Cerebellar Brain Inhibition Research Articles

T118. Cerebellar inhibition in hepatic encephalopathy - A transcranial magnetic stimulation study

Introduction Hepatic Encephalopathy (HE) is a frequent complication in patients suffering from liver cirrhosis. HE comprises a variety of neuropsychiatric and motor symptoms. Increased ammonia levels have been suggested as a key factor in the disease pathology. Using animal models, Cauli and colleagues reported that hyperammonemia may lead to brain area depending alteration of GABAergic neurotransmission with an increase of GABAeric tone in the cerebellum and a decrease in the cerebral cortex. Consistent with this data, recent work from our group revealed a reduced GABAergic tone in the motor cortex of patients with manifest HE using transcranial magnetic stimulation (TMS). The aim of this study is to probe how GABAergic cerebellar tone is altered in patients at different stages of HE and how this alteration is related to clinical parameters such as the critical flicker frequency and ataxia scoring. Methods 30 participants [15 patients with HE (5 minimal HE, 6 HE grade I, and 4 HE grade II) and 15 age matched healthy controls] were subjected to the following: 1- Critical flicker frequency (CFF) which is a sensitive and reliable parameter for quantification of low-grade HE in cirrhotic patients. 2- Cerebellar brain inhibition TMS paradigm (CBI): in this paradigm, a conditioning TMS pulse is applied over one hemisphere of the cerebellum followed by a test pulse over the contralateral motor cortex resulting in a motor evoked potential (MEP). In healthy subjects, the MEP is inhibited when the test stimulus is preceded by the conditioning stimulus at an interval between 5 and 7 ms through inhibition of the fascilitatory disynaptic dentato-thalamo-cortical pathway. 3- Score for assessment and rating of ataxia (SARA) to detect symptoms of cerebellar affection. Results Cerebellar inhibition at ISI 5–7 ms was significantly reduced in patients with HE compared to healthy controls. However, the magnitude of cerebellar inhibition at 7 ms increased with disease severity and correlated with SARA score and with CFF by trend. Conclusion Overall cerebellar inhibition is significantly reduced in patients with HE, suggesting affection of the dentato-thalamo-cortical pathway in this disease. However, the magnitude of cerebellar inhibition at 7 ms increases with disease severity and correlates with SARA score and with CFF by trend, supporting the hypothesis of disease stage dependent increase of GABAergic tone in the Purkinje cells. Our results are consistent with pervious animal in vitro data suggesting increased GABA-ergic tone in the cerebellum and decreased GABA-ergic tone in the motor cortex.

Consensus Paper: Neurophysiological Assessments of Ataxias in Daily Practice

The purpose of this consensus paper is to review electrophysiological abnormalities and to provide a guideline of neurophysiological assessments in cerebellar ataxias. All authors agree that standard electrophysiological methods should be systematically applied in all cases of ataxia to reveal accompanying peripheral neuropathy, the involvement of the dorsal columns, pyramidal tracts and the brainstem. Electroencephalography should also be considered, although findings are frequently non-specific. Electrophysiology helps define the neuronal systems affected by the disease in an individual patient and to understand the phenotypes of the different types of ataxia on a more general level. As yet, there is no established electrophysiological measure which is sensitive and specific of cerebellar dysfunction in ataxias. The authors agree that cerebellar brain inhibition (CBI), which is based on a paired-pulse transcranial magnetic stimulation (TMS) paradigm assessing cerebellar-cortical connectivity, is likely a useful measure of cerebellar function. Although its role in the investigation and diagnoses of different types of ataxias is unclear, it will be of interest to study its utility in this type of conditions. The authors agree that detailed clinical examination reveals core features of ataxia (i.e., dysarthria, truncal, gait and limb ataxia, oculomotor dysfunction) and is sufficient for formulating a differential diagnosis. Clinical assessment of oculomotor function, especially saccades and the vestibulo-ocular reflex (VOR) which are most easily examined both at the bedside and with quantitative testing techniques, is of particular help for differential diagnosis in many cases. Pure clinical measures, however, are not sensitive enough to reveal minute fluctuations or early treatment response as most relevant for pre-clinical stages of disease which might be amenable to study in future intervention trials. The authors agree that quantitative measures of ataxia are desirable as biomarkers. Methods are discussed that allow quantification of ataxia in laboratory as well as in clinical and real-life settings, for instance at the patients' home. Future studies are needed to demonstrate their usefulness as biomarkers in pharmaceutical or rehabilitation trials.

O-1-25. Task-dependent modulation of cerebellar brain inhibition during motor imagery

The aim of study was to investigate cerebellar brain inhibition (CBI) is affected by imaginary muscle contraction (Contract-I) and relaxation (Relax-I) using paired pulse paradigm with transcranial magnetic stimulation (TMS) in healthy human. Participants performed tonic actual contraction and relaxation of right first dorsal interosseous (FDI) muscle with visual feedback using electromyography. The motor evoked potential (MEP) in right FDI induced by TMS over the left primary motor cortex with or without conditioning TMS over the right cerebellum was measured during no-imagery (No-I), Contract-I (1st experiment, n = 9) and Relax-I (2nd experiment, n = 20). MEP during Contract-I were larger than No-I, and MEP during Relax-I were smaller than those during No-I. In contrast, CBI (conditioned/unconditioned MEP) was higher during Contract-I compared to No-I, while there was no difference in CBI between Relax-I and No-I. These findings indicate that the cerebellum contributes facilitatory control of corticospinal excitability during imaginary muscle contraction, but the cerebellum have not affect the inhibitory control of corticospinal excitability during imaginary muscle relaxation.

The effects of imaginary voluntary muscle contraction and relaxation on cerebellar brain inhibition

The purpose of this study was to investigate cerebellar brain inhibition (CBI) of the contralateral primary motor cortex (M1) during imaginary muscle contraction (Contract-I) and relaxation (Relax-I) using transcranial magnetic stimulation (TMS). Twenty-nine healthy adults completed two experiments. Motor evoked potentials (MEPs) in the right first dorsal interosseous (FDI) muscle were induced by TMS over the left M1 and measured with or without TMS over the right cerebellum during Contract-I (first experiment) and Relax-I (second experiment) of the right FDI, and these were compared to the findings in a no-imagery (No-I) condition. MEPs during Contract-I were significantly higher than those during No-I, and MEPs during Relax-I were significantly lower than those during No-I. In contrast, CBI was significantly higher during Contract-I than during No-I, while there was no significant difference in CBI between Relax-I and No-I. These findings indicate that the cerebellum exerts facilitatory control over M1 excitability during imaginary muscle contraction but not during imaginary muscle relaxation.

P046 Cortico-cerebellar pathway contribution to stroke recovery

Introduction Upper limb impairment from stroke is a major factor interfering with the return to independence in activities in daily life. Given the vast number of processes that unfold following stroke, it is critical to explore the pathways for recovery. The cerebellar afferent dentato-thalamo-cortical (DRTC) pathway supports motor learning and motor control, and thus might be important for recovery from stroke. Objective To test for the relative contribution of the DRTC using a multi-modal approach that included assessment of pathway physiology using TMS and DTI. Patients & methods We investigated the contribution of the DRTC in motor recovery in 6 chronic stroke patients. We defined our recovery measure (Δ FM−UE ) as the Fugl-Meyer upper extremity score (FM-UE) change from week 52 (24 weeks for 1 patient) minus the FM-UE at 4 weeks postinfarct. At the chronic stage, we measured the structural and physiological efficacy of the DRTC using TMS, DTI, as well as behavioral assays. This involved: (1) cerebellar-brain inhibition (CBI) paired-pulse TMS to measure the strength of connectivity between the motor cortex and cerebellum; (2) region-based fractional anisotropy (FA) of canonical structures using DTI MultiAtlas Segmentation; (3) a center-out reaching task, which involved slicing movements to 1 of 8 targets spaced 10 cm from a central location without vision of their hand. Results Participants were well recovered (M FM−UE = 62.83) at the time of assessment. Using multiple linear regression to develop a predictive model of Δ FM−UE , we found that explained variance of the model approached 90% ( p = 0.006) with reach endpoint error variance and CBI amplitude selected as the independent variable inputs. Moreover, we found a similar relationship when using the Action Research Arm Test (ARAT) as a recovery scale (Δ ARAT ), with superior peduncle FA and a ratio of CBI between affected and unaffected limb accounting for 85% of the variance ( p = 0.024). Conclusion Our results indicate the importance of the cortico-cerebellar pathway in the recovery from stroke, and suggest that CBI might contribute additional diagnostic information beyond assessment of corticospinal tract integrity. In particular, these results suggest that the DRTC supports recovery for patients that have had a relatively high recovery in terms of FM-UE.

P297 Sensory plasticity changes induced by somatosensory and cerebellar tDCS in alert mice

Introduction During the past years, new evidence has revealed the importance of the cerebellar-brain-inhibition (CBI) pathway on cognitive and sensory processing. The modulation of the cerebellar cortex through non-invasive stimulation techniques, as transcranial direct-current stimulation (tDCS), could contribute to the better understanding of neuronal mechanisms underlying the implication of cerebellar cortex in these processes. Objectives The aim of this study was to explore cerebro-cerebellar interactions affecting long-term plasticity in the somatosensory (SS) cortex by modulating cerebral and cerebellar cortical excitability in behaving mice. Materials and methods Mice were prepared for the chronic recording of local field potentials (LFPs) in the SS cortex in response to electrical whisker pad stimulation, as well as for simultaneous tDCS. Animals received tDCS over the cerebellum or the SS cortex at different current intensities with a duration of 5 s to asses immediate effects, and during 20 min to address after-effects on SS-LFPs. tDCS effects on long-term plasticity processes in the SS cortex were determined by using two conditioning protocols consisting of 8 and 50 Hz whisker stimulation with a duration of 10 min and 96 s, respectively. Each protocol was combined with the simultaneous presentation of tDCS or sham condition. Results Anodal increased and cathodal decreased in an immediate way the amplitude of SS-LFPs when applied to the ipsilateral SS cortex, whereas the opposite effects were obtained when tDCS was presented to the contralateral cerebellar cortex. Concerning long-term after-effects, cathodal tDCS over the SS cortex induced a long-term depression of LFPs whereas no effects were observed after anodal currents. Long-term potentiation of SS-LFPs was evoked by both cathodal and anodal cerebellar tDCS. Finally and as expected, long-term depression and long-term potentiation of SS-LFPs induced by 8 and 50 Hz whisker stimulation were modulated by simultaneous cerebellar tDCS. Conclusions The results demonstrate the capability of tDCS to modulate the excitability of SS and cerebellar cortices, as well as the potential role of the cerebellar cortex in the control of plastic changes occurring in the sensory cortex of behaving animals.

Cerebellar transcranial static magnetic field stimulation transiently reduces cerebellar brain inhibition.

The aim of this study was to investigate whether transcranial static magnetic field stimulation (tSMS) delivered using a compact cylindrical NdFeB magnet over the cerebellum modulates the excitability of the cerebellum and contralateral primary motor cortex, as measured using cerebellar brain inhibition (CBI), motor evoked potentials (MEPs), and resting motor threshold (rMT). These parameters were measured before tSMS or sham stimulation and immediately, 5 minutes and 10 minutes after stimulation. There were no significant changes in CBI, MEPs or rMT over time in the sham stimulation condition, and no changes in MEPs or rMT in the tSMS condition. However, CBI was significantly decreased immediately after tSMS as compared to that before and 5 minutes after tSMS. Our results suggest that tSMS delivered to the cerebellar hemisphere transiently reduces cerebellar inhibitory output but does not affect the excitability of the contralateral motor cortex.

Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia.

Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. The present study investigated whether a two-weeks' treatment with cerebellar anodal tDCS could improve symptoms in patients with neurodegenerative cerebellar ataxia and could modulate cerebello-motor connectivity, at short and long term. We performed a double-blind, randomized, sham controlled trial with cerebellar tDCS (5 days/week for 2 weeks) in twenty patients with ataxia. Each patient underwent a clinical evaluation pre- and post-anodal tDCS or sham stimulation. A follow-up evaluation was performed at one and three months. Cerebello-motor connectivity was evaluated using transcranial magnetic stimulation (TMS) at baseline and at follow-up. Patients who underwent anodal 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) and in cerebellar brain inhibition compared to patients who underwent sham stimulation. A two-weeks' treatment with anodal cerebellar tDCS improves symptoms in patients with ataxia and restores physiological cerebellar brain inhibition pathways. Cerebellar tDCS might represent a promising future therapeutic and rehabilitative approach in patients with neurodegenerative ataxia.

Cerebellar brain inhibition in the target and surround muscles during voluntary tonic activation

Motor surround inhibition is the neural mechanism that selectively favours the contraction of target muscles and inhibits nearby muscles to prevent unwanted movements. This inhibition was previously reported at the onset of a movement, but not during a tonic contraction. Cerebellar brain inhibition (CBI) is reduced in active muscles during tonic activation; however, it has not been studied in the surround muscles. CBI was evaluated in the first dorsal interosseus (FDI) muscle as the target muscle, and the abductor digiti minimi, flexor carpi radialis and extensor carpi radialis muscles as surround muscles, during rest and tonic activation of the FDI muscle in 21 subjects. Cerebellar stimulation was performed under magnetic resonance imaging-guided neuronavigation targeting lobule VIII of the cerebellar hemisphere. Stimulus intensities for cerebellar stimulation were based on the resting motor cortex threshold (RMT) and adjusted for the depth difference between the cerebellar and motor cortices. We used 90-120% of the adjusted RMT as the conditioning stimulus intensity during rest. The intensity that generated the best CBI at rest in the FDI muscle was selected for use during tonic activation. During selective tonic activation of the FDI muscle, CBI was significantly reduced only for the FDI muscle, and not for the surround muscles. Unconditioned motor evoked potential sizes were increased in all muscles during FDI muscle tonic activation as compared with rest, despite background electromyography activity increasing only for the FDI muscle. Our study suggests that the cerebellum may play an important role in selective tonic finger movement by reducing its inhibition in the motor cortex only for the relevant agonist muscle.

Cerebro–cerebellar crosstalk in motor and cognitive domains

Relations between cerebral cortex and cerebellum have been addressed for more than a century, nevertheless, our knowledge of the cerebellar contribution to cerebral processing is far from complete. Cerebro–cerebellar anatomic connectivity is known to be organized in discrete «parallel circuits» organized such that cerebellar regions that receive input from a given cortical area, relay output back to the same cerebral area. Cerebello–cerebral physiologic interactions in the motor domain have been largely addressed and it is now well established that motor cortex excitability can be modulated by cerebellar output, and Cerebellar Brain Inhibition (CBI) is a well-known phenomenon. Recently developed high density EEG methods allow to address cerebro–cerebellar neurophysiologic interactions with a large-scale network approach. Coupling of cortical and cerebellar activity in a variety of motor and non-motor tasks is a well-known phenomenon and cortical activity changes have been observed after cerebellar lesion and more recently after cerebellar transcranial direct current cerebellar stimulation. Overall, coupling mechanisms between cortical and cerebellar activity can be considered bidirectional and cerebral cortex network changes in patients with focal cerebellar lesion may provide insight on the nature of cerebro–cerebellar interactions.

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults.

The cerebellum controls descending motor commands by outputs to primary motor cortex (M1) and the brainstem in response to sensory feedback. The cerebellum may also modulate afferent input en route to M1 and the brainstem. The objective of this study is to determine if anodal transcranial direct current stimulation (tDCS) to the cerebellum influences cerebellar brain inhibition (CBI), short afferent inhibition (SAI) and trigeminal reflexes (TRs) in healthy adults. Data from two studies evaluating effects of cerebellar anodal and sham tDCS are presented. The first study used a twin coil transcranial magnetic stimulation (TMS) protocol to investigate CBI and combined TMS and cutaneous stimulation of the digit to assess SAI. The second study evaluated effects on trigemino-cervical and trigemino-masseter reflexes using peripheral nerve stimulation of the face. Fourteen right-handed healthy adults participated in experiment 1. CBI was observed at baseline and was reduced by anodal cerebellar DCS only (P < 0.01). There was SAI at interstimulus intervals of 25 and 30ms at baseline (both P < 0.0001), but cerebellar tDCS had no effect. Thirteen right-handed healthy adults participated in experiment 2. Inhibitory reflexes were evoked in the ipsilateral masseter and sternocleidomastoid muscles. There was no effect of cerebellar DCS on either reflex. Anodal DCS reduced CBI but did not change SAI or TRs in healthy adults. These results require confirmation in individuals with neurological impairment.

Anodal transcranial direct current stimulation to the cerebellum improves handwriting and cyclic drawing kinematics in focal hand dystonia.

There is increasing evidence that the cerebellum has a role in the pathophysiology of primary focal hand dystonia and might provide an intervention target for non-invasive brain stimulation to improve function of the affected hand. The primary objective of this study was to determine if cerebellar transcranial direct current stimulation (tDCS) improves handwriting and cyclic drawing kinematics in people with hand dystonia, by reducing cerebellar-brain inhibition (CBI) evoked by transcranial magnetic stimulation (TMS). Eight people with dystonia (5 writer’s dystonia, 3 musician’s dystonia) and eight age-matched controls completed the study and underwent cerebellar anodal, cathodal and sham tDCS in separate sessions. Dystonia severity was assessed using the Writer’s Cramp Rating Scale (WRCS) and the Arm Dystonia Disability Scale (ADDS). The kinematic measures that differentiated the groups were; mean stroke frequency during handwriting and fast cyclic drawing and average pen pressure during light cyclic drawing. TMS measures of cortical excitability were no different between people with FHD and controls. There was a moderate, negative relationship between TMS-evoked CBI at baseline and the WRCS in dystonia. Anodal cerebellar tDCS reduced handwriting mean stroke frequency and average pen pressure, and increased speed and reduced pen pressure during fast cyclic drawing. Kinematic measures were not associated with a decrease in CBI within an individual. In conclusion, cerebellar anodal tDCS appeared to improve kinematics of handwriting and circle drawing tasks; but the underlying neurophysiological mechanism remains uncertain. A study in a larger homogeneous population is needed to further investigate the possible therapeutic benefit of cerebellar tDCS in dystonia.

NEUROPHYSIOLOGICAL CHARACTERIZATION OF CEREBELLO-THALAMO-CORTICAL CIRCUIT IN SWEDD PATIENTS.

Event Abstract Back to Event NEUROPHYSIOLOGICAL CHARACTERIZATION OF CEREBELLO-THALAMO-CORTICAL CIRCUIT IN SWEDD PATIENTS. Tommaso Schirinzi1*, Francesco Di Lorenzo1, Viviana Ponzo2, Anna Rita Bentivoglio3, Antonio Pisani1 and Giacomo Koch2 1 Università di Roma Tor Vergata, Italy 2 IRCCS Fondazione Santa Lucia, Italy 3 Università Cattolica del Sacro Cuore, Italy Introduction: Patients with a clinical diagnosis of Parkinson’s Disease (PD) and normal dopaminergic functional imaging are called SWEDD (scans without evidence of dopaminergic deficit). One of the main clinical features of SWEDD is an asymmetric rest tremor poorly responsive to levodopa. Several evidence suggests that an abnormal activity in the Cerebello-Thalamo-Cortical (CTC) circuit is involved in the pathophysiology of tremor. In this study we provided a neurophysiological characterization of the CTC pathway of SWEDD patients in comparison to idiopathic PD patients and healthy subjects (HS). Materials and Methods: We enrolled 11 SWEDD patients, 8 PD patients and 6 HS. CTC circuit was investigated by a Cerebellar-Brain Inhibition (CBI) protocol and also by the after-effects on MEP amplitude of cerebellar Continuous-Theta-Burst-Stimulation (CTBS). Results: in SWEDD patients the CBI differed from PD patients but not from HS. Cerebellar CTBS induced long-lasting cortical inhibition of MEP amplitude in SWEDDs and HS but not in PD. Conclusions: SWEDD patients seem to have normal CTC pathway functioning compared to PD. This data may suggest that in SWEDD patients motor disturbances are unrelated to a CTC dysfunction. However, it must be pointed out that these findings may have been affected by the relatively small number of subjects, that warrants further additional investigations on larger sample groups. Keywords: swedd, Tremor, TMS, CBI, cerebello-cortical networks Conference: 5th Biennial Workshop on Dystonia: “Controversies in Dystonia and Parkinsonism” | Nobile Collegio Chimico Farmaceutico, Rome, May 29-30, 2015, Rome, Italy, 29 May - 30 May, 2015. Presentation Type: Poster presentation Topic: Pathophysiology of dystonia and parkinsonism Citation: Schirinzi T, Di Lorenzo F, Ponzo V, Bentivoglio A, Pisani A and Koch G (2015). NEUROPHYSIOLOGICAL CHARACTERIZATION OF CEREBELLO-THALAMO-CORTICAL CIRCUIT IN SWEDD PATIENTS.. Front. Neurol. Conference Abstract: 5th Biennial Workshop on Dystonia: “Controversies in Dystonia and Parkinsonism” | Nobile Collegio Chimico Farmaceutico, Rome, May 29-30, 2015. doi: 10.3389/conf.fneur.2015.57.00009 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 May 2015; Published Online: 08 May 2015. * Correspondence: MD. Tommaso Schirinzi, Università di Roma Tor Vergata, Rome, Italy, t.schirinzi@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Tommaso Schirinzi Francesco Di Lorenzo Viviana Ponzo Anna Rita Bentivoglio Antonio Pisani Giacomo Koch Google Tommaso Schirinzi Francesco Di Lorenzo Viviana Ponzo Anna Rita Bentivoglio Antonio Pisani Giacomo Koch Google Scholar Tommaso Schirinzi Francesco Di Lorenzo Viviana Ponzo Anna Rita Bentivoglio Antonio Pisani Giacomo Koch PubMed Tommaso Schirinzi Francesco Di Lorenzo Viviana Ponzo Anna Rita Bentivoglio Antonio Pisani Giacomo Koch Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Application of Non-invasive Brain Stimulation for Neurorehabilitation: Cerebellar Stimulation

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

Effects of two weeks of cerebellar theta burst stimulation in cervical dystonia patients.

Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.

Cerebellar transcranial magnetic stimulation: the role of coil geometry and tissue depth.

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

Cerebellar theta burst stimulation in stroke patients with ataxia

Evidence for effective improvement of the symptoms of cerebellar stroke is still limited. Here, we investigated the effects of repetitive transcranial magnetic stimulation (rTMS) applied over the injured cerebellar hemisphere in six patients with posterior circulation stroke. We applied a two-week course of cerebellar intermittent theta burst stimulation (iTBS). Before and after the iTBS treatment, paired-pulse TMS methods were used to explore: i) the functional connectivity between the cerebellar hemisphere and the contralateral primary motor cortex (M1), by means of the cerebellar brain inhibition (CBI) protocol; and ii) the intracortical circuits in the contralateral M1, by means of the short intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF) protocols. Patients were also evaluated using the Modified International Cooperative Ataxia Rating Scale (MICARS). Cerebellar iTBS induced a decrease in CBI and an increase in ICF at an interstimulus interval of 15 msec. These neurophysiological changes were paralleled by a clinical improvement, shown by the MICARS posture and gait subscale scores. Cerebellar iTBS could be a promising tool to promote recovery of cerebellar stroke patients.

54. Cerebellar-cortical-subcortical connectivity in patients with Progressive Sopranuclear Palsy (PSP) is modulated by cerebellar intermittent theta burst stimulation

Progressive-Sopranuclear-Palsy (PSP) is an atypical parkinsonian syndrome. Recent imaging studies revealed specific cerebellar abnormalities able to discriminate PSP from other parkinsonisms. Moreover, transcranial magnetic stimulation (TMS) studies demonstrated a subclinical cerebellar involvement in PSP compatible with the severe degeneration of dentate nucleus. Thus, we applied an intermittent theta burst stimulation (iTBS) protocol over the cerebellum on PSP patients to investigate the cerebello-thalamo-cortical circuits. To characterize the physiological effects of 2 weeks of iTBS applied bilaterally over the cerebellum, we examined cerebellar brain inhibition (CBI), the intracortical inhibition (SICI) and facilitation (ICF), in addition to resting-state functional magnetic resonance (fMRI) and clinical rating state assessment. Cerebellar iTBS increased the deficient functional connectivity in CBI. No effects were seen for SICI and ICF. Resting-state fMRI revealed an increased signal in the head of the caudate nucleus bilaterally. Clinical data showed a significant improvement of dysarthria in all patients and of gait. These findings provide further functional evidence of increasing the excitability of the cerebellar hemispheres by means of iTBS resulted in an improvement of the cerebello-thalamo-cortical circuits, related with some mild clinical improvement. Identify and develop new therapeutic strategies to improve clinical symptoms on PSP patients.

Study of Cerebello-Thalamocortical Pathway by Transcranial Magnetic Stimulation in Parkinson's Disease

BackgroundAlthough functional changes in the activation of the cerebellum in Parkinson's disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms. Objective/HypothesisWe used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment. MethodsWe studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition—CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls. Moreover, we also tested the effects of cerebellar continuous theta-burst stimulation (cTBS) on MEP amplitude, short intracortical inhibition (SICI) and short intracortical facilitation (SICF) tested in the contralateral M1 in 13 PD patients in ON and OFF and in 16 age-matched healthy controls. ResultsCBI was evident in controls but not in PD patients, even when tested in both ON and OFF conditions. Similarly, cerebellar cTBS reduced MEP amplitude and SICI in controls but not in PD patients under any condition. Conclusion(s)These results demonstrate that PD patients have deficient short-latency and long-lasting cerebellar-thalamocortical inhibitory interactions that cannot be promptly restored by standard dopaminergic medication.

Can cerebellar transcranial direct current stimulation become a valuable neurorehabilitation intervention?

Can cerebellar transcranial direct current stimulation become a valuable neurorehabilitation intervention?