Effects of Two Weeks of Cerebellar Theta Burst Stimulation in Cervical Dystonia Patients

Abstract

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 theta burst stimulation modulates the neural activity of interconnected parietal and motor areas

“…Moreover, cerebellar non-invasive stimulation is becoming a promising approach in treating several neurological disorders31, possibly by inducing long-lasting changes in the interconnected cerebello-thalamo-cortical networks26. Recently we found that cerebellar TBS when applied daily for at least two weeks may potentially alleviate symptoms in patients with Parkinson’s disease32 focal dystonia33 and improve recovery in patients with ischemic stroke34.…”

Understanding and Modulating Motor Learning with Cerebellar Stimulation

“…Indeed, recently Bonni and others showed that 2 weeks of excitatory repetitive TMS over the cerebellum in patients with stroke and ataxia lead to an improvement in posture and gait [28]. Similarly, Koch et al showed that two weeks of inhibitory repetitive TMS lead to a reduction of symptoms in patients with cervical dystonia [29]. …”

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

“…Furthermore, excitability of the CBI pathway can be modulated by non-invasive stimulation in healthy adults [5] and in neurological disorders [8, 9,11]. The aim of the present studies was to test whether cerebellar anodal DCS can modify CBI, SAI and TRs in healthy humans.…”

“…Non-invasive stimulation of the cerebellum can modify the connectivity between the cerebellum and primary motor cortex (M1), by putative polarisation of Purkinje cells in the cerebellar cortex [5,6]. Small clinical studies have indicated that non-invasive cerebellar stimulation has potential as a novel treatment intervention in neurological conditions exhibiting cerebellar pathology [7][8][9][10][11][12]. However, the mechanisms of action are incompletely understood [6,10,13].…”