathways, these signatures mechanistically connect circulating proteomic perturbations to intrarenal immune activation, tissue injury, and repair in LN. These findings demonstrate that serum proteomics reflect complex intrarenal immunopathology and offer a promising noninvasive "liquid biopsy" approach to refine LN classification and guide personalized management, potentially reducing the need for repeated invasive biopsies and improving therapeutic decision-making.

immunology↗

bioRxiv2026

Heparin nucleates and promotes tropoelastin coacervation through a transient interaction driven by domain 36

Elastin is the extracellular matrix (ECM) protein responsible for the elastic recoil property of certain tissues including the skin, arteries, and lung. Elastic fibre assembly begins with the coacervation of soluble monomeric tropoelastin and is driven by interactions with other ECM components such as glycosaminoglycans (GAGs). Previous research shows that GAG interactions can promote tropoelastin coacervation but lack structural and mechanistic details of this interaction. In this study, we describe the key interactions between tropoelastin and heparin using NMR spectroscopy and coacervation experiments. We propose a mechanism in which substoichiometric GAGs can act as a nucleating scaffold, primarily through transient multivalent interactions with domain 36 of tropoelastin, reducing the energetic barrier for coacervation. Our results provide the first detailed molecular view of tropoelastin-GAG interactions and support a role for negatively charged GAGs in modulating tropoelastin coacervation and thus initiating elastic fibre assembly.

biochemistry↗

bioRxiv2026

Decoding the BRCA2 reversion principles underlying PARP inhibitor resistance

Reversion mutations that restore BRCA2 function represent a major mechanism of resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) in BRCA2-mutant cancers. Predicting these events could inform treatment strategies, identify patients at increased risk of acquiring PARPi resistance, and improve interpretation of secondary variants. Here, we use an isogenic cell system and CRISPR editing to define the principles governing BRCA2 reversion. We show that local sequence context dictates the spectrum of reversions, whereas domain architecture determines which events confer PARPi resistance. We characterize two routes of reversion that operate both within and across exons: DNA-level reading-frame restoration and transcript-level rescue via alternative splicing. Lastly, we identify distinct exon 11 reversion mechanisms, including large genomic deletions and recurrent splice isoforms predicted to remove all eight BRC repeats. These findings define a predictive code for BRCA2 reversion and PARPi resistance.

cancer biology↗

bioRxiv2026

Plekha7 promotes retina organization and inhibits inflammation and photoreceptor loss

Plekha7 associates with p120 catenin and localizes at apical cell-cell junctions where it has been implicated in junction stabilization. However, its in vivo function and underlying mechanisms of action remain unclear. Here, we show that constitutive Plekha7 loss in mice disrupts retinal organization, reduces retinal thickness, and induces RPE multinucleation, microglia infiltration, and photoreceptor loss. Plekha7 deficiency reduces the accumulation of cadherin-catenin complexes at apical junctions without altering overall cadherin levels, indicating a defect in junctional maintenance. Mechanistically, PLEKHA7 regulates cadherin trafficking by limiting levels of endocytosed E-cadherin, thereby maintaining junctional cadherin pools. Notably, these effects are largely independent of p120 catenin. In addition, further Plekha7 roles in the regulation of centrosome, cilia, microtubule dynamics, and cytokinesis, likely contribute to the phenotypic changes induced by Plekha7 knockout. These findings establish Plekha7 as a key regulator of cadherin trafficking and epithelial organization with relevance to retinal disease.

cell biology↗

bioRxiv2026

HeteroRC: Decoding latent information from dynamic neural responses with interpretable heterogeneous reservoir computing

Time-resolved neural decoding is widely used to track information represented in neural activity, but conventional linear decoders primarily capture phase-locked evoked responses and often fail to recover representations embedded in nonlinear or non-phase-locked dynamics, potentially limiting the interpretation of neural coding. Here, we introduce HeteroRC, a biologically inspired and interpretable decoding framework based on heterogeneous reservoir computing. HeteroRC projects neural signals into a high-dimensional recurrent state space with heterogeneous time constants, enabling nonlinear feature expansion and multiscale temporal integration directly from raw neural time series. Simulations demonstrate that HeteroRC significantly outperforms linear decoders and a suite of artificial neural networks (including RNNs, LSTMs, Transformers and EEGNet) on evoked responses while robustly capturing induced oscillatory power, phase synchrony, and aperiodic modulations--dynamics that are largely latent to conventional linear methods. We further validate HeteroRC on two empirical EEG datasets. In a motor imagery task, it substantially improves decoding accuracy and exhibits superior cross-temporal generalisation, revealing dynamic representational transformations. In an attentional priority task, HeteroRC uncovers statistically learned spatial priority information that remains hidden from conventional methods, successfully decoding these latent states previously thought to be activity-silent. Furthermore, we develop a dual-level interpretability framework linking reservoir dynamics to virtual sources and sensor space, revealing the temporal, spectral, and spatial signatures underlying decoding performance at both the individual and group levels. Together, HeteroRC offers an interpretable approach to decode information from dynamic neural responses, broadening the analytical scope of neural decoding while remaining computationally efficient and free from manual feature engineering, making it particularly suitable for small-sample electrophysiological studies.

neuroscience↗