The Immediate Effects of Intermittent Theta Burst Stimulation of the Cerebellar Vermis on Cerebral Cortical Excitability During a Balance Task in Healthy Individuals: A Pilot Study.

Objective: This pilot study aimed to investigate the immediate effects of single-session intermittent theta-burst stimulation (iTBS) on the cerebellar vermis during a balance task, which could unveil the changes of cerebral cortical excitability in healthy individuals. Subjects: A total of seven right-handed healthy subjects (26.86 ± 5.30 years) were included in this study. Interventions: Each subject received single-session iTBS on cerebellar vermis in a sitting position. Main Measures: Before and after the intervention, all subjects were asked to repeat the balance task of standing on the left leg three times. Each task consisted of 15 s of standing and 20 s of resting. Real-time changes in cerebral cortex oxygen concentrations were monitored with functional near-infrared spectroscopy (fNIRS). During the task, changes in blood oxygen concentration were recorded and converted into the mean HbO2 for statistical analysis. Results: After stimulation, the mean HbO2 in the left SMA (P = 0.029) and right SMA (P = 0.043) significantly increased compared with baseline. However, no significant changes of mean HbO2 were found in the bilateral dorsolateral prefrontal lobe (P > 0.05). Conclusion: Single-session iTBS on the cerebellar vermis in healthy adults can increase the excitability of the cerebral cortex in the bilateral supplementary motor areas during balance tasks. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100048915].

Cerebellar Intermittent Theta-Burst Stimulation Reduces Upper Limb Spasticity After Subacute Stroke: A Randomized Controlled Trial.

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients. Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (Hmax/Mmax ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention. Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in Hmax/Mmax ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group. Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).

Cerebellar Theta Burst Stimulation on Walking Function in Stroke Patients: A Randomized Clinical Trial.

Objectives: The objective of this study was to explore the efficacy of cerebellar intermittent theta burst stimulation (iTBS) on the walking function of stroke patients. Methods: Stroke patients with walking dysfunction aged 25-80 years who had suffered their first unilateral stroke were included. A total of 36 patients [mean (SD) age, 53 (7.93) years; 10 women (28%)] were enrolled in the study. All participants received the same conventional physical therapy, including transfer, balance, and ambulation training, during admission for 50 min per day during 2 weeks (10 sessions). Every session was preceded by 3 min procedure of cerebellar iTBS applyed over the contralesional cerebellum in the intervention group or by a similar sham iTBS in control group. The groups were formed randomly and the baseline characteristics showed no significant difference. The primary outcome measure was Fugl-Meyer Assessment-Lower Extremity scores. Secondary outcomes included walking performance and corticospinal excitability. Measures were performed before the intervention beginning (T0), after the first (T1) and the second (T2) weeks. Results: The Fugl-Meyer Assessment for lower extremity scores slightly improved with time in both groups with no significant difference between the groups and over the time. The walking performance significantly improved with time and between group. Two-way mixed measures ANOVA showed that there was significant interaction between time and group in comfortable walking time (F 2,68 = 6.5242, P = 0.0080, η2 partial = 0.276, ε = 0.641), between-group comparisons revealed significant differences at T1 (P = 0.0072) and T2 (P = 0.0133). The statistical analysis of maximum walking time showed that there was significant interaction between time and groups (F 2,68 = 5.4354, P = 0.0115, η2 partial = 0.198, ε = 0.734). Compared with T0, the differences of maximum walking time between the two groups at T1 (P = 0.0227) and T2 (P = 0.0127) were statistically significant. However, both the Timed up and go test and functional ambulation category scale did not yield significant differences between groups (P > 0.05). Conclusion: Our results revealed that applying iTBS over the contralesional cerebellum paired with physical therapy could improve walking performance in patients after stroke, implying that cerebellar iTBS intervention may be a noninvasive strategy to promote walking function in these patients. This study was registered at ChiCTR, number ChiCTR1900026450.

Extremely low frequency electromagnetic fields promote cognitive function and hippocampal neurogenesis of rats with cerebral ischemia.

Extremely low frequency electromagnetic fields (ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood. In this study, we established rat models of middle cerebral artery occlusion/reperfusion. One day after modeling, a group of rats were treated with ELF-EMF (50 Hz, 1 mT) for 2 hours daily on 28 successive days. Our results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated rats. The number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated rats. The number of BrdU+/NeuN+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated rats. Up-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated rats. These findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling pathway. The study was approved by the Institutional Ethics Committee of Sichuan University, China (approval No. 2019255A) on March 5, 2019.

Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke: a systematic review and network meta-analysis.

Transcranial magnetic stimulation, a type of noninvasive brain stimulation, has become an ancillary therapy for motor function rehabilitation. Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation (rTMS) on motor function in stroke patients. There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke. The MEDLINE, Embase, Cochrane Library, ISI Science Citation Index, Physiotherapy Evidence Database, China National Knowledge Infrastructure Library, and ClinicalTrials.gov databases were searched. Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke, published from inception to November 28, 2019, were included. Standard pairwise meta-analysis was conducted using R version 3.6.1 with the "meta" package. Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions. Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation. Network meta-analysis results of five randomized controlled trials demonstrated that high-frequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency rTMS or sham stimulation. These findings suggest that rTMS can improve motor function in patients with stroke, and that low-frequency rTMS mainly affects motor function, whereas high-frequency rTMS increases the amplitudes of motor evoked potentials. More high-quality randomized controlled trials are needed to validate this conclusion. The work was registered in PROSPERO (registration No. CRD42020147055) on April 28, 2020.

Cerebellar Theta-Burst Stimulation Combined With Physiotherapy in Subacute and Chronic Stroke Patients: A Pilot Randomized Controlled Trial.

BACKGROUND: Intermittent theta-burst stimulation (iTBS) has been suggested to improve poststroke rehabilitation. The cerebellum is considered crucial for motor control. However, the effects of cerebellar iTBS with routine physical therapy on balance and motor recovery in subacute and chronic stroke patients have not been explored. OBJECTIVE: To measure the short-term effects of cerebellar iTBS with physiotherapy on the balance and functional outcomes in subacute and chronic stroke patients with hemiparesis. METHODS: Thirty hemiparetic patients were recruited for this randomized, double-blinded, sham-controlled trial, and randomized into either the treatment or sham group. Both groups participated in physiotherapy 5 times per week for 2 weeks, and cerebellar iTBS or sham iTBS was performed daily, immediately before physiotherapy. The primary outcome was the Berg balance scale (BBS) score. Secondary outcomes included the trunk impairment scale (TIS) score, Fugl-Meyer assessment scale score for lower extremities (FMA-LE), Barthel index (BI), and corticospinal excitability, as measured by transcranial magnetic stimulation. The outcomes were measured before and 1 week and 2 weeks after the intervention. RESULTS: Compared with those at baseline, significant increases were identified in all clinical scores (BBS, TIS, FMA-LE, and BI) in both groups after the 2-week intervention. The BBS and TIS scores improved more in the iTBS group than in the sham group. CONCLUSIONS: Cerebellar iTBS with physiotherapy promotes balance and motor recovery in poststroke patients. Therefore, this method can be used in low-cost, fast, and efficient protocols for stroke rehabilitation (Chinese Clinical Trial Registry: ChiCTR1900026450).

Effect of Repetitive Transcranial Magnetic Stimulation on Gait and Freezing of Gait in Parkinson Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: The purpose of this review was to systematically assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) intervention on gait in individuals with Parkinson disease (PD). DATA SOURCES: We searched online electronic databases up to March 28, 2019, including MEDLINE, Embase, the Cochrane Library, and so on. STUDY SELECTION: The inclusion criteria for this review were randomized controlled trials (RCTs), exploring the effect of rTMS in patients diagnosed with idiopathic PD. DATA EXTRACTION: Data extraction was performed independently by 2 reviewers based on predefined criteria and the methodologic quality of included studies was quantified by the Physiotherapy Evidence Database scale. The outcome measure was walking performance, including walking time (short term and long term), Timed Up and Go (TUG) test, and so on. DATA SYNTHESIS: Among 14 eligible studies, including 298 participants (mean age ± SD [y], 63.24±9.71; 191 [64%] men) were analyzed in this meta-analysis. Walking time was improved with rTMS compared with sham rTMS (standardized mean difference [SMD] -0.30; 95% confidence interval [CI], -0.57 to -0.03; P=.03). The score for the freezing of gait questionnaire did not differ significantly between rTMS and no intervention. Four studies compared TUG between the 2 treatment groups and no significant differences were found between the rTMS and control group (SMD -0.45; 95% CI, -1.32 to 0.41; P=.30). During the off-state, there were no significant differences in estimated effect sizes (SMD=-0.29; 95% CI, -0.79 to 0.21; P=.25), which is significantly different in on-state (SMD -0.98; 95% CI, -1.78 to -0.18; P=.02) evaluation. CONCLUSIONS: The results of the meta-analysis propose the favorable effect of rTMS on walking performance in the short term but not over the long term in individuals with PD.