bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.04.10.588947

Leg choice for volitional goal-directed stepping is primarily influenced by effort rather than success: A preliminary investigation in neurotypical adults

Abstract

During reaching, arm choice depends on success and motor effort. Whether these factors influence leg choice for stepping behavior is unknown. Here, we conducted two experiments (1: proof-of-principle; 2: kinematic analysis) to explore whether limb selection for goal-directed stepping depends on success and/or effort under two Choice conditions: Free (choose either leg) and Constrained (no choice - only left leg). For both experiments, in which Free trials always preceded Constrained trials, we adapted the classic center-out target array in which right-leg dominant neurotypical adults stood in the middle of the array and stepped to pre-cued targets as accurately as possible. The Free condition reflected the preferred limb choice. We compared success, effort, and self-perceived difficulty between Free and Constrained trials, separately for three (Experiment 1) and two (Experiment 2) regions. Overall, in Free condition, participants uniformly selected the limb ipsilateral to lateral left and right targets and with slight leg dominance-based bias for central targets. Success (step accuracy and consistency/precision) did not depend on Choice condition, rather, performance improved over repeated trials. Effort (peak vertical foot lift and step path ratio) depended on Choice condition. Finally, independent of Choice condition, participants perceived posterior targets (particularly far targets) as the most difficult during non-dominant left steps. Present findings suggest that effort may influence leg choice to a greater degree than success for goal-directed stepping. Future work that probes these findings robustness in patients with unilateral paresis (intrinsic constraint) may advance our understanding of the motor decision processes for goal-directed mobility behaviors.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Charalambous, C. C., Espinoza-Wade, E. R., Cesar, G. M., Gerger, M., Lai, Y., Winstein, C. J.. 2024-04-14. Leg choice for volitional goal-directed stepping is primarily influenced by effort rather than success: A preliminary investigation in neurotypical adults. https://doi.org/10.1101/2024.04.10.588947

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↗