Dataset Information

Translational methods to detect asymmetries in temporal and spatial walking metrics in parkinsonian mouse models and human subjects with Parkinson's disease.

ABSTRACT: Clinical signs in Parkinson's disease (PD), including parkinsonian gait, are often asymmetric, but mechanisms underlying gait asymmetries in PD remain poorly understood. A translational toolkit, a set of standardized measures to capture gait asymmetries in relevant mouse models and patients, would greatly facilitate research efforts. We validated approaches to quantify asymmetries in placement and timing of limbs in mouse models of parkinsonism and human PD subjects at speeds that are relevant for human walking. In mice, we applied regression analysis to compare left and right gait metrics within a condition. To compare alternation ratios of left and right limbs before and after induction of parkinsonism, we used circular statistics. Both approaches revealed asymmetries in hind- and forelimb step length in a unilateral PD model, but not in bilateral or control models. In human subjects, a similar regression approach showed a step length asymmetry in the PD but not control group. Sub-analysis of cohorts with predominant postural instability-gait impairment and with predominant tremor revealed asymmetries for step length in both cohorts and for swing time only in the former cohort. This translational approach captures asymmetries of gait in mice and patients. Application revealed striking differences between models, and that spatial and temporal asymmetries may occur independently. This approach will be useful to investigate circuit mechanisms underlying the heterogeneity between models.

SUBMITTER: Broom L

PROVIDER: S-EPMC6385183 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Translational methods to detect asymmetries in temporal and spatial walking metrics in parkinsonian mouse models and human subjects with Parkinson's disease.

Broom Lauren L Worley Audrey A Gao Fay F Hernandez Laura D LD Ashton Christine E CE Shih Ludy C LC VanderHorst Veronique G VG

Scientific reports 20190221 1

Clinical signs in Parkinson's disease (PD), including parkinsonian gait, are often asymmetric, but mechanisms underlying gait asymmetries in PD remain poorly understood. A translational toolkit, a set of standardized measures to capture gait asymmetries in relevant mouse models and patients, would greatly facilitate research efforts. We validated approaches to quantify asymmetries in placement and timing of limbs in mouse models of parkinsonism and human PD subjects at speeds that are relevant f ...[more]

PMID: 30792396

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Project description:BackgroundGait disorders of Parkinson's disease (PD) are characterized by the breakdown of the temporal organization of stride duration variability that was tightly associated to dynamic instability in PD. Activating the upper body during walking, Nordic Walking (NW) may be used as an external cueing to improve spatiotemporal parameters of gait, such as stride length or gait variability, in PD. The aim of this study was to evaluate the beneficial effects of NW on temporal organization of gait variability and spatiotemporal gait variables in PD.MethodsFourteen mild to moderate PD participants and ten age-matched healthy subjects performed 2 × 12 min overground walking sessions (with and without pole in a randomized order) at a comfortable speed. Gait speed, cadence, step length and temporal organization (i.e. long-range autocorrelations; LRA) of stride duration variability were studied on 512 consecutive gait cycles using a unidimensional accelerometer placed on the malleola of the most affected side in PD patients and of the dominant side in healthy controls. The presence of LRA was determined using the Rescaled Range Analysis (Hurst exponent) and the Power Spectral Density (α exponent). To assess NW and disease influences on gait, paired t-tests, Z-score and a two-way (pathological condition x walking condition) ANOVA repeated measure were used.ResultsLeading to significant improvement of LRA, NW enhances step length and reduces gait cadence without any change in gait speed in PD. Interestingly, LRA and step length collected from the NW session are similar to that of the healthy population.ConclusionThis cross-sectional controlled study demonstrates that NW may constitute a powerful way to struggle against the randomness of PD gait and the typical gait hypokinesia. Involving a voluntary intersegmental coordination, such improvement could also be due to the upper body rhythmic movements acting as rhythmical external cue to bypass their defective basal ganglia circuitries.Ethics committee's reference numberB403201318916 TRIAL REGISTRATION: NCT02419768.

Project description:Accurate models that describe temporal-spatial parameters are desirable in gait estimation and rehabilitation. This study aimed to explore simple but relatively accurate models to describe stride length (SL), speed (SP) and walk ratio (WR) at various cadences. Twenty-four able-bodied participants (16 in a test group and 8 in a validation group) walked at seven cadence ratios (CRs). The individual and group mean SL, SP and WR were studied. Suitable temporal-spatial model structures were proposed and used to approximate the individual SL, SP and WR at various CRs. After the temporal-spatial model structures were found to be feasible, the general temporal-spatial models were analysed using the test group mean SL, SP and WR. Accuracy was assessed using the validation group mean values. Individual approximation accuracies showed that the proposed model structure deduced from the linear SL model was suitable for WR approximation. The linear, deduced quadratic and power functions approximated the individual SL, SP and WR, respectively, with high accuracy. Based on the test group mean SL, SP and WR, the general temporal-spatial models were obtained and produced comparable approximation accuracies in the validation group. The general temporal-spatial models predicted well the individual gait parameters with similar individual errors for both groups. These temporal-spatial models clearly describe SL, SP and especially WR at various cadences. They provide accurate reference data for gait estimation and have potential to guide speed modulation in robot-assisted gait rehabilitation. Graphical abstract Twenty-four able-bodied participants (16 in test group and 8 in validation group) walked at seven cadence ratios (CRs), with the individual and group mean stride length (SL), speed (SP) and walk ratio (WR) studied. This work selected the cadence ratio as the independent variable and yielded general temporal-spatial models based on the test group data, which were a linear model for SL, a quadratic function for SP and a power function for WR. The general temporal-spatial model produced comparable approximation accuracies in the validation group. Clearly describing SL, SP and especially WR at various cadences, these temporal-spatial models provide accurate references for gait estimation and have the potential to guide speed modulation in robot-assisted gait rehabilitation. Approximation of the group mean temporal-spatial parameters at seven cadences. Solid lines in parts (a, b): the general linear SL model. Solid lines in (c, d): the general quadratic SP model. Solid lines in (e, f): the general WR model. Dots and stars in (a, c, e): the individual and group mean values for the test group. Dots and stars in (b, d, f): the individual and group mean values for the validation group.

Project description:The ability to maintain dynamic balance in response to unexpected perturbations during walking is largely mediated by reactive control strategies. Reactive control during perturbed walking can be characterized by multiple metrics such as measures of whole-body angular momentum (WBAM), which capture the rotational dynamics of the body, and through Floquet analysis which captures the orbital stability of a limit cycle attractor. Recent studies have demonstrated that people with spatiotemporal asymmetries during gait have impaired control of whole-body dynamics as evidenced by higher peak-to-peak ranges of WBAM over the gait cycle. While this may suggest that spatiotemporal asymmetries could impair stability, no studies have quantified how direct modification of asymmetry influences reactive balance control. Here, we used a biofeedback paradigm that allows participants to systematically adopt different levels of step length asymmetry to test the hypothesis that walking asymmetrically impairs the reactive control of balance. In addition, we tested the hypothesis that perturbations to the non-dominant leg would cause less whole-body rotation due to its hypothesized role in weight support during walking. We characterized reactive control strategies in two ways. We first computed integrated angular momentum to characterize changes in whole-body configuration during multi-step responses to perturbations. We also computed the maximum Floquet multipliers (FMs) across the gait cycle, which represent the rate of convergence back to limit cycle behavior. Our results show that integrated angular momentum during the perturbation step and subsequent recovery steps, as well as the magnitude of maximum FMs over the gait cycle, do not change across levels of asymmetry. However, our results showed both limb-dependent and limb-independent responses to unexpected perturbations. Overall, our findings suggest that there is no causal relationship between step length asymmetry and impaired reactive control of balance in the absence of neuromotor impairments. Our approach could be used in future studies to determine if reducing asymmetries in populations with neuromotor impairments, such people post-stroke or amputees improves dynamic stability.

Dataset Information

Translational methods to detect asymmetries in temporal and spatial walking metrics in parkinsonian mouse models and human subjects with Parkinson's disease.

Publications

Translational methods to detect asymmetries in temporal and spatial walking metrics in parkinsonian mouse models and human subjects with Parkinson's disease.

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