An update on the effects of cerebellar transcranial magnetic stimulation on cognitive function.

BackgroundThe application of cerebellar transcranial magnetic stimulation (TMS) in stroke patients has received increasing attention due to its neuromodulation mechanisms. However, studies on the effect and safety of cerebellar TMS to improve balance capacity and activity of daily living (ADL) for stroke patients are limited. This systematic review and meta-analysis aimed to investigate the effect and safety of cerebellar TMS on balance capacity and ADL in stroke patients.MethodA systematic search of seven electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang and Chinese Scientific Journal) were conducted from their inception to October 20, 2023. The randomized controlled trials (RCTs) of cerebellar TMS on balance capacity and/or ADL in stroke patients were enrolled. The quality of included studies were assessed by Physiotherapy Evidence Database (PEDro) scale.ResultsA total of 13 studies involving 542 participants were eligible. The pooled results from 8 studies with 357 participants showed that cerebellar TMS could significantly improve the post-intervention Berg balance scale (BBS) score (MD = 4.24, 95%CI = 2.19 to 6.29, P < 0.00001; heterogeneity, I2 = 74%, P = 0.0003). The pooled results from 4 studies with 173 participants showed that cerebellar TMS could significantly improve the post-intervention Time Up and Go (TUG) (MD=-1.51, 95%CI=-2.8 to -0.22, P = 0.02; heterogeneity, I2 = 0%, P = 0.41). The pooled results from 6 studies with 280 participants showed that cerebellar TMS could significantly improve the post-intervention ADL (MD = 7.75, 95%CI = 4.33 to 11.17, P < 0.00001; heterogeneity, I2 = 56%, P = 0.04). The subgroup analysis showed that cerebellar TMS could improve BBS post-intervention and ADL post-intervention for both subacute and chronic stage stroke patients. Cerebellar high frequency TMS could improve BBS post-intervention and ADL post-intervention. Cerebellar TMS could still improve BBS post-intervention and ADL post-intervention despite of different cerebellar TMS sessions (less and more than 10 TMS sessions), different total cerebellar TMS pulse per week (less and more than 4500 pulse/week), and different cerebellar TMS modes (repetitive TMS and Theta Burst Stimulation). None of the studies reported severe adverse events except mild side effects in three studies.ConclusionsCerebellar TMS is an effective and safe technique for improving balance capacity and ADL in stroke patients. Further larger-sample, higher-quality, and longer follow-up RCTs are needed to explore the more reliable evidence of cerebellar TMS in the balance capacity and ADL, and clarify potential mechanisms.

This review delves into the emerging field of cerebellar Transcranial Magnetic Stimulation (TMS) in the rehabilitation of limb dysfunction following a stroke. It synthesizes findings from randomized controlled trials and case studies, examining the efficacy, safety, and underlying mechanisms of cerebellar TMS. The review outlines advancements in TMS technologies, such as low-frequency repetitive TMS, intermittent Theta Burst Stimulation, and Cerebello-Motor Paired Associative Stimulation, and their integration with physiotherapy. The role of the cerebellum in motor control, the theoretical underpinnings of cerebellar stimulation on motor cortex excitability, and the indirect effects on cognition and motor learning are explored. Additionally, the review discusses current challenges, including coil types, safety, and optimal timing and modes of stimulation, and suggests future research directions. This comprehensive analysis highlights cerebellar TMS as a promising, though complex, approach in stroke rehabilitation, offering insights for its clinical optimization.

Previously, we reported that cerebellar transcranial magnetic stimulation (C-TMS) facilitates spinal motoneuronal excitability in resting humans. In this study, we aimed to characterize the descending pathway that is responsible for the C-TMS-associated cerebellar spinal facilitation. We evaluated the effect of C-TMS on ipsilateral soleus Ia presynaptic inhibition (PSI) and reciprocal inhibition (RI) because the vestibulospinal and reticulospinal tracts project from the cerebellum to mediate spinal motoneurons via interneurons associated with PSI. PSI and RI were measured with a soleus H-reflex test following operant conditioning using electrical stimulation of the common peroneal nerve. C-TMS was delivered before test tibial nerve stimulation with conditioning-test interstimulus intervals of 110 ms. C-TMS did not generate motor-evoked potentials, and it did not increase electromyography activity in the ipsilateral soleus muscle, indicating that C-TMS does not directly activate the corticospinal tract and motoneurons. However, C-TMS facilitated the ipsilateral soleus H-reflex and reduced the amount of soleus Ia PSI, but not RI. These findings indicate that C-TMS may facilitate the excitability of the spinal motoneuron pool via the vestibulospinal or reticulospinal tracts associated with PSI. Cerebellar spinal facilitation may be useful for assessing the functional connectivity of the cerebellum and vestibular nuclei or reticular formation.

This study aimed to investigate the potential therapeutic effects of cerebellar transcranial magnetic stimulation (TMS) on balance and limb motor impairments in stroke patients. A meta-analysis of randomized controlled trials was conducted to assess the effects of cerebellar TMS on balance and motor impairments in stroke patients. Additionally, an activation likelihood estimation (ALE) meta-analysis was performed on resting-state functional magnetic resonance imaging (fMRI) studies to compare spontaneous neural activity differences between stroke patients and healthy controls using measures including the amplitude of low frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). The analysis included 10 cerebellar TMS studies and 18 fMRI studies. Cerebellar TMS treatment demonstrated significant improvements in the Berg Balance Scale score (p < 0.0001) and the Fugl-Meyer Assessment lower extremity score (p < 0.0001) compared to the control group in stroke patients. Additionally, spontaneous neural activity alterations were identified in motor-related regions after stroke, including the precentral gyrus, putamen, thalamus, and paracentral lobule. Cerebellar TMS shows promise as a therapeutic intervention to enhance balance and lower limb motor function in stroke patients. It is easy for clinical application and addresses the limitations of insufficient direct stimulation depth on the leg area of the cortex. However, further research combining neuroimaging outcomes with clinical measurements is necessary to validate these findings.

Background: In recent years, the potential of non-invasive brain stimulation (NIBS) for therapeutic effects on cognitive functions has been explored for populations with stroke. There are various NIBS methods depending on the stimulation site and stimulation parameters. However, there is no systematic NIBS review of post-stroke cognitive impairment with a focus on stimulation sites and stimulation parameters. The purpose of this study is to conduct a systematic review and meta-analysis on effectiveness and safety of NIBS for cognitive impairment after a stroke to obtain new insights. This study was prospectively registered with the PROSPERO database of systematic reviews (CRD42020183298). Methods: All English articles from MEDLINE, Scopus, CINAHL, Embase, PsycINFO, and CENTRAL were searched from inception up to 31 December 2020. Randomized and prospective controlled trials were included for the analysis. Studies with at least five individuals post-stroke, whereby at least five sessions of NIBS were provided and using standardized neuropsychological measurement of cognition, were included. We assessed the methodological quality of selected studies as described in the Physiotherapy Evidence Database (PEDro) scoring system. Results: A total of 10 studies met eligibility criteria. Six studies used repetitive transcranial magnetic stimulation (rTMS) and four studies used transcranial direct current stimulation (tDCS). The pooled sample size was 221 and 196 individuals who received rTMS and tDCS respectively. Eight studies combined general rehabilitation, cognitive training, or additional therapy with NIBS. In rTMS studies, target symptoms included global cognition (n = 4), attention (n = 3), memory (n = 4), working memory (WM) (n = 3), and executive function (n = 2). Five studies selected the left dorsolateral prefrontal cortex (DPLFC) as the stimulation target. One rTMS study selected the right DLPFC as the inhibitory stimulation target. Four of six studies showed significant improvement. In tDCS studies, target symptoms included global cognition (n = 2), attention (n = 4), memory (n = 2) and WM (n = 2). Three studies selected the frontal area as the stimulation target. All studies showed significant improvement. In the meta-analysis, rTMS showed a significant effect on attention, memory, WM and global cognition classified by neuropsychological tests. On the other hand, tDCS had no significant effect. Conclusions: In post-stroke patients with deficits in cognitive function, including attention, memory, and WM, NIBS shows promising positive effects. However, this effect is limited, suggesting that further studies are needed with more precision in stimulation sites and stimulation parameters. Future studies using advanced neurophysiological and neuroimaging tools to allow for a network-based approach to treat cognitive symptoms post-stroke with NIBS are warranted.

Introduction: Cerebellar transcranial magnetic stimulation (TMS) has emerged as a promising neuromodulatory intervention for addressing motor, cognitive, and socio-affective deficits across a range of clinical populations. Materials and Methods: This systematic review aimed to synthesize recent evidence (2015-2025) on the efficacy, safety, and methodological characteristics of multi-session cerebellar TMS protocols used in rehabilitation settings. Following PRISMA guidelines, a comprehensive search of PubMed and Scopus was conducted to identify peer-reviewed studies applying multi-session cerebellar TMS in clinical populations for motor, cognitive, or affective rehabilitation. A total of 1750 records were screened, and 46 studies met the inclusion criteria. Data extraction included sample characteristics, study design, TMS protocol, targeted symptoms, outcomes, and risk of bias. Results: The results show that repeated sessions of cerebellar TMS are safe, well-tolerated, and associated with functional improvements primarily in motor disorders-such as spinocerebellar ataxia, Parkinson's disease, multiple system atrophy, essential tremor, and post-stroke deficits-as well as in psychiatric populations, particularly patients with schizophrenia. Discussion: Evidence regarding the effects of cerebellar TMS on cognitive functions remains limited, though promising. Despite overall positive findings, the literature is limited by variability in stimulation parameters, protocol designs, and outcome measures, small sample sizes and potential publication bias. Conclusions: The review highlights the need for further large-scale and well-controlled trials to refine stimulation protocols, explore long-term effects, and clarify the underlying mechanisms of cerebellar TMS across motor, cognitive, and affective domains. This systematic review has been registered on PROSPERO (registration number: CRD420251067308).

Cerebellum serves an important function in diverse domain of motor, cognition control. Cerebellar non-invasive brain stimulation (NIBS) can provide a better comprehension of cerebellar circuity connecting to primary motor cortex. Cerebellar transcranial magnetic stimulation (TMS) activates Purkinje cells, causing increased inhibition of dentato-thalamo-cortical pathway. Assessing cerebellar-brain inhibition is useful for evaluating normal cerebellar functions and for understanding specific pathophysiology. Transcranial direct current stimulation (tDCS) has the polarity specific effect on cerebellar activity. Both TMS and tDCS can modulate cerebellar functions: motor learning, visuomotor adaptation, motor coordination, working memory and other cognitive domains. Further studies are encouraged to accumulate clinical and molecular evidences of neural plasticity induced by cerebellar NIBS. In the near future, cerebellar NIBS would play a crucial role in the field of neurorehabiliation. (Brain & NeuroRehabilitation 2015; 8: 90-95)

Purpose: The present study aimed to investigate whether spinal reflex excitability is influenced by the site of cerebellar transcranial magnetic stimulation (C-TMS).Materials and methods: Fourteen healthy volunteers (mean age: 24.6 ± 6.6 years [11 men]) participated. Participants lay on a bed in the prone position, with both ankle joints fixed to prevent unwanted movement. Right tibial nerve stimulation was provided to elicit the H-reflex in the right soleus muscle. Conditioning transcranial magnetic stimulation (TMS) was delivered at one of the following sites 110 ms prior to tibial stimulation: right, central, or left cerebellum; midline parietal (Pz) region; or sham stimulation. A total of 10 test trials were included for each condition, in random order. The unconditioned and conditioned H-reflexes were measured during random inter-test trials, and the cerebellar spinal facilitation (CSpF) ratios for each site were calculated (the ratio of conditioned to unconditioned H-reflexes). CSpF ratios were compared among TMS sites.Results: CSpF ratios were significantly higher at cerebellar sites than at the Pz site or during sham stimulation. However, there was no significant difference in CSpF ratio among cerebellar sites.Conclusions: TMS conditioning over any part of the cerebellum facilitated the excitability of the spinal motoneuron pool. Facilitation of the H-reflex due to C-TMS may involve the effects of the bilateral descending tract of the spinal cord on the spinal motoneuron pool. Alternatively, direct brainstem stimulation may have activated portions of the bilateral descending tract of the spinal cord.

BackgroundThe study of the involvement of the cerebellum in learning and memory has become one of the recent hot topics in the field of cognitive neuroscience. Transcranial magnetic stimulation (TMS) of the cerebellum has gained increasing interest in the treatment of cognition‐related disorders, making it necessary to determine the optimal parameters for cerebellar TMS. In this study, we aim to explore the effects of different frequencies of cerebellar repetitive TMS (rTMS) on working memory regulation and the associated electrophysiological changes. Through this research, we hope to provide objective bioinformatic guiding evidence for parameter optimization of cerebellar TMS.MethodWe recruited 75 healthy university students or graduate students as participants and divided them into five groups: 1Hz rTMS group, 5Hz rTMS group, 10Hz rTMS group, 20Hz rTMS group, and sham stimulation group. Each group received rTMS at different frequencies (1Hz, 5Hz, 10Hz, and 20Hz) over the cerebellar Crus II region, while a control group received sham stimulation. We assessed working memory performance using a 2‐back task and recorded electroencephalographic (EEG) signals during the 2‐back task and resting state before and after the stimulation. Cluster‐based permutation statistics and One‐way analysis of variance were used for the analysis of both neurophysiological and behavioral data.ResultThe 5Hz rTMS significantly increased the induced ERP activity of N100, P150, and N200, showed greater theta and alpha oscillatory activity, and significantly improved working memory performance. Furthermore, using phase locking value to construct brain networks and conduct analysis, we found that 5Hz rTMS significantly enhanced the whole‐brain local and global efficiency of brain networks in the theta frequency band, while 20Hz rTMS improved the local efficiency of the occipital and parietal lobes in the beta frequency band, with no significant differences observed in other frequency bands.ConclusionOur results demonstrate that 5Hz rTMS stimulation can significantly improve subjects' neurophysiological changes and working memory performance, showing a certain frequency‐dependent effect. These findings contribute to providing scientific evidence for the application of cerebellar TMS in memory improvement and offer valuable references for future related research.

In absence of drug therapy options, standard treatment for spinocerebellar ataxia consists of symptomatic physiotherapy and speech therapy. New therapeutic options are urgently needed. Transcranial magnetic stimulation is a promising therapeutic option, but applicability is limited by lengthy duration of stimulation protocols. In this randomized sham controlled clinical trial, patients were assigned to verum (n = 15) or sham (n = 18) cerebellar transcranial magnetic stimulation. To yield best possible treatment effects, both intervention groups received intensified physiotherapy for the duration of the study. Ataxia severity was reduced by 1.6 points on the Scale for assessment and Rating of Ataxia among patients in the verum group (p < 0.001). Clinical improvement was significantly larger in the verum group, compared to the sham group (p < 0.01). The treatment effect was mainly carried by improved appendicular coordination. Patients in the verum group also significantly improved in the 8 Meter Walk Test (p < 0.05) and PATA rate (p < 0.01). Cerebellar rTMS ameliorates ataxia severity in patient with spinocerebellar ataxia. Condensing treatment duration to only 5 days without reduction of treatment effects facilitates applicability and therefore broadens availability to larger patient populations.

Previous studies showed that transcranial magnetic stimulation (TMS) to the cerebellum evokes a long latency motor response in the soleus muscle during a postural task. The cerebellum is activated not only during postural tasks but also during motor tasks for which eye-hand coordination is required. The purpose of this study was to investigate whether TMS over the cerebellum evokes long latency motor responses in the hand during a visually guided manual tracking task. Eight healthy humans tracked an oscillatory moving target with the right index finger or pointed the finger at a stationary target, and TMS was delivered to the scalp over the cerebellum during the motor tasks. Trials with sham TMS were inserted between the trials with cerebellar TMS. The trajectory of finger movement fluctuated 92ms after cerebellar TMS with a 24% probability during tracking of a moving target. The fluctuation was preceded by an electromyographic burst in the first dorsal interosseous muscle starting at 65ms after TMS. The probability of fluctuation evoked by cerebellar TMS was significantly larger than that evoked by sham TMS during tracking of a moving target. This significant difference was absent in trials during which subjects pointed their index finger at a stationary target. These findings indicate that cerebellar TMS evokes a long latency motor response during a visually guided manual tracking task. The long latency motor response may be related to cerebellar activity associated with eye-hand coordination or to the detection of and correction for visuomotor errors.

Stimulation of Category-Selective Brain Areas Modulates ERP to Their Preferred Categories

Cerebellar transcranial direct current stimulation modulates the effect of cerebellar transcranial magnetic stimulation on the excitability of spinal reflex

Cerebellar transcranial magnetic stimulation: The role of coil type from distinct manufacturers

BackgroundWhile transcranial magnetic stimulation (TMS) coil geometry has important effects on the evoked magnetic field, no study has systematically examined how different coil designs affect the effectiveness of cerebellar stimulation.HypothesisThe depth of the cerebellar targets will limit efficiency. Angled coils designed to stimulate deeper tissue are more effective in eliciting cerebellar stimulation.MethodsExperiment 1 examined basic input–output properties of the figure-of-eight, batwing and double-cone coils, assessed with stimulation of motor cortex. Experiment 2 assessed the ability of each coil to activate cerebellum, using cerebellar-brain inhibition (CBI). Experiment 3 mapped distances from the scalp to cerebellar and motor cortical targets in a sample of 100 subjects' structural magnetic resonance images.ResultsExperiment 1 showed batwing and double-cone coils have significantly lower resting motor thresholds, and recruitment curves with steeper slopes than the figure-of-eight coil. Experiment 2 showed the double-cone coil was the most efficient for eliciting CBI. The batwing coil induced CBI only at higher stimulus intensities. The figure-of-eight coil did not elicit reliable CBI. Experiment 3 confirmed that cerebellar tissue is significantly deeper than primary motor cortex tissue, and we provide a map of scalp-to-target distances.ConclusionsThe double-cone and batwing coils designed to stimulate deeper tissue can effectively stimulate cerebellar targets. The double-cone coil was found to be most effective. The depth map provides a guide to the accessible regions of the cerebellar volume. These results can guide coil selection and stimulation parameters when designing cerebellar TMS studies.