Biology subjects

Roy, D.

Publications and source records attributed to Roy, D..

At least 19 recordsLinked to original sources

bioRxiv2026

Hemodynamic-Structural Multi-Fidelity Assessment of Endovascular Flow Diversion Strategies for Cerebral Aneurysm Treatment: An Integrated Computational and Experimental Framework

Subarachnoid hemorrhage after cerebral aneurysm rupture has a 50% first-month fatality rate. Endovascular flow diversion is the primary treatment modality. However, no prior study has compared stents, coils, and the Woven Endo-Bridge hemodynamically integrating hemodynamic results with structural device behavior in one framework. An aneurysm model was reconstructed from computed tomography imaging of a patient, and computational fluid dynamics evaluated multiple hemodynamic metrics across three flow-diversion strategies. Finite element analysis assessed stent geometries with 50%, 55%, and 60% porosity in 316L stainless steel, poly-L-lactic acid, and nitinol. Universal testing machine tests validated the models with printed polylactic acid and thermoplastic polyurethane analogues. Dimensional and elastic-tube analyses tested scale equivalence between the FEA and UTM geometries and the rigid-wall CFD assumption. Patient-specific CFD confirmed a high-risk hemodynamic profile. The stent yielded the lowest peak intra-sac velocity, greatest pressure reduction, near-zero wall shear stress, the only reduction in time-averaged wall shear stress, cycle-averaged TAWSS, and the largest peak-systolic reductions in velocity, WSS, and vorticity. OSI and RRT rose for all three treated configurations, consistent with the hemodynamic signature of flow diversion. FEA reproduced the expected stiffness hierarchy (Steel > Nitinol > PLLA), and TPU was the closest surrogate for Nitinol's elastic recovery. Scaled specimens matched native-scale stiffness within 2.3%. Predicted radial distension was orders of magnitude below native wall values, supporting rigid-wall CFD. Stent-assisted diversion demonstrated the most favorable hemodynamic profile. A 50%-porosity Nitinol stent best matched target elastic mechanics, while 316L stainless steel provided the greatest resistance to radial compression.

neuroscience↗

bioRxiv2026

Root exudates enhance the ecological fitness of a non-native PGPR and reshape rhizosphere microbiome assembly

Root exudates play critical roles in rhizosphere microbiome assembly. Nevertheless, the molecular mechanisms by which plant growth-promoting rhizobacteria (PGPR) perceive these signals, adapt to the rhizosphere, and influence native microbial communities remain poorly understood. Here, using maize (Zea mays cv. Early Golden Bantam) and the rhizobacterium Priestia aryabhattai AB211, we took a multi-omics approach combining metabolomics, bacterial transcriptomics and proteomics, and rhizosphere metagenomics to elucidate the mechanism underlying this process. Maize root exudates were enriched in diverse carbon and nitrogen metabolites that promoted bacterial growth and induced extensive molecular reprogramming of pathways involved in nutrient acquisition, chemotaxis, motility, stress adaptation, and plant growth promotion, thereby enhancing rhizosphere competence. In field-conditioned soil, AB211 persisted as a core member of the maize rhizosphere microbiome, promoted early seedling growth, and reshaped microbial community composition and function. Root exudates-primed (RE-primed) AB211 further enhanced the enrichment of microbial functions associated with nutrient cycling, quorum sensing, plant growth promotion, and rhizosphere fitness, highlighting the role of root exudates in modulating the rhizosphere-adaptative potential of beneficial bacteria. These findings establish a mechanistic framework linking root exudates composition with PGPR adaptation and microbiome assembly, providing a foundation for engineering ecologically adapted microbial inoculants to improve crop productivity and sustainable agriculture.

microbiology↗

bioRxiv2026

Modulation of the speed of Intrinsic Alpha Frequency (IAF) with tACS modulates variability of illusory speech perception

Navigating the world requires our brains to constantly process a massive influx of information from the environment. One of the most remarkable yet complex feats the human brain performs daily is speech perception. It is a multifaceted, hierarchical process that relies heavily on the integration of auditory and visual cues, particularly in noisy environments. Neural integration of these streams is hypothesized to depend on temporal mechanisms governed by individual alpha frequency (IAF, 8-12 Hz), which serves as a key neural correlate of the temporal binding window (TBW). While IAF has been linked to multisensory integration, its role in shaping multisensory illusions remains largely unexplored. Here, we tested this directly using transcranial alternating current stimulation (tACS) to modulate occipital activity during multisensory conflict. In a two-day protocol involving 27 healthy participants, resting-state EEG was recorded to determine IAF. On Day 2, participants then performed a multisensory speech task involving congruent (pa/, /ta/, /ka/) and incongruent McGurk stimuli (auditory /pa/, visual /ka/), both at baseline and during tACS applied at IAF and offset frequencies (IAF +/- 2 Hz) over occipital electrodes. While accuracy for congruent syllables remained high across conditions, results revealed that tACS significantly reduced the perception of illusory /ta/ percepts during McGurk trials. Finally, using a phenomenological model based on Kuramoto oscillators, we provided a mechanistic explanation for the percentage of illusory responses observed across participants under the influence of tACS at IAF and offsets. This study highlights the potential for targeted neuromodulatory interventions to influence multisensory processing in clinical or professional settings.

neuroscience↗

bioRxiv2026

Distinct transcriptomic and hierarchical organization associated with brain hyperconnectivity and hypoconnectivity in autism spectrum disorder

Functional hyperconnectivity and hypoconnectivity in autism spectrum disorder (ASD) are typically treated as opposing expressions of a single circuit-level disturbance, but their molecular and hierarchical basis remains unclear. We combined resting-state fMRI from 1,737 individuals from the Autism Brain Imaging Data Exchange (ABIDE I/II) with gene-expression maps from the Allen Human Brain Atlas and show that hyperconnectivity and hypoconnectivity are dissociable neurobiological phenomena, differing in molecular signatures, cortical-hierarchical embedding, age-group profile, and cognitive associations, rather than a single connectivity axis. Hyperconnectivity was concentrated in higher-order cortical and cerebellar regions and was greater in older participants, while hypoconnectivity was consistent across age groups and localized to subcortical and orbitofrontal systems. ASD was associated with reorganization of the sensory-to-transmodal cortical gradient, most pronounced in association networks. Hyperconnectivity- and hypoconnectivity-associated genes showed partially distinct neurotransmitter profiles and differential embedding within cortical hierarchy, both enriched in transmodal cortex and linked to social-cognitive, perceptual, attentional, and reward-related functions. This dissociation was preserved across developmental stage, sex, and symptom severity. These findings indicate hyperconnectivity and hypoconnectivity are not two poles of one process but two separable components of a reproducible molecular-hierarchical architecture, offering a multi-scale framework linking transcriptomic organization to systems-level brain dysfunction in ASD.

neuroscience↗

bioRxiv2026

Corilagin attenuates high glucose-induced neurotoxicity and mitochondrial dysfunction through restoration of the AMPK-SIRT1-PGC1α-TFAM signaling axis

Mitochondrial dysfunction and oxidative stress represent two interconnected, primary causes for Diabetic Neuropathy (DN); however, the majority of currently available anti-diabetic therapies have focused on glucose control as opposed to neurodegenerative downstream effects. Corilagin, is an ellagitannin having high anti-oxidant properties; however, it has not been evaluated against hyperglycemia induced neuronal injury. The present study demonstrates the ability of Corilagin to protect against mitochondrial dysfunction via models of diabetic nephropathy and cerebral ischemia. High glucose (50 mM, 24 hr) was utilized to induce diabetes like conditions in the SH-SY5Y human neuroblastoma Cell Line. High glucose induced significant decreases in cell viability, increases in intracellular and mitochondrial reactive oxygen species, depletion of reduced glutathione reserves, induces apoptosis, and causes mitochondrial depolarization and fragmentation. Corilagin pre-treatment attenuated each of these high-glucose induced effects by protecting against mitochondrial membrane potential loss and maintaining mitochondrial network morphology while reducing apoptotic cell fraction relative to glucose alone. Additionally, these protective effects were accompanied by restoration of AMPK phosphorylation and up-regulation of SIRT1, PGC1 and TFAM, components that are part of the principal signaling pathway that regulates mitochondrial biogenesis; therefore, therefore, this pathway may contribute mechanistically to the cyto-protective effect of Corilagin. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/740444v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1be4a92org.highwire.dtl.DTLVardef@11d6e9org.highwire.dtl.DTLVardef@1346757org.highwire.dtl.DTLVardef@16c9f1e_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Proposed mechanism underlying the neuroprotective effects of Corilagin against high glucose-induced mitochondrial dysfunction.High glucose suppresses AMPK phosphorylation, leading to downregulation of the SIRT1-PGC-1-TFAM signaling axis, increased intracellular and mitochondrial reactive oxygen species (ROS), glutathione depletion, apoptosis, mitochondrial depolarization, and mitochondrial fragmentation. Corilagin pretreatment restores AMPK activation and the downstream SIRT1-PGC-1-TFAM pathway, thereby reducing oxidative stress, preserving intracellular glutathione, preventing apoptosis, maintaining mitochondrial membrane potential, and protecting mitochondrial network integrity. C_FIG

cell biology↗

bioRxiv2026

Entropy-based integration index for quantifying network integration in resting-state functional MRI

Independent component analysis (ICA) is widely used in resting-state fMRI to identify large-scale functional networks; however, existing approaches provide limited means of quantifying how network representations are distributed across independent components. We introduce an entropy-based network integration framework that characterizes the organizational architecture of canonical resting-state networks by quantifying the distribution of ICA-derived functional contributions within Yeo atlas networks. Spatial overlap between independent components and network templates is normalized to generate a probability distribution, from which Shannon entropy and a normalized integration index are derived. The resulting metric provides a continuous measure of network representational integration, ranging from specialized configurations dominated by a small number of components to distributed configurations involving multiple functional modes. The framework was evaluated and validated using resting-state fMRI data from healthy controls, Parkinsons disease patients with normal cognition, and Parkinsons disease patients with mild cognitive impairment. Global entropy and integration measures were complemented by network-specific analyses, dominance profiling, principal component analysis (PCA), and multivariate centroid-distance assessments. The proposed framework revealed selective alterations in Ventral Attention and Limbic network organization associated with cognitive-status differences, while preserving overall within-group heterogeneity. Group-wise PCA independently further identified these networks as major contributors to altered network organization, and centroid-distance analyses demonstrated that observed differences reflected coherent shifts in network architecture rather than increased variability. By quantifying the distribution of network representations across ICA-derived functional modes, this framework provides a simple, interpretable, and generalizable measure of large-scale brain organization, offering a complementary approach for studying network reorganization in health and disease.

neuroscience↗

bioRxiv2026

Shape, Shrink, Spheroid: A DIY High-throughput Spheroid Generation Device

3D spheroids, which closely replicate three-dimensional cell-cell and cell-extracellular matrix interactions, offer superior predictive capabilities compared to conventional 2D monolayer cultures, positioning them as forward-looking platforms in drug testing, cancer biology, and regenerative medicine. However, high-throughput generation of uniform sized spheroids is still a technological challenge. In one hand, the use of conventional ultra-low attachment (ULA) multiwell plates for this purpose is labour intensive and complex. On the other hand, the use of microfabricated facilities demands cutting-edge infrastructure such as clean room, photolithography, and microfluidic setup which are often unavailable for the resource constrained laboratories. In this study, we addressed these problems by developing a low-cost Do-It-Yourself (DIY), polydimethylsiloxane (PDMS) and agarose-based spheroid generation device, capable of producing and maintaining hundreds of spheroids with minimal user intervention. We have demonstrated two variants based on their size, termed here as S1 and S2 devices which fit into 6-well and 12-well plates, and can generate 600 and 1200 uniform-sized spheroids respectively. We validated our device with various cell lines including primary and cancerous cell lines. We further demonstrated the drug testing capabilities of the device by estimating the IC50 value of the anticancer drug Temozolomide on U87-MG. The value was comparable with the same obtained from the spheroids generated using conventional ULA plates. Additional attachment of a perfusion system made the device suitable for long-term spheroid culture without much user intervention. Furthermore, the devices can also be used for the production of spheroids with gradually changing diameters in a controlled manner, resembling a size gradient. This feature is useful for checking the effect of drugs on different-sized spheroids and for co-culturing spheroids with varying cell densities, mimicking the disease architecture. We have co-cultured two types of the placental trophoblast cells, i.e., extravillous trophoblast (HTR-8) and syncytiotrophoblast (BeWo) with varying densities. In summary, this paper demonstrates a unique DIY method for a high-throughput uniform-sized spheroid generation at a fraction of cost which can be deployed to resource-constrained labs.

bioengineering↗

bioRxiv2026

Scalable Microbiome Network Inference: Mitigating Sparsity and Computational Bottlenecks in Random Effects Models

Withdrawal StatementThe authors have withdrawn their manuscript because the biological validations associated with the inferred microbial interaction directions are currently incomplete and require further verification. We are actively working on validating these biological directions and ensuring the scientific correctness of the reported findings before any further dissemination. Therefore, the authors do not wish this work to be cited as a reference for the project at this stage. If you have any questions, please contact the corresponding author.

bioinformatics↗

bioRxiv2026

Marine Aspergillus terreus produces a chitinase exhibiting a dual mode of enzymatic action

Marine Aspergillus terreus has been explored as an important chitinase-producing fungal strain for-N-Acetyl-D-Glucosamine (GlcNAc) production from chitin substrates. Here, a purified extracellular 45 kDa chitinase of marine Aspergillus terreus (accession number JQ248076) was characterized in terms of substrate specificity. Conventionally, endochitinase cleaves the chitin substrate randomly to produce GlcNAc and its different multimers. So, it requires at least tetramer to characterize the endochitinases; whereas, exochitinases cleaves the chitin substrate from its reducing end and produce either GlcNAc or chitobiose (GlcNAc dimer). In present chitinase characterization, the HPLC followed by HRMS analyses revealed differential product formation from the chitin substrates of varied chain length. With swollen chitin polymer, the enzyme produced GlcNAc as a sole product; whereas with chitohexaose substrate, a mixture of GlcNAc and its oligomers were obtained. Although, mass spectrometry-based proteomics analysis identified the isolated chitinase as an endochitinase 1 precursor (Accession XP_001217186). However, the enzyme kinetic study exhibited higher catalytic efficiency for exochitinase specific dimeric chromogenic substrate in comparison to endochitinase specific tetrameric fluorogenic substrate, which indicated predominantly exochitinase behavior of the enzyme. Further, the in-silico study predicted the differential cleavage pattern of the enzyme, which could be due to different mode of substrate binding and processive mechanism through the tunnel shaped binding cleft of the enzyme. The dual mode of catalytic activity of the present chitinase was further confirmed by a molecular docking study with different lengths of substrates. With the unique dual mode of action, the chitinase of marine Aspergillus terreus offers a great promise towards its utility in the production of GlcNAc.

microbiology↗

bioRxiv2026

Automated Monitoring of Insects system: Building a non-lethal and scalable solution for monitoring of nocturnal insects

There is growing evidence that human-induced climate change and habitat loss are having negative impacts on insect populations. New technologies have a vital role in improving and expanding global biodiversity monitoring capacity to understand where change is happening and to support restoration. Monitoring of insects traditionally needs entomologists in the field, but insect camera traps powered by AI are emerging as a scalable approach to monitoring semi-autonomously. These systems attract, detect, and identify insects using AI algorithms and are being developed by a network of researchers across the world, notably in Europe and North America. The first version of a system for monitoring nocturnal insects was developed by Bjerge et al. 2021. An Automated Light Trap to Monitor Moths (Lepidoptera) Using Computer Vision-Based Tracking and Deep Learning. Here we describe the second generation of the system as an open-source solution. This paper aims to enable anyone to build their own system, and to iterate and improve the design for their needs. This system captures images at set intervals or based on motion detection to monitor insects that are attracted to lights at night. The UKCEH Automated Monitoring of Insects System (UKCEH AMI-system) is an insect camera trap designed using a single board computer, USB camera and attractant lights as the primary components along with peripheral accessories to make an autonomous system capable of long-term deployment in the field. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/704388v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@17ccdc4org.highwire.dtl.DTLVardef@a92179org.highwire.dtl.DTLVardef@1d4aaf8org.highwire.dtl.DTLVardef@1248d07_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2026

A generalized scaling law to characterize coordinated brain activity

Complex ecological systems obey universal scaling laws such as Taylors law, which links population variance to the sample mean. Whether other complex systems with integrated and segregated functional networks--such as the human brain--follow analogous scaling laws, and how these laws behave under synchronized activity, remains unknown. Progress has been hindered because neural signals at all measurement scales contain both positive and negative values, whereas Taylors law was developed for non-negative ecological data. Here we introduce a generalized spatial scaling law that replaces the sample mean with the root-mean-square (RMS) of detrended activity, extending Taylor-like scaling to signed multivariate time series in neural and other complex systems. Within this framework, we quantify synchrony using a dedicated metric of functional coordination and show analytically, and via numerical simulations using multivariate Poisson, binomial, uniform and gamma distributions, that the scaling exponent is inversely related to synchrony. Applying this approach to human fMRI data from three large lifespan cohorts (N = 840, ages 18-88) reveals distinct age-related trajectories of the scaling exponent, with healthy aging characterized by a substantial synchrony-induced reduction in the exponent. The synchrony-scaling relationship remains stable during resting-state activity but progressively shifts during naturalistic tasks across the lifespan, and is particularly strong in limbic, subcortical, and cerebellar subnetworks, indicating preservation at subnetwork levels. Finally, individuals with ADHD exhibit disrupted synchrony-scaling coupling, highlighting the potential clinical and translational utility of this generalized scaling metric.

neuroscience↗

bioRxiv2025

Nucleic acid strand length governs mitochondrial reprogramming and mtROS-associated antiviral responses following TLR3 engagement

Mitochondria are important rheostats that regulate innate sensing processes by producing energy, biosynthetic precursors, and bioactive molecules that affect cellular signaling. When viral nucleic acids engage endosomal and cytosolic pattern recognition receptors (PRR), antiviral immune responses are supported by mitochondrial remodeling but the role of mitochondria in fine tuning ligand-specific responses remains incompletely understood. For example, endosomal TLR3 can detect various lengths of dsRNA (0.4-8 kb) ranging from viral segmented genomes or endogenous nucleic acids have been shown to induce distinct cytokine profiles. However, it is unclear if these differences are associated with differential mitochondrial remodeling. Here, we report that TLR3 engagement with both high (HMW; 1.5-8 kb) or low molecular weight (LMW; 0.2-1 kb) Polyinosinic:polycytidylic acid (Poly(I:C)) is associated with reduced but sustained oxidative phosphorylation (OXPHOS) activity and increased mitochondrial reactive oxygen species (mtROS) production/accumulation to support antiviral responses in bone marrow-derived macrophages (BMDM). They differed in the amount of mtROS production, their spare respiratory capacity (SRC) and their mitochondrial membrane potential (MMP). Interestingly, while uncoupling protein 2 (UCP2) was found required for antiviral cytokine production, it did not contribute to ligand specific responses. Dynamic modulation of complex I of the electron transport chain (ETC), however resulted in the differential accumulation of mtROS (HMW>LMW). Further, selectively targeting the mtROS derived from Complex I leads to augmented type I IFN production. Overall, these findings highlight that targeting specific sources of mtROS without affecting electron flow may be a potential avenue for specific augmentation of antiviral responses during viral infections.

immunology↗

bioRxiv2025

Genomic characterization of type I-E* CRISPR-Cas systems in Klebsiella pneumoniae: association of spacer diversity and antimicrobial resistance

BackgroundKlebsiella pneumoniae, known to acquire antimicrobial resistance genes (ARGs) through horizontal gene transfer, possess type I CRISPR-Cas systems. This study investigated the association of multidrug resistance (MDR) and CRISPR-Cas in septicemic K. pneumoniae, along with comparative analysis of CRISPR-positive global K. pneumoniae. MethodsArchived K. pneumoniae from septicemic neonates (2008-2020) were assessed for CRISPR-Cas system, cas gene expression and correlation with ARG carriage. Whole-genome sequencing was performed and diversity of spacers, protospacers adjacent motifs (PAMs), targeted plasmids, were evaluated. Comparative analyses were performed for CRISPR-positive global K. pneumoniae. ResultsTwenty-five percent of study K. pneumoniae possessed complete type I-E* CRISPR-Cas comparable to 22% of global K. pneumoniae, which were distributed equally to type I-E & I-E*. CRISPR-positive study strains (83%) were MDR, and exhibited no significant association of CRISPR-Cas with MDR phenotype. Spacers noted in non-MDRs were diverse, showed increased average count and identified more diverse PAMs compared to spacers from MDR strains. Plasmids harboring ARGs such as blaNDM, blaCTX-M, qnrS1, mcr-8, etc. were frequently targeted by spacers from non-MDRs. Presence of CRISPR-Cas system in epidemic MDR clones such as ST14/15/23 in I-E* (local, global) and ST147 in I-E (global), indicated a lineage-specific association with CRISPR-Cas subtypes. ConclusionThis study demonstrated the co-existence of CRISPR-Cas systems within both MDR and non-MDR K. pneumoniae, with no significant correlation with either group. However, presence of diverse spacers in non-MDR strains that identified more PAMs and targeted ARG-bearing plasmid implied role of CRISPR-Cas system in limiting ARG acquisition.

genomics↗

bioRxiv2025

Distinct modes of redox-mediated DegP activation govern its role as a general protease

DegP, a bifunctional chaperone-protease central to maintaining envelope proteostasis in Gram-negative bacteria, serves as a paradigm for understanding protein quality control mechanisms. Decades of research, mainly using synthetic peptides/non-native substrates that do not contain cysteines, have established the allosteric mode of DegP activation, where substrate binding remodels inactive DegP into its active conformations. In enteric bacteria, as DegP typically harbours a disulfide bond (DSB) in its protease domain, its redox-mediated activation has also been proposed. However, the cellular factors driving this activation mode and its physiological relevance have remained elusive. Here, we investigated this aspect in Escherichia coli primarily using long-chain fatty acids and alkaline pH as stressors. We show that, under these conditions, DegP considerably accumulates in its thiol form (DegPred), which represents its protease-active conformation. Besides removing damaged proteins, DegPred also induces the Cpx envelope stress response in all tested conditions. Notably, two distinct mechanisms promote redox-mediated DegP activation in a temporal and stress-specific manner: a compromised DSB-forming machinery fails to oxidize DegP, and thiol-containing substrates allosterically convert DegP into DegPred. Because in vitro, the lack of DSB sensitizes DegP to lower substrate levels, we suggest that in vivo DegPred is primed for a robust response to stresses. Finally, the diverse nature of the molecular players that activate Cpx in our tested stress conditions leads us to propose that the DSB of DegP, by acting as a redox sensor, enables DegP to integrate a wide range of inducing cues and thus work as a general protease. Significance StatementThe proteolytic activity of DegP is highly implicated in bacterial survival and virulence. Notably, DegP from the Enterobacteriaceae family of Gram-negative bacteria typically harbours a disulfide bond (DSB) in its protease domain. Because pathogens face redox stress during infection and antibiotic exposure, understanding how redox perturbants modulate DegP function is necessary for exploiting it as a target for therapeutic intervention strategies. Here, using E. coli as the model bacterium, we show that the DSB of DegP acts as a redox sensor under various inducing cues, thereby positioning DegP as a versatile, broad-spectrum protease. The present study opens avenues for investigating whether a similar redox-mediated control of DegP activation influences the pathogenesis of enteric bacteria.

microbiology↗

bioRxiv2025

Multimodal MR Imaging for quantification of brain lipid in mice at 9.4T

BackgroundAdvanced MR imaging techniques like steady state Nuclear Overhauser enhancement (ssNOE), transient NOE (tNOE), and myelin water fraction (MWF) provide a non-invasive way to assess the biochemical and structural integrity of brain tissue. Their sensitivity to endogenous lipids and macromolecules allows for the early detection of neuropathological changes, making them valuable tools in studying brain health and disease progression. In this study, we systematically evaluate the repeatability and sensitivity of NOEMTR, tNOE, and MWF for quantifying lipid and myelin content in the brains of wild-type (WT) mice, correlating the results with immunohistochemistry (IHC). MethodsFive 6-month-old C57BL6/J mice were imaged using 3D-NOE, and four mice underwent imaging with 2D tNOE and MWF across four repeated sessions using a 9.4T Scanner. For ssNOE imaging, CEST-weighted images at 56 frequency offsets were acquired using B1rms of 1.0 T and 3s saturation duration. For tNOE, 52 offsets were acquired with a hyperbolic secant inversion pulse (bandwidth = 400Hz, duration = 44ms) and a mixing time of 200ms. For MWF, a multi-echo spin-echo (MESE) sequence was acquired with 40 evenly spaced echoes from 5.5ms to 200ms. For both ssNOE and tNOE, B0 correction was performed using WASSR. Repeatability was quantified using intra- and inter-subject coefficients of variation (COV%). Pearson correlation was performed to see the association between imaging matrices and IHC measures, Luxol fast blue (LFB) stained sections, and myelin basic protein (MBP). ResultsAll techniques demonstrated high repeatability across the whole brain (WB) and selected regions of interest (ROIs). Whole-brain intra-subject COV% for NOEMTR ranged from 1.92% to 3.40%, with corresponding inter-subject COVs of 1.50%. tNOE exhibited improved intra-subject repeatability with COVs ranging from 0.75% to 5.57%, but a reduced inter-subject COV of 2.97%. MWF imaging showed the highest stability overall, with an intra-subject COV ranging from 0.47% to 2.03% and an inter-subject COV of 0.75%. Visually, tNOE offers superior contrast in myelin-rich areas compared to NOEMTR and MWF imaging, showing greater sensitivity to myelinated regions. tNOE strongly correlates with histological markers: r = 0.83 with MBP staining and r = 0.72 with LFB staining (both p < 0.001). MWF and NOEMTR showed correlations with MBP (r = 0.63 and r = 0.57, respectively). ConclusionNOEMTR, tNOE, and MWF imaging are reliable and repeatable methods for quantifying macromolecules in the brain. Among these, tNOE emerges as the most sensitive for detecting myelin lipids as confirmed by histological validation. These findings highlight the translational potential of tNOE for studying demyelinating disorders and neurodegenerative diseases.

neuroscience↗

bioRxiv2025

Local homeostasis preserves global neural dynamics compensating for structural loss during human lifespan aging

Aging brain undergoes a structural decline over lifespan accompanied by changes in neurotransmitter levels, leading to altered functional markers. Past studies have reported human resting state brain display a remarkable preservation of coordination among neural assemblies stemming from an underlying neuro-computational principles along aging trajectories, however, the true nature of which remains unknown. Here, we identify the computational mechanisms with which neurotransmitters, such as altered GABA and glutamate concentrations, can preserve functional integration across lifespan aging, despite structural decline. We employ multiscale, biophysically grounded modeling, constrained by the empirically derived anatomical connectome of the human brain, where the neurotransmitter concentrations can be free parameters that are algorithmically adjusted to maintain regional homeostasis and optimal working point. The two estimated neurotransmitters can maintain critical firing rates in the brain region and mimic age-associated functional connectivity patterns, consistent with empirical observations. We identified invariant GABA and reduced glutamate as the principle computational mechanism that can explain the topological variation of functional connectivity along lifespan, validated using graph-theoretic metrics. The results are subsequently replicated on three distinct datasets. Thus, the study offers an operational framework that integrates brain network dynamics at macroscopic and molecular scales, to gain insight into age-associated neural disorders.

neuroscience↗

bioRxiv2025

A Mechanistic Whole Brain Model to Capture Simultaneous EEG-fMRI Data

This study introduces a novel oscillatory network model to simulate simultaneous EEG-fMRI data, addressing the reconstruction challenge that arises due to their contrasting spatiotemporal scales. Here, each brain region is modelled by two oscillator clusters - a cluster of low-frequency (LFO) and high-frequency Hopf oscillators (HFO) coupled with an innovative power-coupling rule, facilitating cross-frequency interactions. The model is trained in two stages: learning oscillators frequencies and phase relations using a biologically plausible complex-Hebbian rule in the first stage and, followed by a modified complex backpropagation for amplitude approximation, overcoming limitations of poor accuracy and computational complexity in existing models. This framework outperforms current methods in replicating empirical Functional Connectivity (FC), Functional Connectivity Dynamics (FCD), and modularity over disparate spatio-temporal scales. The correlation between the FC of fMRI and the FCs of various EEG frequency bands is reflected in the strengths of the LFO-HFO coupling. Furthermore, in-silico structural perturbation studies quantified the effect of pruning of the anatomical connectivity on spatiotemporal dynamics in terms of FC, FCD, modularity, and integration level (ISOR). The models ability to reconstruct simultaneous EEG-fMRI data showcases significant advancement in understanding the resting-state brains functionality from multimodal settings and deciphering neurological disorders in diverse spatiotemporal scales.

neuroscience↗

bioRxiv2025

Beta Desynchronization Mediates The Impact Of Internally Directed Attention In A Dual-Task Working Memory Paradigm

Internally directed attention (IDA), whether spontaneous or intentional, has been associated with impaired performance on externally directed cognitive tasks. Yet, the neurophysiological mechanisms underpinning this disruption remain poorly understood. In the present study, we characterized the neural correlates of IDA and identified how they impact on performance in a color-recall working memory task using electroencephalography (EEG). Participants performed a novel dual-task paradigm involving either self-referential (IDA) or perceptual processing of adjectives, involving externally directed attention (EDA) followed by a color-recall task. IDA enhanced late positive potentials (LPP) in EEG over medial-frontal electrodes as a marker of sustained affective and self-referential engagement. Time-frequency analyses further revealed increased event-related desynchronization in alpha and beta bands during stimulus encoding in the IDA condition, as well as increased alpha synchronization during the delay period, consistent with internal attention maintenance. To capture trial-level variability in task performance, we applied conditional quantile regression on the single trial data. Results showed that beta desynchronization in interaction with condition type during encoding influenced performance significantly in trials with low errors, whereas trials with high error in color recall were better explained by increased reaction times. These findings provide converging electrophysiological evidence for distinct neural signatures of internally directed attention and highlight their behavioral consequences in working memory performance.

neuroscience↗