bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.06.18.660402

Structural connectivity-informed dynamic estimation (STRiDE): Multimodal connectivity constrained ICA

Abstract

Understanding the dynamic intrinsic interactions between brain regions has been advanced by functional magnetic resonance imaging (fMRI), particularly through the connectivity analysis used to characterize reoccurring patterns in the brain known as brain states. However, previous studies have primarily focused on unimodal models, which can hinder optimal dynamic state estimation, especially in cognitive disorders, cases where there may be both structure and function disruption. To better estimate intrinsic brain interactions, it is important to account for the factors shaping this estimation not only in terms of time resolved variability of the connectivity but also regarding the underlying physical pathways between brain regions. However current approaches mostly use deterministic weighting of structural connectivity. To address this, we propose a flexible multimodal connectivity constrained independent component analysis (ICA) model, termed structural connectivity-informed dynamic state estimation (STRiDE), that enhances stability and sensitivity by leveraging white matter structural connectivity and dynamic functional connectivity information. Using this model, we decompose brain interactions into independent, reoccurring multimodal patterns or structural-functional states, guided by maximally independent structural connectivity priors derived from the group level data. We first evaluate our proposed model using a simulation pipeline, showing the approach works as design and improves sensitivity to group differences and enhances robustness to noise. Next, we applied the proposed multimodal model to real dataset including a cohort of subjects with schizophrenia (SZ) and healthy controls (HC). Results demonstrated its potential to enhance group-differences in both connectivity domain and temporal dynamics parameters. Specifically results highlighted disruption within and between sensory and trans-modal domains, through a SZ vs HC comparison. Symptoms severity and cognitive scores statistical analysis specifies their significant association with default mode domain, offering insights into the disrupted functional and neural mechanisms underlying schizophrenia. In addition, temporal interplay of the estimated STRiDEs reveals that visual-related STRiDE is significantly impacted in SZ, regarding the speed of processing score, underscoring the link between visual system and speed of processing. In sum, the STRiDE approach provides a flexible way to link structural and functional connectivity at the network level and represents a general approach for studying multimodal dynamic patterns and leveraging these to study the typical and disordered brain.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Fouladivanda, M., Iraji, A., Wu, L., Chen, J., Camazon, P. A., van Erp, T., Belger, A., Pearlson, G. D., Adali, T., Calhoun, V.. 2025-06-24. Structural connectivity-informed dynamic estimation (STRiDE): Multimodal connectivity constrained ICA. https://doi.org/10.1101/2025.06.18.660402

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Synergy-informed bilevel optimization reveals joint-specific benefits for realistic exoskeleton torque prediction

Simulation-driven optimization can guide exoskeleton control design, but its utility is limited by the accuracy with which muscle coordination is predicted. Strict effort-minimization formulations predict non-physiological muscle shutdown under high exoskeleton assistance, leading to peak assistive torques that exceed values reported in human-in-the-loop experiments. We evaluated the accuracy of synergy-informed simulations at predicting assistance across four single-joint exoskeleton configurations: ankle plantarflexion, knee extension, hip flexion, and hip abduction. We implemented a bilevel optimization to predict a parameterized assistive torque that minimizes metabolic cost, with assisted muscle dynamics estimated via either effort-minimization simulations (minimizing muscle effort only) or synergy-informed simulations (minimizing muscle effort constrained to a synergy structure). We used experimental data from five unimpaired adults walking at their preferred speed and compared results descriptively between the two formulations within each subject. Assistance based on effort-minimization simulations shut down agonist muscle activations and overestimated peak assistive torque compared with experimental values. In contrast, constraining muscle controls to a synergy structure prevented non-physiological muscle shutdown and yielded assistive torques closer to those measured in human-in-the-loop experiments. This benefit was not observed equally across all assisted degrees of freedom or subjects, emerging only where no single synergy could be suppressed to unload the assisted muscles. Synergy weights can therefore be interpreted as joint-specific predictors of when simulations can reliably inform wearable robot design.

bioengineering↗

Engineered microvessel networks -- Longitudinal transcriptomic profiling validates chip-grown tissues as a robust model for studying vasculature

Vascularised Organ-on-Chip (OoC) models are promising New Approach Methodologies (NAMs), but their translation requires validation for defined Contexts of Use (CoU). Here, we combine microfluidic microvessel networks (MVNs) with longitudinal bulk and single-cell RNA sequencing to determine how cell provenance influences engineered vascular phenotype. Stromal cell identity produced distinct network architectures and transcriptional trajectories, demonstrating that support cells, commonly treated as interchangeable, represent an important CoU variable. Primary human pancreatic microvascular endothelial cells failed to form stable perfusable networks, but supplementation with 10% Human Umbilical Vein Endothelial Cells (HUVECs) or Blood Outgrowth Endothelial Cells (BOECs) rescued self-assembly. Single-cell transcriptomics identified specialised endothelial populations associated with vascular morphogenesis, including tip, stalk, phalanx, endothelial to mesenchymal transition (EndMT) and pericyte-like endothelial cells. Failed networks lacked coherent endothelial specialisation, whereas rescued networks restored stabilising cell states and revealed FLRT2--UNC5B signalling within pericyte-like HUVECs, recapitulating a pathway implicated in angiogenic development in vivo. These findings establish cell provenance as a critical determinant of microvascular NAM performance and demonstrate how transcriptomic validation can define and strengthen the biological relevance of microvessel-on-chip models for specific CoUs.

bioengineering↗

Benchmarking foundation models for resting-state functional magnetic resonance imaging time series in cognitive aging research

Foundation models trained on large neuroimaging datasets could help smaller studies investigate cognition from brain recordings. However, whether the foundation model-derived representations improve assessment of current cognition, prediction of follow-up cognition, or characterization of cognitive change remains unclear. We evaluated nine configurations from five model families that process regional resting-state functional magnetic resonance imaging time series, using 3,103 scans from 1,653 participants across two observational and five intervention aging cohorts. Primary frozen representations showed no consistent superiority over conventional functional connectivity for concurrent cognitive associations or diagnostic classification. Changing the readout improved selected concurrent cognitive associations without updating model weights, indicating that performance depended partly on how representations were extracted. Additional post-training and embedding alignment yielded gains in selected settings but did not consistently improve performance across outcomes. In the primary longitudinal analyses, imaging representations did not establish added value beyond baseline clinical measures. These findings show that readout choice influences concurrent cognitive associations, while the added value of these representations for longitudinal outcomes remains unestablished.

bioengineering↗