Enhance Motor Recovery Research Articles

Motor imagery technique for motor recovery of hand among sub-acute stroke patient: A randomized controlled trial

Stroke is the second leading cause of death globally, with a rising prevalence in line with increasing life expectancy. Hemiparesis, affecting up to 85% of stroke survivors, leads to impaired arm and hand movement, reduced strength, and limited coordination, significantly affecting daily activities. Despite rehabilitation efforts, many stroke survivors face persistent functional limitations or permanent disabilities. Intensive rehabilitation is often costly and constrained by the limited number of therapy sessions available in many centers. Therefore, strategies to enhance functional recovery while minimizing resource use are crucial. One promising approach is motor imagery (MI), a cognitive rehearsal of physical actions aimed at improving motor function. MI has been shown to activate similar brain areas as actual movement, such as the premotor cortex and supplementary motor area. While evidence supports MI's potential for enhancing motor recovery, clinical guidelines remain insufficient. This study aims to evaluate the effectiveness of motor imagery for improving hand function in subacute stroke patients. The primary objective is to assess the impact of MI on motor recovery using the Chedoke Arm and Hand Activity Inventory over a 4-week period.

Carry-Over Effect of Deep Cerebellar Stimulation-Mediated Motor Recovery in a Rodent Model of Traumatic Brain Injury

Background We previously demonstrated that deep brain stimulation (DBS) of lateral cerebellar nucleus (LCN) can enhance motor recovery and functional reorganization of perilesional cortex in rodent models of stroke or TBI. Objective Considering the treatment-related neuroplasticity observed at the perilesional cortex, we hypothesize that chronic LCN DBS-enhanced motor recovery observed will carry-over even after DBS has been deactivated. Methods Here, we directly tested the enduring effects of LCN DBS in male Long Evans rats that underwent controlled cortical impact (CCI) injury targeting sensorimotor cortex opposite their dominant forepaw followed by unilateral implantation of a macroelectrode into the LCN opposite the lesion. Animals were randomized to DBS or sham treatment for 4 weeks during which the motor performance were characterize by behavioral metrics. After 4 weeks, stimulation was turned off, with assessments continuing for an additional 2 weeks. Afterward, all animals were euthanized, and tissue was harvested for further analyses. Results Treated animals showed significantly greater motor improvement across all behavioral metrics relative to untreated animals during the 4-week treatment, with functional gains persisting across 2-week post-treatment. This motor recovery was associated with the increase in CaMKIIα and BDNF positive cell density across perilesional cortex in treated animals. Conclusions LCN DBS enhanced post-TBI motor recovery, the effect of which was persisted up to 2 weeks beyond stimulation offset. Such evidence should be considered in relation to future translational efforts as, unlike typical DBS applications, treatment may only need to be provided until such time as a new function plateau is achieved.

Focused magnetic stimulation for motor recovery after stroke

Background and objectivesThe effects of noninvasive focused magnetothermal brain stimulation using magnetic nanoparticles (MNPs) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury are not well-established. This study examined if magnetothermal brain stimulation using magnetic nanoparticles (Nano-MS) enhances motor recovery after stroke. MethodsWe randomly distributed rats into Sham, Control, MNP injection only, and Nano-MS groups. We administered focused magnetic stimulation for 30 min daily following an MNP injection (15 mg/mL) into the targeted motor cortex via the carotid artery three weeks after the transient (90 min) middle cerebral artery occlusion. We assessed motor functionality via behavioral tests and conducted positron emission tomography (PET) imaging to verify cerebral metabolic activity. We assessed neuronal excitability, neuroinflammation, blood-brain barrier (BBB) integrity, and neurogenesis four weeks post-stroke. ResultsThe Nano-MS group exhibited significantly improved motor deficits and cerebral metabolic activity compared to the Control and MNP groups (p < 0.05). Focused Nano-MS modulated neuronal excitability, evident by a depolarized action potential threshold for spike initiation and reduced firing frequency post-stroke. The Nano-MS group demonstrated markedly decreased inflammatory markers, such as IL-1β, IL-6, TNF-α, MCP-1, and ICAM-1, compared to the Control and MNP groups. BBB integrity and immunofluorescence for neurogenesis markers were substantially improved in the Nano-MS group. ConclusionsFocused Nano-MS facilitates the recovery of motor deficits and metabolic inactivity in the brain by effectively modulating excitability, reducing neuroinflammation, enhancing BBB stability, and promoting neurogenesis. Nano-MS is a potential novel, noninvasive therapy for stroke rehabilitation. Further investigation is warranted.

Hebbian plasticity induced by temporally coincident BCI enhances post-stroke motor recovery

Functional electrical stimulation (FES) can support functional restoration of a paretic limb post-stroke. Hebbian plasticity depends on temporally coinciding pre- and post-synaptic activity. A tight temporal relationship between motor cortical (MC) activity associated with attempted movement and FES-generated visuo-proprioceptive feedback is hypothesized to enhance motor recovery. Using a brain–computer interface (BCI) to classify MC spectral power in electroencephalographic (EEG) signals to trigger FES-delivery with detection of movement attempts improved motor outcomes in chronic stroke patients. We hypothesized that heightened neural plasticity earlier post-stroke would further enhance corticomuscular functional connectivity and motor recovery. We compared subcortical non-dominant hemisphere stroke patients in BCI-FES and Random-FES (FES temporally independent of MC movement attempt detection) groups. The primary outcome measure was the Fugl-Meyer Assessment, Upper Extremity (FMA-UE). We recorded high-density EEG and transcranial magnetic stimulation-induced motor evoked potentials before and after treatment. The BCI group showed greater: FMA-UE improvement; motor evoked potential amplitude; beta oscillatory power and long-range temporal correlation reduction over contralateral MC; and corticomuscular coherence with contralateral MC. These changes are consistent with enhanced post-stroke motor improvement when movement is synchronized with MC activity reflecting attempted movement.

Efficacy of Motor Imagery in the Rehabilitation of Stroke Patients: A Scope Review

This review examines the efficacy of motor imagery (MI) as a supplementary rehabilitation technique for stroke patients. Nine randomized controlled trials (RCTs) were analyzed, highlighting MI's potential to enhance motor recovery, mobility, balance, and psychological well-being. Significant improvements in upper-limb function were observed with combined mental and physical practice, evidenced by notable gains in Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT) scores. MI-based exercise programs improved mobility and balance in elderly patients, reducing fall risk as measured by the Timed Up and Go (TUG) test and Berg Balance Scale (BBS). MI was also found to enhance self-efficacy and functional performance, with significant increases in Functional Independence Measure (FIM) and General Self-Efficacy Scale (GSES) scores. Neuroimaging studies revealed that MI activates cortical areas associated with motor control, supporting its role in promoting neural plasticity. Despite these promising results, the heterogeneity in participant characteristics, stroke severity, and MI protocols across studies poses challenges to standardization. Additionally, small sample sizes and reliance on self-report measures limit the generalizability of findings. Nevertheless, MI's low cost, minimal risk, and ease of integration into existing rehabilitation protocols make it a valuable adjunct to physical therapy. Standardized guidelines and personalized MI exercises tailored to individual needs are essential for maximizing benefits. Integrating MI into clinical practice can significantly enhance both physical and psychological recovery outcomes for stroke patients, offering a comprehensive approach to rehabilitation.

RTMS for Poststroke Pusher Syndrome: A Randomized, Patient-Blinded Controlled Clinical Trial

Background Patients with poststroke pusher syndrome (PS) require longer duration of rehabilitation and more supplemental care after discharge. Effective treatment of PS remains a challenge. The role of repetitive transcranial magnetic stimulation (rTMS) for PS has not been examined. Objective Assess the efficacy of rTMS for patients with poststroke PS in reducing pushing behavior, enhancing motor recovery and improving mobility. Methods A randomized, patient- and assessor-blinded sham-controlled trial with intention-to-treat analysis was conducted. Thirty-four eligible patients with poststroke PS were randomly allocated to receive either rTMS or sham rTMS for 2 weeks. Pushing behavior on the Burke lateropulsion scale and scale for contraversive pushing, motor function on Fugl-Meyer assessment scale-motor domain (FMA-m) and mobility on modified Rivermead mobility index were measured at baseline, 1 and 2 weeks after intervention. Repeated-measures analysis of covariance was used for data analysis. Results There was no significant interaction between intervention and time on Burke lateropulsion scale (F = 2.747, P = .076), scale for contraversive pushing (F = 1.583, P = .214), or change of modified Rivermead mobility index (F = 1.183, P = .297). However, a significant interaction between intervention and time was observed for FMA-m (F = 5.464, P = .019). Post hoc comparisons of FMA-m show better improvement in rTMS group with mean differences of 12.7 (95% CI −7.3 to 32.7) and 15.7 (95% CI −4.6 to 36.0) at post-treatment week 1 and week 2 respectively. Conclusions rTMS did not demonstrate significant efficacy in improving pushing behavior and mobility in patients with PS. However, rTMS might have potential effect in enhancing motor function for patients with PS. Registration: The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200058015 at http://www.chictr.org.cn/searchprojen.aspx) on March 26, 2022.

Galectin-3 absence alters lymphocytes populations dynamics behavior and promotes functional recovery after spinal cord injury in mice

Spinal cord injury (SCI) results from various mechanisms that damage the nervous tissue and the blood-brain barrier, leading to sensory and motor function loss below the injury site. Unfortunately, current therapeutic approaches for SCI have limited efficacy in improving patients outcomes. Galectin-3, a protein whose expression increases after SCI, influences the neuroinflammatory response by favoring pro-inflammatory M1 macrophages and microglia, while inhibiting pro-regenerative M2 macrophages and microglia, which are crucial for inflammation resolution and tissue regeneration. Previous studies with Galectin-3 knock-out mice demonstrated enhanced motor recovery after SCI. The M1/M2 balance is strongly influenced by the predominant lymphocytic profiles (Th1, Th2, T Reg, Th17) and cytokines and chemokines released at the lesion site. The present study aimed to investigate how the absence of galectin-3 impacts the adaptive immune system cell population dynamics in various lymphoid spaces following a low thoracic spinal cord compression injury (T9-T10) using a 30 g vascular clip for one minute. It also aimed to assess its influence on the functional outcome in wild-type (WT)and Galectin-3 knock-out (GALNEG) mice. Histological analysis with hematoxylin-eosin and Luxol Fast Blue staining revealed that WT and GALNEG animals exhibit similar spinal cord morphology. The absence of galectin-3 does not affect the common neuroanatomy shared between the groups prompting us to analyze outcomes between both groups. Following our crush model, both groups lost motor and sensory functions below the lesion level. During a 42-day period, GALNEG mice demonstrated superior locomotor recovery in the Basso Mouse Scale (BMS) gait analysis and enhanced motor coordination performance in the ladder rung walk test (LRW) compared to WT mice. GALNEG mice also exhibited better sensory recovery, and their electrophysiological parameters suggested a higher number of functional axons with faster nerve conduction. Seven days after injury, flow cytometry of thymus, spleen, and blood revealed an increased number of T Reg and Th2 cells, accompanied by a decrease in Th1 and Th17 cells in GALNEG mice. Immunohistochemistry conducted on the same day exhibited an increased number of Th2 and T Reg cells around the GALNEG's spinal cord lesion site. At 42-day dpi immunohistochemistry analyses displayed reduced astrogliosis and greater axon preservation in GALNEG's spinal cord seem as a reduction of GFAP immunostaining and an increase in NFH immunostaining, respectively. In conclusion, GALNEG mice exhibited better functional recovery attributed to the milder pro-inflammatory influence, compensated by a higher quantity of T Reg and Th2 cells. These findings suggest that galectin-3 plays a crucial role in the immune response after spinal cord injury and could be a potential target for clinical therapeutic interventions.

Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. Thirty male Sprague-Dawley rats underwent sham surgery (group A) or SCI and treated with vehicle (group B) or sovateltide (group C). Clinical tests, including Basso, Beattie, and Bresnahan scoring, inclined plane, and allodynia testing with von Frey hair, were performed at various time points. Statistical analyses assessed treatment effects. Sovateltide administration significantly improved motor function, reducing neurological deficits and enhancing locomotor recovery compared with vehicle-treated rats, starting from day 7 post injury. Additionally, the allodynic threshold improved, suggesting antinociceptive properties. Notably, the sovateltide group demonstrated sustained recovery, and even reached preinjury performance levels, whereas the vehicle group plateaued. This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.

Resting-state brain network remodeling after different nerve reconstruction surgeries: a functional magnetic resonance imaging study in brachial plexus injury rats.

JOURNAL/nrgr/04.03/01300535-202505000-00031/figure1/v/2024-07-28T173839Z/r/image-tiff Distinct brain remodeling has been found after different nerve reconstruction strategies, including motor representation of the affected limb. However, differences among reconstruction strategies at the brain network level have not been elucidated. This study aimed to explore intra-network changes related to altered peripheral neural pathways after different nerve reconstruction surgeries, including nerve repair, end-to-end nerve transfer, and end-to-side nerve transfer. Sprague-Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight: no nerve repair, grafted nerve repair, phrenic nerve end-to-end transfer, and end-to-side transfer with a graft sutured to the anterior upper trunk. Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery. The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component. Alterations in intra-network resting-state functional connectivity were compared among the groups. Target muscle reinnervation was assessed by behavioral observation (elbow flexion) and electromyography. The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway. Nerve repair was related to enhanced connectivity within the sensorimotor network, while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation. The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer. Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer. Our study revealed important brain networks related to different nerve reconstructions. These networks may be potential targets for enhancing motor recovery.

Efficacy test for intermittent theta burst stimulation during motor rehabilitation in patients post‐stroke in a tertiary centre in Hong Kong

AbstractAimStroke represents a significant cause of long‐term disability in adults. Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation method known for its potential to enhance motor recovery. Intermittent theta burst stimulation (iTBS), a standardised rTMS protocol initially utilised in patients with depression, has garnered attention in the realm of stroke rehabilitation. This study seeks to establish the efficacy profile of iTBS in motor rehabilitation for patients with subacute or chronic stroke.Patients and methodsThis study is a prospective cohort trial in which eligible patients with stroke were recruited into the iTBS group. Ten sessions of iTBS were conducted, followed by physiotherapy. An equal number of matched controls were recruited into the conventional physiotherapy group. The differences in various scoring systems related to motor performance at 6 months were analysed using independent two‐sample t test.ResultsForty patients were enrolled in the study. At 6 months, iTBS demonstrated a statistically significant improvement compared with conventional physiotherapy across various scoring systems, including motor power grading (47.4% vs 0%, P &lt; .0001), Upper Extremity Fugl–Meyer Assessment (19.8% vs 0.7%, P &lt; .0001), Box and Block Test (25.6% vs 1.7%, P = .007) and Barthel Index (17.8% vs 0.1%, P = .0002). No major adverse events were reported in the iTBS group at 6 months.ConclusioniTBS resulted in significant improvement in motor performance across various domains at 6 months compared with conventional physiotherapy alone. This method proves to be a safe approach for motor rehabilitation.

Efficacy and safety of transcranial direct current stimulation to the ipsilesional motor cortex in subacute stroke (NETS): a multicenter, randomized, double-blind, placebo-controlled trial

Each year, five million people are left disabled after stroke. Upper-extremity (UE) dysfunction is a leading problem. Neuroplasticity can be enhanced by non-invasive brain stimulation (NIBS) but evidence from large, randomized multicenter trials is lacking. We aimed at demonstrating efficacy of NIBS to enhance motor recovery after ischemic stroke. We randomly assigned patients to receive anodal transcranial direct current (tDCS, 1mA, 20min) or placebo stimulation ('control') over the primary motor cortex of the lesioned hemisphere in addition to standardized rehabilitative training over ten days in the subacute phase after stroke. The original study was planned to enrol 250 but, following a blinded interim analysis, ended with 123 participants. The primary outcome parameter was UE impairment, measured by UE-Fugl-Meyer-Assessment (UEFMA), one to seven days after the end of the treatment intervention (ClinicalTrials.gov, NCT00909714). From 2009 to 2019, 123 patients were included, with 119 entering intention-to-treat analysis (ITT). The control group (N=61) improved 8.9 (SD 7.7) UEFMA points, the tDCS group (N=58) improved 9.0 (8.8) points. ITT was neutral with respect to the primary efficacy endpoint (p=0.820). We found no difference in UEFMA change between active tDCS and control. The safety profile of tDCS was favorable. In particular, there were no seizures. In patients with ischemic stroke, anodal tDCS applied to the motor cortex of the lesioned hemisphere over 10 days in the subacute phase was safe but did not improve the recovery of upper extremity function compared with placebo stimulation. Deutsche Forschungsgemeinschaft (GE 844/4-1).

Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration.

Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide. Despite significant advancements in the field of medicine, effective treatments for traumatic brain injury remain limited. Recently, extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury. Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells, including those in the brain, and can be engineered to contain therapeutic cargo, such as anti-inflammatory molecules, growth factors, and microRNAs. When administered intravenously, extracellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury, where they can be taken up by recipient cells and modulate the inflammatory response, promote neuroregeneration, and improve functional outcomes. In preclinical studies, extracellular vesicle-based therapies have shown promising results in promoting recovery after traumatic brain injury, including reducing neuronal damage, improving cognitive function, and enhancing motor recovery. While further research is needed to establish the safety and efficacy of extracellular vesicle-based therapies in humans, extracellular vesicles represent a promising novel approach for the treatment of traumatic brain injury. In this review, we summarize mesenchymal stem/stromal cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brain-derived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.

Comparative Efficacy of Constrained Induced Movement Therapy and Motor-Relearning Program in Post Stroke Upper Extremity Function

Background: Stroke often leads to significant impairments in motor function, particularly in the upper extremities. Constraint-Induced Movement Therapy (CIMT) and Motor Relearning Program (MRP) are two rehabilitation approaches that have shown potential in addressing these deficits. This study aimed to compare the effectiveness of these two therapies in improving upper extremity function in post-stroke hemiplegia. Objective: To evaluate and compare the efficacy of CIMT and MRP in enhancing motor recovery and functional performance of the upper extremity in patients with post-stroke hemiplegia. Methods: This randomized controlled trial included patients aged 35-60 years diagnosed with ischemic or hemorrhagic stroke, confirmed by CT scans and MRI. Patients were randomly assigned to either the CIMT group or the MRP group, each comprising 16 participants. Both groups underwent respective therapies for two hours daily, six days a week, for four weeks. The Motor Assessment Scale and the Functional Independence Measure (FIM) Scale were employed for pre-, post-, and follow-up evaluations. Results: Both groups showed significant improvements in motor function and daily living activities. The CIMT group exhibited greater advancements, with notable increases in upper extremity strength and active range of motion in the shoulder, elbow, and wrist joints. Quantitative improvements in the CIMT group included an average increase of 2 points in Motor Assessment Scale scores and a 15% improvement in FIM scores. The MRP group demonstrated an average increase of 1.5 points in Motor Assessment Scale scores and a 10% improvement in FIM scores. Conclusion: While both CIMT and MRP are effective in improving motor function and daily living activities in patients with post-stroke hemiplegia, CIMT showed a slight edge in enhancing upper extremity strength and range of motion. These findings suggest that CIMT could be a more efficacious approach in the rehabilitation of upper extremity function in stroke patients.

Neuromodulation for Post-Stroke Motor Recovery: a Narrative Review of Invasive and Non‑Invasive Tools.

Stroke remains a leading disabling condition, and many survivors have permanent disability despite acute stroke treatment and subsequent standard-of-care rehabilitation therapies. Adjunctive neuromodulation is an emerging frontier in the field of stroke recovery. In this narrative review, we aim to highlight and summarize various neuromodulation techniques currently being investigated to enhance recovery and reduce impairment in patients with stroke. For motor recovery, repetitive transcranial magnetic simulation (rTMS) and direct current stimulation (tDCS) have shown promising results in many smaller-scale trials. Still, their efficacy has yet to be proven in large-scale pivotal trials. A promising large-scale study investigating higher dose tDCS combined with constraint movement therapy to enhance motor recovery is currently underway. MRI-guided tDCS studies in subacute and chronic post-stroke aphasia showed promising benefits for picture-naming recovery. rTMS, particularly inhibitory stimulation over the contralesional homolog, could represent a pathway forward in post-stroke motor recovery in the setting of a well-designed and adequately powered clinical trial. Recently evidenced-based guideline actually supported Level A (definite efficacy) for the use of low-frequency rTMS of the primary motor cortex for hand motor recovery in the post-acute stage of stroke based on the meta-analysis result. Adjunctive vagal nerve stimulation has recently received FDA approval to enhance upper limb motor recovery in chronic ischemic stroke with moderate impairment, and progress has been made to implement it in real-world practice. Despite a few small and large-scale studies in epidural stimulation (EDS), further research on the utilization of EDS in post-stroke recovery is needed. Deep brain stimulation or stent-based neuromodulation has yet to be further tested regarding safety and efficacy. Adjunctive neuromodulation to rehabilitation therapy is a promising avenue for promoting post-stroke recovery and decreasing the overall burden of disability. The pipeline for neuromodulation technology remains strong as they span from the preclinical stage to the post-market stage. We are optimistic to see that more neuromodulation tools will be available to stroke survivors in the not-to-distant future.

Activity monitoring of stroke patients by physiotherapist and caregivers in a hospital setting: A pilot study.

Activity monitoring is a necessary technique to ensure stroke survivors' activity levels in the hospital are within optimal levels as this is important for enhanced motor recovery. However, this could be time-consuming for healthcare professionals like physiotherapists. Activity monitoring by caregivers could be an alternate option. Therefore, our aim was to compare the activity monitoring of stroke survivors by caregivers and physiotherapists during early phase in a hospital setting. An observation study was carried out in the neuroscience ward in a tertiary care hospital among 17 stroke survivors. Physiotherapist and caregivers were instructed to use an activity log chart that was developed during previous research conducted by the same authors for observing the activities performed by the patients every 15 minutes from 8 AM to 5 PM across one day. Data collected were analysed using Stata 15. Kappa statistics were carried out to determine the agreement of the observations between the two raters. A total of 10 male and seven female caregivers of stroke survivors with a mean age of 40.11 ± 9.2 years and a trained physiotherapist participated in the study. A total of 272 observations of caregivers were in agreement with that of the physiotherapist. Inter-rater Kappa statistics showed 60% agreement between the physiotherapist and the caregivers (p<0.05). There was moderate agreement between the physiotherapist and caregiver for activity monitoring of stroke survivors. This suggests behavioural mapping by caregivers may be a potential alternative solution in healthcare settings.

Enhancing Upper Limb Performance in Sub-acute Stroke Patients: A Systematic Review of Combined Modified Constraint-Induced Movement Therapy and Mirror Therapy Interventions

Objective: Sub-acute stroke is a common condition that often results in upper limb impairments. This systematic review aims to evaluate the effectiveness of combined modified constraint-induced movement therapy (mCIMT) and mirror therapy on upper limb performance in patients with sub-acute stroke. The review also aimed to identify gaps in the existing literature and provide recommendations for future research.&#x0D; Methods: A comprehensive search was conducted on electronic databases, including PubMed, Google Scholar, ResearchGate, and AJOT. Studies published between 2010 and 2022 were included in the review. Qualitative studies that investigated the effects of combined mCIMT and mirror therapy in patients with sub-acute stroke were included. The PRISMA flow diagram was utilized to track the study selection process. Two independent reviewers assessed the eligibility of the studies and extracted relevant data using predefined criteria.&#x0D; Results: Out of the initial 250 articles, 10 studies met the inclusion criteria and were included in the review. Published between 2010 and 2022, these studies utilized various research designs, including quasi-experimental studies, randomized controlled trials, and pilot studies. The majority of the studies were conducted in hospital settings and involved patients with sub-acute stroke. The findings of the included studies suggest that combined mCIMT and mirror therapy have positive effects on hand functions, motor recovery, functional outcomes, and activities of daily living in patients with sub-acute stroke.&#x0D; Conclusion: This systematic review provides evidence supporting the effectiveness of combined mCIMT and mirror therapy in improving upper limb performance in patients with sub-acute stroke. These interventions have the potential to enhance motor recovery and functional outcomes in this population. However, further research is needed to determine the optimal duration, intensity, and timing of these interventions. Standardized outcome measures and larger sample sizes should be considered in future studies to strengthen the evidence base.

Mesenchymal-derived extracellular vesicles enhance microglia-mediated synapse remodeling after cortical injury in aging Rhesus monkeys

Understanding the microglial neuro-immune interactions in the primate brain is vital to developing therapeutics for cortical injury, such as stroke or traumatic brain injury. Our previous work showed that mesenchymal-derived extracellular vesicles (MSC-EVs) enhanced motor recovery in aged rhesus monkeys following injury of primary motor cortex (M1), by promoting homeostatic ramified microglia, reducing injury-related neuronal hyperexcitability, and enhancing synaptic plasticity in perilesional cortices. A focal lesion was induced via surgical ablation of pial blood vessels over lying the cortical hand representation of M1 of aged female rhesus monkeys, that received intravenous infusions of either vehicle (veh) or EVs 24 h and again 14 days post-injury. The current study used this same cohort to address how these injury- and recovery-associated changes relate to structural and molecular interactions between microglia and neuronal synapses. Using multi-labeling immunohistochemistry, high-resolution microscopy, and gene expression analysis, we quantified co-expression of synaptic markers (VGLUTs, GLURs, VGAT, GABARs), microglia markers (Iba1, P2RY12), and C1q, a complement pathway protein for microglia-mediated synapse phagocytosis, in perilesional M1 and premotor cortices (PMC). We compared this lesion cohort to age-matched non-lesion controls (ctr). Our findings revealed a lesion-related loss of excitatory synapses in perilesional areas, which was ameliorated by EV treatment. Further, we found region-dependent effects of EVs on microglia and C1q expression. In perilesional M1, EV treatment and enhanced functional recovery were associated with increased expression of C1q + hypertrophic microglia, which are thought to have a role in debris-clearance and anti-inflammatory functions. In PMC, EV treatment was associated with decreased C1q + synaptic tagging and microglia–spine contacts. Our results suggest that EV treatment may enhance synaptic plasticity via clearance of acute damage in perilesional M1, and thereby preventing chronic inflammation and excessive synaptic loss in PMC. These mechanisms may act to preserve synaptic cortical motor networks and a balanced normative M1/PMC synaptic function to support functional recovery after injury.

Neural Plasticity Changes Induced by Motor Robotic Rehabilitation in Stroke Patients: The Contribution of Functional Neuroimaging.

Robotic rehabilitation is one of the most advanced treatments helping people with stroke to faster recovery from motor deficits. The clinical impact of this type of treatment has been widely defined and established using clinical scales. The neurofunctional indicators of motor recovery following conventional rehabilitation treatments have already been identified by previous meta-analytic investigations. However, a clear definition of the neural correlates associated with robotic neurorehabilitation treatment has never been performed. This systematic review assesses the neurofunctional correlates (fMRI, fNIRS) of cutting-edge robotic therapies in enhancing motor recovery of stroke populations in accordance with PRISMA standards. A total of 7, of the initial yield of 150 articles, have been included in this review. Lessons from these studies suggest that neural plasticity within the ipsilateral primary motor cortex, the contralateral sensorimotor cortex, and the premotor cortices are more sensitive to compensation strategies reflecting upper and lower limbs' motor recovery despite the high heterogeneity in robotic devices, clinical status, and neuroimaging procedures. Unfortunately, the paucity of RCT studies prevents us from understanding the neurobiological differences induced by robotic devices with respect to traditional rehabilitation approaches. Despite this technology dating to the early 1990s, there is a need to translate more functional neuroimaging markers in clinical settings since they provide a unique opportunity to examine, in-depth, the brain plasticity changes induced by robotic rehabilitation.

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia.

Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses. Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures (P0.1) were evaluated. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E, APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoE knock-in rats were performed to test causality. AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3/4) compared to individuals with other APOE genotypes (P = 0.048) and the other tested SNPs. Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (P = 0.004). Additionally, age was inversely related with change in P0.1 (P = 0.007). In hApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3 controls (P < 0.05). APOE4 genotype, sex, and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults. AIH is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative disease. Figure 5 Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, AIHH, in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.

Brain‐oscillation-synchronized stimulation to enhance motor recovery in early subacute stroke: a randomized controlled double‐blind three‐ arm parallel‐group exploratory trial comparing personalized, non‐ personalized and sham repetitive transcranial magnetic stimulation (Acronym: BOSS-STROKE)

BackgroundStroke is a major cause of death and the most frequent cause of permanent disability in western countries. Repetitive transcranial brain stimulation (rTMS) has been used to enhance neuronal plasticity after stroke, yet with only moderate effect sizes. Here we will apply a highly innovative technology that synchronizes rTMS to specific brain states identified by real-time analysis of electroencephalography.MethodsOne hundred forty-four patients with early subacute ischemic motor stroke will be included in a multicenter 3-arm parallel, randomized, double-blind, standard rTMS and sham rTMS-controlled exploratory trial in Germany. In the experimental condition, rTMS will be synchronized to the trough of the sensorimotor µ-oscillation, a high-excitability state, over ipsilesional motor cortex. In the standard rTMS control condition the identical protocol will be applied, but non-synchronized to the ongoing µ-oscillation. In the sham condition, the same µ-oscillation-synchronized protocol as in experimental condition will be applied, but with ineffective rTMS, using the sham side of an active/placebo TMS coil. The treatment will be performed over five consecutive work days (1,200 pulses per day, 6,000 pulses total). The primary endpoint will be motor performance after the last treatment session as measured by the Fugl-Meyer Assessment Upper Extremity.DiscussionThis study investigates, for the first time, the therapeutic efficacy of personalized, brain-state-dependent rTMS. We hypothesize that synchronization of rTMS with a high-excitability state will lead to significantly stronger improvement of paretic upper extremity motor function than standard or sham rTMS. Positive results may catalyze a paradigm-shift towards personalized brain-state-dependent stimulation therapies.Trial registrationThis study was registered at ClinicalTrials.gov (NCT05600374) on 10–21-2022.