bioRxiv Science⌕ Search

bioRxiv · 10.1101/2025.05.16.654517

Weight-bearing symmetry changes after asymmetric surface stiffness walking

Abstract

Stroke is a leading cause of adult disability in the United States, often presenting as hemiparesis. A priority in hemiparetic gait rehabilitation is the restoration of gait symmetry. While split belt treadmill training has shown promise in correcting spatial gait asymmetry, weight bearing and propulsion asymmetry remain resistant to improvement. As an alternative approach, we tested asymmetric surface stiffness walking to induce signatures of neuromotor adaptation relevant to correcting weight bearing and propulsion asymmetries in hemiparetic stroke. We hypothesized that a bout of asymmetric stiffness walking would elicit aftereffects in the form of asymmetries in weight bearing, propulsion, and plantar flexor activity. Twelve healthy young adults performed a 10-minute bout of asymmetric stiffness walking on an adjustable stiffness treadmill. We measured baseline and post-perturbation ground reaction forces (GRF) and spatio-temporal measures during 5-minute walking bouts on a dual-belt instrumented treadmill. After asymmetric surface stiffness walking, participants walked with increased vertical GRF and plantar flexor muscle excitations during push-off on the perturbed side relative to unperturbed. Participants also decreased their mid-stance vertical GRF and increased their peak braking GRF on the perturbed side relative to unperturbed. Counter to our hypothesis, they did not increase their propulsion GRF on the perturbed side. We conclude that asymmetric stiffness walking elicited a neuromotor adaptation towards a relative increase in push-off in the target limb, albeit primarily vertically aligned in our cohort of healthy young adults, and that gait adaptation to asymmetric stiffness walking should be investigated in individuals with push-off asymmetries. New & NoteworthyWeight-bearing asymmetry in individuals with hemiparetic stroke is resistant to treatments that produce improvements in other gait function measures (e.g., spatio-temporal symmetry). We investigated a novel perturbed ground stiffness intervention applied by an adjustable surface stiffness treadmill and found significant aftereffects in vertical and braking ground reaction force peaks in healthy young adults, as well as increases in perturbed-side plantar flexor activity during push-off, indicating a strong potential for correcting persistent deficiencies in post-stroke gait.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Price, M. A., Schell, E., Jaramillo, J. M., Chiasson, J., Metsker, L., Huber, M. E., Hoogkamer, W.. 2025-05-21. Weight-bearing symmetry changes after asymmetric surface stiffness walking. https://doi.org/10.1101/2025.05.16.654517

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

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗