Cerebellar Transcranial Magnetic Stimulation Research Articles

Feasibility of a randomized, sham-controlled pilot study for accelerated rTMS-treatment of the cerebellum plus physiotherapy in CANVAS patients.

Cerebellar ataxia, neuropathy and bilateral vestibular areflexia (CANVAS) is a rare neurodegenerative disease affecting the cerebellum, the peripheral nervous system and the vestibular system. Due to the lack of approved drugs, therapy comprises physiotherapy and speech therapy. Transcranial magnetic stimulation is a promising non-invasive therapeutic option to complement classical symptomatic therapies. To test feasibility of the combination of transcranial magnetic stimulation using an accelerated protocol and standard symptomatic therapy in patients with CANVAS. Eight patients with genetically confirmed CANVAS were assigned to either verum or sham cerebellar transcranial magnetic stimulation using an accelerated protocol. Treatment duration was limited to 5 days. Additionally, patients in both groups received symptomatic therapy (speech and physiotherapy) for the duration of the study. All patients completed the stimulation protocol. Adverse events were rare. Ataxia severity improved in the verum group only. The combination of transcranial magnetic stimulation and classic symptomatic therapy is feasible in a neuro-rehabilitation setting and potentially ameliorates ataxia severity.

Effects of cerebellar repetitive transcranial magnetic stimulation plus physiotherapy in spinocerebellar ataxias - A randomized clinical trial.

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.

Efficacy of Cerebellar Transcranial Magnetic Stimulation for Post-stroke Balance and Limb Motor Function Impairments: Meta-analyses of Random Controlled Trials and Resting-State fMRI Studies.

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.

Efficacy of Cerebellar Transcranial Magnetic Stimulation in Treating Essential Tremor: A Randomized, Sham-Controlled Trial.

Repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere represents a new option in treating essential tremor (ET) patients. We aimed to determine the efficacy of cerebellar rTMS in treating ET using different protocols regarding the number of sessions, exposure duration, and follow-up duration. A randomized sham-controlled trial was conducted, in which 45 recruit patients were randomly allocated to 2 groups. The first (active group) comprised 23 patients who were exposed to 12 sessions of active rTMS with 900 pulses of 1-Hz rTMS at 90% of the resting motor threshold daily on each side of the cerebellar hemispheres over 4 weeks. The second group (sham group) comprised 22 patients who were exposed to 12 sessions of sham rTMS. Both groups were reassessed at baseline and after 1 day, 1 month, 2 months, and 3 months using the Fahn-Tolosa-Marin tremor-rating scale (FTM). Demographic characteristics did no differ between the two groups. There were significant reductions both in FTM subscores A and B and in the FTM total score in the active-rTMS group during the period of assessment and after 3 months (p=0.031 and 0.011, respectively). However, subscore C did not change significantly from baseline when assessed at 2 and 3 months (p=0.073 and 0.236, respectively). Furthermore, the global assessment score was significantly higher in the active-rTMS group (p>0.001). Low-frequency rTMS over the cerebellar cortex for 1 month showed relative safety and long-lasting efficacy in patients with ET. Further large-sample clinical trials are needed that include different sites of stimulation and longer follow-ups.

Cerebellar repetitive transcranial magnetic stimulation has no effect on contraction-induced facilitation of corticospinal excitability.

This study aimed to investigate whether the cerebellum contributes to contraction-induced facilitation (CIF) of contralateral corticospinal excitability. To this end, repetitive cerebellar transcranial magnetic stimulation (TMS) was used to test whether it modulates CIF. Overall, 20 healthy young individuals participated in the study. Single-pulse TMS was applied to the left primary motor cortex to induce motor-evoked potentials (MEP) on electromyography of the right first dorsal interosseous (FDI) muscle to test corticospinal excitability. This measurement was conducted during contraction (10% maximum voluntary contraction [MVC]) and rest (0% MVC) of the FDI muscle. CIF, cerebellar brain inhibition (CBI), cortical silent period (cSP), and resting motor threshold (rMT) were measured before and after low-frequency repetitive TMS (crTMS) of the right cerebellum to downregulate cerebellar output. The CIF (contraction/rest of the MEP), CBI (conditioned/unconditioned MEP) during contraction, cSP, and rMT were not affected by crTMS. At rest, CBI was decreased. These findings indicated that the primary motor cortex function for the increase in corticospinal excitability was not affected by crTMS. This study contributes to our understanding of the role of the cerebellum in motor control. Additionally, it may inform decision-making for the site of cerebellar ataxia treatment using non-invasive brain stimulation.

Cerebellar transcranial magnetic stimulation in psychotic disorders: intermittent, continuous, and sham theta-burst stimulation on time perception and symptom severity.

The cerebellum contributes to the precise timing of non-motor and motor functions, and cerebellum abnormalities have been implicated in psychosis pathophysiology. In this study, we explored the effects of cerebellar theta burst stimulation (TBS), an efficient transcranial magnetic stimulation protocol, on temporal discrimination and self-reported mood and psychotic symptoms. We conducted a case-crossover study in which patients with psychosis (schizophrenias, schizoaffective disorders, or bipolar disorders with psychotic features) were assigned to three sessions of TBS to the cerebellar vermis: one session each of intermittent (iTBS), continuous (cTBS), and sham TBS. Of 28 enrolled patients, 26 underwent at least one TBS session, and 20 completed all three. Before and immediately following TBS, participants rated their mood and psychotic symptoms and performed a time interval discrimination task (IDT). We hypothesized that cerebellar iTBS and cTBS would modulate these measures in opposing directions, with iTBS being adaptive and cTBS maladaptive. Reaction time (RT) in the IDT decreased significantly after iTBS vs. Sham (LS-mean difference = -73.3, p = 0.0001, Cohen's d = 1.62), after iTBS vs. cTBS (LS-mean difference = -137.6, p < 0.0001, d = 2.03), and after Sham vs. cTBS (LS-mean difference = -64.4, p < 0.0001, d = 1.33). We found no effect on IDT accuracy. We did not observe any effects on symptom severity after correcting for multiple comparisons. We observed a frequency-dependent dissociation between the effects of iTBS vs. cTBS to the cerebellar midline on the reaction time of interval discrimination in patients with psychosis. iTBS showed improved (adaptive) while cTBS led to worsening (maladaptive) speed of response. These results demonstrate behavioral target engagement in a cognitive dimension of relevance to patients with psychosis and generate testable hypotheses about the potential therapeutic role of cerebellar iTBS in this clinical population. clinicaltrials.gov, identifier NCT02642029.

Reply to: “Reflecting the causes of variability of EEG responses elicited by cerebellar TMS”

In their commentary on our recently published paper about electroencephalographic responses induced by cerebellar transcranial magnetic stimulation (Fong et al., 2023), Gassmann and colleagues (Gassmann et al., 2023b) try to explain the differences between our results and their own previous work on the same topic. We agree with them that many of the differences arise from our use of a different magnetic stimulation coil. However, two unresolved questions remain. (1) Which method is most likely to achieve optimal activation of cerebellar output? (2) To what extent are the evoked cerebellar responses contaminated by concomitant sensory input? We highlight the role of careful experimental design and of combining electrophysiological and behavioural data to obtain reliable TMS-EEG data.

C-STIM: Protocol for a randomized, single-blind, crossover study of cerebellar repetitive transcranial magnetic stimulation (rTMS) for postural instability in people with progressive supranuclear palsy (PSP)

BackgroundMethods for modulating the cerebellum with transcranial magnetic stimulation (TMS) are well established, and preliminary data from our group and others has shown evidence of transient improvements in balance after cerebellar repetitive transcranial magnetic stimulation (rTMS) in progressive suprancuclear palsy (PSP). This study examines extensive posturography measures before and after 10 sessions of cerebellar rTMS and sham TMS in PSP. MethodsThirty subjects with PSP and postural instability will undergo cerebellar active and sham rTMS in a single-blind, crossover design with a randomized order of a 10-day intervention. Primary outcomes will be changes in sway area and medio-lateral range of sway with eyes open while standing on a stationary force-plate, and safety, tolerability, and blindedness. Secondary outcomes will include posturography and gait analysis with body-worn, triaxial inertial sensors, clinical balance scales and questionnaires, and a bedside test of vestibular function. Exploratory outcomes are changes in functional near infrared spectroscopy (fNIRS) signal over the prefrontal, supplementary motor, and primary motor cortices while standing and walking, and speech samples for future analysis. DiscussionThe C-STIM crossover intervention study adds a longer duration of stimulation and extensive posturography measures to more finely measure the improvements in balance and exploratory functional near-infrared spectroscopy (fNIRS) over the prefronal, supplementary motor, and primary motor cortices during balance assessments before and after 10 sessions of cerebellar rTMS and 10 sessions of sham cerebellar TMS. This project will improve our understanding of the importance of the cerebellum for control of postural stability in PSP.

Efficacy of cerebellar transcranial magnetic stimulation in spinocerebellar ataxia type 3: a randomized, single-blinded, controlled trial.

Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA without effective treatment. This study aimed to evaluate the comparative efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) in a larger cohort of SCA3 patients. One hundred and twenty patients with SCA3 were randomly assigned to the 3 groups: 40 patients in the 1Hz rTMS, 40 in the iTBS and 40 in the sham group. Patients underwent 10 sessions of rTMS targeting the cerebellum delivering for 5 consecutive days per week for 2weeks (a total of 1200 pulses per session). Primary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Secondary outcomes included 10-m walking test (10MWT), nine-hole peg test (9-HPT), and PATA Rate Test (PRT). Outcome assessments were performed at baseline and on the last day of rTMS intervention. This study revealed that active rTMS outperformed sham in reducing the SARA and ICARS scores in SCA3 patients, but with no difference between the 1Hz rTMS and iTBS protocol. Moreover, no significant differences were observed in SARA and ICARS scores between the mild and moderate to severe groups after the 1Hz rTMS/iTBS therapy. Additionally, no severe adverse events were recorded in this study. The study concluded that both 1Hz rTMS and iTBS interventions targeting the cerebellum are effective to improve the symptoms of ataxia in patients with SCA3.

Balance and gait in progressive supranuclear palsy: a narrative review of objective metrics and exercise interventions.

The use of objective gait and balance metrics is rapidly expanding for evaluation of atypical parkinsonism, and these measures add to clinical observations. Evidence for rehabilitation interventions to improve objective measures of balance and gait in atypical parkinsonism is needed. Our aim is to review, with a narrative approach, current evidence on objective metrics for gait and balance and exercise interventions in progressive supranuclear palsy (PSP). Literature searches were conducted in four computerized databases from the earliest record up to April 2023: PubMed, ISI's Web of Knowledge, Cochrane's Library, and Embase. Data were extracted for study type (cross-sectional, longitudinal, and rehabilitation interventions), study design (e.g., experimental design and case series), sample characteristics, and gait and balance measurements. Eighteen gait and balance (16 cross-sectional and 4 longitudinal) and 14 rehabilitation intervention studies were included. Cross-sectional studies showed that people with PSP have impairments in gait initiation and steady-state gait using wearable sensors, and in static and dynamic balance assessed by posturography when compared to Parkinson's disease (PD) and healthy controls. Two longitudinal studies observed that wearable sensors can serve as objective measures of PSP progression, using relevant variables of change in turn velocity, stride length variability, toe off angle, cadence, and cycle duration. Rehabilitation studies investigated the effect of different interventions (e.g., balance training, body-weight supported treadmill gait, sensorimotor training, and cerebellar transcranial magnetic stimulation) on gait, clinical balance, and static and dynamic balance assessed by posturography measurements. No rehabilitation study in PSP used wearable sensors to evaluate gait and balance impairments. Although clinical balance was assessed in 6 rehabilitation studies, 3 of these studies used a quasi-experimental design, 2 used a case series, only 1 study used an experimental design, and sample sizes were relatively small. Wearable sensors to quantify balance and gait impairments are emerging as a means of documenting progression of PSP. Robust evidence for improving balance and gait in PSP was not found for rehabilitation studies. Future powered, prospective and robust clinical trials are needed to investigate the effects of rehabilitation interventions on objective gait and balance outcomes in people with PSP.

Effect of cerebellar transcranial magnetic stimulation with double-cone coil on dysphagia after subacute infratentorial stroke: A randomized, single-blinded, controlled trial

BackgroundA 10-Hz cerebellar repetitive transcranial magnetic stimulation (rTMS) could increase corticobulbar tract excitability in healthy individuals. However, its clinical efficacy for poststroke dysphagia (PSD) remains unclear. ObjectiveTo investigate the effectiveness of 10-Hz cerebellar rTMS in PSD patients with infratentorial stroke (IS). MethodsIn this single-blinded, randomized controlled trial, 42 PSD patients with subacute IS were allocated to three groups: bilateral cerebellar rTMS (biCRB-rTMS), unilateral cerebellar rTMS (uniCRB-rTMS), or sham-rTMS. The stimulation parameters were 5 trains of 50 stimuli at 10 Hz with an interval of 10 s at 90% of the thenar resting motor threshold (RMT). The Functional Oral Intake Scale (FOIS) was assessed at T0 (baseline), T1 (day 0 after intervention), and T2 (day 14 after intervention), whereas the Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and neurophysiological parameters were evaluated at T0 and T1. ResultsSignificant time and intervention interaction effects were observed for the FOIS score (F = 3.045, p = 0.022). The changes in the FOIS scores at T1 and T2 were both significantly higher in the biCRB-rTMS group than in the sham-rTMS group (p < 0.05). The uniCRB-rTMS and biCRB-rTMS groups demonstrated greater changes in the DOSS and PAS at T1, compared with the sham-rTMS group (p < 0.05). Bilateral corticobulbar tract excitability partly increased in the biCRB-rTMS and uniCRB-rTMS groups at T1, compared with T0. The percent changes in corticobulbar tract excitability parameters at T1 showed no difference among three groups. ConclusionsA 10-Hz bilateral cerebellar rTMS is a promising, noninvasive treatment for subacute infratentorial PSD.

EEG responses induced by cerebellar TMS at rest and during visuomotor adaptation

BackgroundConnections between the cerebellum and the cortex play a critical role in learning and executing complex behaviours. Dual-coil transcranial magnetic stimulation (TMS) can be used non-invasively to probe connectivity changes between the lateral cerebellum and motor cortex (M1) using the motor evoked potential as an outcome measure (cerebellar-brain inhibition, CBI). However, it gives no information about cerebellar connections to other parts of cortex. ObjectivesWe used electroencephalography (EEG) to investigate whether it was possible to detect activity evoked in any areas of cortex by single-pulse TMS of the cerebellum (cerebellar TMS evoked potentials, cbTEPs). A second experiment tested if these responses were influenced by the performance of a cerebellar-dependent motor learning paradigm. MethodsIn the first series of experiments, TMS was applied over either the right or left cerebellar cortex, and scalp EEG was recorded simultaneously. Control conditions that mimicked auditory and somatosensory inputs associated with cerebellar TMS were included to identify responses due to non-cerebellar sensory stimulation. We conducted a follow-up experiment that evaluated whether cbTEPs are behaviourally sensitive by assessing individuals before and after learning a visuomotor reach adaptation task. ResultsA TMS pulse over the lateral cerebellum evoked EEG responses that could be distinguished from those caused by auditory and sensory artefacts. Significant positive (P80) and negative peaks (N110) over the contralateral frontal cerebral area were identified with a mirrored scalp distribution after left vs. right cerebellar stimulation. The P80 and N110 peaks were replicated in the cerebellar motor learning experiment and changed amplitude at different stages of learning. The change in amplitude of the P80 peak was associated with the degree of learning that individuals retained following adaptation. Due to overlap with sensory responses, the N110 should be interpreted with caution. ConclusionsCerebral potentials evoked by TMS of the lateral cerebellum provide a neurophysiological probe of cerebellar function that complements the existing CBI method. They may provide novel insight into mechanisms of visuomotor adaptation and other cognitive processes.

Cerebellar TMS Induces Motor Responses Mediating Modulation of Spinal Excitability: A Literature Review

Since individuals with cerebellar lesions often exhibit hypotonia, the cerebellum may contribute to the regulation of muscle tone and spinal motoneuron pool excitability. Neurophysiological methods using transcranial magnetic stimulation (TMS) of the cerebellum have been recently proposed for testing the role of the cerebellum in spinal excitability. Under specific conditions, single-pulse TMS administered to the cerebellar hemisphere or vermis elicits a long-latency motor response in the upper or lower limb muscles and facilitates the H-reflex of the soleus muscle, indicating increased excitability of the spinal motoneuron pool. This literature review examined the methods and mechanisms by which cerebellar TMS modulates spinal excitability.

Impact of cerebellar beta entrainment using non-invasive brain stimulation: Insights from an ongoing rhythmic TMS—EEG study in healthy human participants

Abstract Oscillations play a pivotal role in shaping cerebellar local activity and its communication with neocortical areas involved in learning motor skills. Previous studies have emphasized the presence and the potentially important role of beta (15-30 Hz) cerebellar oscillations in such processes. Yet, the distribution and causal nature of local and interregional synchronization patterns at such frequencies remain elusive. The present study aims to better understand the functional mechanisms by which the cerebellum synchronizes with widespread cortical regions. This will pave the way to identify and better modulate the specific electrophysiological properties of these networks. To this end, we sought to entrain beta frequency cerebellar oscillations with transcranial magnetic stimulation (TMS) and to characterize the cerebello-cortical synchronization patterns in the sensory-motor networks. A cohort of 20 healthy adult participants received trial-by-trial blocks of 4-pulses bursts of either rhythmic (20 Hz, experimental condition) or arrhythmic (control condition) TMS delivered over the right cerebellum, while EEG was also recorded. The stimulation of a right occipital/parietal cortical site performed in separate blocks served to assess the specificity of cerebellar stimulation. After cleaning and pre-processing, we computed and averaged the power and the inter-trial coherence of EEG signals elicited by TMS in frontal, central and parietal areas. Current interim analyses support the tolerability and feasibility of cerebellar TMS—EEG recordings, and our ability to assess signs of beta-induced entrainment while ruling out unspecific effects (artifacts triggered by the TMS clicking-sound, scalp-tapping, etc). This is the first study overcoming the limitations of ‘offline’ repetitive TMS approaches assessing effective connectivity between cerebellar and cerebral systems using TMS—EEG approaches. The outcome of this study will characterize the neurophysiological properties of cerebello-cortical communication based on frequency-specific synchronization mechanisms, which would ultimately influence learning processes. Research Category and Technology and Methods Basic Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Cerebellum, Oscillations, Entrainment, TMS-EEG

Assessing effective connectivity of the cerebellum with cerebral cortex using TMS-EEG

Background and objectivesThe cerebellum provides important input to the cerebral cortex but its assessment is difficult. Cerebellar brain inhibition tested by paired-coil transcranial magnetic stimulation (TMS) is limited to the motor cortex. Here we sought to measure responses to cerebellar TMS (cbTMS) throughout the cerebral cortex using electroencephalography (EEG). MethodsSingle-pulse TMS was applied with an induced upward current to the right cerebellar hemisphere in 46 healthy volunteers while recording EEG. Multiple control conditions, including TMS of right occipital cortex, cbTMS with induced downward current, and a sham condition modified specifically for cbTMS were tested to provide evidence for the specificity of the EEG responses evoked by cbTMS with an upward induced current. ResultsDistinct EEG response components could be specifically attributed to cbTMS, namely a left-hemispheric prefrontal positive deflection 25 ms after cbTMS, and a subsequent left-hemispheric parietal negative deflection peaking at 45 ms. In the time-frequency-response analysis, cbTMS induced a left-hemispheric prefrontal power increase in the high-beta frequency band. These responses were not seen in the control and sham conditions. ConclusionsThe EEG responses observed in this highly controlled experimental design may cautiously be attributed to reflect specific signatures of the activation of the cerebello-dentato-thalamo-cortical pathway by cbTMS. Therefore, these responses may provide biomarkers for assessing the integrity of this pathway, a proposition that will need further testing in clinical populations.

Bilateral Cerebellar Intermittent Theta Burst Stimulation Combined With Swallowing Speech Therapy for Dysphagia After Stroke: A Randomized, Double-Blind, Sham-Controlled, Clinical Trial

Background: Previous studies have found that high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellar hemisphere could improve swallowing function, but whether intermittent theta burst stimulation (iTBS), which has similar excitatory effect and higher efficiency, can also improve swallowing function for dysphagia after stroke remains unclear. Objective: This trial aimed to explore the efficacy and safety of bilateral cerebellar transcranial magnetic stimulation with iTBS for dysphagia after stroke. Methods: Seventy patients with dysphagia after stroke were divided into 2 treatment groups: true bilateral cerebellar iTBS and sham bilateral cerebellar iTBS. The true iTBS group underwent ten 100% resting motor threshold (RMT) iTBS sessions for 2 weeks. In the sham iTBS group, the parameters were the same except that the figure-eight coil was perpendicular to the skull. Both groups received traditional swallowing rehabilitation treatment 5 times a week for 2 weeks. Swallowing function was assessed with the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS), Penetration/Aspiration Scale (PAS), Standardized Swallowing Assessment (SSA), and Functional Oral Intake Scale (FOIS) at baseline, 2 weeks after the intervention, and at 4 weeks of follow-up. Results: There were significant time and group interaction effects in both multi-factorial adjusted and unadjusted FEDSS, PAS, SSA, and FOIS score (P < .001). In the pairwise comparison of the swallowing parameters among the 2 groups, the FEDSS, PAS, SSA, and FOIS scores at 2 weeks and 4 weeks showed a significantly higher improvement in the iTBS simulation group than sham group (P < .05). In both the true iTBS and sham iTBS stimulation groups, all FEDSS, PAS, SSA, and FOIS scores were significantly improved over time (P < .001). Conclusions: The present study suggested that as a more efficient TMS stimulation mode, iTBS could efficiently improve swallowing function by stimulating the bilateral cerebellar hemisphere. In addition, 100% resting motor threshold bilateral cerebellar iTBS is a relatively safe treatment. Clinical Trial Registration: Effect analysis of repeated transcranial magnetic stimulation of cerebellar on dysphagia after stroke. www.chictr.org.cn. Identifier: ChiCTR2100042092.

Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial

ObjectiveNegative symptoms of schizophrenia are substantially disabling and treatment resistant. Novel treatments like repetitive transcranial magnetic stimulation (TMS) need to be examined for the same using the experimental medicine approach that incorporates tests of mechanism of action in addition to clinical efficacy in trials. MethodsStudy was a double-blind, parallel, randomized, sham-controlled trial recruiting schizophrenia with at least a moderate severity of negative symptoms. Participants were randomized to real or sham intermittent theta burst stimulation (iTBS) under MRI-guided neuro-navigation, targeting the cerebellar vermis area VII-B, at a stimulus intensity of 100% active motor threshold, two sessions/day for five days (total = 6000 pulses). Assessments were conducted at baseline (T0), day-6 (T1) and week-6 (T2) after initiation of intervention. Main outcomes were, a) Scale for the Assessment of Negative Symptoms (SANS) score (T0, T1, T2), b) fronto-cerebellar resting state functional connectivity (RSFC) (T0, T1). ResultsThirty participants were recruited in each arm. Negative symptoms improved in both arms (p < 0.001) but was not significantly different between the two arms (p = 0.602). RSFC significantly increased between the cerebellar vermis and the right inferior frontal gyrus (pcluster-FWER = 0.033), right pallidum (pcluster-FWER = 0.042) and right frontal pole (pcluster-FWER = 0.047) in the real arm with no change in the sham arm. ConclusionCerebellar vermal iTBS engaged a target belonging to the class of cerebello-subcortical-cortical networks, implicated in negative symptoms of schizophrenia. However, this did not translate to a superior clinical efficacy. Future trials should employ enhanced midline cerebellar TMS stimulation parameters for longer durations that can potentiate and translate biological changes into clinical effects.

Probing cerebellar involvement in cognition through a meta-analysis of TMS evidence

Traditionally, the cerebellum has been linked to motor coordination, but growing evidence points to its involvement in a wide range of non-motor functions. Though the number of studies using transcranial magnetic stimulation (TMS) to investigate cerebellar involvement in cognitive processes is growing exponentially, these findings have not yet been synthesized in a meta-analysis. Here, we used meta-analysis to estimate the effects of cerebellar TMS on performance in cognitive tasks for healthy participants. Outcomes included participants’ accuracy and response times (RTs) of several non-motor tasks performed either during or after the administration of TMS. We included overall 41 studies, of which 44 single experiments reported effects on accuracy and 41 on response times (RTs). The meta-analyses showed medium effect sizes (for accuracy: d = 0.61 [95% CI = 0.48, .073]; for RTs: d = 0.40 [95% CI = 0.30, 0.49]), with leave-one-out analyses indicating that cumulative effects were robust, and with moderate heterogeneity. For both accuracy and RTs, the effect of TMS was moderated by the stimulation paradigm adopted but not by the cognitive function investigated, while the timing of the stimulation moderated only the effects on RTs. Further analyses on lateralization revealed no moderation effects of the TMS site. Taken together, these findings indicate that TMS administered over the cerebellum is able to modulate cognitive performance, affecting accuracy or RTs, and suggest that the various stimulation paradigms play a key role in determining the efficacy of cerebellar TMS.

Quantitative Evaluation of Cerebellar Function in Multiple System Atrophy with Transcranial Magnetic Stimulation.

Objective evaluation of cerebellar dysfunction in neurodegenerative disorders is often difficult because of other overlapping symptoms. Cerebellar inhibition (CBI) tested by dual-coil transcranial magnetic stimulation (TMS) is anticipated as a promising measure to estimate cerebellar function. Cerebellar TMS inhibits the primary motor cortex (M1), which can be measured as the decrease of motor evoked potential (MEP) elicited by a single-pulse TMS over the M1. This study was conducted to quantify cerebellar dysfunction using CBI in cerebellar type multiple system atrophy (MSA-C) patients. First, CBI was measured using MEP elicited from a hand muscle by stimulating the hand motor area of M1. The amount of CBI was defined as the degree of decrease in the MEP amplitude in the presence of cerebellar stimulation compared with the condition of M1 stimulation alone. Results of the MSA-C patients were compared with those of healthy volunteers. Correlation between amounts of CBI and a clinical scale of ataxia, the International Cooperative Ataxia Scale Rating (ICARS), was assessed. Healthy volunteers showed more inhibition than MSA-C patients. Moreover, ICARS showed that the CBI amount in the patients is correlated with the degree of ataxia significantly. Results suggest that CBI can be a good marker of disease progression in MSA-C patients.

Cerebellum and semantic memory: A TMS study using the DRM paradigm

Traditionally, the cerebellum has been linked to motor functions, but recent evidence suggest that it is also involved in a wide range of cognitive processes. Given the uniformity of cerebellar cortex microstructure, it has been proposed that the same computational process might underlie cerebellar involvement in both motor and cognitive functions. Within motor functions, the cerebellum it is involved in procedural memory and associative learning. Here, we hypothesized that the cerebellum may participate to semantic memory as well. To test whether the cerebellum is causally involved in semantic memory, we carried out two experiments in which participants performed the Deese-Roediger-McDermott paradigm (DRM) while online transcranial magnetic stimulation (TMS) was administered over the right cerebellum or over a control site. In Experiment 1, cerebellar TMS selectively affected participants' discriminability for critical lures without affecting participants’ discriminability for unrelated words and in Experiment 2 we found that the higher was the semantic association between new and studied words, the higher was the memory impairment caused by the TMS. These results indicate that the right cerebellum is causally involved in semantic memory and provide evidence consistent with theories that proposed the existence of a unified cerebellar function within motor and cognitive domains, as well with recent perspectives about cerebellar involvement in semantic memory and predictive functions.