Cerebellar Brain Inhibition Research Articles

Transcranial direct current stimulation and transcranial random noise stimulation over the cerebellum differentially affect the cerebellum and primary motor cortex pathway

Transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS) are two methods of noninvasively modulating cortical excitability below the placed electrode. Anodal tDCS over the cerebellum has been shown to modulate cerebellar brain inhibition (CBI), which is an indication of cerebellar excitability, but does not alter contralateral M1 excitability. However, the effect of tRNS over the cerebellum has not been investigated. The purpose of this study was thus to compare the effects of tDCS and tRNS over the cerebellum on CBI and the contralateral motor evoked potentials (MEPs), as well as on the relationship between CBI and contralateral MEPs. A total of 15 healthy subjects completed four-condition transcranial electrical stimulation (tES) interventions (anodal tDCS_1 mA, anodal tDCS_2 mA, tRNS, and Sham) on separate days. CBI and MEPs were measured using transcranial magnetic stimulation (TMS) before and after the 20 min tES intervention. For all conditions, there were no significant differences before and after tES in CBI or contralateral MEPs. In contrast, following tRNS, changes in CBI and MEPs were significantly correlated. No significant correlations were found in the other three conditions, indicating that cerebellar tDCS and tRNS have distinct effects on the relationship between CBI and contralateral MEPs. Taken together, these findings suggest that cerebellar tRNS may modulate the cerebellar to contralateral M1 pathway.

Methodology, reliability, and limitations of measuring cerebellar brain inhibition in humans

Methodology, reliability, and limitations of measuring cerebellar brain inhibition in humans

Somatosensory inputs modulate the excitability of cerebellar-cortical interaction

ObjectiveTranscranial magnetic stimulation (TMS) delivered over the cerebellum 5–7 ms prior to a stimulus over the contralateral primary motor cortex (M1) reduces the excitability of M1 output, a phenomenon termed cerebellar brain inhibition (CBI). The cerebellum receives sensory information for adaptive motor coordination and motor planning. Here, we explored through TMS whether a peripheral electrical stimulus modulates CBI. MethodsWe studied the effect of right median nerve electrical stimulation (ES) on CBI from right cerebellum (conditioning stimulus, CS) to left M1 (test stimulus, TS) in 12 healthy subjects. The following ES-CS inter-stimulus intervals (ISIs) were tested: 25, 30 and 35 ms. CS-TS ISI was set at 5 ms. ResultsWe found significantly weaker CBI when the ES was delivered 25 ms (p < 0.001) and 35 ms (p < 0.001) earlier the CS over the ipsilateral cerebellum and a trend for 30 ms ES-CS ISI (p = 0.07). ConclusionsWe hypothesize that the activation of cerebellar interneurons together with intrinsic properties of Purkinje cells may be responsible of the decreased CBI when the peripheral stimulation preceded the cerebellar stimulation of 25 and 35 ms. SignificanceTo test the interaction between somatosensory inputs and cerebello-cortical pathway may be important in a variety of motor tasks and neuropsychiatric disorders.

The reliability of cerebellar brain inhibition

ObjectiveConnectivity between the cerebellum and primary motor cortex (M1) can be assessed by using transcranial magnetic stimulation to measure cerebellar brain inhibition (CBI). The aim of the present study was to determine the intra- and inter-day measurment error and relative reliability of CBI. The former informs the degree to which repeated measurements vary, whereas the latter informs how well the measure can distinguish individuals from one another within a sample. MethodsWe obtained CBI data from 83 healthy young participants (n = 55 retrospective). Intra-day measurements were separated by ~ 30 min. Inter-day measurmenets were separated by a minimum of 24 h. ResultsWe show that CBI has low measurement error (~15%) within and between sessions. Using the measurment error, we demonstrate that change estimates which exceed measurment noise are large at an individual level, but can be detected with modest sample sizes. Finally, we demonstrate that the CBI measurement has fair to good relative reliability in healthy individuals, which may be deflated by low sample heterogeneity. ConclusionsCBI has low measurement error supporting its use for tracking intra- and inter-day changes in cerebellar-M1 connectivity. SignificanceOur findings provide clear reliability guidelines for future studies assessing modulation of cerebellar-M1 connectivity with intervention or disease progression.

Emotional Face Expressions Influence the Delay Eye-blink Classical Conditioning

Recent evidence raised the importance of the cerebellum in emotional processes, with specific regard to negative emotions. However, its role in the processing of face emotional expressions is still unknown. This study was aimed at assessing whether face emotional expressions influence the cerebellar learning processes, using the delay eyeblink classical conditioning (EBCC) as a model. Visual stimuli composed of faces expressing happy, sad and neutral emotions were used as conditioning stimulus in forty healthy subjects to modulate the cerebellum-brainstem pathway underlying the EBCC. The same stimuli were used to explore their effects on the blink reflex (BR) and its recovery cycle (BRRC) and on the cerebellar-brain inhibition (CBI). Data analysis revealed that the learning component of the EBCC was significantly reduced following the passive view of sad faces, while the extinction phase was modulated by both sad and happy faces. By contrast, BR, BRRC and CBI were not significantly affected by the view of emotional face expressions. The present study provides first evidence that the passive viewing of faces displaying emotional expressions, are processed by the cerebellum, with no apparent involvement of the brainstem and the cerebello-cortical connection. In particular, the view of sad faces, reduces the excitability of the cerebellar circuit underlying the learning phase of the EBCC. Differently, the extinction phase was shortened by both happy and sad faces, suggesting that different neural bases underlie learning and extinction of emotions expressed by faces.

Cerebellar Brain Inhibition Is Associated With the Severity of Cervical Dystonia.

Cerebellar connectivity is thought to be abnormal in cervical dystonia (CD) and other dystonia subtypes, based on evidence from imaging studies and animal work. The authors investigated whether transcranial magnetic stimulation-induced cerebellar brain inhibition (CBI), a measure of cerebellar efficiency at inhibiting motor outflow, is abnormal in patients with CD and/or is associated with clinical features of CD. Because of methodological heterogeneity in CBI reporting, the authors deployed additional controls to reduce potential sources of variability in this study. Cerebellar brain inhibition was applied in 20 CD patients and 14 healthy control subjects. Cerebellar brain inhibition consisted of a cerebellar conditioning stimulus delivered at four different interstimulus intervals (ISIs) before a test stimulus delivered to hand muscle representation in the motor cortex. The average ratio of conditioned to unconditioned motor evoked potential was computed for each ISI. Cervical dystonia clinical severity was measured using the Toronto Western Spasmodic Torticollis Rating Scale. Control experiments involved neuronavigated transcranial magnetic stimulation, neck postural control in patients, and careful screening for noncerebellar pathway inhibition via cervicomedullary evoked potentials. There was no difference between CBI measured in healthy control subjects and CD patients at any of the four ISIs; however, CBI efficiency was significantly correlated with worsening CD clinical severity at the 5 ms ISI. Cerebellar brain inhibition is a variable measure in both healthy control subjects and CD patients; much of this variability may be attributed to experimental methodology. Yet, CD severity is significantly associated with reduced CBI at the 5 ms ISI, suggestive of cerebello-thalamo-cortical tract dysfunction in this disorder.

Reduced Cerebellar Brain Inhibition Measured Using Dual-Site TMS in Older Than in Younger Adults.

Dual-site transcranial magnetic stimulation (TMS) can be used to measure the cerebellar inhibitory influence on the primary motor cortex, known as cerebellar brain inhibition (CBI), which is thought to be important for motor control. The aim of this study was to determine whether age-related differences in CBI (measured at rest) were associated with an age-related decline in bilateral motor control measured using the Purdue Pegboard task, the Four Square Step Test, and a 10-m walk. In addition, we examined test re-test reliability of CBI measured using dual-site TMS with a figure-of-eight coil in two sessions. There were three novel findings. First, CBI was less in older than in younger adults, which is likely underpinned by an age-related loss of Purkinje cells. Second, greater CBI was associated with faster 10-m walking performance in older adults, but slower 10-m walking performance in younger adults. Third, moderate intraclass correlation coefficients (ICCs: 0.53) were found for CBI in younger adults; poor ICCs were found for CBI (ICC: 0.40) in older adults. Together, these results have important implications for the use of dual-site TMS to increase our understanding of age- and disease-related changes in cortical motor networks, and the role of functional connectivity in motor control.

Modulation of cerebellar brain inhibition during temporal adaptive learning in a coincident timing task.

In the present study, we examined the role of the cerebellum in temporal adaptive learning during a coincident timing task, i.e., a baseball-like hitting task involving a moving ball presented on a computer monitor. The subjects were required to change the timing of their responses based on imposed temporal perturbations. Using paired-pulse transcranial magnetic stimulation, we measured cerebellar brain inhibition (CBI) before, during, and after the temporal adaptive learning. Reductions in CBI only occurred during and after the temporal adaptive learning, regardless of the direction of the temporal perturbations. In addition, the changes in CBI were correlated with the magnitude of the adaptation. Here, we showed that the cerebellum is essential for learning about and controlling the timing of movements during temporal adaptation. Furthermore, changes in cerebellar-primary motor cortex connectivity occurred during temporal adaptation, as has been previously reported for spatial adaptation.

Single-Session Cerebellar Transcranial Direct Current Stimulation Affects Postural Control Learning and Cerebellar Brain Inhibition in Healthy Individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates cerebellar activity and postural control. However, the effects of ctDCS on postural control learning and the mechanisms associated with these effects remain unclear. To examine the effects of single-session ctDCS on postural control learning and cerebellar brain inhibition (CBI) of the primary motor cortex in healthy individuals. In this triple-blind, sham-controlled study, 36 participants were allocated randomly to one of three groups: (1) anodal ctDCS group, (2) cathodal ctDCS group, and (3) sham ctDCS group. ctDCS (2mA) was applied to the cerebellar brain for 20min prior to six blocks of standing postural control training (each block consisted of five trials of a 30-s tracking task). CBI and corticospinal excitability of the tibialis anterior muscle were assessed at baseline, immediately after, 1day after, and 7days after training. Skill acquisition following training was significantly reduced in both the anodal and cathodal ctDCS groups compared with the sham ctDCS group. Changes in performance measured 1day after and 7days after training did not differ among the groups. In the anodal ctDCS group, CBI significantly increased after training, whereas corticospinal excitability decreased. Anodal ctDCS-induced CBI changes were correlated with the learning formation of postural control (r = 0.55, P = 0.04). Single-session anodal and cathodal ctDCS could suppress the skill acquisition of postural control in healthy individuals. The CBI changes induced by anodal ctDCS may affect the learning process of postural control.

Cerebellar-Motor Cortex Connectivity: One or Two Different Networks?

Anterior-posterior (AP) and posterior-anterior (PA) pulses of transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) appear to activate distinct interneuron networks that contribute differently to two varieties of physiological plasticity and motor behaviors (Hamada et al., 2014). The AP network is thought to be more sensitive to online manipulation of cerebellar (CB) activity using transcranial direct current stimulation. Here we probed CB-M1 interactions using cerebellar brain inhibition (CBI) in young healthy female and male individuals. TMS over the cerebellum produced maximal CBI of PA-evoked EMG responses at an interstimulus interval of 5 ms (PA-CBI), whereas the maximum effect on AP responses was at 7 ms (AP-CBI), suggesting that CB-M1 pathways with different conduction times interact with AP and PA networks. In addition, paired associative stimulation using ulnar nerve stimulation and PA TMS pulses over M1, a protocol used in human studies to induce cortical plasticity, reduced PA-CBI but not AP-CBI, indicating that cortical networks process cerebellar inputs in distinct ways. Finally, PA-CBI and AP-CBI were differentially modulated after performing two different types of motor learning tasks that are known to process cerebellar input in different ways. The data presented here are compatible with the idea that applying different TMS currents to the cerebral cortex may reveal cerebellar inputs to both the premotor cortex and M1. Overall, these results suggest that there are two independent CB-M1 networks that contribute uniquely to different motor behaviors.SIGNIFICANCE STATEMENT Connections between the cerebellum and primary motor cortex (M1) are essential for performing daily life activities, as damage to these pathways can result in faulty movements. Therefore, developing and understanding novel approaches to probe this pathway are critical to advancing our understanding of the pathophysiology of diseases involving the cerebellum. Here, we show evidence for two distinct cerebellar-cerebral interactions using cerebellar stimulation in combination with directional transcranial magnetic stimulation (TMS) over M1. These distinct cerebellar-cerebral interactions respond differently to physiological plasticity and to distinct motor learning tasks, which suggests they represent separate cerebellar inputs to the premotor cortex and M1. Overall, we show that directional TMS can probe two distinct cerebellar-cerebral pathways that likely contribute to independent processes of learning.

The role of the cerebellum in degenerative ataxias and essential tremor: Insights from noninvasive modulation of cerebellar activity.

Over the last three decades, measuring and modulating cerebellar activity and its connectivity with other brain regions has become an emerging research topic in clinical neuroscience. The most important connection is the cerebellothalamocortical pathway, which can be functionally interrogated using a paired‐pulse transcranial magnetic stimulation paradigm. Cerebellar brain inhibition reflects the magnitude of suppression of motor cortex excitability after stimulating the contralateral cerebellar hemisphere and therefore represents a neurophysiological marker of the integrity of the efferent cerebellar tract. Observations that cerebellar noninvasive stimulation techniques enhanced performance of certain motor and cognitive tasks in healthy individuals have inspired attempts to modulate cerebellar activity and connectivity in patients with cerebellar diseases in order to achieve clinical benefit. We here comprehensively explore the therapeutic potential of these techniques in two movement disorders characterized by prominent cerebellar involvement, namely the degenerative ataxias and essential tremor. The article aims to illustrate the (patho)physiological insights obtained from these studies and how these translate into clinical practice, where possible by addressing the association with cerebellar brain inhibition. Finally, possible explanations for some discordant interstudy findings, shortcomings in our current understanding, and recommendations for future research will be provided. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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.

Editors' note: Cerebello-spinal tDCS in ataxia: A randomized, double-blind, sham-controlled, crossover trial

In “Cerebello-spinal tDCS in ataxia: A randomized, double-blind, sham-controlled, crossover trial,” Benussi et al. exposed 20 patients with neurodegenerative ataxia to cerebello-spinal transcranial direct current stimulation (tDCS) and sham stimulation and found that tDCS resulted in significant improvement in performance, motor cortex excitability, and cerebellar brain inhibition. Matsugi speculated that Benussi et al.'s findings demonstrate that spinal-cerebellar functional connectivity is retained in spinocerebellar ataxia and improved with tDCS. He noted that further study into cerebellar brain facilitation and inhibition and spinal direct current stimulation in this patient population are needed. Benussi et al. replied that they believe simultaneous spinal and cerebellar tDCS synergistically improves cerebellar function and spasticity, and agreed that further studies on the distinct and combined effects of cerebellar and spinal tDCS are needed, as stimulation may benefit this patient population for whom no drugs are available. In “Severe hyperhomocysteinemia manifesting as moyamoya vasculopathy and Henoch-Schonlein purpura,” Cho et al. described a 37-year-old woman with a history of Henoch-Schonlein purpura with leukocytoclastic vasculitis and immune mesangiopathic glomerulonephritis who presented with recurrent ischemic infarcts and was found to have hyperhomocysteinemia due to homozygous cystathionine β-synthase (CBS), then developed moyamoya vasculopathy requiring a direct bypass on the left and an encephalo-duro-arterio-synangiosis procedure on the right. The authors suggested that the cerebral, skin, and renal changes are all the result of CBS deficiency. In review of this case, Drs. Gaillard and Arquizan postulate that the underlying mechanism was likely a systemic vasculitis with CNS involvement and question whether (1) inflammatory markers, autoantibodies, and serologies were checked in serum or CSF, (2) a brain biopsy was obtained, or (3) a trial of steroids or immunosuppressants was given. Cho et al. respond that (1) serial cerebral angiograms showed progressive intracranial stenosis consistent with moyamoya vasculopathy, not with vasculitis, and (2) CSF showed no pleocytosis, and inflammatory and infectious tests were negative. They note that there was no recurrence of skin or renal events despite the absence of systemic therapy, making the diagnosis of secondary CNS vasculitis unlikely. While both Cho et al. and Drs. Gaillard and Arquizan agree that the high-resolution MRI was suggestive of vasculitis, Cho et al. believe it is consistent with a moyamoya-like vasculopathy and that this case represents a new phenotype of CBS deficiency.

Effects of cerebellar transcranial direct current stimulation on cerebellar-brain inhibition in humans: A systematic evaluation

BackgroundCerebellar transcranial direct current stimulation (ctDCS) is increasingly used to modulate cerebellar excitability and plasticity in healthy subjects and various patient populations. ctDCS parameters are poorly standardized, and its physiology remains little understood. Our aim was to compare the physiological effects of three different non-target electrode positions (buccinator muscle, supraorbital region, deltoid muscle). MethodsIn the first experiment, physiological after-effects of ctDCS were compared based on cerebellar-brain inhibition (CBI) in a group of 15 healthy right-handed participants. In the second experiment, CBI after-effects of ctDCS were assessed using different transcranial magnetic stimulation (TMS) intensities in 14 participants (CBI recruitment curve). The electric field distribution was calculated for each of the electrode montages based on a single anatomically accurate head model. ResultsAnodal and cathodal ctDCS polarities significantly decreased cerebellar-brain inhibition (CBI) with no substantial differences between the montages. Lower cerebellar TMS intensities resulted in decreased CBI following cathodal and increased CBI after anodal ctDCS. Computational modeling revealed minor differences in the electric field distribution between non-target electrode positions based on the effect size. ConclusionOur results show that the non-target electrode position has no significant impact on modeling results and physiological ctDCS after-effects. The recruitment of the cerebellar-M1 connection, however, varied depending on ctDCS polarity and cerebellar transcranial magnetic stimulation intensity, possibly due to diverse effects on different cell populations in the cerebellar cortex. This may be one of the reasons why ctDCS effects on functional measures are difficult to predict.

Methods for paired-pulse cerebellar-M1 TMS with neuronavigation

Background: Paired-pulse cerebellar brain inhibition (CBI) and cerebellar rTMS studies are inconsistent1. Methods of targeting the cerebellum and coil types used are variable, neuronavigation is difficult, and the availability of cooled double cone coils for cerebellar rTMS treatment protocols is limited.

Cerebello-spinal tDCS in ataxia

To investigate whether a 2-week treatment with cerebellar anodal and spinal cathodal transcranial direct current stimulation (tDCS) could reduce symptoms in patients with neurodegenerative ataxia and could modulate cerebello-motor connectivity at the short and long terms. We performed a double-blind, randomized, sham-controlled, crossover trial with cerebello-spinal tDCS (5 d/wk for 2 weeks) in 20 patients with neurodegenerative ataxia. Each patient underwent a clinical evaluation before and after real tDCS or sham stimulation. A follow-up evaluation was performed at 1 and 3 months with a crossover washout period of 3 months. Cerebello-motor connectivity was evaluated with transcranial magnetic stimulation at baseline and at each follow-up. Cerebello-spinal tDCS showed a significant improvement in all performance scores (Scale for the Assessment and Rating of Ataxia, International Cooperative Ataxia Rating Scale, 9-Hole Peg Test, 8-m walking time), in motor cortex excitability, and in cerebellar brain inhibition compared to sham stimulation. A 2-week treatment with cerebello-spinal tDCS reduces symptoms in patients with ataxia and restores motor cortex inhibition exerted by cerebellar structures. Cerebello-spinal tDCS might represent a promising future therapeutic and rehabilitative approach in patients with neurodegenerative ataxia, still an orphan disorder of any pharmacologic intervention. NCT03120013. This study provides Class II evidence that cerebello-spinal stimulation is effective and safe in cerebellar ataxia.

Both 50 and 30 Hz continuous theta burst transcranial magnetic stimulation depresses the cerebellum

The cerebellum is implicated in the pathophysiology of numerous movement disorders, which makes it an attractive target for noninvasive neurostimulation. Continuous theta burst stimulation (cTBS) can induce long lasting plastic changes in human brain; however, the efficacy of different simulation protocols has not been investigated at the cerebellum. Here, we compare a traditional 50-Hz and a modified 30-Hz cTBS protocols at modulating cerebellar activity in healthy subjects. Seventeen healthy adults participated in two testing sessions where they received either 50-Hz (cTBS50) or 30-Hz (cTBS30) cerebellar cTBS. Cerebellar brain inhibition (CBI), a measure of cerebello-thalamocortical pathway strength, and motor evoked potentials (MEP) were measured in the dominant first dorsal interosseous muscle before and after (up to ~ 40min) cerebellar cTBS. Both cTBS protocols induced cerebellar depression, indicated by significant reductions in CBI (P < 0.001). No differences were found between protocols (cTBS50 and cTBS30) at any time point (P = 0.983). MEP amplitudes were not significantly different following either cTBS protocol (P = 0.130). The findings show cerebellar excitability to be equally depressed by 50-Hz and 30-Hz cTBS in heathy adults and support future work to explore the efficacy of different cerebellar cTBS protocols in movement disorder patients where cerebellar depression could provide therapeutic benefits.

P107. Physiological mechanisms of cerebellar transcranial direct current stimulation in humans

Background Recently, transcranial direct current stimulation (tDCS) became a popular method to non-invasively modulate cerebellar excitability and help us broaden our understanding of cerebellar functions and introduce new therapeutic applications. Despite its popularity, its parameters, such as current polarity, stimulation intensity and electrode positions to induce specific effects have not yet been standardized. We aimed (1) to test the effects of tDCS with different electrode montages (see below) on cerebellar-brain inhibition (CBI) and (2) to explore the effect of tDCS on specific cerebellar-brain connections measured by the CBI recruitment curve (CBI-RC). Methods 15 and 14 young and healthy participants took part in Experiments 1 and 2, respectively. In all experiments, the target tDCS electrode was placed over the right cerebellar cortex. In Exp. 1, the return electrode over one of the following three positions: the right buccinator muscle, the left supraorbital area or the right deltoid muscle and in Exp. 2, it was positioned over the right buccinator muscle. CBI was measured by double-TMS protocol, with the conditioning stimulus (CS) over the right cerebellum with an intensity of 5% below the brainstem motor threshold (BMT) followed by the test pulse over the left primary motor cortex 5 ms later. For CBI-RC, five different CS intensities were used (−5%, −10%, −15%, −20%, −25% below BMT). The after-effects of 2 mA anodal or cathodal cerebellar tDCS on CBI or CBI-RC in Exp. 1 and 2, respectively, were measured before and for two hours after 15 min of tDCS. Results In Exp. 1, both tDCS polarities significantly decreased CBI for at least two hours compared to both sham and pre-stimulation values. No significant differences between different return electrode positions were observed. In Exp. 2, CBI was significantly increased after anodal and was decreased after cathodal tDCS with low CS intensities in a polarity-specific manner. Conclusions In accordance with the results reported by many studies, our results suggest that the return electrode positioning has no significant impact on the tDCS after-effects. The results of Exp. 2 show that the recruitment of the cerebellar-brain connections varies depending on tDCS polarity and CS intensity, suggesting that tDCS differently affects neurons in different layers of the cerebellar cortex. This polarity-specific dependence should be considered for tDCS applications and addressed in future studies. Funded by Mercur Pr-2015-0010 and SFB1280 (TP A05 and A06).

Cerebellar transcranial magnetic stimulation facilitates excitability of spinal reflex, but does not affect cerebellar inhibition and facilitation in spinocerebellar ataxia.

Transcranial magnetic stimulation (TMS) over the cerebellum facilitates the spinal reflex in healthy humans. The aim of this study was to investigate whether such cerebellar spinal facilitation (CSpF) appears in patients with spinocerebellar ataxia (SCA) presenting with atrophy in the cerebellar gray matter and dentate nucleus. One patient with SCA type 6 and another with SCA type 31 participated in this study. TMS over the right primary motor cortex was used to induce motor-evoked potentials in the right first dorsal interosseous muscle, which were detected using electromyography. Conditioning TMS using interstimulus intervals of 1–8 ms was performed over the right cerebellum as a test to measure cerebellar brain inhibition (CBI). To assess the H-reflex and the M-wave recruitment curve of the right soleus muscle, we performed electrical stimulation of the right tibial nerve. The stimulation intensity was set to that at the center of the H-reflex curve of the ascending limb. To measure CSpF, we delivered TMS over the right cerebellum 100, 110, 120, and 130 ms before the right tibial nerve stimulation. Voxel-based morphometry was used to verify the presence of atrophy in the cerebellar gray matter and dentate nucleus. CBI was absent in both cases. However, a significant facilitation of the H-reflex occurred with an interstimulus interval of 120 ms in both cases. These findings indicate that the pathways associated with the induction of CSpF and CBI are different, and that the cerebellar gray matter and dentate nucleus are not needed for the induction of CSpF. The possible origin of CSpF may be examined by stimulation of other cerebellar deep nuclei or the brainstem.

The Impact of Stimulation Intensity and Coil Type on Reliability and Tolerability of Cerebellar Brain Inhibition (CBI) via Dual-Coil TMS.

Cerebellar brain inhibition (CBI) describes the inhibitory tone the cerebellum exerts on the primary motor cortex (M1). CBI can be indexed via a dual-coil transcranial magnetic stimulation protocol, whereby a conditioning stimulus (CS) is delivered to the cerebellum in advance of a test stimulus (TS) to M1. The CS is typically delivered at intensities over 60% maximum stimulus output (MSO) via a double-cone coil. This is reportedly uncomfortable for participants, reducing the reliability and validity of outcomes. This feasibility study investigates the reliability and tolerability of eliciting CBI across a range of CS intensities using both a double-cone and high-powered figure-of-8 coil, the D702. It was expected that the double-cone coil would elicit CBI at intensities upwards of 60%MSO. The range for the D702 coil was exploratory. The double-cone coil was expected to be less tolerable than the D702 coil. CBI was assessed in 13 participants (25.92 ± 5.42years, six female) using each coil (randomized) over intensities 40, 50, 60, 70, 80%MSO. Tolerability was assessed via visual analog scales. Comparisons across intensities and tolerability were assessed non-parametrically and via a linear model. The double-cone coil elicited CBI at intensities 60, 70, and 80%MSO (p < .05), with suppression elicited at 60%MSO not significantly different to that at higher intensities. CBI was not reliably elicited by the D702 coil at any intensity. The double-cone coil was significantly less tolerable than the D702. A CS of 60%MSO with a double-cone coil provides a balance between the reliability and tolerability of CBI.