Transcranial AC stimulation (tACS) of the cerebellum can entrain spiking activity in the Purkinje cells (PCs) of the cerebellar cortex and, through their projections, the cells in the cerebellar nuclei (CN). In this paper, we investigated if the cells in the motor thalamus (Mthal) can also be modulated (i.e. spikes entrained) via the CN-Mthal projections in rodents. A total of 82 thalamic cells were found, presumably in the Mthal by their stereotaxic coordinates, that were modulated by tACS of the cerebellum. Out of the 346 cells isolated, the thalamic cells with shorter action potentials and regular firing patterns had a higher probability of modulation by cerebellar stimulation than the cells with wider action potentials. The modulation level had a tuning curve with a maximum around 100-200 Hz. Spike histograms over the stimulation cycle transitioned between unimodal and bimodal distributions depending on the frequency. Most cells had a unimodal distribution at low frequencies, a bimodal distribution for frequencies between 80-125 Hz, and then a unimodal one for frequencies above 150 Hz. In addition, tACS of the motor cortex (MC) was also tested in a subset of thalamic cells. Unlike cerebellar stimulation, modulation levels peaked at two distinct frequencies, presumably due to entrainment through multiple MC-Mthal pathways with different preferred frequencies. The results demonstrate the feasibility of modulating a deep brain structure such as the thalamus through multi-synaptic pathways by stimulation of the cerebellar cortex (and the motor cortex) using a non-invasive neuromodulation method.

Mapping Cerebellar Connectivity to Cognition in Psychosis: Convergent Evidence From Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation.

Cerebellar transcranial direct current stimulation in spinocerebellar ataxia type 3: An electric field modelling study.

Both the primary motor cortex (M1) and the cerebellum can be viable targets for noninvasive brain stimulation (NIBS) to improve balance after stroke; however, the optimal stimulation target is unknown. The study objective was to compare the role of two neural loci (M1 and cerebellum) in modulating balance performance in individuals with chronic stroke using repetitive transcranial magnetic stimulation (rTMS). Nineteen individuals with chronic stroke (mean age = 57.2 ± 11.1 years, 13 males) received a single session of 5-Hz rTMS applied to bilateral M1 and the contralesional cerebellum in a crossover randomized manner with a washout period of 7 ± 2 days. Anticipatory and reactive balance was assessed before and after rTMS using the Limits of Stability (LOS) test and modified Clinical Test of Sensory Interaction on Balance (mCTSIB), respectively. M1 rTMS significantly improved LOS sway angle compared to cerebellar rTMS (p < 0.001). The rTMS effect on the mCTSIB sway index was mediated by stimulation target, surface, vision, and time (p = 0.006). Sway index measured under the eyes-open conditions was not influenced by rTMS. Under eyes-closed conditions, M1 rTMS significantly improved sway index on the firm surface (p = 0.002), whereas cerebellar rTMS improved sway index on the foam surface (p = 0.001). M1 and cerebellum are viable rTMS targets for improving balance. M1 stimulation enhances anticipatory balance, whereas cerebellar rTMS improves reactive balance, especially under sensory-deprived conditions. This study provides critical information for future tailored NIBS intervention in individuals with stroke.

Cerebellar transcranial magnetic stimulation (TMS) may serve as an adjuvant therapy for psychosis symptoms, most recently we have shown improvements in negative symptoms. Historically, cerebellum TMS has not utilized functional neuroanatomy for targeting, and the precision of TMS to the cerebellum is unclear. A classical view of the cerebellum as solely involved in motor computations has been updated with the discovery of rich non-motor connectivity including the default, dorsal attention, frontoparietal control and ventral attention networks. We sought to assess cerebellar TMS magnetic field effect within individually defined networks of the cerebellum. Imaging data from schizophrenia and schizoaffective participants (n=27) in a double-blinded trial of cerebellar TMS ( NCT05343598 ) was used. Individualized resting-state connectivity fMRI maps of the cerebellum was computed for 7 canonical networks (Yeo et al 2011; Buckner et al 2011). Individualized TMS simulations were computed in SimNIBS with real-world participant-specific coil placement and intensity determination. The peak stimulation effect (99th percentile) for each network in each participant was computed. The electric field induced by cerebellar TMS predominantly engaged specific functional networks more than others (p<0.001), indicating selective targeting of these networks. The strongest effects were found on default (44.4%), limbic (37%) and frontoparietal control (11.1%) networks. Cerebellar brain network organization was found to be similar in the patient sample to previously published large-sample organization. For personalized TMS, it is important to consider the targeted network, as well as the potential off-target network effects. Our findings demonstrate that cerebellar TMS has the strongest field effect on non-motor, cognitive and affective networks within the cerebellum. These results suggest cerebellar TMS may be ideal for schizophrenia symptoms unaddressed by pharmacological treatments, and effects may vary by individual network topology.

Background: Emotional prosody refers to the variations in pitch, pause, melody, rhythm, and stress of pronunciation conveying emotional meaning during speech. Although several studies demonstrated that the cerebellum is involved in the network subserving recognition of emotional facial expressions, there is only preliminary evidence suggesting its possible contribution to recognising emotional prosody by modulating the activity of cerebello-prefrontal circuits. The present study aims to further explore the role of the left and right cerebellum in the recognition of emotional prosody in a sample of healthy individuals who were required to identify emotions (happiness, anger, sadness, surprise, disgust, and neutral) from vocal stimuli selected from a validated database (EMOVO corpus). Methods: Anodal transcranial Direct Current Stimulation (tDCS) was used in offline mode to modulate cerebellar activity before the emotional prosody recognition task, and functional near-infrared spectroscopy (fNIRS) was used to monitor stimulation-related changes in oxy- and deoxy- haemoglobin (O2HB and HHB) in prefrontal areas (PFC). Results: Right cerebellar stimulation reduced reaction times in the recognition of all emotions (except neutral and disgust) as compared to both the sham and left cerebellar stimulation, while accuracy was not affected by the stimulation. Haemodynamic data revealed that right cerebellar stimulation reduced O2HB and increased HHB in the PFC bilaterally relative to the other stimulation conditions. Conclusions: These findings are consistent with the involvement of the right cerebellum in modulating emotional processing and in regulating cerebello-prefrontal circuits.

Transcranial magnetic stimulation (TMS) has recently been used to great effect to enhance the motor function and performance of patients with stroke by modifying cerebral cortex excitability. But few studies have directly compared the effectiveness of stimulating the M1 and cerebellar regions in using rTMS to improve lower limb motor function in stroke patients. To assess the effectiveness of high-frequency (HF) repetitive TMS (rTMS) applied to the primary motor cortex (M1) versus the cerebellar region for improving lower limb dsyfunction and maintaining balance ability in people suffering from stroke. Randomized, double-blind, sham controlled clinical trial. Department of rehabilitation medicine in a general hospital. Patients with stroke with first unilateral lesions were enrolled in the study. Seventy-one patients were randomly allocated to sham stimulation group, acerebellum group, and M1 group. Each group received rTMS alongside their routine rehabilitation. The M1 group received stimulation to the affected lower limb motor cortex, while the cerebellum group received stimulation to the contralesional cerebellum. The sham stimulation group had a non-stimulating setup. The stimulation parameters were as follows: the stimulation intensity of 80%RMTand frequency of 10 Hz. The stimulation lasted 20 minutes per session, comprising 3 seconds of stimulation followed by a 17-second interval. This equated to 1,800 pulses per day, five times a session for two weeks. Before the intervention, no significant differences was found in terms of the Fugl-Meyer Assessment for the Lower Extremities (FAM-LE), the Berg Balance Scale (BBS), movement trajectory length, center of movement trajectory area and the Modified Barthel Index (MBI) (P>0.05). Two weeks later, however, the M1 group and cerebellar group demonstrated statistically significant improvements in the FAM-LE, BBS and MBI (P<0.05). The cerebellar and M1 groups outperformed the sham stimulation group in terms of movement trajectory measures (P<0.05), with the cerebellar group achieving the best results. Both M1 and cerebellar HF stimulation have been shown to play a positive role in the functionality of the lower limbs and the ability of balance in stroke patients, with cerebellar stimulation proving to be especially efficacious in the amelioration of balance. M1 and cerebellar can improve stroke patient lower limb function, but cerebellar maybe a more perfect region for improving balance function compare with M1.

BackgroundThe cerebellum has emerged as a key region involved in cognitive functions through cerebro‐cerebellar circuits. However, its electrophysiological features and the mechanisms underlying cerebellar repetitive transcranial magnetic stimulation (rTMS) in improving cognition remain unclear. This study investigated cerebellar electroencephalographic patterns in mild cognitive impairment (MCI) and explored the effects of bilateral cerebellar rTMS.MethodWe recruited 31 healthy controls (HC), 41 MCI and 27 patients with Alzheimer's disease (AD) for this study. Fifteen MCI participants received 10‐day 5 Hz rTMS. Resting‐state electroencephalography(EEG) was recorded using 71 channels to monitor cerebrum and cerebellum electrical signals. We analyzed the spectral power and functional connectivity changes. Additionally, correlation analyses were conducted between spectral power and neuropsychological assessment scores.ResultMCI group showed significantly increased cerebellar theta band relative power compared to the HC group. Functional connectivity analysis indicated that enhanced functional connectivity was observed between the cerebellum and the left frontal lobe as well as the right parieto‐occipital region in the theta band. In the high‐gamma band, decreased functional connectivity was observed between the left cerebellum and the left frontal lobe, as well as the right central region. Cerebellar relative power in the theta band was negatively associated with MMSE and MoCA scores in the MCI group. After 5 Hz rTMS, a significant increase theta band relative power in frontal lobe was observed compared to the pre‐stimulation condition, accompanied by enhanced functional connectivity between the cerebellum and the left frontal lobe. Changes in theta band relative power were positively correlated with changes in MMSE and MoCA scores.ConclusionThe cerebellum relative power spectrum and functional connectivity in the theta band of resting‐state EEG holds promise as sensitive biomarkers for the early detection of MCI. Bilateral cerebellum 5 Hz rTMS enhanced theta band cerebellar relative power and functional connectivity between the cerebellum and the left frontal lobe, thereby augmenting the compensatory role of the cerebellum under cognitive impairment conditions and improving cognitive function in MCI.

BackgroundResearch increasingly shows that the cerebellum plays a key role in regulating non‐motor functions like cognition, language, and emotion, through complex interactions with brain circuits. Its synaptic plasticity and information integration abilities make it a promising target for cognitive modulation therapies. Our previous studies have shown that 5Hz rTMS can improve cognition, but the iTBS protocol, more commonly applied to the brain, induces stronger oscillatory activity and better cognitive improvements. This study aims to explore the effects of different TMS protocols on working memory when applied to the cerebellar Crus II region, and investigate the underlying neural mechanisms.MethodSixty healthy adults participated in this study, with the right cerebellar Crus II region as the target for intervention, localized using MRI and neuronavigation. Participants were randomly assigned to one of three groups: 5Hz rTMS, iTBS, or sham stimulation. Before and after the intervention, all participants performed a 2‐back working memory task, and EEG signals were continuously recorded using a 71‐channel system. Behavioral measures, event‐related potential (ERP) amplitudes, time‐frequency changes, and brain network topology were compared within and between groups.ResultBoth the 5Hz rTMS and iTBS groups showed significantly shorter reaction times than the sham group, with the 5Hz rTMS group showing a more pronounced improvement. Neurophysiological data revealed increased P150 amplitudes in both active groups, with the 5Hz rTMS group showing significantly higher P150 amplitudes than the iTBS and sham groups. Time‐frequency analysis showed that 5Hz rTMS enhanced θ and α oscillations, while iTBS and sham groups did not. The 5Hz rTMS group also had significantly higher α oscillatory activity compared to iTBS and sham groups. Resting‐state brain network analysis showed increased global efficiency in the θ frequency band in both active groups, with no differences between them.ConclusionThe 5Hz rTMS intervention to the cerebellar Crus II region more significantly enhanced brain oscillatory activity and improved working memory performance compared to the iTBS intervention. These findings provide insights into optimizing parameters for cerebellar TMS in the improvement of memory functions.

ABSTRACTPurposeThe primary motor cortex (M1) and the cerebellum are important sites of processing for motor learning of complex, bimanual tasks. However, little is known about the current and polarity effects of transcranial direct current stimulation (tDCS) when applied concurrently to these sites during learning. Therefore, the present study sought to examine the effect of bilateral primary motor cortex (M1) anodal tDCS coupled with anodal cerebellar tDCS (biM1a + CBa) on learning of a bimanual racing videogame.MethodForty‐six subjects were enrolled and received either biM1a + CBa (n = 23) or biM1a + CBsham (n = 23) stimulation for a single practice session. Additional data from a previous study in our lab using bilateral primary motor cortex (M1) anodal tDCS coupled with cathodal cerebellar tDCS (biM1a + CBc, n = 21) and a SHAM condition (n = 20) was included in our analysis. Videogame performance was assessed before and after the practice session, and a follow‐up assessment took place 24 h later.FindingLearning and previous gaming experience were negatively correlated, so experience was included as a covariant in the analysis of results. Consistent with the current literature, simultaneous tDCS of both motor cortices, without any cerebellar stimulation, improved learning the most within a single day (p = 0.025). No significant retention effects were observed for any of the conditions (p = 0.87).ConclusionThese results reinforce the benefits of tDCS to M1 and that, at least in the video game task used in this study, cerebellar stimulation does not add to the learning effect. When using multifocal stimulation montages, careful consideration needs to be given to the relationship between electrode placement, task specificity, previous experience, and individual differences of the participants.

BackgroundUpper extremity motor impairment is a prevalent and disabling consequence of stroke. While conventional rehabilitation improves function, recovery often plateaus. Cerebellar transcranial direct current stimulation (c-tDCS) presents a promising neuromodulatory adjunct by targeting cerebellar involvement in motor coordination, timing, and learning. However, robust evidence from well-designed randomized controlled trials (RCTs) is needed to establish its efficacy in enhancing post-stroke upper limb recovery.ObjectiveThis RCT protocol aims to evaluate the efficacy of anodal c-tDCS applied sequentially with conventional upper limb rehabilitation (CULR), compared to sham stimulation plus the same rehabilitation, on improving motor function of the paretic upper extremity in subacute/chronic stroke patients.MethodsA double-blind, randomized, sham-controlled trial will be conducted. Fourty-eight participants with unilateral stroke and moderate to severe upper limb motor impairment will be randomized to either active or sham group. Anodal tDCS will be conducted to the ipsilesional cerebellar hemisphere in the active group, while sham delivery will be performed in the sham group. Both groups receive CULR after each c-tDCS session. Multimodal assessments will be administered pre- and post-intervention, comprising: Fugl-Meyer assessment upper extremity (FMA-UE) for motor impairment quantification, functional near-infrared spectroscopy (fNIRS) capturing resting-state and c-tDCS-induced cortical hemodynamic responses and transcranial magnetic stimulation-derived motor evoked potentials (TMS-MEPs) evaluating cortical excitability.ConclusionThis rigorously designed RCT will provide high-level evidence on the therapeutic potential of c-tDCS as an adjunct to rehabilitation for improving upper limb motor function post-stroke. Findings will inform clinical practice regarding novel neuromodulation strategies to augment recovery.Clinical trial registrationhttps://www.chictr.org.cn, identifier ChiCTR2500101094.

Spinocerebellar ataxia type 3 (SCA3) is a hereditary neurodegenerative disorder that progressively impairs balance and gait, without effective pharmacological treatments available. Cerebellar and cerebello-spinal transcranial direct current stimulation (tDCS) have shown neuromodulatory potential. However, extended protocols combined with exercise have not yet been tested in these individuals in a public health service.To assess the feasibility and safety of 20 sessions of cerebello-spinal tDCS combined with exercise in individuals with SCA3 in real-world conditions, and to explore preliminary changes in ataxia severity, balance, and mobility.In this single-arm, open-label pragmatic feasibility study, 39 participants [67% female; 46 ± 10 (23-70) years-old; mean ± SD (min.-max.)] with mild-to-moderate SCA3 completed 20 sessions over four weeks under real-world public-health conditions. Feasibility was evaluated through adherence and tolerability, and safety was assessed by monitoring adverse events. Secondary outcomes included disease severity (SARA), balance (Berg Balance Scale), and mobility (Timed Up and Go), assessed at baseline, post-intervention, and one-month follow-up. Analyses included between-moments standardized individual differences (SID) and multiple linear regression adjusted for baseline values.Adherence was 97.3%, with no serious adverse events. Significant improvements were observed in SARA (SID - 0.72 ± 1.00; mean ± SD; P < 0.001), BBS (SID 0.47 ± 1.00; P < 0.001), and TUG (SID - 0.49 ± 1.00; P = 0.011). Improvements were maintained at one month (P > 0.171).A combination of multiple sessions of cerebello-spinal tDCS and exercise in a public health service was feasible, safe, and may improve ataxia severity, balance, and mobility in individuals with SCA3. As a study without a control group, these findings should be confirmed in randomized controlled trials but encourage further investigation of the proposed intervention as a potential rehabilitation strategy for cerebellar neurodegeneration.

Impaired balance is one of the most disabling symptoms in people with Parkinson's disease (PwPD). While motor intervention can improve balance control, its effects might be enhanced through cerebellar transcranial direct current stimulation (ctDCS). However, the optimal stimulation intensity remains a point open to investigation.To compare the effects of dynamic balance training combined with different intensities of anodal ctDCS on improvements in body balance and modulation of prefrontal cortex (PFC) activation in PwPD.Thirty-three PwPD were randomized into three groups varying in the intensity of ctDCS (4mA, 2mA, Sham) in a double-blind, sham-controlled design. Participants underwent 6 sessions of progressively challenging dynamic balance training combined with ctDCS/sham. Balance improvements were assessed through center of pressure excursion in quiet standing and dynamic transfer tasks. Training-related effects were also evaluated in PFC activation using functional near-infrared spectroscopy. Balance training combined with ctDCS led to higher improvements in balance compared to training without cerebellar stimulation. The 4mA stimulation intensity led to greater balance gains than the 2mA and sham stimulation across all transfer task categories assessed. Balance training led to decreased PFC activation, with no detectable differences between the groups.Six sessions of dynamic balance training combined with the ctDCS intensity of 4mA resulted in superior improvement of balance in PwPD. Balance training led to decreased PFC activation in the performance of different transfer tasks regardless of the ctDCS condition. Brazilian Registry of Clinical Trials (ReBEC) URL: ensaiosclinicos.gov.br/rg/RBR-7yt65zp, data of registration 08/12/2024, retrospectively registered.

Previous studies have shown that intermittent theta burst stimulation (iTBS) can promote the recovery of swallowing function in stroke patients. However, the therapeutic mechanism is not well understood. No study has elucidated the swallowing mechanism of iTBS and its cortical excitability changes in controlled healthy samples. Changes in cortical excitability can reflect the improvement of swallowing function. The purpose of this study was to observe the activation of the cerebral cortex during voluntary swallowing in healthy adults and to investigate the direct effect of cerebellar iTBS on the excitability of the pharyngeal motor cortex, to explore further the potential mechanisms by which cerebellar iTBS improves swallowing function. Thirty healthy subjects were recruited for this study and randomized to left and right cerebellar iTBS stimulation. The order of stimulation of the left and right cerebellum was randomized, and the stimulation interval was approximately one week. Functional near-infrared spectroscopy (fNIRS) was used to assess brain activation before and after iTBS stimulation and the parameter "β-value." fNIRS was paradigmatized as a classical block task, and the whole procedure consisted of three identical blocks, each consisting of a 30-s swallowing task and a 30-s rest period. Bilateral superior temporal gyrus (STG), middle temporal gyrus (MTG), primary motor cortex (PMC), pre-motor and supplementary motor cortex (PSMC), primary somatosensory cortex (PSC), pars triangularis (PTG), frontopolar area (FPA), frontal eye fields (FEF), and dorsolateral prefrontal area (DLPFC)were significantly activated during the performance of a voluntary swallowing task. Compared with pre-stimulation, the beta values significantly increased in channels 5 (P = 0.013), 17 (P = 0.025), 18 (P = 0.027), 19 (P = 0.046), 34 (P = 0.045), and 37(P = 0.045) after left cerebellar stimulation; After cerebellar right side stimulation, the beta values significantly increased in channels 3 (P = 0.043), 18 (P = 0.022), 20 (P = 0.047), 38 (P = 0.032), 46 (P = 0.028), and 48 (P = 0.028). Bilateral STG, MTG, PMC, PSMC, PSC, PTG, FPA, FEF, and DLPFC were involved in regulating volitional swallowing. Both iTBS to the left and right cerebellum significantly increased the excitability of swallowing cortical areas under a swallowing-specific task.

Cerebello-cortical inhibition underlies the effects of cerebellar magnetic stimulation on spinocerebellar ataxia type 3: A randomized controlled trial.

Cerebellar transcranial direct current stimulation combined with virtual reality training for the balance of older adults: study protocol for a randomized controlled trial

This study investigated the effects of repetitive transcranial magnetic stimulation (rTMS) over the right cerebellar hemisphere on visuomotor adaptation and interlimb coordination learning. Specifically, we examined the impact of cerebellar stimulation on the acquisition of new visuomotor transformations and subsequent adaptation under interference conditions during a bimanual tracking task. A total of 42 healthy adults performed a bimanual visuomotor tracking task in which the left and right hands controlled horizontal and vertical cursor movements, respectively. The experiment consisted of two phases: (1) an Initial learning phase involving adaptation to a visuomotor transformation, and (2) an Interference adaptation phase, defined as adaptation to a new visuomotor mapping under interference from the previously learned transformation, in which only the right-hand mapping was altered. Participants received either active or sham 1Hz rTMS over the right cerebellar hemisphere before the task. Performance was assessed using tracking error and interlimb error structure measures. Tracking errors decreased over trials in both learning phases. While rTMS had no significant effect during the Initial learning phase, it significantly reduced tracking errors during the Interference adaptation phase. In the active-rTMS group, interlimb error correlation and the directional error slope also declined across trials, suggesting reduced cross-limb interference and enhanced coordination flexibility. These findings suggest that cerebellar rTMS facilitates the adaptation of altered visuomotor mappings, particularly during interference adaptation, by modulating interlimb coordination. The results support the hypothesis that bimanual coordination relies on modular internal models that dynamically interact during motor learning. This study underscores the cerebellum's essential role in optimizing interlimb adaptation, especially under interference adaptation, and highlights the potential of cerebellar neuromodulation for motor rehabilitation.

Efficacy of cerebellar cathodal transcranial direct current stimulation for post-stroke aphasia: A randomized controlled trial

Cerebellar stimulation influences performance to a food-related Go/NoGo task.

Modulating language and executive functions in bilingual aphasia with cerebellar tDCS: a case series.