bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/588103

Direction of gait asymmetry following stroke determines acute response to locomotor task

Little, V. L.·Perry, L. A.·Mercado, M. W.·Kautz, S. A.·Patten, C.
View original source ↗Export metadata ↓

Abstract

BackgroundGiven the prevalence of gait dysfunction following stroke, walking recovery is a primary goal of rehabilitation. However, current gait rehabilitation approaches fail to demonstrate consistent benefits. Furthermore, asymmetry is a prominent feature of gait dysfunction following stroke. Differential patterns of gait asymmetry may respond differently to gait training parameters.\n\nObjectiveThe purpose of this study was to determine whether differential responses to locomotor task condition occur on the basis of direction of step length asymmetry (Symmetrical, NPshort, Pshort) observed during overground walking.\n\nMethodsParticipants first walked overground at their self-selected walking speed. Overground data were compared against three task conditions all tested during treadmill walking: self-selected speed with 0% body weight support (TM); self-selected speed with 30% body weight support (BWS); and fastest comfortable speed with 30% body weight support and nonparetic leg guidance (GuidanceNP). Our primary outcomes were: step length, single limb support duration, and stride length.\n\nResultsWe identified differences in the response to locomotor task conditions for each step length asymmetry subgroup. GuidanceNP induced an acute spatial symmetry only in the NPshort group and temporal symmetry in the Symmetrical group.\n\nConclusionsTask conditions consistent with locomotor training do not produce uniform effects across subpatterns of gait asymmetry. We identified differential responses to locomotor task conditions between groups with distinct asymmetry patterns, suggesting these subgroups may require unique intervention strategies. Despite group differences in asymmetry characteristics, improvements in symmetry noted in the Symmetrical and NPshort groups were driven by changes in both the paretic and nonparetic limbs.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Little, V. L., Perry, L. A., Mercado, M. W., Kautz, S. A., Patten, C.. 2019-03-25. Direction of gait asymmetry following stroke determines acute response to locomotor task. https://doi.org/10.1101/588103

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

KEEP EXPLORING

Related preprints

bioRxiv2026

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↗
bioRxiv2026

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↗
bioRxiv2026

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↗