Rhythm and Music-Based Interventions in Motor Rehabilitation: Current Evidence and Future Perspectives

Research in basic and clinical neuroscience of music conducted over the past decades has begun to uncover music’s high potential as a tool for rehabilitation. Advances in our understanding of how music engages parallel brain networks underpinning sensory and motor processes, arousal, reward, and affective regulation, have laid a sound neuroscientific foundation for the development of theory-driven music interventions that have been systematically tested in clinical settings. Of particular significance in the context of motor rehabilitation is the notion that musical rhythms can entrain movement patterns in patients with movement-related disorders, serving as a continuous time reference that can help regulate movement timing and pace. To date, a significant number of clinical and experimental studies have tested the application of rhythm- and music-based interventions to improve motor functions following central nervous injury and/or degeneration. The goal of this review is to appraise the current state of knowledge on the effectiveness of music and rhythm to modulate movement spatiotemporal patterns and restore motor function. By organizing and providing a critical appraisal of a large body of research, we hope to provide a revised framework for future research on the effectiveness of rhythm- and music-based interventions to restore and (re)train motor function.

Proprioceptive Training with Visual Feedback Improves Upper Limb Function in Stroke Patients: A Pilot Study

Proprioceptive deficit is one of the common sensory impairments following stroke and has a negative impact on motor performance. However, evidence-based training procedures and cost-efficient training setups for patients with poststroke are still limited. We compared the effects of proprioceptive training versus nonspecific sensory stimulation on upper limb proprioception and motor function rehabilitation. In this multicenter, single-blind, randomized controlled trial, 40 participants with poststroke hemiparesis were enrolled from 3 hospitals in China. Participants were assigned randomly to receive proprioceptive training involving passive and active movements with visual feedback (proprioceptive training group [PG]; n = 20 ) or nonspecific sensory stimulation (control group [CG]; n = 20 ) 20 times in four weeks. Each session lasted 30 minutes. A clinical assessor blinded to group assignment evaluated patients before and after the intervention. The primary outcome was the change in the motor subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-M). Secondary outcomes were changes in box and block test (BBT), thumb localization test (TLT), the sensory subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-S), and Barthel Index (BI). The results showed that the mean change scores of FMA-UE were significantly greater in the PG than in the CG ( p = 0.010 for FMA-UE-M, p = 0.033 for FMA-UE-S). The PG group was improved significantly in TLT ( p = 0.010 ) and BBT ( p = 0.027 ), while there was no significant improvement in TLT ( p = 0.083 ) and BBT ( p = 0.107 ) for the CG group. The results showed that proprioceptive training was effective in improving proprioception and motor function of the upper extremity in patients with poststroke. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2000037808).

Therapeutic Effects of a Newly Developed 3D Magnetic Finger Rehabilitation Device in Subacute Stroke Patients: A Pilot Study

We developed a magnetic-force-based three-dimensional (3D) rehabilitation device that can perform motor rehabilitation treatment for paralyzed fingers, regardless of upper extremity movement and position, and investigated the therapeutic effects of the device. An end-effector type rehabilitation device that can generate magnetic fields in three directions was developed using electromagnets and permanent magnetics. A double-blinded randomized controlled pilot study was conducted with a total of 12 patients. The intervention group had rehabilitation treatment using the developed magnetic finger rehabilitation device for 30 min a day for four weeks. The control group underwent exercise rehabilitation treatment. The control group received conventional occupational therapy on the upper limbs, including hands, from an occupational therapist, for the same amount of time. Adverse effects were monitored, and the patient’s sensory or proprioceptive deficits were examined before the intervention. No participants reported safety concerns while the intervention was conducted. The Wolf Motor Function Test (WMFT) scores were significantly improved in the intervention group (from 13.4 ± 3.6 to 20.9 ± 4.0 points) compared to the control group (from 13.1 ± 4.0 to 15.2 ± 3.8 points) (p = 0.016). The patients in the intervention group (from 88 ± 12 to 67 ± 13 s) showed greater improvement of WMFT times compared to the control group (from 89 ± 10 to 73 ± 11 s) (p = 0.042). The Manual Function Test and the upper limb score of the Fugl-Meyer Assessment were significantly improved in the intervention group compared with the control group (p = 0.038 and p = 0.042). The patients in the intervention group also showed significantly greater enhancement of the Korean version of the modified Barthel Index than the control group (p = 0.042). Rehabilitation treatment using the 3D magnetic-force-driven finger rehabilitation device helped improve finger motor function and activities of daily living in subacute stroke patients.

Upper extremity motor abilities and cognitive capability mediate the causal dependency between somatosensory capability and daily function in stroke individuals

Stroke individuals’ daily function has been demonstrated to be influenced by their somatosensory capability, cognitive capability, and upper extremity (UE) motor abilities. However, the structural relationships among these abilities on stroke individuals’ independence in daily function remain unclear. We analyzed the pretest measures of 153 stroke individuals in outpatient rehabilitation settings by structural equation modeling to determine the structural relationship among somatosensory capability, UE muscle strength, UE motor function, and cognitive capability that influences independence in daily function. The standardized results indicated somatosensory capability negatively influenced UE muscle strength, but positively influenced UE muscle strength mediated by UE motor function. UE muscle strength, then, positively influenced individuals’ independence in daily function. On the other hand, somatosensory capability positively influenced cognitive capability, which marginally and positively affected the performance of independence in daily function. To the best of our knowledge, this is the first study to demonstrate the influence of somatosensory capability on the daily function is mediated mainly by motor functions and marginally by cognitive capability. This structural model may allow future clinical therapists to design more effective task-related training protocols to promote the independence in daily function for stroke individuals.

Correlation Between Proprioceptive Impairment and Motor Deficits After Stroke: A Meta-Analysis Review

Introduction: Proprioceptive impairment is a common symptom after stroke. Clarifying how proprioception correlates with motor function after stroke may be helpful in optimizing proprioception-augmented movement training. Previous studies have shown inconsistent findings. A meta-analysis is an optimal method to explore the correlation and identify the factors contributing to these inconsistencies.Objective: To explore the correlation between proprioception and motor function after stroke through a meta-analysis, taking into account characteristics of the measurements used in these studies.Methods: We searched multiple databases until November 2021 for eligible studies that measured both proprioception and motor functions in persons with stroke and reported their correlation or data for correlation analysis. A meta-analysis of the correlations was performed. The subgroup analysis and meta-regression were further conducted to investigate potential factors contributing to the heterogeneity of correlation strength, based on the participants' characteristics, proprioception, and motor function measures.Results: In total, 28 studies comprising of 1,829 participants with stroke were included in the meta-analysis. The overall correlation between proprioception and motor function was significant (r = 0.267, p < 0.05), but there was heterogeneity across studies (I2 = 45%, p < 0.05). The results of the subgroup analysis showed proprioception of the axial segment in weight-bearing conditions (r = 0.443, p < 0.05) and upper limb without weight-bearing (r = 0.292, p < 0.05) had a stronger correlation with motor function than proprioception of the lower limb without weight-bearing. The proprioception measured through ipsilateral matching (r = 0.412, p < 0.05) showed a stronger correlation with motor function than through contralateral matching. The International Classification of Functioning, Disability, and Health (ICF) domains of motor function, movement function (r = 0.338, p < 0.05), activity performance (r = 0.239, p < 0.05), and independence (r = 0.319, p < 0.05) showed a stronger correlation with proprioception than with other domains.Conclusion: There is a significant correlation between proprioception and motor dysfunction after stroke. The proprioception measured in the axial segment under weight-bearing conditions or measured with ipsilateral matching, and motor function, specifically in the ICF domains of movement function, activity performance, and independence showed a positive contribution to the association between proprioception and motor function. The correlation does not imply causation and might be underestimated by attributes of current tests for proprioception and motor function. Further studies are needed to clarify the cause-effect relationship.

Effectiveness of a Novel Contralaterally Controlled Neuromuscular Electrical Stimulation for Restoring Lower Limb Motor Performance and Activities of Daily Living in Stroke Survivors: A Randomized Controlled Trial

Background. Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is a novel electrical stimulation treatment for stroke; however, reports on the efficacy of CCNMES on lower extremity function after stroke are scarce. Objective. To compare the effects of CCNMES versus NMES on lower extremity function and activities of daily living (ADL) in subacute stroke patients. Methods. Forty-four patients with a history of subacute stroke were randomly assigned to a CCNMES group and a NMES group ( n = 22 per group). Twenty-one patients in each group completed the study per protocol, with one subject lost in follow-up in each group. The CCNMES group received CCNMES to the tibialis anterior (TA) and the peroneus longus and brevis muscles to induce ankle dorsiflexion motion, whereas the NMES group received NMES. The stimulus current was a biphasic waveform with a pulse duration of 200 μs and a frequency of 60 Hz. Patients in both groups underwent five 15 min sessions of electrical stimulation per week for three weeks. Indicators of motor function and ADL were measured pre- and posttreatment, including the Fugl–Meyer assessment of the lower extremity (FMA-LE) and modified Barthel index (MBI). Surface electromyography (sEMG) assessments included average electromyography (aEMG), integrated electromyography (iEMG), and root mean square (RMS) of the paretic TA muscle. Results. Values for the FMA-LE, MBI, aEMG, iEMG, and RMS of the affected TA muscle were significantly increased in both groups after treatment ( p < 0.01 ). Patients in the CCNMES group showed significant improvements in all the measurements compared with the NMES group after treatment. Within-group differences in all post- and pretreatment indicators were significantly greater in the CCNMES group than in the NMES group ( p < 0.05 ). Conclusion. CCNMES improved motor function and ADL ability to a greater extent than the conventional NMES in subacute stroke patients.

Effects of virtual reality-based motor control training on inflammation, oxidative stress, neuroplasticity and upper limb motor function in patients with chronic stroke: a randomized controlled trial

Background Immersive virtual reality (VR)-based motor control training (VRT) is an innovative approach to improve motor function in patients with stroke. Currently, outcome measures for immersive VRT mainly focus on motor function. However, serum biomarkers help detect precise and subtle physiological changes. Therefore, this study aimed to identify the effects of immersive VRT on inflammation, oxidative stress, neuroplasticity and upper limb motor function in stroke patients. Methods Thirty patients with chronic stroke were randomized to the VRT or conventional occupational therapy (COT) groups. Serum biomarkers including interleukin 6 (IL-6), intracellular adhesion molecule 1 (ICAM-1), heme oxygenase 1 (HO-1), 8-hydroxy-2-deoxyguanosine (8-OHdG), and brain-derived neurotrophic factor (BDNF) were assessed to reflect inflammation, oxidative stress and neuroplasticity. Clinical assessments including active range of motion of the upper limb and the Fugl-Meyer Assessment for upper extremity (FMA-UE) were also used. Two-way mixed analyses of variance (ANOVAs) were used to examine the effects of the intervention (VRT and COT) and time on serum biomarkers and upper limb motor function. Results We found significant time effects in serum IL-6 (p = 0.010), HO-1 (p = 0.002), 8-OHdG (p = 0.045), and all items/subscales of the clinical assessments (ps < 0.05), except FMA-UE-Coordination/Speed (p = 0.055). However, significant group effects existed only in items of the AROM-Elbow Extension (p = 0.007) and AROM-Forearm Pronation (p = 0.048). Moreover, significant interactions between time and group existed in item/subscales of FMA-UE-Shoulder/Elbow/Forearm (p = 0.004), FMA-UE-Total score (p = 0.008), and AROM-Shoulder Flexion (p = 0.001). Conclusion This was the first study to combine the effectiveness of immersive VRT using serum biomarkers as outcome measures. Our study demonstrated promising results that support the further application of commercial and immersive VR technologies in patients with chronic stroke.

Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells From Different Donors on Spinal Cord Injury in Mice

Spinal cord injury (SCI) is caused by an external force, leading to severe dysfunction of the limbs below the injured segment. The inflammatory response plays a vital role in the prognosis of SCI. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation can promote repair of SCI by reducing the inflammatory response. We previously showed that hUCMSCs from 32 donors had different inhibitory abilities on BV2 cell proliferation. In this study, three experimental groups were established, and the mice were injected with different lines of hUCMSCs. Hind limb motor function, hematoxylin-eosin (H&amp;E) staining, immunohistochemistry, Western blot (WB), qualitative real-time polymerase chain reaction (qRT-PCR), and RNA sequencing and correlation analysis were used to investigate the effects of hUCMSC transplantation on SCI mice and the underlying mechanisms. The results showed that the therapeutic effects of the three hUCMSC lines were positively correlated with their inhibitory abilities of BV2 cell proliferation rates in vitro. The MSC_A line had a better therapeutic effect on improving the hind limb motor function and greater effect on reducing the expression of glial fibrillary acidic protein (Gfap) and ionized calcium binding adaptor molecule 1 (Iba1) and increasing the expression of neuronal nuclei (NeuN). Differentially expressed genes including Zbtb16, Per3, and Hif3a were probably the key genes involved in the protective mechanism by MSC_A after nerve injury. qRT-PCR results further verified that Zbtb16, Per3, and Hif3a expressions reduced by SCI could be reversed by MSC_A application. These results suggest that the effect of hUCMSCs transplantation on acute SCI depends on their inhibitory abilities to inflammation reaction after nerve injury, which may help to shape future use of hUCMSCs combined with improving the effectiveness of clinical transformation.

Sensitive-stage embryo irradiation affects embryonic neuroblasts and adult motor function

Background Cranial radiation therapy for treating childhood malignancies in the central nervous system or accidental radiation exposure may result in neurological side effects in surviving adults. As tissue homeostasis is maintained by stem cells, understanding the effect of radiation on neural stem cells will provide clues for managing the neurological effects. Drosophila embryos were used as a model system whose sensitivity to irradiation-induced cell death changes from the sensitive to resistant stage during development. Objective Drosophila embryos at the radiation-sensitive stage were irradiated at various doses and the radiation sensitivity was tested regarding the appearance of apoptotic cells in the embryos and the embryonic lethality. Cell fates of the neural stem cells called neuroblasts (NBs) and adult motor function after irradiation were also investigated. Result Irradiation of Drosophila embryos at the radiation-sensitive stage resulted in a dose-dependent increase in the number of embryos containing apoptotic cells 75 min after treatment starting at 3 Gy. Embryonic lethality assayed by hatch rate was induced by 1 Gy irradiation, which did not induce cell death. Notably, no apoptosis was detected in NBs up to 2 h after irradiation at doses as high as 40 Gy. At 3 h after irradiation, as low as 3 Gy, the number of NBs marked by Dpn and Klu was decreased by an unidentified mechanism regardless of the cell death status of the embryo. Furthermore, embryonic irradiation at 3 Gy, but not 1 Gy, resulted in locomotor defects in surviving adults. Conclusion Embryonic NBs survived irradiation at doses as high as 40 Gy, while cells in other parts of the embryos underwent apoptosis at doses higher than 3 Gy within 2 h after treatment. Three hours after exposure to a minimum dose of 3 Gy, the number of NBs marked by Dpn and Klu decreased, and the surviving adults exhibited defects in locomotor ability.