Cerebellar Intermittent Theta Burst Stimulation Research Articles

Effects of one-week bilateral cerebellar iTBS on resting-state functional brain network and multi-task attentional performance in healthy individuals: A randomized, sham-controlled trial

Background:Cerebellar intermittent theta burst stimulation (iTBS) modulates the excitability of the cerebral cortex and may enhance attentional performance. To date, few studies have conducted iTBS on healthy subjects for one week and used electroencephalography (EEG) to investigate the effect of multiple stimulation sessions on resting-state functional brain networks and the daily stimulation effect on attentional performance. Methods:16 healthy subjects participated in a one-week experiment, receiving bilateral cerebellar iTBS or sham stimulation and engaging in multi-task attentional training. The primary measures were the one-week attentional performance and pre- and post-experiment resting-state EEG activities. Amplitude Envelope Correlation (AEC) was used to construct the functional connectivity in the eye-open (EO) and eye-closed (EC) phases. Results:At least three sessions of iTBS were required to enhance multi-task performance significantly, whereas only one or two sessions failed to elicit the improvement. Compared with the control group, iTBS induced significant changes in PSD, AEC functional connectivity, and AEC network properties during the EO phase, while it had little effect during the EC phase. During the EO phase, the network property changes of the iTBS subject were correlated with improved attentional performance. Conclusion:The multi-task performance requires multiple stimulations to enhance. iTBS affects the resting-state alpha band brain activities during the EO rather than the EC phase. The AEC network properties may serve as a biomarker to assess the attentional potential of healthy subjects.

EEG microstates analysis after TMS in patients with subacute stroke during the resting state.

To investigate whether intermittent theta burst stimulation over the cerebellum induces changes in resting-state electroencephalography microstates in patients with subacute stroke and its correlation with cognitive and emotional function. Twenty-four stroke patients and 17 healthy controls were included in this study. Patients and healthy controls were assessed at baseline, including resting-state electroencephalography and neuropsychological scales. Fifteen patients received lateral cerebellar intermittent theta burst stimulation as well as routine rehabilitation training (intermittent theta burst stimulation-RRT group), whereas 9 patients received only conventional rehabilitation training (routine rehabilitation training group). After 2wk, baseline data were recorded again in both groups. Stroke patients exhibited reduced parameters in microstate D and increased parameters in microstate C compared with healthy controls. However, after the administration of intermittent theta burst stimulation over the lateral cerebellum, significant alterations were observed in the majority of metrics for both microstates D and C. Lateral cerebellar intermittent theta burst stimulation combined with conventional rehabilitation has a stronger tendency to improve emotional and cognitive function in patients with subacute stroke than conventional rehabilitation. The improvement of mood and cognitive function was significantly associated with microstates C and D. We identified electroencephalography microstate spatiotemporal dynamics associated with clinical improvement following a course of intermittent theta burst stimulation therapy.

Specific sensorimotor interneuron circuits are sensitive to cerebellar-attention interactions.

Background: Short latency afferent inhibition (SAI) provides a method to investigate mechanisms of sensorimotor integration. Cholinergic involvement in the SAI phenomena suggests that SAI may provide a marker of cognitive influence over implicit sensorimotor processes. Consistent with this hypothesis, we previously demonstrated that visual attention load suppresses SAI circuits preferentially recruited by anterior-to-posterior (AP)-, but not posterior-to-anterior (PA)-current induced by transcranial magnetic stimulation. However, cerebellar modulation can also modulate these same AP-sensitive SAI circuits. Yet, the consequences of concurrent cognitive and implicit cerebellar influences over these AP circuits are unknown.Objective: We used cerebellar intermittent theta-burst stimulation (iTBS) to determine whether the cerebellar modulation of sensory to motor projections interacts with the attentional modulation of sensory to motor circuits probed by SAI.Methods: We assessed AP-SAI and PA-SAI during a concurrent visual detection task of varying attention load before and after cerebellar iTBS.Results: Before cerebellar iTBS, a higher visual attention load suppressed AP-SAI, but not PA-SAI, compared to a lower visual attention load. Post-cerebellar iTBS, the pattern of AP-SAI in response to visual attention load, was reversed; a higher visual attention load enhanced AP-SAI compared to a lower visual attention load. Cerebellar iTBS did not affect PA-SAI regardless of visual attention load.Conclusion: These findings suggest that attention and cerebellar networks converge on overlapping AP-sensitive circuitry to influence motor output by controlling the strength of the afferent projections to the motor cortex. This interaction has important implications for understanding the mechanisms of motor performance and learning.

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

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

Cerebellar Intermittent Theta-Burst Stimulation Reduces Upper Limb Spasticity After Subacute Stroke: A Randomized Controlled Trial.

Objective: This study aims to explore the efficacy of cerebellar intermittent theta-burst stimulation (iTBS) on upper limb spasticity in subacute stroke patients.Methods: A total of 32 patients with upper limb spasticity were enrolled and randomly assigned to treatment with cerebellar iTBS or sham stimulation before conventional physical therapy daily for 2 weeks. The primary outcomes included the modified Ashworth scale (MAS), the modified Tardieu scale (MTS), and the shear wave velocity (SWV). The secondary outcomes were the H-maximum wave/M-maximum wave amplitude ratio (Hmax/Mmax ratio), motor-evoked potential (MEP) latency and amplitude, central motor conduction time (CMCT), and the Barthel Index (BI). All outcomes were evaluated at baseline and after 10 sessions of intervention.Results: After the intervention, both groups showed significant improvements in the MAS, MTS, SWV, and BI. In addition, patients treated with cerebellar iTBS had a significant increase in MEP amplitude, and patients treated with sham stimulation had a significant decrease in Hmax/Mmax ratio. Compared with the sham stimulation group, the MAS, MTS, and SWV decreased more in the cerebellar iTBS group.Conclusion: Cerebellar iTBS is a promising adjuvant tool to reinforce the therapeutic effect of conventional physical therapy in upper limb spasticity management after subacute stroke (Chinese Clinical Trial Registry: ChiCTR1900026516).

Cerebellar Theta Burst Stimulation on Walking Function in Stroke Patients: A Randomized Clinical Trial.

Objectives: The objective of this study was to explore the efficacy of cerebellar intermittent theta burst stimulation (iTBS) on the walking function of stroke patients.Methods: Stroke patients with walking dysfunction aged 25–80 years who had suffered their first unilateral stroke were included. A total of 36 patients [mean (SD) age, 53 (7.93) years; 10 women (28%)] were enrolled in the study. All participants received the same conventional physical therapy, including transfer, balance, and ambulation training, during admission for 50 min per day during 2 weeks (10 sessions). Every session was preceded by 3 min procedure of cerebellar iTBS applyed over the contralesional cerebellum in the intervention group or by a similar sham iTBS in control group. The groups were formed randomly and the baseline characteristics showed no significant difference. The primary outcome measure was Fugl–Meyer Assessment–Lower Extremity scores. Secondary outcomes included walking performance and corticospinal excitability. Measures were performed before the intervention beginning (T0), after the first (T1) and the second (T2) weeks.Results: The Fugl–Meyer Assessment for lower extremity scores slightly improved with time in both groups with no significant difference between the groups and over the time. The walking performance significantly improved with time and between group. Two-way mixed measures ANOVA showed that there was significant interaction between time and group in comfortable walking time (F2,68 = 6.5242, P = 0.0080, η2partial = 0.276, ε = 0.641), between-group comparisons revealed significant differences at T1 (P = 0.0072) and T2 (P = 0.0133). The statistical analysis of maximum walking time showed that there was significant interaction between time and groups (F2,68 = 5.4354, P = 0.0115, η2partial = 0.198, ε = 0.734). Compared with T0, the differences of maximum walking time between the two groups at T1 (P = 0.0227) and T2 (P = 0.0127) were statistically significant. However, both the Timed up and go test and functional ambulation category scale did not yield significant differences between groups (P > 0.05).Conclusion: Our results revealed that applying iTBS over the contralesional cerebellum paired with physical therapy could improve walking performance in patients after stroke, implying that cerebellar iTBS intervention may be a noninvasive strategy to promote walking function in these patients. This study was registered at ChiCTR, number ChiCTR1900026450.

Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)

Spinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38.

Repetitive transcranial magnetic stimulation of the cerebellum improves ataxia and cerebello-fronto plasticity in multiple system atrophy: a randomized, double-blind, sham-controlled and TMS-EEG study.

Cerebellar ataxia is the predominant motor feature of multiple system atrophy cerebellar subtype (MSA-C). Although repetitive transcranial magnetic stimulation (TMS) of the cerebellum is growingly applied in MSA, the mechanism is unknown. We examined dynamic connectivity changes of 20 patients with MSA and 25 healthy controls using TMS combined with electroencephalography. Observations that significantly decreased dynamic cerebello-frontal connectivity in patients have inspired attempts to modulate cerebellar connectivity in order to benefit MSA. We further explore the therapeutic potential of a 10-day treatment of cerebellar intermittent theta burst stimulation (iTBS) in MSA by a randomized, double-blind, sham-controlled trial. The functional reorganization of cerebellar networks was investigated after the end of treatment in active and sham groups. The severity of the symptoms was evaluated using the Scale for Assessment and Rating of Ataxia scores. Patients treated with active stimulation showed an improvement of cerebello-frontal connectivity and balance functions, as revealed by a significant decrease in the ataxia scores (P < 0.01). Importantly, the neural activity of frontal connectivity from 80 to 100 ms after a single TMS was significantly related to the severity of the disease. Our study provides new proof that cerebellar iTBS improves motor imbalance in MSA by acting on cerebello-cortical plasticity.

Cerebellar Intermittent Theta-Burst Stimulation Combined with Vestibular Rehabilitation Improves Gait and Balance in Patients with Multiple Sclerosis: a Preliminary Double-Blind Randomized Controlled Trial.

Difficulties in gait and balance disorders are among the most common mobility limitations in multiple sclerosis (MS), mainly due to a damage of cerebellar circuits. Moreover, the cerebellum plays a critical role in promoting new motor tasks, which is an essential function for neurorehabilitation. In this study, we investigated the effects of cerebellar intermittent theta burst stimulation (c-iTBS), a high-frequency rTMS protocol able to increase cerebellar activity, on gait and balance in a sample of 20 hospitalized participants with MS, undergoing vestibular rehabilitation (VR), an exercise-based program primarily designed to reduce vertigo and dizziness, gaze instability, and/or imbalance and falls in MS. Patients were assigned to receive either c-iTBS or sham iTBS before being treated with VR during 2weeks. VR consisted of two types of training: gaze stability and postural stability exercises. The primary outcome measure was the change from baseline in the Tinetti Balance and Gait scale (TBG). The secondary outcome measures were changes from baseline in Berg Balance Scale (BBS), Fatigue Severity Scale (FSS), Two Minute Walking Test (2MWT), and Timed 25-ft walk test (T25FW) scales. MS patients treated with c-iTBS-VR showed a significant improvement in the TBG as compared to patients treated with sham iTBS-VR. Moreover, MS patients in the c-iTBS groups showed better performances in the vestibular-ocular reflex exercises. Combined c-iTBS and VR improves gait and balance abilities more than standard VR treatment in MS patients with a high level of disability.

Intermittent Cerebellar Theta Burst Stimulation Improves Visuo-motor Learning in Stroke Patients: a Pilot Study.

The cerebellum plays a critical role in promoting learning of new motor tasks, which is an essential function for motor recovery. Repetitive transcranial magnetic stimulation (rTMS) of the cerebellum can be used to enhance learning. In this study, we investigated the effects of cerebellar intermittent theta burst stimulation (c-iTBS), a high-frequency rTMS protocol, on visuo-motor learning in a sample of hemiparetic patients due to recent stroke in the territory of the contralateral middle cerebral artery. Eight stroke patients were enrolled for the purposes of the study in the chronic stage of recovery (i.e., at least 6months after stroke). In two sessions,Patients were randomly assigned to treatment with real or sham c-iTBS applied over the cerebellar hemisphere ipsilateral to the affected body side. c-iTBS was applied immediately before the learning phase of a visuo-motor adaptation task. Real, but not sham, c-iTBS improved visuo-motor learning as revealed by an increased performance in of the learning phase of the visuo-moto adaptation task. Moreover, we also found that real but not sham c-iTBS induced a sustained improvement in the re-adaptation of the recently learned skill (i.e., when patients were re-tested after 30min). Taken together, these data point to c-iTBS as a potential novel strategy to promote motor learning in patients with stroke.

Abstract WP195: Cerebellar Magnetic Stimulation for Long-Lasting Dizziness After Brainstem Stroke

Introduction: Brainstem stroke sometimes causes long-lasting dizziness. A cerebellar control disorder of the vestibulo-ocular reflex (VOR) has been postulated as a mechanism of dizziness in such patients. We conducted a proof-of-principle cohort study to assess the potential efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) as treatment for long-lasting post-brainstem stroke dizziness. Methods: We first applied cerebellar rTMS in healthy volunteers (n=11) and showed that cerebellar intermittent theta burst stimulation (iTBS) affected vestibulocerebellar neural activity. Then, we enrolled 11 patients with long-lasting post-brainstem stroke dizziness (lateral medullary infarction, 9; lateral pontine infarction, 1; and lateral pontine hemorrhage, 1), applied cerebellar rTMS (iTBS for 5 days), and followed these patients up for clinical symptoms (Dizziness Handicap Inventory [DHI]), signs (nystagmus), and VOR gain. Results: After rTMS, DHI scores were significantly reduced with disappearance or attenuation of the ipsilesional nystagmus characteristic of the long-lasting post-brainstem stroke dizziness. Reduction in the absolute VOR gain was also associated with reduced DHI scores. Relative cerebellar blood flow to the brainstem, measured in 4 patients, was increased. However, the effects of cerebellar rTMS did not always persist. Conclusion: Our study showed the potential efficacy of cerebellar rTMS for treatment of long-lasting post-brainstem stroke dizziness. Further large-scale randomized studies are warranted to confirm our findings.

Effects of cerebellar magnetic stimulation on chronic post-lateral medullary infarction dizziness: A proof-of-principle cohort study

Background and purposeLateral medullary infarction (LMI) sometimes causes long-lasting dizziness. Although the precise mechanism of chronic post-LMI dizziness is unknown, a cerebellar control disorder of the vestibulo-ocular reflex (VOR) has been reported in such patients. We conducted a proof-of-principle cohort study to assess the potential efficacy of cerebellar repetitive transcranial magnetic stimulation (rTMS) as treatment for chronic post-LMI dizziness. MethodsWe first applied cerebellar rTMS in healthy volunteers (n = 11) and showed that cerebellar intermittent theta burst stimulation (iTBS) affected vestibulocerebellar neural activity. Then, between September and December 2015, we enrolled six patients (aged≥20 years) with chronic post-LMI dizziness (duration≥6 months), applied cerebellar rTMS (iTBS for 5 days), and followed these patients up for up to 25 months for clinical symptoms (Dizziness Handicap Inventory [DHI]), signs (nystagmus), and VOR gain. ResultsFour of the six patients completed the study without complications. After rTMS, DHI scores were reduced (mean pre-rTMS DHI score minus post-rTMS DHI score was 13.0 [P = 0.036]) with disappearance of the ipsilesional nystagmus characteristic of the post-LMI dizziness. Reduction in the absolute VOR gain (mean pre- rTMS gain minus post-rTMS gain in the ipsilesional direction was 0.135 [P = 0.036] and that in the contralesional direction was 0.137 [P = 0.031]) were also associated with reduced DHI scores. Relative cerebellar blood flow to the brainstem was increased in four of five patients. The effects of cerebellar rTMS did not always persist, and three of four patients elected to undergo more than one rTMS series. The repeat cerebellar rTMS treatments had same beneficial effects. ConclusionOur study showed, for the first time, the potential efficacy of cerebellar rTMS for treatment of chronic post-LMI dizziness. The short duration of the cerebellar rTMS effects can be compensated for by repeating the rTMS treatment every few months. Further large-scale randomized studies are warranted to confirm our findings.

Cerebellar Intermittent Theta-Burst Stimulation and Motor Control Training in Individuals with Cervical Dystonia.

Background: There is emerging evidence that cervical dystonia is a neural network disorder with the cerebellum as a key node. The cerebellum may provide a target for neuromodulation as a therapeutic intervention in cervical dystonia. Objective: This study aimed to assess effects of intermittent theta-burst stimulation of the cerebellum on dystonia symptoms, quality of life, hand motor dexterity and cortical neurophysiology using transcranial magnetic stimulation. Methods: Sixteen participants with cervical dystonia were randomised into real or sham stimulation groups. Cerebellar neuromodulation was combined with motor training for the neck and an implicit learning task. The intervention was delivered over 10 working days. Outcome measures included dystonia severity and pain, quality of life, hand dexterity, and motor-evoked potentials and cortical silent periods recorded from upper trapezius muscles. Assessments were taken at baseline and after 5 and 10 days, with quality of life also measured 4 and 12 weeks later. Results: Intermittent theta-burst stimulation improved dystonia severity (Day 5, −5.44 points; p = 0.012; Day 10, −4.6 points; p = 0.025), however, effect sizes were small. Quality of life also improved (Day 5, −10.6 points, p = 0.012; Day 10, −8.6 points, p = 0.036; Week 4, −12.5 points, p = 0.036; Week 12, −12.4 points, p = 0.025), with medium or large effect sizes. There was a reduction in time to complete the pegboard task pre to post intervention (both p < 0.008). Cortical neurophysiology was unchanged by cerebellar neuromodulation. Conclusion: Intermittent theta-burst stimulation of the cerebellum may improve cervical dystonia symptoms, upper limb motor control and quality of life. The mechanism likely involves promoting neuroplasticity in the cerebellum although the neurophysiology remains to be elucidated. Cerebellar neuromodulation may have potential as a novel treatment intervention for cervical dystonia, although larger confirmatory studies are required.

Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study.

Multimodal treatments are emerging as effective approaches for motor recovery in traumatic brain injury (TBI). Various evidence has demonstrated that repetitive transcranial magnetic stimulation (rTMS) may improve outcomes in people with motor disorders. Behavioral gains from rTMS protocols may be maximized when brain stimulation is coupled with carefully designed occupational/physical therapy. We present the case of a 25-year-old man with chronic TBI (a bilateral corticosubcortical parieto-occipital lesion) who underwent three weeks of cerebellar intermittent theta burst stimulation (iTBS), a form of rTMS, combined with neurorehabilitation treatment. The Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), Jebsen-Taylor Hand Function Test, and accelerometer gait analysis were administered before and after treatment. The results showed improvements in balance performance (BBS: T0=47; T1=53; +10.72%), motor recovery (FMA: T0=93/100; T1=96/100; +3.00%), step length (T0=50.4±7.2; T1=53.8±2.2 cm, p<0.001), and walking speed (T0=0.87±0.06; T1=0.91±0.04 m/sec,p<0.001). Combined cerebellar rTMS and neurore-Clinical effects of non-invasive cerebellar magnetic stimulation treatment combined with neuromotor rehabilitation in traumatic brain injury. A single case study. habilitation seems to be a promising treatment for motor and balance dysfunctions in TBI patients.

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.

Theta Burst Stimulation Modulates Cerebellar-Cortical Connectivity in Patients with Progressive Supranuclear Palsy

BackgroundProgressive Supranuclear Palsy (PSP) is an atypical degenerative Parkinsonism characterized by postural instability, supranuclear gaze palsy and frontal deficits. Recent imaging studies revealed that the volume of cerebellar peduncles and midbrain were reduced in PSP. Transcranial magnetic stimulation (TMS) studies demonstrated a cerebellar involvement in PSP showing an impairment of functional connectivity between the cerebellar hemisphere (Cb) and the contralateral primary motor cortex (M1) (cerebellar brain inhibition-CBI). ObjectiveTo investigate the plasticity of the cerebello-thalamo-cortical circuits in ten PSP patients after two-week course of cerebellar intermittent theta burst stimulation (iTBS), a form of repetitive TMS. MethodsBefore and after the iTBS sessions we measured functional connectivity between Cb and contralateral M1 (CBI), short intracortical inhibition (SICI) and intracortical facilitation (ICF) and short latency afferent inhibition (SLAI) in contralateral M1. We also performed resting state functional magnetic resonance (rs-fMRI) and we administered clinical rating scale (PSP-RS). ResultsAt baseline PSP patients had decreased efficiency of CBI, SICI and SLAI in comparison to PD patients and healthy subjects. Cerebellar iTBS increased the deficient functional cerebellar-motor connectivity as assessed by CBI. No effect was seen for SICI/ICF and SLAI circuits. Following iTBS there was an increased signal in the head of the caudate nucleus bilaterally as shown by rs-fMRI. Moreover, PSP-RS showed an improvement of dysarthria in all patients. ConclusionsiTBS enhanced functional connectivity between the cerebellar hemisphere, the caudate nucleus and the cortex, that was paralleled by some clinical improvement. Future randomized, sham-stimulation controlled studies are warranted to support the clinical efficacy of this technique.