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Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia.

ABSTRACT: To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities.Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTBS). The effects of cerebellar cTBS were quantified as excitability changes in the contralateral primary motor cortex, as well as possible changes in arm and neck movements in patients.Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects and in patients with cervical dystonia, though not in patients with focal hand dystonia. There was no correlation between changes in primary motor cortex excitability and arm and neck movement kinematics in patients. There were no changes in clinical scores or in kinematic measures, after either real or sham cerebellar cTBS in patients.The reduced cerebellar inhibitory modulation of primary motor cortex excitability in focal dystonia may be related to the body areas affected by dystonia as opposed to being a widespread pathophysiological abnormality.The present study yields information on the differential role played by the cerebellum in the pathophysiology of different focal dystonias.

SUBMITTER: Bologna M

PROVIDER: S-EPMC5098212 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia.

Bologna Matteo M Paparella Giulia G Fabbrini Andrea A Leodori Giorgio G Rocchi Lorenzo L Hallett Mark M Berardelli Alfredo A

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 20160915 11

<h4>Objective</h4>To investigate the cerebellar inhibitory influence on the primary motor cortex in patients with focal dystonia using a cerebellar continuous theta-burst stimulation protocol (cTBS) and to evaluate any relationship with movement abnormalities.<h4>Methods</h4>Thirteen patients with focal hand dystonia, 13 patients with cervical dystonia and 13 healthy subjects underwent two sessions: (i) cTBS over the cerebellar hemisphere (real cTBS) and (ii) cTBS over the neck muscles (sham cTB ...[more]

PMID: 27721106

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Project description:BackgroundIndividuals with Mal de Debarquement syndrome (MdDS) experience persistent oscillating vertigo lasting for months or years. Transcranial magnetic stimulation (TMS) can modulate the motion perception of MdDS.Materials and methodsTwenty-six TMS naive individuals received single administrations of continuous theta burst stimulation (cTBS) over the occipital cortex, cerebellar vermis, and lateral cerebellar hemisphere, in randomized order. A 0-100 point Visual Analogue Scale was used to assess acute changes in oscillating vertigo severity after each session. Repeated treatments were given over the target that led to the most acute reduction in symptoms. All treatments were performed with neuronavigation using the participant's own brain MRI. The Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS) were assessed weekly at four pretreatment and six posttreatment time points.ResultsTwenty participants chose either the occipital cortex (11) or cerebellar vermis (9) targets as most effective in reducing the oscillating vertigo; one chose lateral cerebellar hemisphere; five chose none. After 10 to 12 sessions of 1,200 pulses over the target of choice, 19 of 25 treatment completers noted ≥ 25% reduction, 12 of 25 ≥50% reduction, and 8 of 25 ≥75% reduction in oscillating vertigo intensity. A one-way repeated measures ANOVA of DHI, MBRS, and HADS scores before and after treatment showed significant reductions in DHI, MBRS, and the HADS Anxiety subscore immediately after treatment with most improvement lasting through posttreatment week 6. There were no significant Depression subscore changes. Participants who had chosen vermis stimulation had comparatively worse balance at baseline than those who had chosen occipital cortex stimulation.ConclusioncTBS over either the occipital cortex or cerebellar vermis is effective in reducing the oscillating vertigo of MdDS acutely and may confer long-term benefits. Sustained improvement requires more frequent treatments.

Project description:IntroductionRepetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.Materials and methodsWe performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.ResultsSeven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.ConclusionWe report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).

Project description:OBJECTIVE:Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD. METHODS:Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors. RESULTS:Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity. CONCLUSIONS:iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.

Project description:Introduction:Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. Methods:We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). Results:Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. Conclusion:Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Dataset Information

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia.

Publications

Effects of cerebellar theta-burst stimulation on arm and neck movement kinematics in patients with focal dystonia.

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