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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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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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Frenkel-Toledo, S., Yamanaka, J., Friedman, J., Feldman, A. G., & Levin, M. F. (2019). Referent control of anticipatory grip force during reaching in stroke: an experimental and modeling study. Exp Brain Res, 237(7), 1655–1672.
Abstract: To evaluate normal and impaired control of anticipatory grip force (GF) modulation, we compared GF production during horizontal arm movements in healthy and post-stroke subjects, and, based on a physiologically feasible dynamic model, determined referent control variables underlying the GF-arm motion coordination in each group. 63% of 13 healthy and 48% of 13 stroke subjects produced low sustained initial force (< 10 N) and increased GF prior to arm movement. Movement-related GF increases were higher during fast compared to self-paced arm extension movements only in the healthy group. Differences in the patterns of anticipatory GF increases before the arm movement onset between groups occurred during fast extension arm movement only. In the stroke group, longer delays between the onset of GF change and elbow motion were related to clinical upper limb deficits. Simulations showed that GFs could emerge from the difference between the actual and the referent hand aperture (Ra) specified by the CNS. Similarly, arm movement could result from changes in the referent elbow position (Re) and could be affected by the co-activation (C) command. A subgroup of stroke subjects, who increased GF before arm movement, could specify different patterns of the referent variables while reproducing the healthy typical pattern of GF-arm coordination. Stroke subjects, who increased GF after arm movement onset, also used different referent strategies than controls. Thus, altered anticipatory GF behavior in stroke subjects may be explained by deficits in referent control.
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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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Lerner, O., Friedman, J., & Frenkel-Toledo, S. (2021). The effect of high-definition transcranial direct current stimulation intensity on motor performance in healthy adults: a randomized controlled trial. J NeuroEngineering Rehabil, 18, 103.
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