Theta burst stimulation for enhancing upper extremity motor functions after stroke: a systematic review of clinical and mechanistic evidence.

This systematic review aimed to evaluate the effects of different theta burst stimulation (TBS) protocols on improving upper extremity motor functions in patients with stroke, their associated modulators of efficacy, and the underlying neural mechanisms. We conducted a meta-analytic review of 29 controlled trials published from January 1, 2000, to August 29, 2023, which investigated the effects of TBS on upper extremity motor, neurophysiological, and neuroimaging outcomes in poststroke patients. TBS significantly improved upper extremity motor impairment (Hedge's g = 0.646, p = 0.003) and functional activity (Hedge's g = 0.500, p < 0.001) compared to controls. Meta-regression revealed a significant relationship between the percentage of patients with subcortical stroke and the effect sizes of motor impairment (p = 0.015) and functional activity (p = 0.018). Subgroup analysis revealed a significant difference in the improvement of upper extremity motor impairment between studies using 600-pulse and 1200-pulse TBS (p = 0.002). Neurophysiological studies have consistently found that intermittent TBS increases ipsilesional corticomotor excitability. However, evidence to support the regional effects of continuous TBS, as well as the remote and network effects of TBS, is still mixed and relatively insufficient. In conclusion, TBS is effective in enhancing poststroke upper extremity motor function. Patients with preserved cortices may respond better to TBS. Novel TBS protocols with a higher dose may lead to superior efficacy compared with the conventional 600-pulse protocol. The mechanisms of poststroke recovery facilitated by TBS can be primarily attributed to the modulation of corticomotor excitability and is possibly caused by the recruitment of corticomotor networks connected to the ipsilesional motor cortex.

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.

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.

Effects of rTMS treatment on global cognitive function in Alzheimer's disease: A systematic review and meta-analysis.

Background: Although repetitive transcranial magnetic stimulation (rTMS) has been extensively studied in patients with Alzheimer's disease (AD), the clinical evidence remains inconsistent. The purpose of this meta-analysis was to evaluate the effects of rTMS on global cognitive function in patients with AD. Methods: An integrated literature search using 4 databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed to identify English language articles published up to October 6, 2021. We pooled Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) scores using a random-effects model via RevMan 5.4 software. We calculated estimates of mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were pre-post treatment changes in global cognition as measured using MMSE and ADAS-Cog immediately after rTMS treatment, and the secondary outcome was duration of cognitive improvement (1-1.5 and ≥3 months). Results: Nine studies with 361 patients were included in this meta-analysis. The results showed that rTMS significantly improved global cognitive function immediately following rTMS treatment [(MD) 1.82, 95% confidence interval (CI) 1.41-2.22, p < 0.00001, MMSE; 2.72, 95% CI, 1.77-3.67, p < 0.00001, ADAS-Cog], and the therapeutic effects persisted for an extended duration (2.20, 95% CI, 0.93-3.47, p =0.0007, MMSE; 1.96, 95% CI, 0.96-2.95, p = 0.0001, ADAS-Cog). Subgroup analyses showed that high frequency rTMS targeted to the left dorsolateral prefrontal cortex (DLPFC) for over 20 sessions induced the greatest cognitive improvement, with effects lasting for more than 1 month after the final treatment. There were no significant differences in dropout rate (p > 0.05) or adverse effect rate (p > 0.05) between the rTMS and control groups. Conclusions: Repetitive TMS is a potentially effective treatment for cognitive impairment in AD that is safe and can induce long-lasting effects. Our results also showed that ADAS-cog and MMSE differed in determination of global cognitive impairment. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO, PROSPERO CRD42022315545.

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.