Effects Of Cerebellar Stimulation Research Articles

Theta burst stimulation over left cerebellum does not modulate auditory feedback control of vocal production.

Accumulating evidence has shown significant contributions of the right cerebellum to auditory-motor integration for vocal production. Whether the left cerebellum is likewise involved in vocal motor control, however, remains unclear. By applying neuronavigated continuous and intermittent theta burst stimulation (cTBS/iTBS) over the left cerebellar lobule VII (Crus I), the present event-related potential (ERP) study investigated whether the left cerebellum exerts causal effects in modulating auditory feedback control of vocal pitch production. After receiving cTBS, iTBS, or sham stimulation over the left cerebellum, a group of fifteen young adults produced sustained vowels while hearing their voice unexpectedly shifted in pitch upwards or downwards by 200 cents. The effects of cerebellar stimulation were assessed by measuring the vocal and ERP (N1/P2) responses to pitch perturbations across the conditions. When compared to sham stimulation, cTBS or iTBS over the left cerebellar lobule VII (Crus I) led to no systematic changes in vocal compensations for pitch perturbations in auditory feedback. Also, the cortical N1/P2 responses did not vary significantly across the three stimulation sessions. These findings present the first neurobehavioral evidence suggesting that the left cerebellum is not causally associated with auditory feedback control of vocal production. Together with previously reported causal effects of the right cerebellum in modulating vocal pitch regulation, the present study lends support to the hypothesis that there is a functional lateralization of the cerebellum in vocal motor control though auditory feedback.

Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network

Chronic Levodopa therapy, the gold-standard treatment for Parkinson’s Disease (PD), leads to the emergence of involuntary movements, called levodopa-induced dyskinesia (LID). Cerebellar stimulation has been shown to decrease LID severity in PD patients. Here, in order to determine how cerebellar stimulation induces LID alleviation, we performed daily short trains of optogenetic stimulations of Purkinje cells (PC) in freely moving LID mice. We demonstrated that these stimulations are sufficient to suppress LID or even prevent their development. This symptomatic relief is accompanied by the normalization of aberrant neuronal discharge in the cerebellar nuclei, the motor cortex and the parafascicular thalamus. Inhibition of the cerebello-parafascicular pathway counteracted the beneficial effects of cerebellar stimulation. Moreover, cerebellar stimulation reversed plasticity in D1 striatal neurons and normalized the overexpression of FosB, a transcription factor causally linked to LID. These findings demonstrate LID alleviation and prevention by daily PC stimulations, which restore the function of a wide motor network, and may be valuable for LID treatment.

Combined effects of cerebellar tDCS and task-oriented circuit training in people with multiple sclerosis: A pilot randomized control trial.

Balance and mobility impairments are frequent in people with multiple sclerosis, partly due to cerebellar dysfunctions. Task-oriented behavioural approaches were previously shown to promote physical function. The possibility exists that cerebellar transcranial direct current stimulation (ctDCS) applied during training, known to increase the excitability of the brain, can boost rehabilitation effects through modulation of cerebellum-brain inhibition. To test the efficacy of cerebellar ctDCS stimulation combined with motor training on mobility and balance in people with multiple sclerosis. 16 subjects were randomly assigned to receive real- or sham-ctDCS and task-oriented training daily over two weeks in a double-blind, randomised clinical pilot trial. Functional mobility, balance, walking performance and quality of life were tested before and after treatment and at two-week follow-up. Effects of cerebellar stimulation on psychological and executive functions were also recorded. Walking performance, balance and quality of life improved for both groups at post-treatment assessment which was maintained at 2-weeks follow up. A two-way ANOVA revealed a significant time effect for balance and walking performance. A significant interaction effect of time-treatment (F = 3.12, df = 2,26; p = 0.03) was found for motor aspects of quality of life assessment in patients who received real-ctDCS. Task-oriented training improves balance and mobility in people with multiple sclerosis, but ctDCS does not boost motor training effects.

Cerebellar tDCS as Therapy for Cerebellar Ataxias.

In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques to influence cerebellar activity and the effects of cerebellar stimulation on other brain regions through its multiple complex projections. From the early 1990s, with the discovery of the so-called cerebellar inhibition (CBI), several studies have focused their attention on the use of cerebellar NIBS as treatment for different motor disorders. Cerebellar ataxias (CAs) represent the prototypical clinical manifestation of cerebellar alterations, but other movement disorders, such as Parkinson's disease, essential tremor, and dystonia have also been associated with alterations of networks which include the cerebellum, or of the cerebellum itself. Cerebellar transcranial direct current stimulation (ctDCS) could indeed represent an economical, non-invasive therapeutic tool with minimal side effects, thus improving the clinical management of patients and their quality of life. Studies show that ctDCS is effective as a therapeutic option for motor symptoms in patients with CAs, and especially in those with less severe forms, suggesting that ctDCS efficacy could result from augmented neuronal compensation, which itself relies on preserved cerebellar volume. Evidence for the efficacy of ctDCS is less conclusive for the other aforementioned motor disorders, although preliminary results are promising. Future studies should adopt more rigorous methods (e.g., larger sample sizes, double blinding, better characterization of the sample, reliable biomarkers), in order to allow the scientific community to derive higher-quality evidence on the efficacy of ctDCS as a therapeutic option for motor disorders.

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

BackgroundStimulating the cerebellum with transcranial magnetic stimulation is often perceived as uncomfortable. No study has systematically tested which coil design can effectively trigger a cerebellar response with the least discomfort. ObjectiveTo determine the relationship between perceived discomfort and effectiveness of cerebellar stimulation using different coils: MagStim (70 mm, 110 mm-coated, 110-uncoated), MagVenture and Deymed. MethodsUsing the cerebellar-brain inhibition (CBI) protocol, we conducted a CBI recruitment curve with respect to each participant’s maximum tolerated-stimulus intensity (MTI) to assess how effective each coil was at activating the cerebellum. ResultsOnly the Deymed double-cone coil elicited CBI at low intensities (−20% MTI). At the MTI, the MagStim (110 mm coated/uncoated) and Deymed coils produced reliable CBI, whereas no CBI was found with the MagVenture coil. Conclusions: The Deymed double-cone coil was most effective at cerebellar stimulation at tolerable intensities. These results can guide coil selection and stimulation parameters when designing cerebellar TMS studies.

Cerebellar repetitive transcranial magnetic stimulation restores pharyngeal brain activity and swallowing behaviour after disruption by a cortical virtual lesion.

Key points Despite evidence that the human cerebellum has an important role in swallowing neurophysiology, the effects of cerebellar stimulation on swallowing in the disrupted brain have not been explored.In this study, for the first time, the application of cerebellar neurostimulation is characterized in a human model of disrupted swallowing (using a cortical virtual lesion).It is demonstrated that cerebellar stimulation can reverse the suppressed activity in the cortical swallowing system and restore swallowing function in a challenging behavioural task, suggesting the findings may have important therapeutic implications. Repetitive transcranial magnetic stimulation (rTMS) can alter neuronal activity within the brain with therapeutic potential. Low frequency stimulation to the ‘dominant’ cortical swallowing projection induces a ‘virtual‐lesion’ transiently suppressing cortical excitability and disrupting swallowing behaviour. Here, we compared the ability of ipsi‐lesional, contra‐lesional and sham cerebellar rTMS to reverse the effects of a ‘virtual‐lesion’ in health. Two groups of healthy participants (n = 15/group) were intubated with pharyngeal catheters. Baseline pharyngeal motor evoked potentials (PMEPs) and swallowing performance (reaction task) were measured. Participants received 10 min of 1 Hz rTMS to the pharyngeal motor cortex which elicited the largest PMEPs to suppress cortical activity and disrupt swallowing behaviour. Over six visits, participants were randomized to receive 250 pulses of 10 Hz cerebellar rTMS to the ipsi‐lesional side, contra‐lesional side or sham while assessing PMEP amplitude or swallowing performance for an hour afterwards. Compared to sham, active cerebellar rTMS, whether administered ipsi‐lesionally (P = 0.011) or contra‐lesionally (P = 0.005), reversed the inhibitory effects of the cortical ‘virtual‐lesion’ on PMEPs and swallowing accuracy (ipsi‐lesional, P < 0.001, contra‐lesional, P < 0.001). Cerebellar rTMS was able to reverse the disruptive effects of a ‘virtual lesion’. These findings provide evidence for developing cerebellar rTMS into a treatment for post‐stroke dysphagia.

Effect of Cerebellar Stimulation on Gait and Balance Recovery in Patients With Hemiparetic Stroke

Gait and balance impairment is associated with poorer functional recovery after stroke. The cerebellum is known to be strongly implicated in the functional reorganization of motor networks in patients with stroke, especially for gait and balance functions. To determine whether cerebellar intermittent θ-burst stimulation (CRB-iTBS) can improve balance and gait functions in patients with hemiparesis due to stroke. This randomized, double-blind, sham-controlled phase IIa trial investigated efficacy and safety of a 3-week treatment of CRB-iTBS coupled with physiotherapy in promoting gait and balance recovery in patients with stroke. Thirty-six patients with consecutive ischemic chronic stroke in the territory of the contralateral middle cerebral artery with hemiparesis were recruited from a neuro-rehabilitation hospital. Participants were screened and enrolled from March 2013 to June 2017. Intention-to-treat analysis was performed. Patients were randomly assigned to treatment with CRB-iTBS or sham iTBS applied over the cerebellar hemisphere ipsilateral to the affected body side immediately before physiotherapy daily during 3 weeks. The primary outcome was the between-group difference in change from baseline in the Berg Balance Scale. Secondary exploratory measures included the between-group difference in change from baseline in Fugl-Meyer Assessment scale, Barthel Index, and locomotion assessment with gait analysis and cortical activity measured by transcranial magnetic stimulation in combination with electroencephalogram. A total of 34 patients (mean [SD] age, 64 [11.3] years; 13 women [38.2%]) completed the study. Patients treated with CRB-iTBS, but not with sham iTBS, showed an improvement of gait and balance functions, as revealed by a pronounced increase in the mean (SE) Berg Balance Scale score (baseline: 34.5 [3.4]; 3 weeks after treatment: 43.4 [2.6]; 3 weeks after the end of treatment: 47.5 [1.8]; P < .001). No overall treatment-associated differences were noted in the Fugl-Meyer Assessment (mean [SE], baseline: 163.8 [6.8]; 3 weeks after treatment: 171.1 [7.2]; 3 weeks after the end of treatment: 173.5 [6.9]; P > .05) and Barthel Index scores (mean [SE], baseline: 71.1 [4.92]; 3 weeks after treatment: 88.8 [2.1]; 3 weeks after the end of treatment: 92.2 [2.4]; P > .05). Patients treated with CRB-iTBS, but not sham iTBS, showed a reduction of step width at the gait analysis (mean [SE], baseline: 16.8 [4.8] cm; 3 weeks after treatment: 14.3 [6.2] cm; P < .05) and an increase of neural activity over the posterior parietal cortex. Cerebellar intermittent θ-burst stimulation promotes gait and balance recovery in patients with stroke by acting on cerebello-cortical plasticity. These results are important to increase the level of independent walking and reduce the risk of falling. ClinicalTrials.gov Identifier: NCT03456362.

Effects of Cerebellar Stimulation on Processing Semantic Associations

Current research in cerebellar cognitive and linguistic functions makes plausible the idea that the cerebellum is involved in processing temporally contiguous linguistic input. In order to assess this hypothesis, a lexical decision task was constructed to study the effects of cerebellar transcranial magnetic stimulation on semantic noun-to-verb priming based on association (e.g. 'soap-cleaning') or similarity (e.g. 'robbery-stealing'). The results demonstrated a selective increase in associative priming size after stimulation of a lateral cerebellar site. The findings are discussed in the contexts of a cerebellar role in linguistic expectancy generation and the corticocerebellar 'prefrontal' reciprocal loop.

Theta-burst stimulation of the right neocerebellar vermis selectively disrupts the practice-induced acceleration of lexical decisions.

The present study reports an experiment of cerebellar transcranial magnetic stimulation in a lexical decision task. In contrast to the study by Argyropoulos (2011), no effect of cerebellar stimulation was observed on priming sizes. However, when subjects confronted the same stimuli in the second session of participation, lexical decision latencies did not become any shorter after stimulation of the right neocerebellar vermis, in contrast to all other conditions. This finding is discussed in the light of current research in cerebellar cognitive and linguistic functions, and provides some first evidence for the recently entertained hypothesis that neocerebellar loci are significant in acquiring, storing, and retrieving associative memory traces of repeatedly co-occurring neural events in the language domain.

The effects of cerebellar stimulation on the motor cortical excitability in neurological disorders: a review.

The cerebellum regulates execution of skilled movements through neural connections with the primary motor cortex. A main projection from the cerebellum to the primary motor cortex is a disynaptic excitatory pathway relayed at the ventral thalamus. This dentatothalamocortical pathway receives inhibitory inputs from Purkinje cells of the cerebellar cortex. These pathways (cerebellothalamocortical pathways) have been characterized extensively using cellular approaches in animals. Advances in non-invasive transcranial activation of neural structures using electrical and magnetic stimulation have allowed us to investigate these neural connections in humans. This review summarizes various studies of the cerebellothalamocortical pathway in humans using current transcranial electrical and magnetic stimulation techniques. We studied effects on motor cortical excitability elicited by electrical or magnetic stimulation over the cerebellum by recording surface electromyographic (EMG) responses from the first dorsal interosseous (FDI) muscle. Magnetic stimuli were given with a round or figure eight coil (test stimulation) for primary motor cortical activation. For cerebellar stimulation, we gave high-voltage electrical stimuli or magnetic stimuli through a cone-shaped coil ipsilateral to the surface EMG recording (conditioning stimulation). We examined effects of interstimulus intervals (ISIs) with randomized condition-test paradigm, using a test stimulus given preceded by a conditioning stimulus by ISIs of several milliseconds. We demonstrated significant gain of EMG responses at an ISI of 3 ms (facilitatory effect) and reduced responses starting at 5 ms, which lasted 3-7 ms (inhibitory effect). We applied this method to patients with ataxia and showed that the inhibitory effect was only absent in patients with a lesion at cerebellar efferent pathways or dentatothalamocortical pathway. These results imply that this method activates the unilateral cerebellar structures. We confirmed facilitatory and inhibitory natures of cerebellothalamocortical pathways in humans. We can differentiate ataxia attributable to somewhere in the cerebello-thalamo-cortical pathways from that caused by other pathways.

The effects of cerebellar stimulation on alpha motoneuron excitability and the stretch reflex in the cat

The effects of cerebellar surface stimulation on electrically evoked monosynaptic and polysynaptic reflexes and the stretch reflex were investigated in cats anesthetized with alpha-chloralose. The electrically evoked monosynaptic and polysynaptic reflexes were recorded from the ventral root following stimulation of nerves innervating the anterior tibial and gastrocnemius-soleus muscles. These responses were averaged at various times after the initiation of cerebellar stimulation and compared with the amplitude of the control response. The effects of cerebellar surface stimulation on the stretch reflex were assessed while recording the multiunit EMG activity evoked by a passive sinusoidal stretch of the gastrocnemius-soleus muscle. Cycle histograms of this EMG activity were constructed during control periods and during cerebellar stimulation. The stimuli were applied to the lateral vermis of the anterior lobe and crus I and crus II of the posterior lobe. The effects of stimulating at different frequencies and charge densities were evaluated in each animal. The magnitude of the effects produced by cerebellar stimulation on these reflexes was highly dependent on the charge density and intensity of the cerebellar stimulus. In general, higher intensities and frequencies of surface stimulation produced greater reductions in the excitability of alpha motoneurons and the amplitude of the stretch reflex. Occasionally low frequency stimulation produced an increase in alpha-motoneuron excitability, particularly when the cerebellar stimuli were applied to the hemisphere. The results of this study indicate that the maximal reduction in motoneuron excitability and the amplitude of the stretch reflex is produced at different stimulus parameters in different animals. However, in each animal the effects evoked by a single set of stimulus parameters were consistent throughout the experiment. These results demonstrate that in an animal with an intact neuraxis cerebellar stimulation applied at relatively safe charge densities can produce dramatic reductions in the amplitudes of segmental reflexes. The inter-animal variability observed emphasizes the importance of establishing the optimal set of stimulus parameters in order to maximize the reduction in motoneuron excitability and stretch reflexes in each animal.

Effects of cerebellar stimulation on abnormal proprioceptive reflexes in spastic primates

The effects of cerebellar stimulation on the passively evoked electromyogram (EMG) responses of the biceps and triceps in spastic primates were studied. High-frequency stimulation decreased the abnormal cocontraction present during passive flexion and extension of the forearm. Furthermore, cerebellar stimulation resulted in a reciprocal pattern of EMG activity in the biceps and triceps, not present in control periods.

Correlation of clinical and physiological effects of cerebellar stimulation.

The value of clinical assessment of patients undergoing chronic cerebellar stimulation (CCS) is limited by lack of objective measures but neurophysiological tests can be used to "biocalibrate" the stimulator and may be used to predict effects of CCS. Eighty-seven patients undergoing CCS have been assessed clinically and neurophysiologically over the last 4 years. Somatosensory evoked responses were significantly ( p less than 0.05) reduced in amplitude in 35 patients, cortical somatosensory evoked responses in 44 patients and one or both responses were reduced in 55 patients. There were no clinical or physiological changes in 16 patients. Evoked responses showed significant changes in only 3 patients who did not show clinical improvement. The mean voltage settings were 5.2 volts and most patients were stimulated at 200 herz. These results indicate that significant changes in those somatosensory evoked potentials are a good indication of clinical benefits from CCS but clinical improvement may occur in the absence of any acute effect on evoked responses.

Two groups of cerebellar Purkinje cells in relation to the velocity of wrist movement

The effect of cerebellar stimulation on the accomodation of the lens was examined in anesthetized cats. An infrared optometer was used to measure the refractive power of the lens during stimulation of the cerebellum. The area giving responses within latencies shorter than 160 msec and amplitudes larger than 0.15 diopters is localized in the contralateral interpositus and fastigial nuclei and the ipsilateral interpositus nucleus. No responses could be evoked by stimulating the bilateral lateral nuclei. Accomodation responses were also evoked by cerebellar cortex stimulation. Accomodation responses evoked by stimulating the cerebellar nuclei were inhibited by preceding cerebellar cortical stimulation.

The cerebellar control of accomodation of the eye in the cat

The effect of cerebellar stimulation on the accomodation of the lens was examined in anesthetized cats. An infrared optometer was used to measure the refractive power of the lens during stimulation of the cerebellum. The area giving responses within latencies shorter than 160 msec and amplitudes larger than 0.15 diopters is localized in the contralateral interpositus and fastigial nuclei and the ipsilateral interpositus nucleus. No responses could be evoked by stimulating the bilateral lateral nuclei. Accomodation responses were also evoked by cerebellar cortex stimulation. Accomodation responses evoked by stimulating the cerebellar nuclei were inhibited by preceding cerebellar cortical stimulation.

Time course of clinical and physiological effects of stimulation of the cerebellar surface in patients with spasticity.

A double-blind study of the short-term (12--48 hours) effects of cerebellar stimulation was performed on 11 selected patients with spasticity. Six of patients had a good clinical long-term response to chronic stimulation, four had a moderate response, and one had no response. Each patient received stimulation for two periods of 24 hours and was off stimulation for two periods of 24 hours. The periods were randomised over four consecutive days. Neither the patients nor the observer could distinguish between the days on stimulation and the days off stimulation. Simple tests of function of the upper limbs during stimulation, measurements of H responses, tonic vibration responses, vibration-induced suppression of H responses, stretch responses, and co-contraction, showed no differences between the four days. These results are contrasted with acute physiological changes seen in some patients during stimulation and also with the slow progressive improvement in clinical function that characterises the successful clinical response. It is suggested that lack of either acute or short-term changes in response to cerebellar stimulation does not predict the clinical outcome. If the strength of stimulation is changed, at least three days and preferably 10 days should be allowed for the effects to appear. The mechanisms responsible for the alleviation of spasticity are likely to be more complex than those mediating acute and reversible changes in reflex activity.

The effect of cerebellar stimulation on focal seizure activity and spasticity in monkeys

Experiments were carried out in awake, unmedicated monkeys to determine the effect of application of current to the cerebellar hemispheres on electrically induced focal motor seizures and surgically induced spasticity. Application of current at various frequencies and pulse amplitudes did not significantly alter focal motor seizures but did significantly reduce spasticity. Analysis of evoked potential recordings carried out during various experimental procedures suggests that application of current to the cerebellar hemispheres may reduce cortical neuronal responsiveness.

Cortical seizures following cerebellar stimulation in primates

The effects of cerebellar stimulation were studied in monkeys with chronic alumina-cream epileptogenic foci in motor cortex. Low-frequency stimulation (5–15 c/sec) was ineffective in altering spontaneous cortical spiking. Clinical and electrographic seizures were elicited following high-frequency cerebellar stimulation (100 c/sec). This was a consistent finding following cerebellar stimulation, although no spontaneous seizures had been seen in these animals. These studies suggest the existence of facilitatory cerebellar mechanisms and indicate the need for further studies in chronic animal models.

Some effects of cerebellar stimulation

Rats were tested for approach and escape to cerebellar stimulation. None of the quantitative measures taken indicated that the stimulation was either rewarding or aversive. Face washing, face quivering, and freezing were observed during the escape trials, suggesting that the stimulation may not have been altogether neutral

Effects of cerebellar stimulation on cobalt-induced epilepsy in the cat

The occurrence of clinical and electrographic focal seizures following cobalt lesions in the contralateral sensori-motor cerebral cortex in the cat has been confirmed. Cerebellar cortical stimulation in the cat was not as effective in influencing these seizures as was cerebellar stimulation in the rat. If an influence was to be seen, it was most apt to be in initiating a seizure. This could occur either during or at the termination of stimulation. If cerebellar cortical stimulation was applied during a seizure, the latter was usually prolonged (but only seen when the stimulus rate was less than 10/sec). Midline cerebellar stimulation sites were more effective than were those located in the hemispheres. Of all areas studied, the pyramis (VIII A) was the stimulus site with the greatest probability of activating a cortical seizure focus. Stimulation of lobulus simplex (VI) seemed most apt to prolong the seizure activity. What evidence is available at this time suggests that the influence of the cerebellum on cobalt experimental epilepsy is more likely to be mediated by way of the reticular activating system rather than via the dentate thalamic projection system.