Design and validation of a wearable dynamometry system for knee extension-flexion torque measurement.

Muscle strength assessments are vital in rehabilitation, orthopedics, and sports medicine. However, current methods used in clinical settings, such as manual muscle testing and hand-held dynamometers, often lack reliability, and isokinetic dynamometers (IKD), while reliable, are not easily portable. The aim of this study was to design and validate a wearable dynamometry system with high accessibility, accuracy, and reliability, and to validate the device. Therefore, we designed a wearable dynamometry system (WDS) equipped with knee joint torque sensors. To validate this WDS, we measured knee extension and flexion strength in 39 healthy adults using both the IKD and WDS. Comparing maximal isometric torque measurements, WDS and IKD showed strong correlation and good reliability for extension (Pearson's r: 0.900; intraclass correlation coefficient [ICC]: 0.893; standard error of measurement [SEM]: 9.85%; minimal detectable change [MDC]: 27.31%) and flexion (Pearson's r: 0.870; ICC: 0.857; SEM: 11.93%; MDC: 33.07%). WDS demonstrated excellent inter-rater (Pearson's r: 0.990; ICC: 0.993; SEM: 4.05%) and test-retest (Pearson's r: 0.970; ICC: 0.984; SEM: 6.15%) reliability during extension/flexion. User feedback from 35 participants, including healthcare professionals, underscores WDS's positive user experience and clinical potential. The proposed WDS is a suitable alternative to IKD, providing high accuracy, reliability, and potentially greater accessibility.

Multiplexed Quantitative Proteomics Reveals Proteomic Alterations in Two Rodent Traumatic Brain Injury Models.

In many cases of traumatic brain injury (TBI), conspicuous abnormalities, such as scalp wounds and intracranial hemorrhages, abate over time. However, many unnoticeable symptoms, including cognitive, emotional, and behavioral dysfunction, often last from several weeks to years after trauma, even for mild injuries. Moreover, the cause of such persistence of symptoms has not been examined extensively. Recent studies have implicated the dysregulation of the molecular system in the injured brain, necessitating an in-depth analysis of the proteome and signaling pathways that mediate the consequences of TBI. Thus, in this study, the brain proteomes of two TBI models were examined by quantitative proteomics during the recovery period to determine the molecular mechanisms of TBI. Our results show that the proteomes in both TBI models undergo distinct changes. A bioinformatics analysis demonstrated robust activation and inhibition of signaling pathways and core proteins that mediate biological processes after brain injury. These findings can help determine the molecular mechanisms that underlie the persistent effects of TBI and identify novel targets for drug interventions.

Inter-rater and Intra-rater Reliability of the Videofluoroscopic Dysphagia Scale with the Standardized Protocol.

This study aimed to develop a standardized protocol for the assessment of videofluoroscopic dysphagia scale (VDS) and to demonstrate the inter-rater and intra-rater reliability of the VDS by applying the new standard protocol. A standardized protocol for the VDS was developed by dysphagia experts, including the original developer. To identify the reliability of the VDS using the protocol, 60 patients who underwent videofluoroscopic swallowing study (VFSS) for various etiologies were recruited retrospectively from three tertiary medical centers. Ten randomly selected cases were duplicated to evaluate the intra-rater reliability. Six physicians evaluated the VFSS data sets. Intraclass correlation coefficients were calculated for inter-rater and intra-rater reliability of the VDS score, and Gwet's kappa values for each VDS item were calculated. The inter-rater and intra-rater reliability of the total VDS score was 0.966 and 0.896, respectively. Notably, the evaluators' experience did not appear to have a significant impact on the reliability (physiatrists: 0.933/0.869, residents: 0.922/0.922). The reliability was consistent across different centers and dysphagia etiologies. The inter-rater and intra-rater reliability of the oral and pharyngeal sub-scores were 0.953/0.861 and 0.958/0.907, respectively. The inter-rater agreement of individual items ranged from 0.456 to 0.929, and nine items demonstrated good to very good level of agreement. Assessment of dysphagia using the VDS with the standard protocol showed excellent inter-rater and intra-rater reliabilities regardless of the evaluator's experience, VFSS equipment, and dysphagia etiologies. The VDS can be a useful assessment scale in the quantitative analysis of dysphagia based on VFSS findings.

Changes of neural coupling between cognitive and motor networks associated with dual-task performance in Parkinson's disease.

BACKGOUND: Although cognitive control is essential for efficient gait, the associations between cognitive and motor networks regarding gait in individuals with Parkinson's disease (PD) remain to be determined. Herein, we enrolled 28 PD and 28 controls to compare internetwork coupling among cognitive and motor networks and examine its relationship with single- and dual-task gait performance in PD. METHODS: The dorsal attention network (DAN), left and right frontoparietal control networks (FPNs), sensorimotor network, and lateral motor network were identified using resting-state functional magnetic resonance imaging data. The time taken to complete a 10-m walk test during cognitive or physical dual-tasks in PD was calculated representing gait performance. RESULTS: We observed that the internetwork couplings between the DAN and motor networks and between the motor networks decreased whereas those between the left FPN and DAN and motor networks increased in PD compared to controls using a permutation test. There was no significant correlation between the internetwork couplings and single- and dual-task gait performance in PD. Nevertheless, improved cognitive dual-task performance showed a positive correlation with the DAN and left FPN coupling and a negative correlation with the DAN and lateral motor network coupling in a good performance group. The opposite relationship was observed in the poor cognitive dual-task performance group. CONCLUSION: Our findings suggest a neural mechanism of cognitive control on gait to compensate for reduced goal-directed attention in PD who maintain cognitive dual-task performance.

Proteomic discovery of prognostic protein biomarkers for persisting problems after mild traumatic brain injury.

Some individuals with mild traumatic brain injury (mTBI), also known as concussion, have neuropsychiatric and physical problems that last longer than a few months. Symptoms following mTBI are not only impacted by the kind and severity of the injury but also by the post-injury experience and the individual's responses to it, making the persistence of mTBI particularly difficult to predict. We aimed to identify prognostic blood-based protein biomarkers predicting 6-month outcomes, in light of the clinical course after the injury, in a longitudinal mTBI cohort (N = 42). Among 420 target proteins quantified by multiple-reaction monitoring-mass spectrometry assays of blood samples, 31, 43, and 15 proteins were significantly associated with the poor recovery of neuropsychological symptoms at < 72 h, 1 week, and 1 month after the injury, respectively. Sequential associations among clinical assessments (depressive symptoms and cognitive function) affecting the 6-month outcomes were evaluated. Then, candidate biomarker proteins indirectly affecting the outcome via neuropsychological symptoms were identified. Using the identified proteins, prognostic models that can predict the 6-month outcome of mTBI were developed. These protein biomarkers established in the context of the clinical course of mTBI may have potential for clinical application.

Assessment of vocal fold movement through anterior-posterior view of videofluoroscopic swallowing study.

Objective: The aim of this study is to assess the value of using videofluoroscopic swallowing study (VFSS) for assessing vocal fold paralysis. Methods: This was a retrospective study of patients who underwent VFSS with a vocal fold testing maneuver from June 2020 to February 2022, and who had undergone laryngoscopy within 2 weeks before or after VFSS. The vocal fold testing maneuver consisted of making an 'e' sound for about 2-3 seconds during VFSS anterior-posterior (AP) view. The diagnostic value of the VFSS was evaluated by a trained reviewer, who assessed the presence and laterality of vocal fold paralysis by examining videos of the patients performing the vocal fold testing maneuver. Intra-rater reliability was determined by evaluation of the videos by the same reviewer 2 weeks later, and inter-rater reliability was determined by evaluation by a second reviewer. Results: Seventy patients were enrolled in the study. The positive predictive value was 91.43% and the intra-rater and inter-rater reliabilities, as determined by Cohen's kappa value, were 0.746 and 0.824 respectively. Conclusions: The presence and laterality of vocal fold paralysis were identified accurately and reliably by the reviewers, showing that VFSS can be used to assess vocal fold paralysis. Level of evidence: 2.

Kinematic mechanism of the rehabilitative effect of 4-channel NMES: post-hoc analysis of a prospective randomized controlled study.

The sequential 4-channel neuromuscular electrical stimulation (NMES), based on the normal contractile sequences of swallowing-related muscles, is a new rehabilitative treatment. The objective of this study was to explore the mechanism of the rehabilitative effect of the 4-channel NMES using kinematic analysis of videofluoroscopic swallowing study (VFSS) data. For this post-hoc analysis, we included a subset of participants from the prospective randomized controlled study on the clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES. Seventeen subjects (11 and six in the 4- and 2-channel NMES groups, respectively) were eligible for the kinematic analysis of VFSS data. The hyoid bone movement was analyzed by evaluating the distance and time parameters with four peak points (A, B, C, D). The 4-channel NMES group showed significant improvement in vertical distances (A-C), horizontal distance (A-B, A-C), time interval (A-B-C) and total time, compared with their pretreatment data. The 2-channel NMES group showed significant improvements in time interval (A-B); however, the Euclidean distance (A-D) and mean velocity of the Euclidean distance (A-C) were significantly decreased. When the two groups were directly compared, the 4-channel group showed significantly greater improvement in horizontal distance (A-B), Euclidean distance (A-D), time interval (A-B-C), and mean velocity the Euclidean distance (A-D). The results in this study suggest that the sequential 4-channel NMES might lead to the physiologic circular movement of the hyoid bone during swallowing, and therefore be an effective treatment for dysphagia.Trial registration: Clinicaltrials.gov, registration number: NCT03670498.

Clinical Practice Guideline for Stroke Rehabilitation in Korea-Part 1: Rehabilitation for Motor Function (2022).

This clinical practice guideline (CPG) is the fourth edition of the Korean guideline for stroke rehabilitation, which was last updated in 2016. The development approach has been changed from a consensus-based approach to an evidence-based approach using the Grading of Recommendations Assessment Development and Evaluation (GRADE) method. This change ensures that the guidelines are based on the latest and strongest evidence available. The aim is to provide the most accurate and effective guidance to stroke rehabilitation teams, and to improve the outcomes for stroke patients in Korea. Fifty-five specialists in stroke rehabilitation and one CPG development methodology expert participated in this development. The scope of the previous clinical guidelines was very extensive, making it difficult to revise at once. Therefore, it was decided that the scope of this revised CPG would be limited to Part 1: Rehabilitation for Motor Function. The key questions were selected by considering the preferences of the target population and referring to foreign guidelines for stroke rehabilitation, and the recommendations were completed through systematic literature review and the GRADE method. The draft recommendations, which were agreed upon through an official consensus process, were refined after evaluation by a public hearing and external expert evaluation.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Development and validation of a portable articulated dynamometry system to assess knee extensor muscle strength.

Muscle strength assessment is important in predicting clinical and functional outcomes in many disorders. Manual muscle testing, although commonly used, offers suboptimal accuracy and reliability. Isokinetic dynamometers (IKDs) have excellent accuracy and reliability; but are bulky and expensive, offering limited accessibility. This study aimed to design a portable dynamometer that is accessible, accurate and reliable, and to validate the device in a general population. The portable articulated dynamometry system (PADS) is a portable device with an embedded high-precision load cell, designed to measure muscle strength with optimal accuracy. Seventy-two participants underwent maximal isometric and isokinetic knee extensor torque measurement with the PADS and IKD, respectively. The PADS results were cross-validated against IKD results using change in mean (CIM). Interrater and intra-rater reliabilities were assessed using intraclass correlation coefficients, standard error of measurement, and minimal detectable change. The PADS maximal knee extensor strength results were not significantly different from those by IKD (CIM: - 2.13 Nm; 95% CI - 4.74, 0.49 Nm). The PADS showed interrater reliability (Pearson's r: 0.958; ICC: 0.979; SEM: 5.51%) and excellent intra-rater reliability (Pearson's r: 0.912; ICC: 0.954; SEM: 8.38%). The proposed PADS may be an effective alternative to IKD, offering good accuracy, reliability, and potentially better accessibility.

Fully immersive virtual reality exergames with dual-task components for patients with Parkinson's disease: a feasibility study.

BACKGROUND: Dual-task training in Parkinson's disease (PD) improves spatiotemporal gait parameters, cognition, and quality of life. Virtual reality (VR) has been used as a therapeutic tool for patients to participate in activities in a safe environment, engage in multisensory experiences, and improve motivation and interest in rehabilitation. This study aimed to investigate the feasibility of fully immersive VR exergames with dual-task components in patients with PD. METHODS: We developed VR exergames (go/no-go punch game, go/no-go stepping game, and number punch game) to improve habitual behavior control using motor-cognitive dual-task performance in patients with PD. The participants underwent 10 sessions 2-3 times a week, consisting of 30 min per session. The Unified Parkinson's Disease Rating Scale, Timed Up and Go test (TUG) under single- and dual-task (cognitive and physical) conditions, Berg balance scale (BBS), Stroop test, trail-making test, and digit span were evaluated before and after intervention. The Simulator Sickness Questionnaire (SSQ) was used to assess VR cybersickness. Usability was assessed using a self-reported questionnaire. RESULTS: Twelve patients were enrolled and completed the entire training session. The mean age of participants was 73.83 ± 6.09 years; mean disease duration was 128.83 ± 76.96 months. The Hoehn and Yahr stages were 2.5 in seven patients and 3 in five patients. A significant improvement was observed in BBS and Stroop color-word test (p = 0.047 and p = 0.003, respectively). TUG time and dual-task interferences showed positive changes, but these changes were not statistically significant. The median SSQ total score was 28.05 (IQR: 29.92), 13.09 (IQR: 11.22), and 35.53 (IQR: 52.36) before, after the first session, and after the final session, respectively; the differences were not significant. Overall satisfaction with the intervention was 6.0 (IQR: 1.25) on a 7-point Likert-type scale. CONCLUSIONS: Fully immersive VR exergames combined with physical and cognitive tasks may be used for rehabilitation of patients with PD without causing serious adverse effects. Furthermore, the exergames using dual-task components improved executive function and balance. Further development of VR training content may be needed to improve motor and dual-task performances. Trial registration NCT04787549 ( https://clinicaltrials.gov/ct2/show/NCT04787549 ).

Development of Korea Neuroethics Guidelines.

BACKGROUND: Advances in neuroscience and neurotechnology provide great benefits to humans though unknown challenges may arise. We should address these challenges using new standards as well as existing ones. Novel standards should include ethical, legal, and social aspects which would be appropriate for advancing neuroscience and technology. Therefore, the Korea Neuroethics Guidelines were developed by stakeholders related to neuroscience and neurotechnology, including experts, policy makers, and the public in the Republic of Korea. METHOD: The guidelines were drafted by neuroethics experts, were disclosed at a public hearing, and were subsequently revised by opinions of various stakeholders. RESULTS: The guidelines are composed of twelve issues; humanity or human dignity, individual personality and identity, social justice, safety, sociocultural prejudice and public communication, misuse of technology, responsibility for the use of neuroscience and technology, specificity according to the purpose of using neurotechnology, autonomy, privacy and personal information, research, and enhancement. CONCLUSION: Although the guidelines may require a more detailed discussion after future advances in neuroscience and technology or changes in socio-cultural milieu, the development of the Korea Neuroethics Guidelines is a milestone for the scientific community and society in general for the ongoing development in neuroscience and neurotechnology.

Clinical and Swallowing Characteristics Related With Respiratory Infection in Parkinsonism Patients.

OBJECTIVE: To investigate the clinical and swallowing characteristics related to respiratory infection in patients with parkinsonism. METHODS: One hundred and forty-two patients with parkinsonism who underwent videofluoroscopic swallowing studies (VFSS) were enrolled in this study. The initial clinical and VFSS characteristics were compared between patients with and without a history of respiratory infection in the past year. A multivariate logistic regression model was applied to identify clinical and swallowing characteristics related to respiratory infections. RESULTS: Patients with respiratory infections were older (74.75±10.20 years vs. 70.70±8.83 years, p=0.037), had a higher Hoehn and Yahr (H&Y) stage (stage IV-V, 67.9% vs. 49.1%; p=0.047), and were more likely to have a diagnosis of idiopathic Parkinson's disease (IPD) (67.9% vs. 41.2%, p=0.011) than those without respiratory infections. Among VFSS findings, bolus formation, premature bolus loss, oral transit time, pyriform sinus residues, pharyngeal wall coatings, and penetration/aspiration were significantly worse in patients with respiratory infections (p<0.05). Regarding clinical characteristics, higher H&Y stage (odds ratio [OR], 3.174; 95% confidence interval [CI], 1.226-8.216; p=0.017) and diagnosis of IPD (OR, 0.280, 95% CI, 0.111-0.706; p=0.007) were significantly related to respiratory infections in the multivariate analysis. Among VFSS findings, pyriform sinus residue (OR, 14.615; 95% CI, 2.257-94.623; p=0.005) and premature bolus loss (OR, 5.151; 95% CI, 1.047-25.338; p=0.044) were also significantly associated with respiratory infection. CONCLUSION: This study suggests that disease severity, diagnosis, pyriform sinus residue, and premature bolus loss observed in VFSS are associated with respiratory infection in patients with parkinsonism.

Rehabilitation for Impaired Attention in the Acute and Post-Acute Phase After Traumatic Brain Injury: A Narrative Review.

Impaired attention is the most common and debilitating cognitive deficit following a traumatic brain injury (TBI). Attention is a fundamental function that profoundly influences the performance of other cognitive components such as memory and execution. Intriguingly, attention can be improved through cognitive rehabilitation. This narrative review summarizes the essential elements of rehabilitation for attention problems in acute and post-acute TBI. In the acute phase of mild TBI, investigations into the medical history and daily life performance, neurological examination, screening and management of concomitant sleep-wake disorders or neuropsychiatric disorders, and support and education on the natural course of concussion are covered. Rehabilitation for patients with moderate-to-severe TBI consists of serial assessment for patients with disorders of consciousness and a post-traumatic confusion state. In the post-acute phase after TBI, components of rehabilitation include investigating medical history; neurological, imaging, and electrophysiological tests; evaluation and treatment of factors that may impact attention, including sleep-wake, emotional, and behavioral disorders; evaluation of attention function; and cognitive rehabilitation as a matter of course. We summarized metacognitive strategy, direct attention training, computer-based cognitive interventions, medication, and environmental control as interventions to enhance attention.

Deciphering Functional Connectivity Differences Between Motor Imagery and Execution of Target-Oriented Grasping.

This study aimed to delineate overlapping and distinctive functional connectivity in visual motor imagery, kinesthetic motor imagery, and motor execution of target-oriented grasping action of the right hand. Functional magnetic resonance imaging data were obtained from 18 right-handed healthy individuals during each condition. Seed-based connectivity and multi-voxel pattern analyses were employed after selecting seed regions with the left primary motor cortex and supplementary motor area. There was equivalent seed-based connectivity during the three conditions in the bilateral frontoparietal and temporal areas. When the seed region was the left primary motor cortex, increased connectivity was observed in the left cuneus and superior frontal area during visual and kinesthetic motor imageries, respectively, compared with that during motor execution. Multi-voxel pattern analyses revealed that each condition was differentiated by spatially distributed connectivity patterns of the left primary motor cortex within the right cerebellum VI, cerebellum crus II, and left lingual area. When the seed region was the left supplementary motor area, the connectivity patterns within the right putamen, thalamus, cerebellar areas IV-V, and left superior parietal lobule were significantly classified above chance level across the three conditions. The present findings improve our understanding of the spatial representation of functional connectivity and its specific patterns among motor imagery and motor execution. The strength and fine-grained connectivity patterns of the brain areas can discriminate between motor imagery and motor execution.

Suicidal behaviors in patients with chronic physical illness: A test on the interpersonal theory of suicide.

INTRODUCTION: The unalleviated burden of chronic physical illness (CPI) increases the risk of suicidal behaviors (SB) in affected individuals. This study tested the interpersonal theory of suicide (ITS) in patients with CPI. METHODS: Patients diagnosed with cardiovascular, cerebrovascular, and renal diseases were recruited from two hospitals in South Korea. Data from 257 participants who completed Time (T) 1 and T2 surveys were analyzed. Hierarchical regression analyses for passive and active suicide ideation (PSI and ASI), and suicide plans and attempts (SP and SA) at both time points were conducted. RESULTS: Interpersonal theory of suicide hypotheses were partially supported. Even accounting for factors such as depression, anxiety, and lifetime SA, some main and interaction effects of the ITS constructs explained SB in a cross-sectional examination, but to a lesser degree in a longitudinal examination that controlled for T1 SB. PB was a consistent correlate of SB. TB was also relevant, as PB-SA association was significant among participants with high TB both times. ASI was associated with SP and SA at T1, and the ASI-SP association at T1 was stronger at a high CS level. CONCLUSIONS: Overall, the results suggest the relevance of ITS constructs that warrant attention to prevent SB in patients with CPI.

Exploratory Investigation of the Effects of Tactile Stimulation Using Air Pressure at the Auricular Vagus Nerve on Heart Rate Variability.

OBJECTIVE: To explore the effects of tactile stimulation using air pressure at the auricular branch of the vagus nerve on autonomic activity in healthy individuals. METHODS: Three types of tactile stimulation were used in this study: continuous low-amplitude, continuous high-amplitude, and pulsed airflow. The tactile stimulations were provided to the cymba concha to investigate autonomic activity in 22 healthy participants. The mean heart rate (HR) and parameters of HR variability, including the standard deviation of R-R intervals (SDNN) and root mean square of successive R-R interval differences (RMSSD) were compared at baseline, stimulation, and recovery periods. RESULTS: Two-way repeated measures ANOVA indicated a significant main effect of time on HR (p=0.001), SDNN (p=0.003), and RMSSD (p<0.001). These parameters showed significant differences between baseline and stimulation periods and baseline and recovery periods in the post-hoc analyses. There were no significant differences in the changes induced by stimulation type and the interaction between time and stimulation type for all parameters. One-way repeated measures ANOVA showed that HR, SDNN, and RMSSD did not differ significantly among the three time periods during sham stimulation. CONCLUSION: Parasympathetic activity can be enhanced by auricular tactile stimulation using air pressure, targeting the cymba concha. Further studies are warranted to investigate the optimal stimulation parameters for potential clinical significance.

Low-Frequency Repetitive Transcranial Magnetic Stimulation in the Early Subacute Phase of Stroke Enhances Angiogenic Mechanisms in Rats.

OBJECTIVE: To characterize the repetitive transcranial magnetic stimulation (rTMS) induced changes in angiogenic mechanisms across different brain regions. METHODS: Seventy-nine adult male Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (day 0) and then treated with 1-Hz, 20-Hz, or sham stimulation of their lesioned hemispheres for 2 weeks. The stimulation intensity was set to 100% of the motor threshold. The neurological function was assessed on days 3, 10, and 17. The infarct volume and angiogenesis were measured by histology, immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) assays. Brain tissue was harvested from the ischemic core (IC), ischemic border zone (BZ), and contralateral homologous cortex (CH). RESULTS: Optical density of angiopoietin1 and synaptophysin in the IC was significantly greater in the low-frequency group than in the sham group (p=0.03 and p=0.03, respectively). The 1-Hz rTMS significantly increased the level of Akt phosphorylation in the BZ (p<0.05 vs. 20 Hz). Endothelial nitric oxide synthase phosphorylation was increased in the IC (p<0.05 vs. 20 Hz), BZ (p<0.05 vs. 20 Hz), and CH (p<0.05 vs. 20 Hz and p<0.05 vs. sham). Real-time PCR demonstrated that low-frequency stimulation significantly increased the transcriptional activity of the TIE2 gene in the IC (p<0.05). CONCLUSION: Low-frequency rTMS of the ipsilesional hemisphere in the early subacute phase of stroke promotes the expression of angiogenic factors and related genes in the brain, particularly in the injured area.