Vagus nerve stimulation paired with rehabilitation for motor function, mental health and activities of daily living after stroke: a systematic review and meta-analysis.

OBJECTIVE: Vagus nerve stimulation (VNS) plus rehabilitation (Rehab) has shown a potential effect on recovery with a stroke. We systematically synthesised studies examining VNS+Rehab for improving motor function, mental health and activities of daily living (ADL) postintervention and at the end of follow-up in patients with a stroke. METHODS: The search was performed in electronic databases EMBASE, Medline, EBSCO, Cochrane Library, PubMed, PsycINFO, CINAHL, CNKI, and WANFANG and three clinical trial registries from inception to February 2022. Randomised controlled trials (RCTs) applied VNS+Rehab in stroke were included. RESULTS: Seven RCTs involving 263 (analysed) participants was included. The effect size of VNS+Rehab over Rehab for motor function was medium postintervention (g=0.432; 95% CI 0.186 to 0.678) and large at the end of follow-up (g=0.840; 95% CI 0.288 to 1.392). No difference was found in the effect of VNS+Rehab over traditional rehabilitation for ADL, mental health or safety outcomes. Subgroup analyses revealed larger effects for patients received taVNS (transcutaneous auricular VNS) devices (at acute/subacute phase of stroke, with lower VNS stimulation frequency or pluses per session, greater VNS on-off time or sessions, higher VNS intervention weekly frequency). CONCLUSION: The results suggest VNS+Rehab showed better motor function outcomes in patients after stroke, while no better than Rehab on mental health or ADL. Combinations of phase of stroke, specific parameters of VNS and VNS intervention frequency are key modulators of VNS effects. TRIAL REGISTRATION NUMBER: CRD42022310194.

Brain activation of the PFC during dual-task walking in stroke patients: A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Background: Dual-task walking is a good paradigm to measure the walking ability of stroke patients in daily life. It allows for a better observation of brain activation under dual-task walking to assess the impact of the different tasks on the patient when combining with functional near-infrared spectroscopy (fNIRS). This review aims to summarize the cortical change of the prefrontal cortex (PFC) detected in single-task and dual-task walking in stroke patients. Methods: Six databases (Medline, Embase, PubMed, Web of Science, CINAHL, and Cochrane Library) were systematically searched for relevant studies, from inception to August 2022. Studies that measured the brain activation of single-task and dual-task walking in stroke patients were included. The main outcome of the study was PFC activity measured using fNIRS. In addition, a subgroup analysis was also performed for study characteristics based on HbO to analyze the different effects of disease duration and the type of dual task. Results: Ten articles were included in the final review, and nine articles were included in the quantitative meta-analysis. The primary analysis showed more significant PFC activation in stroke patients performing dual-task walking than single-task walking (SMD = 0.340, P = 0.02, I 2 = 7.853%, 95% CI = 0.054-0.626). The secondary analysis showed a significant difference in PFC activation when performing dual-task walking and single-task walking in chronic patients (SMD = 0.369, P = 0.038, I 2 = 13.692%, 95% CI = 0.020-0.717), but not in subacute patients (SMD = 0.203, P = 0.419, I 2 = 0%, 95% CI = -0.289-0.696). In addition, performing walking combining serial subtraction (SMD = 0.516, P < 0.001, I 2 = 0%, 95% CI = 0.239-0.794), obstacle crossing (SMD = 0.564, P = 0.002, I 2 = 0%, 95% CI = 0.205-0.903), or a verbal task (SMD = 0.654, P = 0.009, I 2 = 0%, 95% CI = 0.164-1.137) had more PFC activation than single-task walking, while performing the n-back task did not show significant differentiation (SMD = 0.203, P = 0.419, I 2 = 0%, 95% CI = -0.289-0.696). Conclusions: Different dual-task paradigms produce different levels of dual-task interference in stroke patients with different disease durations, and it is important to choose the matching dual-task type in relation to the walking ability and cognitive ability of the patient, in order to better improve the assessment and training effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022356699.

Resting-state functional connectivity for determining outcomes in upper extremity function after stroke: A functional near-infrared spectroscopy study.

Objective: Functional near-infrared spectroscopy (fNIRS) is a non-invasive and promising tool to map the brain functional networks in stroke recovery. Our study mainly aimed to use fNIRS to detect the different patterns of resting-state functional connectivity (RSFC) in subacute stroke patients with different degrees of upper extremity motor impairment defined by Fugl-Meyer motor assessment of upper extremity (FMA-UE). The second aim was to investigate the association between FMA-UE scores and fNIRS-RSFC among different regions of interest (ROIs) in stroke patients. Methods: Forty-nine subacute (2 weeks-6 months) stroke patients with subcortical lesions were enrolled and were classified into three groups based on FMA-UE scores: mild impairment (n = 17), moderate impairment (n = 13), and severe impairment (n = 19). All patients received FMA-UE assessment and 10-min resting-state fNIRS monitoring. The fNIRS signals were recorded over seven ROIs: bilateral dorsolateral prefrontal cortex (DLPFC), middle prefrontal cortex (MPFC), bilateral primary motor cortex (M1), and bilateral primary somatosensory cortex (S1). Functional connectivity (FC) was calculated by correlation coefficients between each channel and each ROI pair. To reveal the comprehensive differences in FC among three groups, we compared FC on the group level and ROI level. In addition, to determine the associations between FMA-UE scores and RSFC among different ROIs, Spearman's correlation analyses were performed with a significance threshold of p < 0.05. For easy comparison, we defined the left hemisphere as the ipsilesional hemisphere and flipped the lesional right hemisphere in MATLAB R2013b. Results: For the group-level comparison, the one-way ANOVA and post-hoc t-tests (mild vs. moderate; mild vs. severe; moderate vs. severe) showed that there was a significant difference among three groups (F = 3.42, p = 0.04) and the group-averaged FC in the mild group (0.64 ± 0.14) was significantly higher than that in the severe group (0.53 ± 0.14, p = 0.013). However, there were no significant differences between the mild and moderate group (MD ± SE = 0.05 ± 0.05, p = 0.35) and between the moderate and severe group (MD ± SE = 0.07 ± 0.05, p = 0.16). For the ROI-level comparison, the severe group had significantly lower FC of ipsilesional DLPFC-ipsilesional M1 [p = 0.015, false discovery rate (FDR)-corrected] and ipsilesional DLPFC-contralesional M1 (p = 0.035, FDR-corrected) than those in the mild group. Moreover, the result of Spearman's correlation analyses showed that there were significant correlations between FMA-UE scores and FC of the ipsilesional DLPFC-ipsilesional M1 (r = 0.430, p = 0.002), ipsilesional DLPFC-contralesional M1 (r = 0.388, p = 0.006), ipsilesional DLPFC-MPFC (r = 0.365, p = 0.01), and ipsilesional DLPFC-contralesional DLPFC (r = 0.330, p = 0.021). Conclusion: Our findings indicate that different degrees of post-stroke upper extremity impairment reflect different RSFC patterns, mainly in the connection between DLPFC and bilateral M1. The association between FMA-UE scores and the FC of ipsilesional DLPFC-associated ROIs suggests that the ipsilesional DLPFC may play an important role in motor-related plasticity. These findings can help us better understand the neurophysiological mechanisms of upper extremity motor impairment and recovery in subacute stroke patients from different perspectives. Furthermore, it sheds light on the ipsilesional DLPFC-bilateral M1 as a possible neuromodulation target.

Corrigendum: Effects of virtual reality-based intervention on cognition, motor function, mood, and activities of daily living in patients with chronic stroke: A systematic review and meta-analysis of randomized controlled trials.

[This corrects the article DOI: 10.3389/fnagi.2021.766525.].

Age-Related Differences in Stepping Reactions to a Balance Perturbation: A Functional Near-Infrared Spectroscopy and Surface Electromyography Study.

We sought to investigate age-related differences in stepping reactions to a sudden balance perturbation, focusing on muscle activity and cortical activation. A total of 18 older healthy adults (older group, OG) and 16 young healthy adults (young group, YG) were recruited into this study. A cable-pull instrument was used to induce a forward perturbation at the waist level among participants, who were required to take the right step to maintain their postural balance. The seven right lower-limb muscle activities during periods of compensatory postural adjustments (CPAs) were recorded by surface electromyography. At the same time, the signals of channels located in the prefrontal, temporal and parietal lobes were recorded by functional near-infrared spectroscopy (fNIRS) during the whole process. Integral electromyograms of the right peroneus muscle, gluteus medius, and lateral gastrocnemius muscles showed greater activity for the OG in the CPA periods. Two channels belonging to the right pre-frontal (PFC) and pre-motor cortex (PMC) revealed lower activation in the OG compared with the YG. These findings can help us to better understand the differences at the peripheral and central levels and may provide some suggestions for future neuromodulation techniques and other clinical treatments.

Contralaterally controlled neuromuscular electrical stimulation-induced changes in functional connectivity in patients with stroke assessed using functional near-infrared spectroscopy.

Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is an innovative therapy in stroke rehabilitation which has been verified in clinical studies. However, the underlying mechanism of CCNMES are yet to be comprehensively revealed. The main purpose of this study was to apply functional near-infrared spectroscopy (fNIRS) to compare CCNMES-related changes in functional connectivity (FC) within a cortical network after stroke with those induced by neuromuscular electrical stimulation (NMES) when performing wrist extension with hemiplegic upper extremity. Thirty-one stroke patients with right hemisphere lesion were randomly assigned to CCNMES (n = 16) or NMES (n = 15) groups. Patients in both groups received two tasks: 10-min rest and 10-min electrical stimulation task. In each task, the cerebral oxygenation signals in the prefrontal cortex (PFC), bilateral primary motor cortex (M1), and primary sensory cortex (S1) were measured by a 35-channel fNIRS. Compared with NMES, FC between ipsilesional M1 and contralesional M1/S1 were significantly strengthened during CCNMES. Additionally, significantly higher coupling strengths between ipsilesional PFC and contralesional M1/S1 were observed in the CCNMES group. Our findings suggest that CCNMES promotes the regulatory functions of ipsilesional prefrontal and motor areas as well as contralesional sensorimotor areas within the functional network in patients with stroke.

Effects of Virtual Reality Intervention on Cognition and Motor Function in Older Adults With Mild Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis.

Background: Virtual reality (VR) intervention is an innovative and efficient rehabilitative tool for patients affected by stroke, Parkinson's disease, and other neurological disorders. This meta-analysis aims to evaluate the effects of VR intervention on cognition and motor function in older adults with mild cognitive impairment or dementia. Methods: Seven databases were systematically searched for relevant articles published from inception to April 2020. Randomized controlled trials examining VR intervention in adults with mild cognitive impairment or dementia aged >60 years were included. The primary outcome of the study was cognitive function, including overall cognition, global cognition, attention, executive function, memory, and visuospatial ability. The secondary outcome was motor function, consisting of overall motor function, balance, and gait. A subgroup analysis was also performed based on study characteristics to identify the potential factors for heterogeneity. Results: Eleven studies including 359 participants were included for final analysis. Primary analysis showed a significant moderate positive effect size (ES) of VR on overall cognition (g = 0.45; 95% confidence interval (CI) = 0.31-0.59; P < 0.001), attention/execution (g = 0.49; 95% CI = 0.26-0.72; P < 0.001), memory (g = 0.57; 95% CI = 0.29-0.85; P < 0.001), and global cognition (g = 0.32; 95% CI = 0.06-0.58; P = 0.02). Secondary analysis showed a significant small positive ES on overall motor function (g = 0.28; 95% CI = 0.05-0.51; P = 0.018). The ES on balance (g = 0.43; 95% CI = 0.06-0.80; P = 0.02) was significant and moderate. The ES on visuospatial ability and gait was not significant. In the subgroup analysis, heterogeneity was detected in type of immersion and population diagnosis. Conclusions: VR intervention is a beneficial non-pharmacological approach to improve cognitive and motor function in older adults with mild cognitive impairment or dementia, especially in attention/execution, memory, global cognition, and balance. VR intervention does not show superiority on visuospatial ability and gait performance.

Effects of Virtual Reality-Based Intervention on Cognition, Motor Function, Mood, and Activities of Daily Living in Patients With Chronic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy of virtual reality (VR)-based intervention for improving cognition in patients with the chronic stage of stroke is controversial. The aims of this meta-analysis were to evaluate the effect of VR-based training combined with traditional rehabilitation on cognition, motor function, mood, and activities of daily living (ADL) after chronic stroke. Methods: The search was performed in the Cochrane Library (CENTRAL), EBSCO, EMBASE, Medline (OVID), Web of Science databases, PubMed, CINAHL Ovid, and Scopus from inception to May 31, 2021. All included studies were randomized controlled trials (RCTs) examining VR-based intervention combined with traditional rehabilitation for chronic stroke. The main outcomes of this study were cognition, including overall cognition (combined with all cognitive measurement results), global cognition (measured by the Montreal Cognitive Assessment, MoCA, and/or Mini-Mental State Examination, MMSE), and attention/execution. The additional outcomes were motor function, mood, and ADL. Subgroup analyses were conducted to verify the potential factors for heterogeneity. Results: Six RCTs including 209 participants were included for systematic review, and five studies of 177 participants were included in meta-analyses. Main outcome analyses showed large and significant effect size (ES) of VR-based training on overall cognition (g = 0.642; 95% CI = 0.134-1.149; and P = 0.013) and attention/execution (g = 0.695; 95% CI = 0.052-1.339; and P = 0.034). Non-significant result was found for VR-based intervention on global cognition (g = 0.553; 95% CI = -0.273-1.379; and P = 0.189). Additional outcome analyses showed no superiority of VR-based intervention over traditional rehabilitation on motor function and ADL. The ES of VR-based intervention on mood (g = 1.421; 95% CI = 0.448-2.393; and P = 0.004) was large and significant. In the subgroup analysis, large effects for higher daily intensity, higher weekly frequency, or greater dose of VR intervention were found. Conclusion: Our findings indicate that VR-based intervention combined with traditional rehabilitation showed better outcomes for overall cognition, attention/execution, and depressive mood in individuals with chronic stroke. However, VR-based training combined with traditional rehabilitation showed a non-significant effect for global cognition, motor function, and ADL in individuals with chronic stroke.