While rapid eye movement (REM) sleep is conventionally treated as a unified state, it comprises two distinct microstates: phasic and tonic REM. Recent research emphasizes the importance of understanding the interplay between these microstates, hypothesizing their role in transient shifts between sensory detachment and external awareness. Previous studies primarily employed linear metrics to probe cognitive states, such as oscillatory power, while in this study, we adopt Lempel-Ziv Complexity (LZC), to examine the nonlinear features of electroencephalographic (EEG) data from the REM microstates and to gain complementary insights into neural dynamics during REM sleep. Our findings demonstrate a noteworthy reduction in LZC during phasic REM compared to tonic REM states, signifying diminished EEG complexity in the former. Additionally, we noted a negative correlation between decreased LZC and delta band power, along with a positive correlation with alpha band power. This study highlights the potential of nonlinear EEG metrics, particularly LZC, in elucidating the distinct features of REM microstates. Overall, this research contributes to advancing our understanding of the complex dynamics within REM sleep and opens new avenues for exploring its implications in both clinical and non-clinical contexts.
Research advancement has spurred the usage of electroencephalography (EEG)-based neural oscillatory rhythms as a biomarker to complement clinical rehabilitation strategies for the recovery of motor functions in stroke survivors. However, the inevitable contamination of EEG signals with artifacts from various sources limits its utilization and effectiveness. Thus, the integration of Independent Component Analysis (ICA) and Independent Component Label (ICLabel) has been widely employed to separate neural activity from artifacts. A crucial step in the ICLabel preprocessing pipeline is the artifactual ICs rejection threshold (TH) parameter, which determines the overall signal's quality. For instance, selecting a high TH will cause many ICs to be rejected, thereby leading to signal over-cleaning, and choosing a low TH may result in under-cleaning of the signal. Toward determining the optimal TH parameter, this study investigates the effect of six different TH groups (NO-TH and TH1-TH6) on EEG signals recorded from post-stroke patients who performed four distinct motor imagery (MI) tasks including wrist and grasping movements. Utilizing the EEG-beta band signal at the brain's sensorimotor cortex, the performance of the TH groups was evaluated using three notable EEG quantifiers. Overall, the obtained result shows that the considered THs will significantly alter neural oscillatory patterns. Comparing the performance of the TH-groups, TH-3 with a confidence level of 60% showed consistently stronger signal desynchronization and lateralization. The correlation result shows that most of the electrode pairs with high correlation values are replicable across all the MI tasks. It also revealed that brain activity correlates linearly with distance, and a strong correlation between electrode pairs is independent of the different brain cortices. The study outcome may facilitate adequate therapeutic intervention for stroke rehab.Clinical Relevance: This study indicated that optimal selection of the ICLabel artifactual rejection threshold is essential for EEG enhancement for adequate signal characterization. Thus, a TH-values with a confidence level between 50% - 70% would be suggested for artifactual ICs rejection in MI-EEG.
Stroke , Humans , Stroke/complications , Stroke/diagnosis , Brain , Electroencephalography , Movement , Wrist
Objective: The aim of the study was to evaluate non-invasive brain stimulation (NIBS) [including transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES)] on neurological symptoms in patients with multiple sclerosis (PwMS). Method: We searched PubMed, Embase, Cochrane Library, Web of Science and Ovid MEDLINE until February 2022. And we evaluated the included studies for methodological quality by the Cochrane bias risk assessment tool and assessed the studies' certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We performed network meta analysis (NMA) by using Stata 15 and ranked the results of the NMA by using the surface under the cumulative ranking curve (SUCRA) ranking chart. Result: Twenty seven clinical trials were finally included (N = 596, 66.4% women). For the immediate effects, rTMS over M1 yielded the most optimal scheme for fatigue reduction among all the interventions compared to the sham stimulation groups [MD = -0.85, 95% CI (-1.57, -0.14)] (SUCRA = 82.6%). iTBS over M1 yielded the most signifcant reduced pain level than the sham groups did [MD = -1.26, 95% CI (-2.40, -0.11)] (SUCRA = 98.4%). tDCS over F3 was the best protocol of NIBS to improve quality of life (QOL) [MD = 1.41, 95% CI = (0.45,2.36)] (SUCRA = 76.7%), and iTBS over M1 may significantly reduce spasticity compared to sham stimulation [MD = -1.20, 95% CI = (-1.99, -0.41)] (SUCRA = 90.3%). Furthermore, rTMS, tRNS, and tDCS on certain areas may improve PwMS accuracy, response time, manual dexterity, pain relief and QOL, but does not show statistically significant differences. The evidence assessed using GRADE is very low. Conclusion: Based on the NMA and SUCRA ranking, we can conclude that symptoms including fatigue, pain, spasticity, and QOL can be improved by following NIBS protocol after treatment. Nonetheless, most of the included studies lack a good methodology, and more high-quality randomized clinical trials are needed.
The study aimed to characterize phenolic compounds of the Inonotus sanghuang's ethyl-acetate fraction (EAF) and assess the neuroprotective effect of EAF using the H2O2-treated primary cortical neuronal cells (PCNC) model. Using HPLC-ECD, 5 phenolics were identified and quantified from EAF. H2O2-treated PCNC experiments in vitro showed that pretreatment with EAF increased the GSH-PX and SOD activities and reduced the NO, MDA, and Aß contents. Furthermore, EAF suppressed the production of IL-1ß, IFN-γ, IL-6, and TNF-α in H2O2-treated PCNC. Other mechanisms found that EAF reduced Bax, caspase 9, and caspase 3 expressions at the mRNA and protein levels while increasing Bcl-2 expression at the mRNA and protein levels. These results showed that EAF could serve as potential agents for anti-NDD. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01107-x.
An enriched environment is used as a behavioral intervention therapy that applies sensory, motor, and social stimulation, and has been used in basic and clinical research of various neurological diseases. In this study, we established mouse models of photothrombotic stroke and, 24 hours later, raised them in a standard, enriched, or isolated environment for 4 weeks. Compared with the mice raised in a standard environment, the cognitive function of mice raised in an enriched environment was better and the pathological damage in the hippocampal CA1 region was remarkably alleviated. Furthermore, protein expression levels of tumor necrosis factor receptor-associated factor 6, nuclear factor κB p65, interleukin-6, and tumor necrosis factor α, and the mRNA expression level of tumor necrosis factor receptor-associated factor 6 were greatly lower, while the expression level of miR-146a-5p was higher. Compared with the mice raised in a standard environment, changes in these indices in mice raised in an isolated environment were opposite to mice raised in an enriched environment. These findings suggest that different living environments affect the hippocampal inflammatory response and cognitive function in a mouse model of stroke. An enriched environment can improve cognitive function following stroke through up-regulation of miR-146a-5p expression and a reduction in the inflammatory response.
Background: The motor imagery brain computer interface (MI-BCI) is now available in a commercial product for clinical rehabilitation. However, MI-BCI is still a relatively new technology for commercial rehabilitation application and there is limited prior work on the frequency effect. The MI-BCI has become a commercial product for clinical neurological rehabilitation, such as rehabilitation for upper limb motor dysfunction after stroke. However, the formulation of clinical rehabilitation programs for MI-BCI is lack of scientific and standardized guidance, especially limited prior work on the frequency effect. Therefore, this study aims at clarifying how frequency effects on MI-BCI training for the plasticity of the central nervous system. Methods: Sixteen young healthy subjects (aged 22.94 ± 3.86 years) were enrolled in this randomized clinical trial study. Subjects were randomly assigned to a high frequency group (HF group) and low frequency group (LF group). The HF group performed MI-BCI training once per day while the LF group performed once every other day. All subjects performed 10 sessions of MI-BCI training. functional near-infrared spectroscopy (fNIRS) measurement, Wolf Motor Function Test (WMFT) and brain computer interface (BCI) performance were assessed at baseline, mid-assessment (after completion of five BCI training sessions), and post-assessment (after completion of 10 BCI training sessions). Results: The results from the two-way ANOVA of beta values indicated that GROUP, TIME, and GROUP × TIME interaction of the right primary sensorimotor cortex had significant main effects [GROUP: F (1,14) = 7.251, P = 0.010; TIME: F (2,13) = 3.317, P = 0.046; GROUP × TIME: F (2,13) = 5.676, P = 0.007]. The degree of activation was affected by training frequency, evaluation time point and interaction. The activation of left primary sensory motor cortex was also affected by group (frequency) (P = 0.003). Moreover, the TIME variable was only significantly different in the HF group, in which the beta value of the mid-assessment was higher than that of both the baseline assessment (P = 0.027) and post-assessment (P = 0.001), respectively. Nevertheless, there was no significant difference in the results of WMFT between HF group and LF group. Conclusion: The major results showed that more cortical activation and better BCI performance were found in the HF group relative to the LF group. Moreover, the within-group results also showed more cortical activation after five sessions of BCI training and better BCI performance after 10 sessions in the HF group, but no similar effects were found in the LF group. This pilot study provided an essential reference for the formulation of clinical programs for MI-BCI training in improvement for upper limb dysfunction.
Objective: The primary purpose of our study is to systemically evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on recovery of dysphagia after stroke. Search Methods: We searched randomized controlled trials (RCTs) and non-RCTs published by PubMed, the Cochrane Library, ScienceDirect, MEDLINE, and Web of Science from inception until April 24, 2021. Language is limited to English. After screening and extracting the data, and evaluating the quality of the selected literature, we carried out the meta-analysis with software RevMan 5.3 and summarized available evidence from non-RCTs. Results: Among 205 potentially relevant articles, 189 participants (from 10 RCTs) were recruited in the meta-analysis, and six non-RCTs were qualitatively described. The random-effects model analysis revealed a pooled effect size of SMD = 0.65 (95% CI = 0.04-1.26, p = 0.04), which indicated that rTMS therapy has a better effect than conventional therapy. However, the subgroup analysis showed that there was no significant difference between low-frequency and high-frequency groups. Even more surprisingly, there were no statistically significant differences between the two groups and the conventional training group in the subgroup analysis, but the combined effect was positive. Conclusion: Our study suggests that rTMS might be effective in treating patients with dysphagia after stroke.
BACKGROUND: Upper limb motor dysfunction caused by stroke greatly affects the daily life of patients, significantly reduces their quality of life, and places serious burdens on society. As an emerging rehabilitation training method, brain-computer interface (BCI)-based training can provide closed-loop rehabilitation and is currently being applied to the restoration of upper limb function following stroke. However, because of the differences in the type of experimental clinical research, the quality of the literature varies greatly, and debate around the efficacy of BCI for the rehabilitation of upper limb dysfunction after stroke has continued. OBJECTIVE: We aimed to provide medical evidence-based support for BCI in the treatment of upper limb dysfunction after stroke by conducting a meta-analysis of relevant clinical studies. METHODS: The search terms used to retrieve related articles included "brain-computer interface," "stroke," and "upper extremity." A total of 13 randomized controlled trials involving 258 participants were retrieved from five databases (PubMed, Cochrane Library, Science Direct, MEDLINE, and Web of Science), and RevMan 5.3 was used for data analysis. RESULTS: The total effect size for BCI training on upper limb motor function of post-stroke patients was 0.56 (95% CI: 0.29-0.83). Subgroup analysis indicated that the standard mean differences of BCI training on upper limb motor function of subacute stroke patients and chronic stroke patients were 1.10 (95% CI: 0.20-2.01) and 0.51 (95% CI: 0.09-0.92), respectively (p = 0.24). CONCLUSION: Brain-computer interface training was shown to be effective in promoting upper limb motor function recovery in post-stroke patients, and the effect size was moderate.
OBJECTIVES: Cognitive dysfunction and dementia are common following ischemic stroke. Endothelial nitric oxide synthase (eNOS) has been found to play an important role in neurologic function and cognition. The purpose of the present study was to assess the specific role of eNOS in cognitive performance after stroke. DESIGN: Male wild-type and mice lacking eNOS (eNOS) underwent middle cerebral artery occlusion or sham-surgery. Primary outcomes were repeated measures of neurologic score, limb asymmetry, sensory/motor function, and spatial memory/learning assessed at intervals up to 28 days postsurgery. Group differences in brain microglia activation and infiltration and levels of interferon-gamma were examined. RESULTS: There was no genotype × surgery interaction effect on the pattern of change in neurologic score, limb asymmetry, or sensory motor function across the 28 days postsurgery. In the Morris water maze, eNOS-/- middle cerebral artery occlusion mice displayed learning and memory deficits not evident in wild-type middle cerebral artery occlusion mice. Poorer spatial memory and learning in eNOS-/- middle cerebral artery occlusion mice was associated with a reduction in the number of activated microglia in the striatum on the lesion side and decreased brain tissue levels of interferon-gamma. CONCLUSIONS: This study's data support a role for eNOS in cognitive performance after stroke. This finding may lead to the development of novel interventions to treat poststroke cognitive deficits.
Cerebral Infarction/prevention & control , Cognition/physiology , Infarction, Middle Cerebral Artery/metabolism , Neovascularization, Physiologic/physiology , Nitric Oxide Synthase Type III/metabolism , Animals , Disease Models, Animal , Male , Mice , Mice, Knockout
L-3-n-Butylphthalide (L-NBP) exerts neuroprotective effects in animal models of cerebral ischemia, but its potential benefits in repeated cerebral ischemia-reperfusion (RCIR) injury remain unknown. We investigated the effect of L-NBP on cognitive impairment induced by RCIR in mice. Male C57Bl/6 mice received sham surgery or bilateral common carotid artery occlusion (3 times, 20 min each) and were orally administered preoperative L-NBP (30 mg/kg/day, 7 days), postoperative L-NBP (30 or 60 mg/kg/day, 28 days) or postoperative vehicle (28 days). Learning and memory were assessed by the Morris water maze task and step-down passive avoidance test. Nissl staining was used to identify pathologic changes in the hippocampal CA1 region. The expressions of proteins associated with signaling, apoptosis and autophagy were assessed by quantitative PCR and western blot. RCIR induced deficits in learning and memory that were alleviated by preoperative or postoperative L-NBP administration. Pathologic lesions in the hippocampal CA1 region induced by RCIR were less severe in mice treated with L-NBP. Preoperative or postoperative L-NBP administration in mice receiving RCIR promoted hippocampal expression of phospho-Akt and phospho-mTOR (suggesting activation of Akt/mTOR signaling), increased the Bcl-2/Bax ratio (indicating suppression of apoptosis) and reduced the LC3-II/LC3-I ratio (implying inhibition of autophagy). Preoperative or postoperative L-NBP administration also depressed hippocampal levels of beclin-1 mRNA (indicating suppression of autophagy). These findings suggest that the effect of L-NBP to alleviate learning and memory deficits in mice following RCIR may involve activation of Akt/mTOR signaling and regulation of the expressions of proteins related to apoptosis and autophagy.
Apoptosis/drug effects , Autophagy/drug effects , Benzofurans/pharmacology , Cognitive Dysfunction/drug therapy , Proto-Oncogene Proteins c-akt/drug effects , Animals , Brain Ischemia/pathology , Cognition Disorders/drug therapy , Cognitive Dysfunction/metabolism , Disease Models, Animal , Male , Memory Disorders/drug therapy , Mice, Inbred C57BL , Neuroprotective Agents/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Reperfusion , TOR Serine-Threonine Kinases/drug effects , TOR Serine-Threonine Kinases/metabolism
As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed extract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that l-3-n-butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cerebral repetitive ischemia/reperfusion, and intragastrically administered l-3-n-butylphthalide daily for 28 consecutive days after ischemia/reperfusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of l-3-n-butylphthalide, especially pretreatment with l-3-n-butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of l-3-n-butylphthalide can reduce loss of pyramidal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular dementia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after l-3-n- butylphthalide treatment. Experimental findings demonstrate that l-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.
