Marked reduction of cerebellar deficits in upper limbs following transcranial cerebello-cerebral DC stimulation: tremor reduction and re-programming of the timing of antagonist commands

Abstract

Cerebellar ataxias represent a very heterogeneous group of disabling disorders for which we lack effective symptomatic therapies in most cases. There is currently an intense interest in the use of non-invasive transcranial DC stimulation (tDCS) to modulate the activity of the cerebellum in ataxic disorders. We performed a detailed laboratory assessment of the effects of transcranial cerebello-cerebral DC stimulation (tCCDCS, including a sham procedure) on upper limb tremor and dysmetria in 2 patients presenting a dominant spinocerebellar ataxia (SCA) type 2, one of the most common SCAs encountered during practice. Both patients had a very similar triplet expansion size in the ATXN2 gene (respectively, 39 and 40 triplets). tCCDCS reduced both postural tremor and action tremor, as confirmed by spectral analysis. Quadratical PSD (power spectral density) of postural tremor dropped to 38.63 and 41.42% of baseline values in patient 1 and 2, respectively. The integral of the subband 4–20 Hz dropped to 46.9 and 62.3% of baseline values, respectively. Remarkably, tCCDCS canceled hypermetria and reduced dramatically the onset latency of the antagonist EMG activity associated with fast goal-directed movements toward 3 aimed targets (0.2, 0.3, and 0.4 rad). Following tCCDCS, the latency dropped from 108–98 to 63–57 ms in patient 1, and from 74–87 to 41–46 ms in patient 2 (mean control values ± SD: 36 ± 8 to 45 ± 11 ms), corresponding to a major drop of z scores for the 2 patients from 7.12 ± 0.69 to 1.28 ± 1.27 (sham procedure: 6.79 ± 0.71). This is the first demonstration that tCCDCS improves upper limb tremor and hypermetria in SCA type 2. In particular, this is the first report of a favorable effect on the onset latency of the antagonist EMG activity, a neurophysiological marker of the defect in programming of timing of motor commands. Our results indicate that tCCDCS should be considered in the symptomatic management of upper limb motor deficits in cerebellar ataxias. Future studies addressing a tDCS-based neuromodulation to improve motor control of upper limbs are required (a) in a large group of cerebellar disorders, and (b) in different subgroups of ataxic patients. The anatomical location of the cerebellum below the skull is particularly well suited for such studies.

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

“…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].…”

Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

“…), or contralateral supra‐orbital area (Grimaldi & Manto, ; Grimaldi et al . ), or the motor cortex (Macher et al . ).…”

“…In a further study, the same authors (Grimaldi et al . ) assessed the effects of a novel protocol using transcranial DC stimulation applied in the same session to the motor cortex (cathodal) and cerebellum (anodal) (cerebello‐cerebral DC stimulation) on tremor, EMG activity and dysmetria in two patients with spinocerebellar ataxia type 2. The rationale for using this paired cerebro‐cerebellar stimulation arises from the observation that cathodal motor cortical DC stimulation improves some features related to a cerebellar deficit (Pozzi et al .…”

Physical Therapy for Cerebellar Ataxia

“…In another report, tDCS over the cerebellum and contralateral motor cortex reduced postural and action tremor due to the degenerative cerebellum in patients [140]. rTMS over the cerebellum in patients with cerebellar stroke and cerebellar ataxia improves ICARS subscore on gait and posture with improvement in neurophysiological parameters, such as CBI [61].…”

“…Furthermore, the NIBS to the cerebellum modulates cerebellar excitability [98,[129][130][131], motor function [132,133], and motor learning [32,[134][135][136][137][138] in healthy population. In patients with cerebellar ataxia, some previous studies reported about the effect of tDCS to the cerebellum on motor function [131,[139][140][141]. A double-blind, randomized and sham-controlled study revealed that cerebellar tDCS improved SARA, ICARS, nine-hole peg test, and gait speed [141].…”