Gamma oscillations induced by 40-Hz visual-auditory stimulation for the treatment of acute-phase limb motor rehabilitation after stroke: study protocol for a prospective randomized controlled trial.

BACKGROUND: The incidence of hemiparetic limb dysfunction reaches 85% in stroke patients, emerging as a critical factor influencing their daily lives. However, the effectiveness of current rehabilitation treatments is considerably limited, particularly in patients with upper extremity impairment. This study aims to conduct a prospective clinical trial to validate the safety and effectiveness of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating post-stroke upper limb dysfunction and to explore the relevant mechanisms. METHODS: This trial is a prospective, randomized controlled, double-blind study. All enrolled patients were randomly assigned to two groups. The experimental group received intervention through 40-Hz visual-auditory stimulation, while the control group underwent intervention with randomly matched visual-auditory stimulation frequencies. The primary efficacy endpoint is the change in motor function. Secondary efficacy endpoints include motor-evoked potentials, cerebral hemodynamic changes, neural network connectivity, and alterations in synaptic-related genes. Safety evaluation included major adverse events, all-cause mortality, and photosensitive epilepsy. Assessments will be conducted at baseline, after a 14-day treatment period, and during subsequent follow-up visits (at 3 and 6 months) post-treatment. The differences between the two groups will be compared. DISCUSSION: This study will evaluate the safety and efficacy of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating patients with upper extremity dysfunction after an acute cerebral stroke. Concurrently, we will explore potential mechanisms, including changes in synaptic-related genes and neural network connectivity. This trial is expected to provide evidence for the effectiveness of this new technique in treating upper extremity dysfunction after a stroke and improving patients' quality of life. TRIAL REGISTRATION: The study protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2300076579 on October 12, 2023.

Effectiveness and mechanism of action of rTMS combined with quadriceps strength training in individuals with knee osteoarthritis: study protocol for a randomized controlled trial.

BACKGROUND: Quadriceps training is necessary in function and activity of daily living for patients with knee osteoarthritis (KOA). However, it did not reduce the rate of surgical treatment for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial Magnetic Stimulation (TMS) could enhance the functional connectivity of brain regions and improves maladaptive plasticity. However, the synergistic effect of the combination of the two for treat KOA is still unclear. Therefore, the purpose of this study is to investigate whether the High-Frequency rTMS combined with quadriceps strength training can improve the pain and function in KOA more effectively than quadriceps training alone and explore the mechanism of action. METHODS: This study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks of intervention and 6 months follow-up. 148 participants with KOA will receive usual care management and be randomized into four subgroups equally, including quadriceps strength training, high-frequency rTMS training, sham rTMS and quadriceps strength training, high-frequency rTMS and quadriceps strength training. The rehabilitation interventions will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during the intervention and 1 month, 3 months and 6 months during the follow-up period. The effectiveness outcomes will be included visual analog scale, isokinetic knee muscle strength, Knee Injury and Osteoarthritis Outcome score and 36-Item Short-Form Health Survey score; The act mechanism outcomes will be included motor evoked potential, grey matter density, white matter, subcortical nuclei volumes, cortical thickness and functional connectivity by MRI. Two-way of variance with repeated measures will be used to test the group and time effect for outcome measures. DISCUSSION: The study will be the first protocol to examine whether there are synergistic effects following high-frequency rTMS combined with quadriceps strength training for treat KOA and clarify the mechanism of action. High-frequency rTMS can be added into the training program for KOA patients if it is proven effective. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.

Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Transcranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). METHODS: This study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase. DISCUSSION: The study's findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.

Electroacupuncture stimulation to modulate neural oscillations in promoting neurological rehabilitation.

Electroacupuncture (EA) stimulation is a modern neuromodulation technique that integrates traditional Chinese acupuncture therapy with contemporary electrical stimulation. It involves the application of electrical currents to specific acupoints on the body following acupuncture. EA has been widely used in the treatment of various neurological disorders, including epilepsy, stroke, Parkinson's disease, and Alzheimer's disease. Recent research suggests that EA stimulation may modulate neural oscillations, correcting abnormal brain electrical activity, therefore promoting brain function and aiding in neurological rehabilitation. This paper conducted a comprehensive search in databases such as PubMed, Web of Science, and CNKI using keywords like "electroacupuncture," "neural oscillations," and "neurorehabilitation", covering the period from year 1980 to 2023. We provide a detailed overview of how electroacupuncture stimulation modulates neural oscillations, including maintaining neural activity homeostasis, influencing neurotransmitter release, improving cerebral hemodynamics, and enhancing specific neural functional networks. The paper also discusses the current state of research, limitations of electroacupuncture-induced neural oscillation techniques, and explores prospects for their combined application, aiming to offer broader insights for both basic and clinical research.

Efficacy and safety of platelet-rich plasma combined with Tai Chi for knee osteoarthritis: study protocol for a placebo-controlled randomized trial.

BACKGROUND: No definitive treatment methods of curative for knee osteoarthritis (KOA). The combined therapies that into account both the biochemical and biomechanical may provide potential opportunities for treat KOA, and previous studies have demonstrated that the platelet-rich plasma of intra-articular injection (IAI-PRP) and exercise treatments afford more benefits than do their corresponding monotherapies. The absence of a specific exercise plan and detailed explanation renders the aforementioned study results questionable. Furthermore, Tai Chi (TC) with moderate-intensity, whole body movements and good adherence may prove to be more effective for treating KOA. However, few studies examined the effectiveness and safety of combined IAI-PRP and TC for KOA. METHODS: This study protocol will be a placebo-controlled, assessor-blinded randomized trial involving 12-week intervention and 1-year follow-up. The stratified randomization will be used to randomly assign the 212 participants to four groups: group A (placebo IAI); group B (PRP IAI); group C (TC and placebo IAI); group D (TC and PRP IAI). Injection will be performed once a week, three consecutive times as a course, after a week of rest to continue the next course, a total of 3 courses (12 week). Additionally, the TC interventions will be carried out 3 days per week for a total of 12 weeks. The primary outcome measures will include the efficacy (Western Ontario and McMaster Universities Osteoarthritis Index), acceptability and safety of these interventions. The secondary outcome measures will include physical function (Timed Up and Go test), walking function (Gait Analysis), inflammatory factor levels (e.g., Interleukin-1 ß, interleukin-6, vascular endothelial growth factor), quality of life (36-Item Short Form Health Survey), volume of patellofemoral cartilage and effusion-synovitis (MRI). Two-way of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. DISCUSSION: This trial will be first one to propose an integrated scheme combing IAI-PRP and TC for treatment of KOA, based on the consideration of the biochemical and biomechanical pathogenesis of KOA. These results of the study will provide evidence with high quality for integrated IAI-PRP and TC to treatment KOA. Trial Registration Chinese Clinical Trial Registry ChiCTR2300067559. Registered on 11 January 2023.

Synergy-based functional electrical stimulation and robotic-assisted for retraining reach-to-grasp in stroke: a study protocol for a randomized controlled trial.

BACKGROUND: Stroke survivors have long-term upper limb impairment, which impacts the quality of life (QOL) and social reintegration, but there is lack of effective therapeutic strategies and novel technologies. Customized multi-muscle functional electrical stimulation (FES) based on the muscle synergy of healthy adults and robotic-assisted therapy (RAT) have been proved efficacy respectively. Synergy-based FES combined with RAT can be a novel and more effective therapy for upper limb recovery of stroke survivors from the perspective of synergistic enhancement. However, few studies have examined the effectiveness of combined synergy-based FES and RAT, especially for motor control evaluated by reach-to-grasp (RTG) movements. The main objective of the following research protocol is to evaluate the effectiveness and efficacy, as well as adoptability, of FES-RAT and FES or RAT rehabilitation program for upper limb function improvement after stroke. METHODS: This will be an assessor-blinded randomized controlled trial involving a 12-week intervention and a 6-month follow-up. Stratified randomization will be used to equally and randomly assign 162 stroke patients into the FES + conventional rehabilitation program (CRP) group, RAT + CRP group and FES-RAT + CRP group. Interventions will be provided in 5 sessions per week, with a total of 60 sessions. The primary outcome measurements will include the Fugl-Meyer Assessment and Biomechanical Assessment of RTG movements. The secondary outcome measurements will include quality of life and brain neuroplasticity assessments by MRI. Evaluations will be performed at five time points, including at baseline, 6 weeks and 12 weeks from the start of treatment, and 3 months and 6 months following the end of treatment. A two-way analysis of variance with repeated measures will be applied to examine the main effects of the group, the time factor and group-time interaction effects. DISCUSSION: The results of the study protocol will provide high quality evidence for integrated synergy-based FES and RAT, and synergy-based FES alone and guide the design of more effective treatment methods for stroke rehabilitation. TRIAL REGISTRATION: ChiCTR2300071588.

Transcranial direct current stimulation combined with bodyweight support-tai chi footwork for motor function of stroke survivors: a study protocol of randomised controlled trial.

INTRODUCTION: Our previous studies have proposed the bodyweight support-t'ai chi (BWS-TC) footwork training for stroke survivors with severe motor dysfunction and fear of falling, and have proven its positive effects for motor function. Transcranial direct current stimulation (tDCS) provides a non-invasive and safe way to modulate neuronal activity and provoke neuroplastic changes and to improve the motor function of stroke survivors. However, it is unclear whether the integration of BWS-TC and tDCS has synergistic effects on improving motor function of the stroke survivors. METHODS AND ANALYSIS: This study will be an assessor-blinded randomised controlled trial involving 12-week intervention and 6-month follow-up. One hundred and thirty-five individuals with stroke will be randomly divided in a ratio of 1:1:1 into three groups. Control group A, control group B and intervention group C will receive tDCS and conventional rehabilitation programmes (CRPs), BWS-TC and CRP, tDCS-BWS-TC and CRP for 12 weeks, respectively. The primary outcome measures will include the efficacy (Fugl-Meyer Assessment), acceptability and safety of these interventions. The secondary outcome measures will include balance ability (ie, limits of stability and modified clinical test of sensory integration), walking function, brain structure and function, risk of falling, Barthel Index and 36-Item Short Form Survey. All outcomes will be assessed at baseline, 6 and 12 weeks during intervention, and 1, 3 and 6 months during the follow-up period. Two-way analysis of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Shanghai Seventh People's Hospital (2021-7th-HIRB-017). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059329.