Muscle Synergy Plasticity in Motor Function Recovery After Stroke.

In certain neurological disorders such as stroke, the impairment of upper limb function significantly impacts daily life quality and necessitates enhanced neurological control. This poses a formidable challenge in the realm of rehabilitation due to its intricate nature. Moreover, the plasticity of muscle synergy proves advantageous in assessing the enhancement of motor function among stroke patients pre and post rehabilitation training intervention, owing to the modular control strategy of central nervous system. It also facilitates the investigation of long-term alterations in remodeling of muscle functional performance among patients undergoing clinical rehabilitation, aiming to establish correlations between changes in muscle synergies and stroke characteristics such as type, stage, and sites. In this study, a three-week rehabilitation monitoring experiment was conducted to assess the motor function of stroke patients at different stages of rehabilitation based on muscle synergy performance. Additionally, we aimed to investigate the correlation between clinical scale scores, rehabilitation stages, and synergy performance in order to provide a more comprehensive understanding of stroke patient recovery. The results of 7 healthy controls and 16 stroke patients showed that high-functioning patients were superior to low-functioning patients in terms of motor function plasticity towards healthy individuals. Moreover, there was a high positive correlation between muscle synergies and clinical scale scores in high-functioning patients, and the significance gradually emerged with treatment, highlighting the potential of muscle synergy plasticity as a valuable tool for monitoring rehabilitation progress. The potential of this study was also demonstrated for elucidating the physiological mechanisms underlying motor function reconstruction within the central nervous system, which is expected to promote the further application of muscle synergy in clinical assessment.

A single-cell atlas of lung homeostasis reveals dynamic changes during development and aging.

Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung's development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

A Generalized Cortico-Muscular-Cortical Network to Evaluate the Effects of Three-Week Brain Stimulation.

OBJECTIVE: Post-stroke transcranial magnetic stimulation (TMS) has gradually become a brain intervention to assist patients in the recovery of motor function. The long lasting regulatory of TMS may involve the coupling changes between cortex and muscles. However, the effects of multi-day TMS on motor recovery after stroke is unclear. METHODS: This study proposed to quantify the effects of three-week TMS on brain activity and muscles movement performance based on a generalized cortico-muscular-cortical network (gCMCN). The gCMCN-based features were further extracted and combined with the partial least squares (PLS) method to predict the Fugl-Meyer of upper extremity (FMUE) in stroke patients, thereby establishing an objective rehabilitation method that can evaluate the positive effects of continuous TMS on motor function. RESULTS: We found that the improvement of motor function after three-week TMS was significantly correlated with the complexity trend of information interaction between hemispheres and the intensity of corticomuscular coupling. In addition, the fitting coefficient ([Formula: see text]) for predicted and actual FMUE before and after TMS were 0.856 and 0.963, respectively, suggesting that the gCMCN-based measurement may be a promising method for evaluating the therapeutic effect of TMS. CONCLUSION: From the perspective of a novel brain-muscles network with dynamic contraction as the entry point, this work quantified TMS-induced connectivity differences while evaluating the potential efficacy of multi-day TMS. SIGNIFICANCE: It provides a unique insight for the further application of intervention therapy in the field of brain diseases.

Ruxolitinib attenuates acute rejection and can serve as an immune induction therapy in heart transplantation.

The benefits of IL2RA antagonists in heart transplant patients are controversial. We aimed to elucidate the effects of IL2RA antagonists and identify targets that could be better than IL2RA antagonists. By using single-cell RNA sequencing of immune cells at different time points in patients receiving IL2RA antagonists, we identified nineteen types of cells. We revealed higher IL2RA expression in regulatory T cells (Tregs), suggesting that IL2RA antagonists attenuated IL-2-induced Treg activation. CD4_C04_IFNGR1 and CD8_C05_IFITM2 which had more cytotoxic effects, remained elevated at later time points. IFNGR1 was upregulated in these two subtypes, but was not expressed in Treg. Ruxolitinib targeted the pathways of IFNGR1 (JAK1/2) while not affecting the pathway of IL-2-induced Tregs activation (JAK3). Ruxolitinib showed prolonged survival compared to IL2RA mAb-treated mice. Our study provided dynamic changes of immune cells after IL2RA antagonists treatment at single-cell resolution. Ruxolitinib has potential as a new immunoinduction therapy without affecting Treg.

Tomo-seq identifies NINJ1 as a potential target for anti-inflammatory strategy in thoracic aortic dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a life-threatening disease caused by an intimal tear in the aorta. The histological characteristics differ significantly between the tear area (TA) and the distant area. Previous studies have emphasized that certain specific genes tend to cluster at the TA. Obtaining a thorough understanding of the precise molecular signatures near the TA will assist in discovering therapeutic strategies for TAD. METHODS: We performed a paired comparison of the pathological patterns in the TA with that in the remote area (RA). We used Tomo-seq, genome-wide transcriptional profiling with spatial resolution, to obtain gene expression signatures spanning from the TA to the RA. Samples from multiple sporadic TAD patients and animal models were used to validate our findings. RESULTS: Pathological examination revealed that the TA of TAD exhibited more pronounced intimal hyperplasia, media degeneration, and inflammatory infiltration compared to the RA. The TA also had more apoptotic cells and CD31+α-SMA+ cells. Tomo-seq revealed four distinct gene expression patterns from the TA to the RA, which were inflammation, collagen catabolism, extracellular matrix remodeling, and cell stress, respectively. The spatial distribution of genes allowed us to identify genes that were potentially relevant with TAD. NINJ1 encoded the protein-mediated cytoplasmic membrane rupture, regulated tissue remodeling, showed high expression levels in the tear area, and co-expressed within the inflammatory pattern. The use of short hairpin RNA to reduce NINJ1 expression in the beta-aminopropionitrile-induced TAD model led to a significant decrease in TAD formation. Additionally, it resulted in reduced infiltration of inflammatory cells and a decrease in the number of CD31+α-SMA+ cells. The NINJ1-neutralizing antibody also demonstrated comparable therapeutic effects and can effectively impede the formation of TAD. CONCLUSIONS: Our study showed that Tomo-seq had the advantage of obtaining spatial expression information of TAD across the TA and the RA. We pointed out that NINJ1 may be involved in inflammation and tissue remodeling, which played an important role in the formation of TAD. NINJ1 may serve as a potential therapeutic target for TAD.

Deciphering mechanisms of cardiomyocytes and non-cardiomyocyte transformation in myocardial remodeling of permanent atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and it significantly increases the risk of cardiovascular complications and morbidity, even with appropriate treatment. Tissue remodeling has been a significant topic, while its systematic transcriptional signature remains unclear in AF. OBJECTIVES: Our study aims to systematically investigate the molecular characteristics of AF at the cellular-level. METHODS: We conducted single-nuclei RNA-sequencig (snRNA-seq) analysis using nuclei isolated from the left atrial appendage (LAA) of AF patients and sinus rhythm. Pathological staining was performed to validate the key findings of snRNA-seq. RESULTS: A total of 30 cell subtypes were identified among 80, 592 nuclei. Within the LAA of AF, we observed a specific subtype of dedifferentiated cardiomyocytes (CMs) characterized by reduced expression of cardiac contractile proteins (TTN and TRDN) and heightened expression of extracellular-matrix related genes (COL1A2 and FBN1). Transcription factor prediction analysis revealed that gene expression patterns in dedifferentiated CMs were primarily regulated by CEBPG and GISLI. Additionally, we identified a distinct subtype of endothelial progenitor cells (EPCs) demonstrating elevated expression of PROM1 and KDR, a population decreased within the LAA of AF. Epicardial adipocytes disclosed a reduced release of the anti-inflammatory and anti-fibrotic factor PRG4, and an augmented secretion of VEGF signals targeting CMs. Additionally, we noted accumulation of M2-like macrophages and CD8+ T cells with high pro-inflammatory score in LAA of AF. Furthermore, the analysis of intercellular communication revealed specific pathways related to AF, such as inflammation, extracellular matrix, and vascular remodeling signals. CONCLUSIONS: This study has discovered the presence of dedifferentiated CMs, a decrease in endothelial progenitor cells, a shift in the secretion profile of adipocytes, and an amplified inflammatory response in AF. These findings could offer crucial insights for future research on AF and serve as valuable references for investigating novel therapeutic approaches for AF.

Dynamic cellular changes in acute kidney injury caused by different ischemia time.

Ischemia reperfusion injury (IRI), often related to surgical procedures, is one of the important causes of acute kidney injury (AKI). To decipher the dynamic process of AKI caused by IRI (with prolonged ischemia phase), we performed single-cell RNA sequencing (scRNA-seq) of clinically relevant IRI murine model with different ischemic intervals. We discovered that Slc5a2hi proximal tubular cells were susceptible to AKI and highly expressed neutral amino acid transporter gene Slc6a19, which was dramatically decreased over the time course. With the usage of mass spectrometry-based metabolomic analysis, we detected that the level of neutral amino acid isoleucine dropped off in AKI mouse plasma metabolites. And the reduction of plasma isoleucine was also verified in patients with cardiac surgery-associated acute kidney injury (CSA-AKI). The findings advanced the understanding of dynamic process of AKI and introduced reduction of isoleucine as a potential biomarker for CSA-AKI.

A framework for quantifying the effects of transcranial magnetic stimulation on motor recovery from hemiparesis: corticomuscular network.

Objective. Transcranial magnetic stimulation (TMS) is an experimental therapy for promoting motor recovery from hemiparesis. At present, hemiparesis patients' responses to TMS are variable. To maximize its therapeutic potential, we need an approach that relates the electrophysiology of motor recovery and TMS. To this end, we propose corticomuscular network (CMN) representing the holistic motor system, including the cortico-cortical pathway, corticospinal tract, and muscle co-activation.Approach. CMN is made up of coherence between pairs of electrode signals and spatial locations of the electrodes. We associated coherence and graph features of CMN with Fugl-Meyer Assessment (FMA) for the upper extremity. Besides, we compared CMN between 8 patients with hemiparesis and 6 healthy controls and contrasted CMN of patients before and after a 1 Hz TMS.Main results. Corticomuscular coherence (CMC) correlated positively with FMA. The regression model between FMA and CMC between five pairs of channels had 0.99 adjusted and ap-value less than 0.01. Compared to healthy controls, CMN of patients tended to be a small-world network and was more interconnected with higher CMC. CMC between cortex and triceps brachii long head was higher in patients. 15 min 1 Hz TMS protocol induced coherence changes beyond the stimulation side and had a limited impact on CMN parameters that are related to motor recovery.Significance. CMN is a potential clinical approach to quantify rehabilitating progress. It also sheds light on the desirable electrophysiological effects of TMS based on which rehabilitating strategies can be optimized.

Upper Limb Motor Function Quantification in Post-Stroke Rehabilitation Using Muscle Synergy Space Model.

The muscle synergy hypothesis assumes that the nervous system controls muscles in groups to simplify behavioral tasks, which makes it possible for modularizing motor function assessment. This paper presents a new assessment method based on muscle synergy space (MSS) model to evaluate motor functions after stroke. It consists of spatiotemporal feature module, muscle activation module and synergy activation module, and focuses on the spatial and temporal characteristics of muscle synergies via synergy vectors and activation coefficients. We further applied this method to reveal spatial and temporal characteristics difference of muscle synergy between healthy controls and stroke patients. The effectiveness and accuracy of MSS model were proved by significant positive correlations between Fugl-Meyer score and the total number of optimal synergies of three modules. This measurement methodology could serve as a quantitative indicator for motor function and provide more scientific rehabilitation guidance.

Closed-Loop Construction and Analysis of Cortico-Muscular-Cortical Functional Network After Stroke.

Brain networks allow a topological understanding into the pathophysiology of stroke-induced motor deficits, and have been an influential tool for investigating brain functions. Unfortunately, currently applied methods generally lack in the recognition of the dynamic changes in the cortical networks related to muscle activity, which is crucial to clarify the alterations of the cooperative working patterns in the motor control system after stroke. In this study, we integrate corticomuscular and intermuscular interactions to cortico-cortical network and propose a novel closed-loop construction of cortico-muscular-cortical functional network, named closed-loop network (CLN). Directional characteristic in terms of differentiating causal interactions is endowed on basis of the CLN framework, further expanding the definition of functional connectivity (FC) and effective connectivity (EC) dedicated to CLN. Next, CLN is applied to stroke patients to reveal the underlying after-effects mechanism of low frequency repetitive transcranial magnetic stimulation (rTMS) induced alterations of cortical physiologic functions during movement. Results show that the short-term modulation of rTMS is reflected in the enhancement of information interaction within the interhemispheric primary motor regions and inhibition of the coupling between motor cortex and effector muscles. CLN provides a new perspective for the study of motor-related cortical networks with muscle activities involvement instead of being restricted to brain network analysis of behaviors.

A Novel Delay Estimation Method for Improving Corticomuscular Coherence in Continuous Synchronization Events.

OBJECTIVE: While the corticomuscularcoupling between motor cortex and muscle tissue has received considerable attention, which is typically quantitative measure to evaluate neural signals synchronization in the motor control system, little work has been published regarding the effect of underlying delay of two coupled physiological signals on coherence. METHODS: In this study, we developed a novel delay estimation method, named rate of voxels change (RVC), detecting time delay in two coupled physiological signals. Based on RVC framework, delay compensation was used to adjust magnitude squared coherence (MSC) image. To illustrate the effectiveness of the RVC method, we compared the estimated delays and the adjusted MSC results based on RVC method and corticomuscular coherence with time lag (CMCTL) method. RESULTS: The simulation results suggested that RVC method was not only superior to the CMCTL method in estimating different time delays, but also has better optimization effect on MSC image. The experimental results further confirmed that delay estimated by the proposed RVC method was more in line with the underlying physiology (controls: 22.8 ms vs patients: 34.5 ms). Meanwhile, RVC-based delay compensation could significantly optimize the MSC of specific regions. SIGNIFICANCE: This study proved that RVC has remarkably higher reliability in detecting time delay between coupled neurophysiological signals, and the application of RVC was an improvement on the previous studies that mainly focused on biased MSC estimation.

Metabonomic Study on the Plasma of High-Fat Diet-Induced Dyslipidemia Rats Treated with Ge Gen Qin Lian Decoction by Ultrahigh-Performance Liquid Chromatography-Mass Spectrometry.

Gegen Qinlian decoction (GGQLD) has a definite effect on T2DM in clinic, and it has the effect of lowering blood sugar, improving insulin resistance, and improving the blood lipid level of rats with dyslipidemia, but the intervention mechanism of GGQLD on dyslipidemia has not been clarified. The changes in endogenous metabolites in the plasma of high-fat diet-induced dyslipidemia rats treated with Ge Gen Qin Lian Decoction (GGQLD) were studied to elucidate the therapeutic effects and mechanism of action of GGQLD in dyslipidemia. Based on ultrahigh-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS), the metabolic profiles of rat serum samples were collected. The rat model of dyslipidemia was induced by a 60% fat-fed high-fat diet. After feeding the rats with a high-fat diet for 4 weeks, dyslipidemia appeared. After 5 weeks of GGQLD (14.85 g kg-1) administration, the metabonomics of rats' plasma samples in the normal group, model group, and administration group were analyzed. Mass profiler professional (MPP), SIMCA-P 14.1, and Graphpad prism 6.0 software were used combined with METLIN biological database and human metabolite database HMDB to screen and identify endogenous biomarkers. Metaboanalyst 4.0 software was used by combining with HMDB and KEGG databases; the enrichment and metabolic pathway of biomarkers were analyzed to explore the metabolic mechanism of dyslipidemia rats induced by high-fat diet and the intervention mechanism of Gegen Qinlian decoction. After 5 weeks of administration of GGQLD, the levels of serum TC and TG were significantly decreased (P < 0.05, P < 0.01), while HDL-C and LDL-C were not significantly affected. After administration, the food intake of rats in the administration group decreased gradually, and the change trend of body weight gradually slowed down. The metabonomics of rat plasma samples results showed that 23 potential biomarkers including α-linolenic acid, arachidonic acid, and lysophosphatidylcholine were significantly changed in positive ion mode. Studies have shown that GGQLD has a significant lipid-lowering effect on dyslipidemia rats induced by a high-fat diet, and its preventive mechanism is related to tryptophan metabolism, fatty acid biosynthesis, α-linolenic acid metabolism, arachidonic acid, and glycerophosphatidyl metabolism pathway.

Correlation Evaluation of Functional Corticomuscular Coupling With Abnormal Muscle Synergy After Stroke.

OBJECTIVE: While neuroplasticity and functional reorganization during motor recovery can be indirectly reflected and evaluated by functional corticomuscular coupling (fCMC), little work has been published regarding the cortical origin of abnormal muscle synergy and compensatory mechanism in the separation movement of stroke patients. METHODS: In this study, we proposed to use extended partial directed coherence (ePDC) combined with an optimal spatial filtering approach to estimate fCMC in stroke patients and healthy controls, and further established muscle synergy model (MSM) to jointly explore the modulation mechanism between cortex and muscles. RESULTS: Compared to healthy controls, stroke patients had significantly reduced coupling strength in both descending and ascending pathway. Moreover, the MSM were abnormal with high variability and low similarity in the separation stage of stroke patients. Further exploration of the positive relationship between fCMC characteristics and MSM parameters proved the possibility of using fCMC-MSM-based correlation indicator to evaluate abnormality of the cortical related synergy movement as well as the rehabilitation level of stroke patients. CONCLUSION: We developed a computational procedure to evaluate the correlation between fCMC and MSM in stroke patients. SIGNIFICANCE: This article provides a quantitative evaluation metrics based on fCMC to reveal the deficits during poststroke motor restoration and a promising approach to help patients correct abnormal movement habits, paving the way for neurophysiological assessment of neuromuscular control in conjunction with clinical scores.

Multiscale Transfer Spectral Entropy for Quantifying Corticomuscular Interaction.

Corticomuscular coupling reflects nonlinear interactions and multi-layer neural information transmission between the motor cortex and effector muscle in the sensorimotor system. Transfer spectral entropy (TSE) method has been used to describe corticomuscular coupling within single scale. As an extension of TSE, multiscale transfer spectral entropy (MSTSE) is proposed in this paper to depict multi-layer of neural information transfer between two coupling signals. The reliability and effectiveness of MSTSE were verified on data generated by nonlinear numerical models and those of a force tracking task. Compared with TSE, MSTSE is more robust to the embedding dimension and performs optimally in the detection of the coupling properties. Further analysis of the physiological signals showed that the MSTSE provided more detailed band characteristics than the single scale TSE measurement. MSTSE indicates significant coupling scattered in alpha, beta and low gamma bands during the force tracking task. Besides, the coupling strength in the descending direction of the beta band was significantly higher than that in the ascending direction. This study constructs multi-scale coupling information to provide a new perspective for exploring corticomuscular interaction.

Identification of "antigen-specific" neutrophils in atherosclerosis patients that compromise vascular endothelial barrier function.

The vascular endothelial barrier dysfunction is associated with the pathogenesis of many cardiovascular diseases, such as atherosclerosis (AS). This study aims to identify specific antigen (Ag, in short)-specific polymorphonuclear neutrophils (PMN) in AS patients and to investigate the role of "Ag-specific" PMN activation in causing vascular endothelial barrier dysfunction. In this study, PMNs were isolated from blood samples collected from patients with AS and analyzed with immunological approaches. Human umbilical vein endothelial cells (HUVEC) monolayers were used as a vascular endothelial barrier model. The results showed that "Ag-specific" PMNs were identified in the blood of 50 AS patients. This subset of PMN was featured as the FcγRI and specific IgG (sIgG) complexes on the cell surface; exposure to specific Ags triggered the "Ag-specific" PMNs to release proinflammatory cytokines. PMN-derived cytokine levels in the serum were positively correlated with the serum levels of sIgG in AS patients. Exposure of naive PMNs to sIgG formed FcγRI and sIgG complexes on the surface; this conferred PMNs the property to be recognized and activated by specific Ag. Stimulation of "Ag-specific" PMN activated the mitogen-activated protein kinase and the activities of nuclear factor activated T cells and promoted the gene transcription of tumor necrosis factor-α. Coculture of "Ag-specific" PMNs and HUVEC monolayers in the presence of specific Ag resulted in the HUVEC monolayer barrier dysfunction. In conclusion, "Ag-specific" PMNs were identified in AS patients. Activation of the PMNs compromised vascular endothelial barrier function. Therefore, to regulate the "Ag-specific" PMN's activities may have translational potential in the treatment of AS.

Novel Potential Biomarker of Adult Cardiac Surgery-Associated Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) occurs in about 30% of patients with cardiac surgery, but the pathogenesis of cardiac surgery-associated acute kidney injury (CSA-AKI) remains unclear and there are no predictive biomarkers or diagnostic criteria specific for CSA-AKI beyond the general clinical variables for AKI like serum creatinine (SCr). METHODS AND RESULTS: We measured the plasma levels of 48 cytokines within 24 h after cardiac surgery in a total of 306 adult patients including 204 with and 102 without AKI, and then evaluated the diagnostic efficacy of these cytokines for the development of CSA-AKI via ANOVA and Pearson correlation analysis. Among these 48 cytokines, 20 of them were significantly different in the AKI patients compared with the non-AKI patients. In particularly, 13 cytokines displayed tremendous changes with the P < 1E-5. Moreover, 10 of the 48 cytokines in the plasma were significantly different among the patients with different stages of AKI. Specifically, 6 cytokines exhibited immense differences with the P < 1E-5. Additionally, 7 of the 48 cytokines have the correlation coefficient of r > 0.5 with the postoperative changes of SCr after cardiac surgery. CONCLUSION: Taken all the results together, IFN-γ and SCGF-ß were the most relevant two cytokines that were not only remarkably changed in adult CSA-AKI patients during the first 24 h after cardiac surgery, but also significantly correlated with the postoperative changes of SCr after cardiac surgery. Therefore, IFN-γ and SCGF-ß might be novel predictive plasma biomarker, as well as potential therapeutic targets specific for adult CSA-AKI.

Corticomuscular Coherence for Upper Arm Flexor and Extensor Muscles During Isometric Exercise and Cyclically Isokinetic Movement.

Cortical-muscular functional coupling reflects the interaction between the cerebral cortex and the muscle activities. Corticomuscular coherence (CMC) has been extensively revealed in sustained contractions of various upper- and lower-limb muscles during static and dynamic force outputs. However, it is not well-understood that the CMC modulation mechanisms, i.e., the relation between a cerebral hemisphere and dynamic motor controlling limbs at constant speeds, such as isokinetic movement. In this paper, we explore the CMC between upper arm flexors/extensors movement and motor cortex during isometric exercise and cyclically isokinetic movement. We also provide further insights of frequency-shift and the neural pathway mechanisms in isokinetic movement by evaluating the coherence between motor cortex and agonistic or antagonistic muscles. This study is the first to investigate the relationship between cortical-muscular functional connections in elbow flexion-extension movement with constant speeds. The result shows that gamma-range coherence for isokinetic movement is greatly increased compared with isometric exercise, and significant CMC is observed in the entire flexion-extension stage regardless the nature of muscles contraction, although dominant synchronization of cortical oscillation and muscular activity resonated in sustained contraction stage principally. Besides, the CMC for extensors and flexors are explicitly consistent in contraction stage during cyclically isokinetic elbow movement. It is concluded that cortical-muscular coherence can be dynamically modulated as well as selective by cognitive demands of the body, and the time-varying mechanisms of the synchronous motor oscillation exist in healthy individuals during dynamic movement.

Corticomuscular Coherence and Its Applications: A Review.

Corticomuscular coherence (CMC) is an index utilized to indicate coherence between brain motor cortex and associated body muscles, conventionally. As an index of functional connections between the cortex and muscles, CMC research is the focus of neurophysiology in recent years. Although CMC has been extensively studied in healthy subjects and sports disorders, the purpose of its applications is still ambiguous, and the magnitude of CMC varies among individuals. Here, we aim to investigate factors that modulate the variation of CMC amplitude and compare significant CMC between these factors to find a well-developed research prospect. In the present review, we discuss the mechanism of CMC and propose a general definition of CMC. Factors affecting CMC are also summarized as follows: experimental design, band frequencies and force levels, age correlation, and difference between healthy controls and patients. In addition, we provide a detailed overview of the current CMC applications for various motor disorders. Further recognition of the factors affecting CMC amplitude can clarify the physiological mechanism and is beneficial to the implementation of CMC clinical methods.