Levin, M. F., Banina, M. C., Frenkel-Toledo, S., Berman, S., Soroker, N., Solomon, J. M., et al. (2018). Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial. Trials, 19(1), 7.
Abstract: BACKGROUND: Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved (“active control zone”) after identification of a “spasticity zone”. Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function. METHODS: This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task. DISCUSSION: This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02725853 . Initially registered on 12 January 2016.
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Frenkel-Toledo, S., Levin, M. F., Berman, S., Liebermann, D. G., Baniña, M. C., Solomon, J. M., et al. (2022). Shared and distinct voxel-based lesion-symptom mappings for spasticity and impaired movement in the hemiparetic upper limb. Sci Rep, 12(1).
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Swissa, Y., Hacohen, S., Friedman, J., & Frenkel-Toledo, S. (2022). Sensorimotor performance after high-definition transcranial direct current stimulation over the primary somatosensory or motor cortices in men versus women. Sci Rep, 12, 11117.
Abstract: The primary somatosensory (S1) cortex is a central structure in motor performance. However, transcranial direct current stimulation (tDCS) research aimed at improving motor performance usually targets the primary motor cortex (M1). Recently, sex was found to mediate tDCS response. Thus, we investigated whether tDCS with an anodal electrode placed over S1 improves motor performance and sensation perception in men versus women. Forty-five participants randomly received 15-min high-definition tDCS (HD-tDCS) at 1 mA to S1, M1, or sham stimulation. Reaching performance was tested before and immediately following stimulation. Two-point orientation discrimination (TPOD) of fingers and proprioception of a reaching movement were also tested. Although motor performance did not differ between groups, reaching reaction time improved in the M1 group men. Reaching movement time and endpoint error improved in women and men, respectively. Correct trials percentage for TPOD task was higher in the S1 compared to the M1 group in the posttest and improved only in the S1 group. Reaching movement time for the proprioception task improved, overall, and endpoint error did not change. Despite the reciprocal connections between S1 and M1, effects of active tDCS over S1 and M1 may specifically influence sensation perception and motor performance, respectively. Also, sex may mediate effects of HD-tDCS on motor performance.
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Levin, M. F., Berman, S., Weiss, N., Parmet, Y., Banina, M. C., Frenkel-Toledo, S., et al. (2023). ENHANCE proof-of-concept three-arm randomized trial: effects of reaching training of the hemiparetic upper limb restricted to the spasticity-free elbow range (Vol. 13).
Abstract: Post-stroke motor recovery processes remain unknown. Timescales and patterns of upper-limb (UL) recovery suggest a major impact of biological factors, with modest contributions from rehabilitation. We assessed a novel impairment-based training motivated by motor control theory where reaching occurs within the spasticity-free elbow range. Patients with subacute stroke (</= 6 month; n = 46) and elbow flexor spasticity were randomly allocated to a 10-day UL training protocol, either personalized by restricting reaching to the spasticity-free elbow range defined by the tonic stretch reflex threshold (TSRT) or non-personalized (non-restricted) and with/without anodal transcranial direct current stimulation. Outcomes assessed before, after, and 1 month post-intervention were elbow flexor TSRT angle and reach-to-grasp arm kinematics (primary) and stretch reflex velocity sensitivity, clinical impairment, and activity (secondary). Results were analyzed for 3 groups as well as those of the effects of impairment-based training. Clinical measures improved in both groups. Spasticity-free range training resulted in faster and smoother reaches, smaller (i.e., better) arm-plane path length, and closer-to-normal shoulder/elbow movement patterns. Non-personalized training improved clinical scores without improving arm kinematics, suggesting that clinical measures do not account for movement quality. Impairment-based training within a spasticity-free elbow range is promising since it may improve clinical scores together with arm movement quality.Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique Identifier: NCT02725853; Initial registration date: 01/04/2016.
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Davidowitz, I., Parmet, Y., Frenkel-Toledo, S., Banina, M. C., Soroker, N., Solomon, J. M., et al. (2019). Relationship Between Spasticity and Upper-Limb Movement Disorders in Individuals With Subacute Stroke Using Stochastic Spatiotemporal Modeling. Neurorehabil Neural Repair, 33(2), 141–152.
Abstract: BACKGROUND: Spasticity is common in patients with stroke, yet current quantification methods are insufficient for determining the relationship between spasticity and voluntary movement deficits. This is partly a result of the effects of spasticity on spatiotemporal characteristics of movement and the variability of voluntary movement. These can be captured by Gaussian mixture models (GMMs). OBJECTIVES: To determine the influence of spasticity on upper-limb voluntary motion, as assessed by the bidirectional Kullback-Liebler divergence (BKLD) between motion GMMs. METHODS: A total of 16 individuals with subacute stroke and 13 healthy aged-equivalent controls reached to grasp 4 targets (near-center, contralateral, far-center, and ipsilateral). Two-dimensional GMMs (angle and time) were estimated for elbow extension motion. BKLD was computed for each individual and target, within the control group and between the control and stroke groups. Movement time, final elbow angle, average elbow velocity, and velocity smoothness were computed. RESULTS: Between-group BKLDs were much larger than within control-group BKLDs. Between-group BKLDs for the near-center target were lower than those for the far-center and contralateral targets, but similar to that for the ipsilateral target. For those with stroke, the final angle was lower for the near-center target, and the average velocity was higher. Velocity smoothness was lower for the near-center than for the ipsilateral target. Elbow flexor and extensor passive muscle resistance (Modified Ashworth Scale) strongly explained BKLD values. CONCLUSIONS: Results support the view that individuals with poststroke spasticity have a velocity-dependent reduction in active elbow joint range and that BKLD can be used as an objective measure of the effects of spasticity on reaching kinematics.
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