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      Dissociating motor learning from recovery in exoskeleton training post-stroke

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          Abstract

          Background

          A large number of robotic or gravity-supporting devices have been developed for rehabilitation of upper extremity post-stroke. Because these devices continuously monitor performance data during training, they could potentially help to develop predictive models of the effects of motor training on recovery. However, during training with such devices, patients must become adept at using the new “tool” of the exoskeleton, including learning the new forces and visuomotor transformations associated with the device. We thus hypothesized that the changes in performance during extensive training with a passive, gravity-supporting, exoskeleton device (the Armeo Spring) will follow an initial fast phase, due to learning to use the device, and a slower phase that corresponds to reduction in overall arm impairment. Of interest was whether these fast and slow processes were related.

          Methods

          To test the two-process hypothesis, we used mixed-effect exponential models to identify putative fast and slow changes in smoothness of arm movements during 80 arm reaching tests performed during 20 days of exoskeleton training in 53 individuals with post-acute stroke.

          Results

          In line with our hypothesis, we found that double exponential models better fit the changes in smoothness of arm movements than single exponential models. In contrast, single exponential models better fit the data for a group of young healthy control subjects. In addition, in the stroke group, we showed that smoothness correlated with a measure of impairment (the upper extremity Fugl Meyer score - UEFM) at the end, but not at the beginning, of training. Furthermore, the improvement in movement smoothness due to the slow component, but not to the fast component, strongly correlated with the improvement in the UEFM between the beginning and end of training. There was no correlation between the change of peaks due to the fast process and the changes due to the slow process. Finally, the improvement in smoothness due to the slow, but not the fast, component correlated with the number of days since stroke at the onset of training – i.e. participants who started exoskeleton training sooner after stroke improved their smoothness more.

          Conclusions

          Our results therefore demonstrate that at least two processes are involved in in performance improvements measured during mechanized training post-stroke. The fast process is consistent with learning to use the exoskeleton, while the slow process independently reflects the reduction in upper extremity impairment.

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          Most cited references33

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          Effects of robot-assisted therapy on upper limb recovery after stroke: a systematic review.

          The aim of the study was to present a systematic review of studies that investigate the effects of robot-assisted therapy on motor and functional recovery in patients with stroke. A database of articles published up to October 2006 was compiled using the following Medline key words: cerebral vascular accident, cerebral vascular disorders, stroke, paresis, hemiplegia, upper extremity, arm, and robot. References listed in relevant publications were also screened. Studies that satisfied the following selection criteria were included: (1) patients were diagnosed with cerebral vascular accident; (2) effects of robot-assisted therapy for the upper limb were investigated; (3) the outcome was measured in terms of motor and/or functional recovery of the upper paretic limb; and (4) the study was a randomized clinical trial (RCT). For each outcome measure, the estimated effect size (ES) and the summary effect size (SES) expressed in standard deviation units (SDU) were calculated for motor recovery and functional ability (activities of daily living [ADLs]) using fixed and random effect models. Ten studies, involving 218 patients, were included in the synthesis. Their methodological quality ranged from 4 to 8 on a (maximum) 10-point scale. Meta-analysis showed a nonsignificant heterogeneous SES in terms of upper limb motor recovery. Sensitivity analysis of studies involving only shoulder-elbow robotics subsequently demonstrated a significant homogeneous SES for motor recovery of the upper paretic limb. No significant SES was observed for functional ability (ADL). As a result of marked heterogeneity in studies between distal and proximal arm robotics, no overall significant effect in favor of robot-assisted therapy was found in the present meta-analysis. However, subsequent sensitivity analysis showed a significant improvement in upper limb motor function after stroke for upper arm robotics. No significant improvement was found in ADL function. However, the administered ADL scales in the reviewed studies fail to adequately reflect recovery of the paretic upper limb, whereas valid instruments that measure outcome of dexterity of the paretic arm and hand are mostly absent in selected studies. Future research into the effects of robot-assisted therapy should therefore distinguish between upper and lower robotics arm training and concentrate on kinematical analysis to differentiate between genuine upper limb motor recovery and functional recovery due to compensation strategies by proximal control of the trunk and upper limb.
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            Nonlinear mixed effects models for repeated measures data.

            We propose a general, nonlinear mixed effects model for repeated measures data and define estimators for its parameters. The proposed estimators are a natural combination of least squares estimators for nonlinear fixed effects models and maximum likelihood (or restricted maximum likelihood) estimators for linear mixed effects models. We implement Newton-Raphson estimation using previously developed computational methods for nonlinear fixed effects models and for linear mixed effects models. Two examples are presented and the connections between this work and recent work on generalized linear mixed effects models are discussed.
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              Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery.

              Stroke remains a leading cause of adult disability. Some degree of spontaneous behavioral recovery is usually seen in the weeks after stroke onset. Variability in recovery is substantial across human patients. Some principles have emerged; for example, recovery occurs slowest in those destined to have less successful outcomes. Animal studies have extended these observations, providing insight into a broad range of underlying molecular and physiological events. Brain mapping studies in human patients have provided observations at the systems level that often parallel findings in animals. In general, the best outcomes are associated with the greatest return toward the normal state of brain functional organization. Reorganization of surviving central nervous system elements supports behavioral recovery, for example, through changes in interhemispheric lateralization, activity of association cortices linked to injured zones, and organization of cortical representational maps. A number of factors influence events supporting stroke recovery, such as demographics, behavioral experience, and perhaps genetics. Such measures gain importance when viewed as covariates in therapeutic trials of restorative agents that target stroke recovery.
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                Author and article information

                Contributors
                schweigh@usc.edu
                chunjiw@gmail.com
                denis.mottet@umontpellier.fr
                i-laffont@chu-montpellier.fr
                k-bakhti@chu-montpellier.fr
                dreinken@uci.edu
                Olivier.Remy-Neris@univ-brest.fr
                Journal
                J Neuroeng Rehabil
                J Neuroeng Rehabil
                Journal of NeuroEngineering and Rehabilitation
                BioMed Central (London )
                1743-0003
                5 October 2018
                5 October 2018
                2018
                : 15
                : 89
                Affiliations
                [1 ]ISNI 0000 0001 2156 6853, GRID grid.42505.36, Biokinesiology and Physical Therapy, , University of Southern California, ; Los Angeles, USA
                [2 ]ISNI 0000 0001 2156 6853, GRID grid.42505.36, Neuroscience graduate Program, , University of Southern California, ; Los Angeles, USA
                [3 ]ISNI 0000 0001 2097 0141, GRID grid.121334.6, STAPS, , Université de Montpellier, ; Euromov, Montpellier, France
                [4 ]Montpellier University Hospital, Euromov, IFRH, Montpellier University, Montpellier, France
                [5 ]ISNI 0000 0001 0668 7243, GRID grid.266093.8, Departments of Mechanical and Aerospace Engineering, Anatomy and Neurobiology, , University of California, ; Irvine, USA
                [6 ]Université de Bretagne Occidentale, Centre hospitalier universitaire, LaTIM-INSERM UMR1101, Brest, France
                Author information
                http://orcid.org/0000-0003-3362-6088
                Article
                428
                10.1186/s12984-018-0428-1
                6173922
                30290806
                caeef677-6fd3-4c14-b3cd-29583b4010f7
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 June 2018
                : 11 September 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000071, National Institute of Child Health and Human Development;
                Award ID: HD065438
                Award Recipient :
                Funded by: French ministry of health
                Award ID: STIC program
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Neurosciences
                motor learning,motor adaptation,motor recovery,stroke,neurorehabilitation,exoskeleton,rehabilitation robotics,movement analysis

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