Cerebellar rTMS stimulation may induce prolonged clinical benefits in essential tremor,and subjacent changes in functional connectivity: An open label trial

BackgroundCerebello-thalamo-cortical (CTC) pathways dysfunction is involved in pathological oscillations causing tremor in essential tremor (ET). Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the cerebellum can effectively modulate the cerebellar output.ObjectiveAs one session of rTMS can induce a brief improvement, we hypothesized that repeated sessions might have a cumulative and potentially long-term therapeutic effect on ET. We assessed, in an open label trial, the efficacy of one-week rTMS treatment on tremor and on the motor-CTC dysfunction in ET patients.MethodsResting-state fMRI functional connectivity was used as an indicator of CTC network integrity in 11 ET patients and 11 healthy subjects. Resting-state fMRI connectivity was quantified at baseline in patients and control subjects between the cerebellum and the motor network, and between the cerebellum and the default brain network (DBN) taken as control. The fMRI study was repeated in patients after 5 days of bilateral 1 Hz rTMS applied to the posterior cerebellar cortex. Tremor was assessed clinically (Fahn–Tolosa–Marin scale) and quantified using electromyographic and accelerometric recordings at baseline (day 1, before the cerebellar stimulation) and after the end of the cerebellar stimulation period at day 5, day 12 and day 29.ResultsRepeated rTMS over the cerebellum significantly improved total and specific (tremor, drawing, functional disability) scores, and reduced tremor amplitude (P < 0.006). It also re-established the defective information processing in the CTC network (P(Δ|y) > 0.909), but not in the DBN. The effects persisted for 3 weeks after the last session.ConclusionCerebellar stimulation could be an effective treatment option for patients with severe essential tremor.     

高低频重复经颅磁刺激治疗卒中后上肢痉挛的对照研究

目的 探讨高、低频重复经颅磁刺激（repetitive transcranial magnetic stimulation,rTMS）大脑初级运动皮层（M1区）治疗卒中后上肢痉挛的临床疗效及差异。      

Effects of high-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex on motor recovery in severe hemiplegic stroke: A randomized clinical trial

BackgroundThe contralesional hemisphere compensation may play a critical role in the recovery of stroke when there is extensive damage to one hemisphere. There is little research on the treatment of hemiplegia by high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the contralesional cortex.ObjectiveWe conducted a 2-week randomized, sham-controlled, single-blind trial to determine whether high-frequency rTMS (HF-rTMS) over the contralesional motor cortex can improve motor function in severe stroke patients.MethodsForty-five patients with ischemic or hemorrhagic stroke in the middle cerebral artery territory were randomly assigned to treatment with 10 Hz rTMS (HF group), 1 Hz rTMS (LF group) or sham rTMS (sham group) applied over the contralesional motor cortex (M1) before physiotherapy daily for two weeks. The primary outcome was the change in the Fugl-Meyer Motor Assessment (FMA) Scale score from baseline to 2 weeks. The secondary endpoints included root mean square of surface electromyography (RMS-SEMG), Barthel Index (BI), and contralesional hemisphere cortical excitability.ResultsThe HF group showed a more significant improvement in FMA score (p < 0.05), BI (p < 0.005), contralesional hemisphere cortical excitability and conductivity (p < 0.05), and RMS-SEMG of the key muscles (p < 0.05) compared with the LF group and sham group. There were no significant differences between the LF group and sham group. There was a positive correlation between cortical conductivity of the uninjured hemisphere and recovery of motor impairment (p = 0.039).ConclusionsHF-rTMS over the contralesional cortex was superior to low-frequency rTMS and sham stimulation in promoting motor recovery in patients with severe hemiplegic stroke by acting on contralesional cortex plasticity.Trial registrationClinical trial registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn/showproj.aspx?proj=23264 (ChiCTR-IPR-17013580).     

Radiocirugía estereotáctica con Gamma Knife® como tratamiento del temblor esencial y parkinsoniano: experiencia a largo plazo

IntroductionUnilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit.MethodsWe reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months’ follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events.ResultsThirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects.ConclusionsThis is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.     

Epicranial Direct Current Stimulation Suppresses Harmaline Tremor in Rats

IntroductionEssential tremor (ET) is the most common neurologic movement disorder worldwide. It is characterized by a postural tremor, mostly in the upper extremities, causing difficulties in daily activities that may lead to social exclusion. Some patients with ET do not respond well to or do not tolerate medication. Thus, deep brain stimulation can be offered. In a recent study, we proposed a novel neuromodulation technique called epicranial current stimulation (ECS) that works in a minimally invasive way by placing the electrodes subcutaneously under the skin and directly over the skull. In this study, we investigated the feasibility of using epicranial direct current stimulation (EDCS) to suppress tremor in a rat harmaline ET model.Materials and MethodsIn experiment 1, seven Sprague Dawley rats were implanted with ECS electrodes placed over the motor cortex (MC) and the cerebellum to investigate whether stimulating between them could suppress tremor. In experiments 2 and 3, eight rats were implanted with ECS electrodes placed over the MC, cerebellum, and the rostral skull to separate the effects on tremor caused by stimulating each target. During each experiment, the rats were injected with harmaline, which induced tremor that was quantified using an accelerometer. EDCS was then applied through the different electrode configurations to evaluate their tremor suppression effectiveness.ResultsResults from experiment 1 showed that MC_cathode-Cerebellar_anode suppressed tremor compared with stimulation-OFF but MC_anode-Cerebellar_cathode did not. Furthermore, experiments 2 and 3 showed that it was the cerebellar anodal electrode that was driving tremor suppression.ConclusionCerebellar EDCS suppressed harmaline tremor in rats in a polarity-dependent manner. EDCS could be a promising neuromodulation method for patients with ET.     

Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain — A pilot double-blind,randomized cross-over study

ObjectivesPeripheral neuropathic pain (pNeP) is prevalent, and current treatments, including drugs and motor cortex repetitive transcranial magnetic stimulation (rTMS) leave a substantial proportion of patients with suboptimal pain relief.MethodsWe explored the intensity and short-term duration of the analgesic effects produced in pNeP patients by 5 days of neuronavigated deep rTMS targeting the posterior superior insula (PSI) with a double-cone coil in a sham-controlled randomized cross-over trial.ResultsThirty-one pNeP patients received induction series of five active or sham consecutive sessions of daily deep-rTMS to the PSI in a randomized sequence, with a washout period of at least 21 days between series. The primary outcome [number of responders (>50% pain intensity reduction from baseline in a numerical rating scale ranging from 0 to 10)] was significantly higher after real (58.1%) compared to sham (19.4%) stimulation (p = 0.002). The number needed to treat was 2.6, and the effect size was 0.97 [95% CI (0.6; 1.3)]. One week after the 5th stimulation day, pain scores were no longer different between groups, and no difference in neuropathic pain characteristics and interference with daily living were present. No major side effects occurred, and milder adverse events (i.e., short-lived headaches after stimulation) were reported in both groups. Blinding was effective, and analgesic effects were not affected by sequence of the stimulation series (active-first or sham-first), age, sex or pain duration of participants.DiscussionPSI deep-rTMS was safe in refractory pNeP and was able to provide significant pain intensity reduction after a five-day induction series of treatments. Post-hoc assessment of neuronavigation targeting confirmed deep-rTMS was delivered within the boundaries of the PSI in all participants.ConclusionPSI deep-rTMS provided significant pain relief during 5-day induction sessions compared to sham stimulation.     

Effect of intensive motor training with repetitive transcranial magnetic stimulation on upper limb motor function in chronic post-stroke patients with severe upper limb motor impairment

Background Intensive motor training with low-frequency repetitive transcranial magnetic stimulation (rTMS) has efficacy as a therapeutic method for motor dysfunction of the affected upper limb in patients with mild to moderate stroke. However, it is not clear whether this combination therapy has the same effect in chronic post-stroke patients with severe upper limb motor impairment.

Objectives The aim of this study was to test the treatment effects of intensive motor training with low-frequency rTMS in chronic post-stroke patients with severe upper limb motor impairment.

Methods A convenience sample of 26 chronic post-stroke patients with severe upper limb motor impairment participated in this study with the non-randomized, non-controlled clinical trial. All subjects were hospitalized to receive intensive motor training with low-frequency rTMS. During 2 weeks in which Sundays were excluded, a total of 24 sessions (2 sessions per day) of the intervention were conducted. The Fugl–Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were used to assess motor impairment and function of the affected upper limb, respectively, before and after intervention. Paired t-test was used to analyze the effects of the intervention.

Results The FMA total score and WMFT log performance time significantly improved from before to after intervention (FMA: 12.6–18.0; WMFT: 3.6–3.3, p < 0.001).

Conclusions The present results suggest that intensive motor training with low-frequency rTMS could improve motor impairment in chronic post-stroke patients with severe upper limb motor impairment and contribute to the expansion of the application range of this combination therapy.     

Differences in cerebral perfusion according to phenotypes of essential tremor: brain perfusion SPECT study using SPM analysis

Essential tremor (ET) is one of the most common movement disorders. However, few studies regarding the differences of pathophysiology according to phenotypes of ET have been reported. We investigated whether a functional difference occurs between ET with only a limb tremor (L-ET) and ET with only a head tremor (H-ET). We recruited 13 patients with L-ET, 10 patients with H-ET, and 33 healthy subjects. We compared the severity of tremor symptoms using the Fahn-Tolosa-Marin rating scale (FTM) to compare L-ET with H-ET. All subjects underwent magnetic resonance imaging and perfusion SPECT of the brain. The total score of FTM was significantly higher in the L-ET than in the H-ET. However, Part A in FTM did not show significant differences between the two ET groups. A brain perfusion SPECT analysis demonstrated no significant difference between L-ET and H-ET, but a regional perfusion of subjects with ET compared with healthy subjects showed hypoperfusion in the insular, cingulate gyrus, frontal lobe, and cerebellum. In conclusion, we suggested that cerebellar dysfunction might be involved in the pathogenesis of ET. In addition, we assumed that ET has the same pathogenesis in the origin of the disease, regardless of the clinical difference of ET.     

A pilot, double-blind, placebo-controlled trial of pregabalin (Lyrica) in the treatment of essential tremor.

We performed a pilot, double-blind, placebo-controlled, randomized trial to evaluate the efficacy and tolerability of pregabalin (PGB, Lyrica), an antiepileptic agent, in treating essential tremor (ET). Twenty two patients with ET were randomly assigned to receive PGB or placebo. PGB was initiated at 50 mg/day and was escalated by 75 mg/day every 4 days to a maximum dose of 600 mg/day. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale. There was a significant reduction in tremor amplitude in the PGB group compared with the placebo group, as measured by accelerometry, at a mean dose of 286.76+/-100.05 mg/day. Action tremor limb scores on the FTM also improved in the PGB group compared with the placebo group (P-value for multilevel modeling=0.04). PGB was fairly well tolerated, with about one-third of patients dropping out of the study because of adverse events. PGB provided significant improvements in accelerometry and in action tremor limb scores on the FTM. However, larger studies are needed to further evaluate the potential effect of PGB on ET.     

Cerebellar rTMS for motor control in progressive supranuclear palsy

BackgroundStimulatory cerebellar TMS is a promising tool to improve motor control in neurodegenerative disorders.Objective/hypothesis: Our goal was to use 10Hz cerebellar rTMS to augment cerebellar-brain inhibition (CBI) for improved postural stability and speech in patients with progressive supranuclear palsy (PSP).MethodsWe performed CBI assessments with neuronavigation before and after high frequency cerebellar rTMS or sham TMS in two patients with PSP, using a double cone coil for the conditioning pulse and a figure-of-eight coil for the test pulse and treatments. We collected posturography data and speech samples before and after treatment.ResultsAfter treatment, CBI increased by 50% in subject 1 and by 32% in subject 2, and postural stability and speech improved. The protocol was well tolerated, but the sham was not consistently believable.ConclusionCerebellar rTMS may improve postural stability and speech in PSP, but cooled coils with vibrotactile sham capability are needed for larger future studies.     

Cerebellar involvement in timing accuracy of rhythmic finger movements in essential tremor

The cerebellum is involved in the generation of essential tremor (ET) and cerebellar timing function is altered in patients with ET showing an increased variability of rhythmic hand movements. Using a sensor‐engineered glove, we evaluated motor behaviour during repetitive finger tapping movements in 15 patients with ET and in 11 age‐ and gender‐matched normal subjects. In addition, we investigated whether, in patients with ET, an inhibitory repetitive transcranial magnetic stimulation (1 Hz‐rTMS) over lateral cerebellum was able to change timing properties and motor behaviour. Patients with ET showed a longer touch duration (TD) and a lower inter tapping interval (ITI) than normal subjects. The temporal variability of the movement (coefficient of variation of ITI) was increased in patients with ET. Neither clinical rating scale or tremor measurements correlated with any parameter of motor performance in the ET group. 1 Hz‐rTMS over ipsilateral lateral cerebellum transiently affected the performance of patients with ET, by reducing TD values and normalizing ITI values. After 1 Hz‐rTMS, the coefficient of variation of ITI was restored to values similar to those of normal subjects. We postulate that the strategy to increase TD, probably adopted to allow a better perception of movement, can affect ITI and its variability. The results support the idea that the cerebellum plays a central role in the selection of motor strategy of rhythmic finger movements, particularly in terms of temporal organization of movement.     

The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: A randomized,double‐blind,placebo‐controlled study

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. © 2010 Movement Disorder Society     

Brain SPECT can differentiate between essential tremor and early-stage tremor-dominant Parkinson’s disease

There are no confirmatory or diagnostic tests or tools to differentiate between essential tremor (ET) and tremor in idiopathic Parkinson’s disease (PD). Although a number of imaging studies have indicated that there are differences between ET and PD, the functional imaging study findings are controversial. Therefore, we analyzed regional cerebral blood flow (CBF) by perfusion brain single-photon emission computed tomography (SPECT) to identify differences between ET and tremor-dominant Parkinson’s disease (TPD). We recruited 33 patients with TPD, 16 patients with ET, and 33 healthy controls. We compared the severity of tremor symptoms by comparing the Fahn-Tolosa-Marin rating scale (FTM) score and the tremor score from Unified Parkinson’s Disease Rating Scale (UPDRS) between TPD and ET patients. Subjects were evaluated by neuropsychological assessments, MRI and perfusion SPECT of the brain. Total FTM score was significantly higher in ET patients than TPD patients. However, there was no significant difference in FTM Part A scores between the two patient groups, while the scores for FTM Part B and C were significantly higher in ET patients than TPD patients. Brain SPECT analysis of the TPD group demonstrated significant hypoperfusion of both the lentiform nucleus and thalamus compared to the ET group. Brain perfusion SPECT may be a useful clinical method to differentiate between TPD and ET even during early-phase PD, because the lentiform nucleus and thalamus show differences in regional perfusion between these two groups during this time period. Additionally, we found evidence of cerebellar dysfunction in both TPT and ET.     

重复经颅磁刺激对帕金森病运动功能及运动诱发电位的影响

目的:探讨低频重复经颅磁刺激(rTMS)对PD患者运动皮质兴奋性影响的持续效应。方法:对38例PD患者,予0.5Hz rTMS刺激其主要受累肢体对侧的M1Hand(20×80,100%RMT),连续7d。于首次干预前及末次干预后20min、1周及1个月分别评价其临床运动功能和运动诱发电位。结果:低频rTMS干预后,PD患者UPDRS Ⅲ、僵直、运动迟缓评分、计时运动试验及CSP均存在显著时间效应(P<0.001)。结论:低频rTMS可改善PD患者运动迟缓症状,其对运动功能的影响可持续到刺激停止后1个月,与运动皮质兴奋性的改变一致。     

Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke: a systematic review and network meta-analysis

Transcranial magnetic stimulation, a type of noninvasive brain stimulation, has become an ancillary therapy for motor function rehabilitation. Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS) on motor function in stroke patients. There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke. The MEDLINE, Embase, Cochrane Library, ISI Science Citation Index, Physiotherapy Evidence Database, China National Knowledge Infrastructure Library, and ClinicalTrials.gov databases were searched. Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke, published from inception to November 28, 2019, were included. Standard pairwise meta-analysis was conducted using R version 3.6.1 with the "meta" package. Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions. Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation. Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency r TMS or sham stimulation. These findings suggest that rTMS can improve motor function in patients with stroke, and that low-frequency rTMS mainly affects motor function, whereas high-frequency rTMS increases the amplitudes of motor evoked potentials. More highquality randomized controlled trials are needed to validate this conclusion. The work was registered in PROSPERO(registration No. CRD42020147055) on April 28, 2020.     

rTMS over human motor cortex can modulate tremor during movement

Abnormally large tremor during movement is a symptom of many movement disorders and significantly impairs activities of daily living. The aim of this study was to investigate whether repetitive magnetic brain stimulation (rTMS) can reduce tremor size during human movement. We hypothesised that inhibitory rTMS over motor cortex would reduce tremor size during subsequent movement. The study involved 26 healthy young adults (21 ± 2 years) and began with application of single TMS stimuli to measure baseline corticospinal excitability. The response to stimulation was recorded in hand muscles with electromyography. Subjects then performed a 3‐min task to measure baseline tremor during movement. This involved matching index finger position with a moving target on a computer screen. Tremor was recorded with an accelerometer on the fingernail. Finger acceleration was analysed with fast‐Fourier transform to quantify tremor in the physiological range (7.8–12.2 Hz). Subjects then received 10 min of real (n = 13) or sham (n = 13) inhibitory rTMS. Tremor and corticospinal excitability were then remeasured. Real rTMS significantly decreased corticospinal excitability by ~30% (P = 0.022) and increased tremor size during movement by ~120% (P = 0.047) relative to sham rTMS. However, the direction of tremor change was opposite to that hypothesised for inhibitory rTMS. The results suggest that rTMS over human motor cortex can modulate action tremor and the level of corticospinal excitability may be important for setting the amplitude of action tremor in healthy young adults.     

Low-frequency repetitive transcranial magnetic stimulation for dyskinesia and motor performance in Parkinson’s disease

Dyskinesias are one of the most frequent and disabling complications of the long-term treatment of Parkinson’s disease (PD). Although the cause is not completely understood, it appears that an imbalance between excitatory and inhibitory inputs from the basal ganglia to the motor cortex leads to overactivation of motor and premotor areas. Overactivation of the supplementary motor area (SMA) has been observed in neuroimaging studies in dyskinetic PD patients. We investigated the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the SMA on levodopa-induced dyskinesias (LID) and motor performance in PD. We tested whether longer duration (10 days) and higher number of total pulses (1800 pulses) would enhance the beneficial effect. Seventeen dyskinetic PD patients were randomly assigned to real rTMS or sham (placebo) rTMS, and 1 Hz rTMS or sham rTMS was applied over the SMA for 10 consecutive days. Patients were assessed at baseline and 1 day after the last rTMS with a levodopa challenge test, and video recordings were taken. Dyskinesias and motor performance were rated off-line by two blinded raters using video recordings. After 10 days of treatment with rTMS, we observed that 1 Hz rTMS delivered over the SMA had decreased LID lasting for 24 hours without a change in motor performance, whereas sham rTMS induced no significant change in dyskinesia scores. These results support a possible therapeutic effect of low-frequency rTMS in LID. However, in order to suggest rTMS as an effective treatment, long-term observations and further investigations with a larger patient population are essential.     

Decoding voluntary movements and postural tremor based on thalamic LFPs as a basis for closed-loop stimulation for essential tremor

BackgroundHigh frequency Deep brain stimulation (DBS) targeting motor thalamus is an effective therapy for essential tremor (ET). However, conventional continuous stimulation may deliver unnecessary current to the brain since tremor mainly affects voluntary movements and sustained postures in ET.ObjectiveWe aim to decode both voluntary movements and the presence of postural tremor from the Local field potentials (LFPs) recorded from the electrode implanted in motor thalamus for stimulation, in order to close the loop for DBS so that stimulation could be delivered on demand, without the need for peripheral sensors or additional invasive electrodes.MethodsLFPs from the motor thalamus, surface electromyographic (EMG) signals and/or behavioural measurements were simultaneously recorded in seven ET patients during temporary lead externalisation 3–5 days after the first surgery for DBS when they performed different voluntary upper limb movements. Nine different patients were recorded during the surgery, when they were asked to lift their arms to trigger postural tremor. A machine learning based binary classifier was used to detect voluntary movements and postural tremor based on features extracted from thalamic LFPs.ResultsCross-validation demonstrated that both voluntary movements and postural tremor can be decoded with an average sensitivity of 0.8 and false detection rate of 0.2. Oscillatory activities in the beta frequency bands (13–23 Hz) and the theta frequency bands (4–7 Hz) contributed most to the decoding of movements and postural tremor, respectively, though incorporating features in different frequency bands using a machine learning approach increased the accuracy of decoding.     

An Exploration of the Application of Noninvasive Cerebellar Stimulation in the Neuro-rehabilitation of Dysphagia after Stroke (EXCITES) Protocol

Background: Poststroke dysphagia is common, associated with a poor outcome and has no definitive treatments. Repetitive transcranial magnetic stimulation (rTMS) targeting the cerebellum is a noninvasive technique requiring minimal physical or cognitive input from the patient, and has been shown to induce positive swallow-related brain changes in physiological studies as measured by increased cortical excitability. Aim: To explore in patients with acute/sub-acute poststroke dysphagia: (1) the feasibility and immediate effect; and (2) the optimal dose for long-term benefit, of cerebellar rTMS in patients with dysphagia in acute/sub-acute stroke. Methods: Two double-blind sham-controlled randomized phase II trials. Participants will be recruited from stroke units in Nottingham and Greater Manchester. Dysphagia will be confirmed via baseline videofluoroscopy (VFS). Participants will be blinded to treatment and receive cerebellar rTMS or sham stimulation: (1) single treatment of (10Hz, 250 pulse) in 24 participants; (2) daily for 3 days, twice-daily for 5 days, or twice-daily sham treatment for 5 days, in 48 participants. Results: The severity of dysphagia will be assessed with VFS, using the penetration aspiration scale (PAS) at: (1) 1-hour, (2) 2-weeks, post-treatment. Additional comparative measures will be taken from: (1) pharyngeal motor evoked potential (MEP) amplitudes, (2) the functional oral intake score and dysphagia severity rating scale. Conclusions: If these studies demonstrate feasibility and identify optimal dosing, further trials to assess the safety and efficacy of cerebellar rTMS as a treatment for poststroke dysphagia will be warranted.