Long COVID patients' brain activation is suppressed during walking and severer symptoms lead to stronger suppression.

This research aims to study the factors contributing to Long COVID and its effects on motor and cognitive brain regions using population surveys and brain imaging. The goal is to provide new insights into the neurological effects of the illness and establish a basis for addressing neuropsychiatric symptoms associated with Long COVID. Study 1 used a cross-sectional design to collect data on demographic characteristics and factors related to Long COVID symptoms in 551 participants. In Study 2, subjects with Long COVID and SARS-CoV-2 uninfected individuals underwent fNIRS monitoring while performing various tasks. Study 1 found that gender, age, BMI, Days since the first SARS-CoV-2 infection, and Symptoms at first onset influenced Long COVID performance. Study 2 demonstrated that individuals in the SARS-CoV-2 uninfected group exhibited greater activation of cognitive function-related brain regions than those in the Long COVID group while performing a level walking task. Furthermore, individuals in the Long COVID group without functional impairment displayed higher activation of brain regions associated with motor function during a weight-bearing walking task than those with functional impairment. Among individuals with Long COVID, those with mild symptoms at onset exhibited increased activation of brain regions linked to motor and cognitive function relative to those with moderate symptoms at onset. Individuals with Long COVID exhibited decreased activation in brain regions associated with cognitive and motor function compared to SARS-CoV-2 uninfected individuals. Moreover, those with more severe initial symptoms or functional impairment displayed heightened inhibition in these brain regions.

Identifying biomarkers related to motor function in chronic stroke: A fNIRS and TMS study.

BACKGROUND: Upper limb motor impairment commonly occurs after stroke, impairing quality of life. Brain network reorganization likely differs between subgroups with differing impairment severity. This study explored differences in functional connectivity (FC) and corticospinal tract (CST) integrity between patients with mild/moderate versus severe hemiplegia poststroke to clarify the neural correlates underlying motor deficits. METHOD: Sixty chronic stroke patients with upper limb motor impairment were categorized into mild/moderate and severe groups based on Fugl-Meyer scores. Resting-state FC was assessed using functional near-infrared spectroscopy (fNIRS) to compare connectivity patterns between groups across motor regions. CST integrity was evaluated by inducing motor evoked potentials (MEP) via transcranial magnetic stimulation. RESULTS: Compared to the mild/moderate group, the severe group exhibited heightened premotor cortex-primary motor cortex (PMC-M1) connectivity (t = 4.56, p < 0.01). Absence of MEP was also more frequent in the severe group (χ2 = 12.31, p = 0.01). Bayesian models effectively distinguished subgroups and identified the PMC-M1 connection as highly contributory (accuracy = 91.30%, area under the receiver operating characteristic curve [AUC] = 0.86). CONCLUSION: Distinct patterns of connectivity and corticospinal integrity exist between stroke subgroups with differing impairments. Strengthened connectivity potentially indicates recruitment of additional motor resources to compensate for damage. These findings elucidate the neural correlates underlying motor deficits poststroke and could guide personalized, network-based therapies targeting predictive biomarkers to improve rehabilitation outcomes.

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.

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.

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.

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.

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.