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.

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective way to stimulate changes in structural and functional plasticity, which is a part of learning and memory. However, to our knowledge, rTMS-induced specific activity and neural plasticity in different brain regions that affect cognition are not fully understood; nor are its mechanisms. Therefore, we aimed to investigate rTMS-induced cognition-related neural plasticity changes and their mechanisms in different brain regions.Methods: A total of 30 healthy adult rats were randomly divided into the control group and the rTMS group (n = 15 rats per group). The rats in the control and the rTMS group received either 4 weeks of sham or high-frequency rTMS (HF-rTMS) over the prefrontal cortex (PFC). Cognitive function was detected by Morris water maze. Functional imaging was acquired by resting-state functional magnetic resonance imaging (rs-fMRI) before and after rTMS. The protein expressions of BDNF, TrkB, p-Akt, Akt, NR1, NR2A, and NR2B in the PFC, hippocampus, and primary motor cortex (M1) were detected by Western blot following rTMS.Results: After 4 weeks of rTMS, the cognitive ability of healthy rats who underwent rTMS showed a small but significant behavioral improvement in spatial episodic learning and memory performance. Compared with the pre-rTMS or the control group, rats in the rTMS group showed increased regional homogeneity (ReHo) in multiple brain regions in the interoceptive/default mode network (DMN) and cortico-striatal-thalamic network, specifically the bilateral PFC, bilateral hippocampus, and the left M1. Western blot analyses showed that rTMS led to a significant increase in the expressions of N-methyl-D-aspartic acid (NMDA) receptors, including NR1, NR2A, and NR2B in the PFC, hippocampus, and M1, as well as an upregulation of BDNF, TrkB, and p-Akt in these three brain regions. In addition, the expression of NR1 in these three brain regions correlated with rTMS-induced cognitive improvement.Conclusion: Overall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity.

The brain-computer interface-based soft robotic glove (BCI-SRG) holds promise for upper limb rehabilitation in subacute stroke patients, yet its efficacy and neural mechanisms are unclear. This study aimed to investigate the therapeutic effects and neural mechanisms of BCI-SRGs by functional near-infrared spectroscopy (fNIRS). Forty subacute stroke patients with left-sided hemiparesis were randomized into the BCI-SRG (n = 20) and soft robotic glove (SRG) (n = 20) groups. Both groups received 20 sessions of intervention over 4 weeks in addition to conventional rehabilitation. The BCI-SRG group was trained using a soft robotic glove controlled by a brain‒computer interface (BCI), whereas the SRG group used the same soft robotic glove without BCI control. The clinical outcomes included the Action Research Arm Test (ARAT), the Fugl-Meyer Assessment Upper Limb (FMA-UL), and Modified Barthel Index (MBI) scores. In addition, fNIRS was used to explore potential clinical brain mechanisms. All assessments were performed before treatment and after 4 weeks of treatment. A total of 39 participants completed the intervention and clinical assessments (BCI-SRG: n = 20; SRG: n = 19). Compared with the SRG group, the BCI-SRG group showed greater improvements in the ARAT (Z = − 2.139, P = 0.032) and FMA-UL (Z = − 2.588, P = 0.010), with no notable difference in the MBI (Z = − 1.843, P = 0.065). fNIRS data were available for 35 participants (BCI-SRG: n = 17; SRG: n = 18). Within-group comparisons revealed significant postintervention increases in cortical activation in the bilateral sensorimotor cortex (SMC) and medial prefrontal cortex (MPFC) in the BCI-SRG group, whereas no significant changes were observed in the SRG group. Between-group comparisons further revealed significantly greater changes in HbO concentrations in the BCI-SRG group than in the SRG group across the same cortical regions. Moreover, changes in prefrontal activation (post–pre) were positively correlated with improvements in ARAT scores, with significant correlations observed in the left dorsal lateral prefrontal cortex (LDLPFC) (Ch9, r = 0.592, P = 0.012; Ch25, r = 0.488, P = 0.047) and right dorsal lateral prefrontal cortex (RDLPFC) (Ch19, r = 0.671, P = 0.003). BCI-SRG training significantly enhances upper limb function and facilitates bilateral motor and sensory cortical reorganization. PFC activation is correlated with functional improvements, suggesting a potential mechanism underlying the benefits of rehabilitation in stroke patients. This trial was registered under the Chinese Clinical Trial Registry (ChiCTR2400082786) and was retrospectively registered on April 8, 2024.

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.

Objective: To investigate the effectiveness of high-intensity laser therapy (HILT) on chronic refractory wounds. Design Randomised controlled trial. Setting: The outpatient wound care department of the Affiliated Jiangsu Shengze Hospital of Nanjing Medical University from August 2019 to June 2020. Participants: Sixty patients were enrolled in this study and were randomised into control (n=30) and treatment (n=30) groups. Interventions and outcome measures: The control group was treated only with conventional wound dressing, whereas the treatment group received irradiation with HILT in addition to standard wound care, such as debridement, wound irrigation with normal saline solution and application of dressing and sterile gauze. Patient scores on the Bates-Jensen Wound Assessment Tool (BWAT) and Pressure Ulcer Scale for Healing (PUSH) were evaluated before and after 1, 2 and 3 weeks of treatment. Results: One patient was excluded from the control group, and a total of 59 subjects completed the trial. The BWAT scores significantly decreased in the treatment group compared with the control group at the end of 3-week treatment (difference=−3.6; 95% CI −6.3 to–0.8; p<0.01). Similarly, patients in treatment group showed a significant reduction of PUSH scores compared with the control group (difference=−5.3; 95% CI −8.1 to –2.6; p<0.01). Conclusions: The therapeutic effects of HILT on chronic refractory wounds are significant and far more superior to those of conventional wound dressing. Trial registration number: Chinese Clinical Trial Registry; ChiCTR1900023157. URL: http://www.chictr.org.cn/showproj.aspx?proj=38866

Previous research has demonstrated that regular exercise modulates motor cortical plasticity and cognitive function, but the influence of short-term high-intensity interval training (HIIT) remains unclear. In the present study, the effect of short-term HIIT on neuroplasticity and executive function was assessed in 32 sedentary females. Half of the participants undertook 2 weeks of HIIT. Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure motor cortical plasticity via short intracortical inhibition (SICI) and intracortical facilitation (ICF). We further adapted the Stroop task using functional near-infrared spectroscopy (fNIRS) to evaluate executive function in the participants. The results indicated that, compared with the control group, the HIIT group exhibited decreased ICF. In the Stroop task, the HIIT group displayed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left orbitofrontal cortex (OFC) even though no significant difference in task performance was observed. These findings indicate that short-term HIIT may modulate motor cortical plasticity and executive function at the neural level.