Non-invasive brain stimulation effectively improves post-stroke sensory impairment: a systematic review and meta-analysis.

More than half of stroke patients experience sensory dysfunction that affects their quality of life. Previous training modalities are ineffective in improving sensory function. In contrast, non-invasive brain stimulation (NIBS) is a new promising intervention for stroke rehabilitation. The aim of this meta-analysis was to summarize the current effectiveness of NIBS in the treatment of post-stroke sensory dysfunction. Articles published in PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese scientific journals full-text database (VIP), and Wanfang database from the inception to March 8, 2023 were searched. There were no restrictions on language. A total of 14 RCTs were included (combined n = 804). Moderate-quality evidence suggested that NIBS significantly improved sensory function after stroke, and significant effects were observed up to 1 year after the intervention. In subgroup analysis, treatment with transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) was significantly more effective than controls for recovery of sensory function in stroke patients. Stimulation of the primary motor cortex (M1), primary somatosensory cortex (S1) or M1 + S1 stimulation sites significantly improved sensory function. NIBS for sensory dysfunction showed significant therapeutic potential in patients with different stages of stroke. No significant effects were observed in subjects with less than 10 NIBS stimulations. Significant therapeutic effects were observed with either high-frequency or low-frequency rTMS.

Electroencephalography oscillations can predict the cortical response following theta burst stimulation.

BACKGROUND: Continuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. METHOD: Twenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. RESULT: Among the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. CONCLUSION: These findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

Biomarkers associated with functional improvement after stroke rehabilitation: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study aims to identify blood and cerebrospinal fluid biomarkers that are correlated to the functional improvement of stroke patients after rehabilitation therapy, and provide ideas for the treatment and evaluation of stroke patients. Methods: The PubMed, Web of Science, and Embase databases were searched for articles published in the English language, from inception to December 8, 2022. Results: A total of 9,810 independent records generated 50 high-quality randomized controlled trials on 119 biomarkers. Among these records, 37 articles were included for the meta-analysis (with a total of 2,567 stroke patients), and 101 peripheral blood and cerebrospinal fluid biomarkers were included for the qualitative analysis. The quantitative analysis results revealed a moderate quality evidence that stroke rehabilitation significantly increased the level of brain-derived neurotrophic factor (BDNF) in serum. Furthermore, the low-quality evidence revealed that stroke rehabilitation significantly increased the concentration of serum noradrenaline (NE), peripheral blood superoxide dismutase (SOD), peripheral blood albumin (ALB), peripheral blood hemoglobin (HB), and peripheral blood catalase (CAT), but significantly decreased the concentration of serum endothelin (ET) and glutamate. In addition, the changes in concentration of these biomarkers were associated with significant improvements in post-stroke function. The serum BNDF suggests that this can be used as a biomarker for non-invasive brain stimulation (NIBS) therapy, and to predict the improvement of stroke patients. Conclusion: The concentration of serum BNDF, NE, ET and glutamate, and peripheral blood SOD, ALB, HB and CAT may suggest the function improvement of stroke patients.

Causal Association of Cytokines and Growth Factors with Stroke and Its Subtypes: a Mendelian Randomization Study.

Cytokines and growth factors contribute to nerve growth and angiogenesis and are associated with the development of vascular disease. This Mendelian randomization (MR) study was designed to examine the causal relationship between factors associated with stem cell paracrine mechanisms and with stroke and its subtypes. We used pooled statistics on cytokine levels from three studies (INTERIAL, Olink Proseek CVD array, and KORA) encompassing 7795 participants in Europe. Data for stroke and its subtypes were pooled from these European populations (40,585 cases and 406,111 controls) in a multiprogenitor genome-wide association study (GWAS). MR was performed using established analytical methods, including inverse variance weighting (IVW), weighted median (WM), and MR-Egger. Genetically determined high IGF-1 levels were found to associate negatively with risk of stroke, ischemic stroke (large-artery atherosclerosis), and ischemic stroke (cardiogenic embolism). Meanwhile, high IL-13 levels had a positive causal relationship with ischemic stroke (large-artery atherosclerosis). An additional 27 cytokines were found to have a causal association with stroke or its subtypes. However, these results should be interpreted with caution given that the power efficacy was <80%. This MR study supports the concept of a causal relationship of 29 cytokines with stroke or its subtypes. Our genetic analysis provides new insights into stroke prevention and treatment by demonstrating an association of stem cell paracrine-related cytokines with stroke risk.

Effects of repetitive transcranial magnetic stimulation on sequelae in patients with chronic stroke: A systematic review and meta-analysis of randomized controlled trials.

Background: Stroke is the second leading cause of death worldwide, with a large proportion of survivors suffering from motor dysfunction and neuropsychiatric sequelae. Repetitive transcranial magnetic stimulation (rTMS) is a promising stroke rehabilitation intervention and is effective in improving neurological system function in stroke patients. In the current systemic review and meta-analysis, an overview of the most recent studies regarding the effectiveness of rTMS's potential to help chronic stroke patients recover from sequelae was provided. Methods: Relevant randomized controlled trials were retrieved from three online databases (Web of Science, Medline, and Embase). A total of 25 RCTs (N = 535 participants) were included. A meta-analysis was performed using a fixed-effects model or a random-effects model, and effect sizes were reported as weighted mean differences or standardized mean differences. Results: Administration of rTMS significantly improved upper limb function, hand function, and muscle tone in stroke patients throughout the chronic phase [≥6 months], but not lower limb mobility and strength. In terms of cognitive function, rTMS has a considerable positive impact on patients' cognitive performance. rTMS also alleviated apathy in stroke patients more than post-stroke depressive symptoms regarding mental functioning. Balance and walking function, as well as functional activities of daily living, of patients were dramatically improved by rTMS. However, the current conclusions should be taken carefully due to the small sample size of the meta-analysis. Conclusions: This is the first meta-analysis of rTMS treatment in patients with chronic stroke to inform the selection of the optimal treatment strategy for patients with chronic stroke, which demonstrated that rTMS treatment has the potential to improve the effects of sequelae by improving upper limb function, hand function, and muscle tone. Systematic review registration: https://inplasy.com/inplasy-2022-7-0095/, identifier: INPLASY202270095.

Effects of repetitive transcranial magnetic stimulation on upper-limb and finger function in stroke patients: A systematic review and meta-analysis of randomized controlled trials.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for stroke rehabilitation. Several studies have demonstrated the effectiveness of rTMS in restoring motor function. This meta-analysis aimed to summarize the current evidence of the effect of rTMS in improving upper limb function and fine motor recovery in stroke patients. Methods: Three online databases (Web of Science, PubMed, and Embase) were searched for relevant randomized controlled trials. A total of 45 studies (combined n = 2064) were included. Random effects model was used for meta-analysis and effect size was reported as standardized mean difference (SMD). Results: rTMS was effective in improving fine motor function in stroke patients (SMD, 0.38; 95% CI 0.19-0.58; P = 0). On subgroup analyses, for post-stroke functional improvement of the upper extremity, bilateral hemisphere stimulation was more effective than unilateral stimulation during the acute phase of stroke, and a regimen of 20 rTMS sessions produced greater improvement than <20 sessions. In the subacute phase of stroke, affected hemispheric stimulation with a 40-session rTMS regimen was superior to unaffected hemispheric stimulation or bilateral hemispheric stimulation with <40 sessions. Unaffected site stimulation with a 10-session rTMS regimen produced significant improvement in the chronic phase compared to affected side stimulation and bilateral stimulation with >10 rTMS sessions. For the rTMS stimulation method, both TBS and rTMS were found to be significantly more effective in the acute phase of stroke, but TBS was more effective than rTMS. However, rTMS was found to be more effective than TBS stimulation in patients in the subacute and chronic phases of stroke. rTMS significantly improved upper limb and fine function in the short term (0-1-month post-intervention) and medium term (2-5 months), but not for upper limb function in the long term (6 months+). The results should be interpreted with caution due to significant heterogeneity. Conclusions: This updated meta-analysis provides robust evidence of the efficacy of rTMS treatment in improving upper extremity and fine function during various phases of stroke. Systematic Review Registration: https://inplasy.com/inplasy-2022-5-0121/, identifier: INPLASY202250121.

MRI radiomic features of peritumoral edema may predict the recurrence sites of glioblastoma multiforme.

Background and purpose: As one of the most aggressive malignant tumor in the central nervous system, the main cause of poor outcome of glioblastoma (GBM) is recurrence, a non-invasive method which can predict the area of recurrence pre-operation is necessary.To investigate whether there is radiological heterogeneity within peritumoral edema and identify the reproducible radiomic features predictive of the sites of recurrence of glioblastoma(GBM), which may be of value to optimize patients' management. Materials and methods: The clinical information and MR images (contrast-enhanced T1 weighted and FLAIR sequences) of 22 patients who have been histologically proven glioblastoma, were retrospectively evaluated. Kaplan-Meier methods was used for survival analysis. Oedematous regions were manually segmented by an expert into recurrence region, non-recurrence region. A set of 94 radiomic features were obtained from each region using the function of analyzing MR image of 3D slicer. Paired t test was performed to identify the features existing significant difference. Subsequently, the data of two patients from TCGA database was used to evaluate whether these features have clinical value. Results: Ten features with significant differences between the recurrence and non-recurrence subregions were identified and verified on two individual patients from the TCGA database with pathologically confirmed diagnosis of GBM. Conclusions: Our results suggested that heterogeneity does exist in peritumoral edema, indicating that the radiomic features of peritumoral edema from routine MR images can be utilized to predict the sites of GBM recurrence. Our findings may further guide the surgical treatment strategy for GBM.

Influence of iTBS on the Acute Neuroplastic Change After BCI Training.

Objective: Brain-computer interface (BCI) training is becoming increasingly popular in neurorehabilitation. However, around one third subjects have difficulties in controlling BCI devices effectively, which limits the application of BCI training. Furthermore, the effectiveness of BCI training is not satisfactory in stroke rehabilitation. Intermittent theta burst stimulation (iTBS) is a powerful neural modulatory approach with strong facilitatory effects. Here, we investigated whether iTBS would improve BCI accuracy and boost the neuroplastic changes induced by BCI training. Methods: Eight right-handed healthy subjects (four males, age: 20-24) participated in this two-session study (BCI-only session and iTBS+BCI session in random order). Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) and single-pulse transcranial magnetic stimulation (TMS). In BCI-only session, fNIRS was measured at baseline and immediately after BCI training. In iTBS+BCI session, BCI training was followed by iTBS delivered on the right primary motor cortex (M1). Single-pulse TMS was measured at baseline and immediately after iTBS. fNIRS was measured at baseline, immediately after iTBS, and immediately after BCI training. Paired-sample t-tests were used to compare amplitudes of motor-evoked potentials, cortical silent period duration, oxygenated hemoglobin (HbO2) concentration and functional connectivity across time points, and BCI accuracy between sessions. Results: No significant difference in BCI accuracy was detected between sessions (p > 0.05). In BCI-only session, functional connectivity matrices between motor cortex and prefrontal cortex were significantly increased after BCI training (p's < 0.05). In iTBS+BCI session, amplitudes of motor-evoked potentials were significantly increased after iTBS (p's < 0.05), but no change in HbO2 concentration or functional connectivity was observed throughout the whole session (p's > 0.05). Conclusions: To our knowledge, this is the first study that investigated how iTBS targeted on M1 influences BCI accuracy and the acute neuroplastic changes after BCI training. Our results revealed that iTBS targeted on M1 did not influence BCI accuracy or facilitate the neuroplastic changes after BCI training. Therefore, M1 might not be an effective stimulation target of iTBS for the purpose of improving BCI accuracy or facilitate its effectiveness; other brain regions (i.e., prefrontal cortex) are needed to be further investigated as potentially effective stimulation targets.

The Corticospinal Excitability Can Be Predicted by Spontaneous Electroencephalography Oscillations.

Transcranial magnetic stimulation (TMS) has a wide range of clinical applications, and there is growing interest in neural oscillations and corticospinal excitability determined by TMS. Previous studies have shown that corticospinal excitability is influenced by fluctuations of brain oscillations in the sensorimotor region, but it is unclear whether brain network activity modulates corticospinal excitability. Here, we addressed this question by recording electroencephalography (EEG) and TMS measurements in 32 healthy individuals. The resting motor threshold (RMT) and active motor threshold (AMT) were determined as markers of corticospinal excitability. The least absolute shrinkage and selection operator (LASSO) was used to identify significant EEG metrics and then correlation analysis was performed. The analysis revealed that alpha2 power in the sensorimotor region was inversely correlated with RMT and AMT. Innovatively, graph theory was used to construct a brain network, and the relationship between the brain network and corticospinal excitability was explored. It was found that the global efficiency in the theta band was positively correlated with RMT. Additionally, the global efficiency in the alpha2 band was negatively correlated with RMT and AMT. These findings indicated that corticospinal excitability can be modulated by the power spectrum in sensorimotor regions and the global efficiency of functional networks. EEG network analysis can provide a useful supplement for studying the association between EEG oscillations and corticospinal excitability.

Short intracortical facilitation associates with motor-inhibitory control.

The ability of motor-inhibitory control is important in daily life. Inhibitory control deficits are commonly observed in psychiatric conditions with enhanced impulsivity. The physiological mechanisms underlying the inhibitory control deficits are not well elucidated. We systematically investigated the relationship between resting-state intracortical inhibition or facilitation and inhibitory control (indicated by stop signal reaction time, SSRT) to determine whether reduced intracortical inhibition or increased intracortical facilitation was related to the poorer inhibitory control. Thirty-three healthy subjects (age: 21.46 ± 1.40 years) participated in this study. We used paired-pulse transcranial magnetic stimulation to induce short intracortical inhibition, intracortical facilitation, long intracortical inhibition, and short intracortical facilitation at rest. SSRT was derived from stop signal task. We performed all measurements in two repeat sessions conducted two weeks apart. A negative correlation between short intracortical inhibition and SSRT was only observed in session 1; however, the correlation did not persist after controlling for short intracortical facilitation. Positive correlation between short intracortical facilitation and SSRT was observed in both sessions, indicating that individuals with greater resting-state short intracortical facilitation tend to have less efficient stopping performance. Our results help explain the inconsistency with respect to the relationship between short intracortical inhibition and SSRT in the existing literature. Short intracortical facilitation may be used as a potential physiological biomarker for motor-inhibitory control, which may have clinical implications for disorders associated with inhibitory control deficits.

Comparison of Activation Patterns in Mirror Neurons and the Swallowing Network During Action Observation and Execution: A Task-Based fMRI Study.

BACKGROUND: Observation of a goal-directed motor action can excite the respective mirror neurons, and this is the theoretical basis for action observation (AO) as a novel tool for functional recovery during stroke rehabilitation. To explore the therapeutic potential of AO for dysphagia, we conducted a task-based functional magnetic resonance imaging (fMRI) study to identify the brain areas activated during observation and execution of swallowing in healthy participants. METHODS: Twenty-nine healthy volunteers viewed the following stimuli during fMRI scanning: an action-video of swallowing (condition 1, defined as AO), a neutral image with a Chinese word for "watching" (condition 2), and a neutral image with a Chinese word for "swallowing" (condition 3). Action execution (AE) was defined as condition 3 minus condition 2. One-sample t-tests were performed to define the brain regions activated during AO and AE. RESULTS: Many brain regions were activated during AO, including the middle temporal gyrus, inferior frontal gyrus, pre- and postcentral gyrus, supplementary motor area, hippocampus, brainstem, and pons. AE resulted in activation of motor areas as well as other brain areas, including the inferior parietal lobule, vermis, middle frontal gyrus, and middle temporal gyrus. Two brain areas, BA6 and BA21, were activated with both AO and AE. CONCLUSION: The left supplementary motor area (BA6) and left middle temporal gyrus (BA21), which contains mirror neurons, were activated in both AO and AE of swallowing. In this study, AO activated mirror neurons and the swallowing network in healthy participants, supporting its potential value in the treatment of dysphagia.

3-D printing for constructing the burr hole ring of lead fixation device in deep brain stimulation.

BACKGROUND: As the bearing structure of fixation device in deep brain stimulation (DBS), burr hole ring is fixed on the skull and used in conjunction with Stimloc and plastic cap. But in patients with traumatic event, excessive movements are likely to bring strain on the anchoring system, which will finally cause the fixation device to fall off from the skull. METHOD: AutoCAD was used to construct two-dimension (2-D) images for traditional burr hole ring and innovative burr hole ring, respectively. According to the 2-D image, pro/Engineer (Pro/E) will be applied to construct the three-dimension (3-D) geometries. And then, 3-D printing technology was used to build the solid model. These two kinds of burr hole rings were divided into two groups: Innovative group (N = 21) and Traditional group (N = 21). Pull-out strength of these two groups of burr hole rings will be measured by manual tensile force testing machine on the full-size skull model, and the data were transmitted to the notebook in real time for recording and further analyzing. RESULT: The fixation strength of the innovative group is stronger than traditional group, pull-out strength value of traditional group and innovative group were 34.08 ±â€¯1.31 N and 99.73 ±â€¯2.14 N, respectively. (P < 0.001). CONCLUSION: We provide an innovative burr hole ring, which can fix on the burr hole steadily. Moreover, 3-D printing technology may be suitable for personalized and customized medical treatment in the future.