A Pilot Study on the Effects of Transcranial Direct Current Stimulation on Brain Rhythms and Entropy during Self-Paced Finger Movement using the Epoc Helmet.

Transcranial direct current stimulation (tDCS) of the cerebellum is emerging as a novel non-invasive tool to modulate the activity of the cerebellar circuitry. In a single blinded study, we applied anodal tDCS (atDCS) of the cerebellum to assess its effects on brain entropy and brain rhythms during self-paced sequential finger movements in a group of healthy volunteers. Although wearable electroencephalogram (EEG) systems cannot compete with traditional clinical/laboratory set-ups in terms of accuracy and channel density, they have now reached a sufficient maturity to envision daily life applications. Therefore, the EEG was recorded with a comfortable and easy to wear 14 channels wireless helmet (Epoc headset; electrode location was based on the 10-20 system). Cerebellar neurostimulation modified brain rhythmicity with a decrease in the delta band (electrode F3 and T8, p < 0.05). By contrast, our study did not show any significant change in entropy ratios and laterality coefficients (LC) after atDCS of the cerebellum in the 14 channels. The cerebellum is heavily connected with the cerebral cortex including the frontal lobes and parietal lobes via the cerebello-thalamo-cortical pathway. We propose that the effects of anodal stimulation of the cerebellar cortex upon cerebral cortical rhythms are mediated by this key-pathway. Additional studies using high-density EEG recordings and behavioral correlates are now required to confirm our findings, especially given the limited coverage of Epoc headset.

The Click Test: A Novel Tool to Quantify the Age-Related Decline of Fast Motor Sequencing of the Thumb.

BACKGROUND: The thumb plays a critical role for manual tasks during the activities of daily life and the incidence of neurological or musculoskeletal disorders affecting the voluntary movements of the thumb is high in the elderly. There is currently no tool to assess repetitive motor sequencing of the thumb during ageing. OBJECTIVES: To report a novel procedure (the Click Test) assessing the effects of ageing on fast motor sequencing of the thumb. METHOD: Healthy subjects (n = 252; mean age +/- SD: 49.76 +/- 19.97 years; range: 19-89 years; F/M: 151/101) were asked to perform fast repeated flexion/extension movements of the thumb using a mechanical counter. RESULTS: Motor performances (assessed by the number of clicks during 3 time periods: 15, 30 and 45 sec), significantly decreased as a function of age for both the dominant (age effect; p< 0.0001 for 15, 30 and 45 sec) and the non-dominant hand (p<0.0001 for 15, 30 and 45 sec). The number of clicks was significantly higher in males (gender effect; p<0.001) and was higher on the dominant side as compared to the non-dominant side (handedness effect: p<0.001). The Click Test is characterized by high repeatability (coefficients of variation from 3.20 to 4.47%), excellent intra-rater reliability (intra-class coefficients ICC ranging from 0.89 to 0.98), high inter-rater reproducibility (Pearson's product correlation ranging from 0.85 to 0.96), high internal consistency (Cronbach alpha coefficient=0.95) and is highly correlated in terms of relative performances with the box and block test and the 9-hole peg test (positive linear correlation with the results of the box and block test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand; negative linear correlation with the results of the 9-hole peg test: p<0.001 for 15, 30 and 45 sec for both the dominant and the non-dominant hand). CONCLUSION: The Click Test is an entirely novel and very low cost tool to reliably discriminate the ageing effects upon the performances during fast repetitive motor sequencing of the thumb. The potential clinical and research applications for motor functions are multiple, especially in acute and chronic neurological disorders affecting the thumb as well as in the field of rheumatology and orthopedics.

A Postural Tremor Highly Responsive to Transcranial Cerebello-Cerebral DCS in ARCA3.

BACKGROUND AND OBJECTIVES: Cerebellar ataxias are disabling disorders that impact the quality of life of patients. In many cases, an effective treatment is missing. Despite the increasing knowledge on the pathogenesis of cerebellar disorders including genetic aspects, there is currently a gap in the therapeutical management of cerebellar deficits. Cerebellar ataxia associated with ANO10 mutation (ARCA3) presents a disabling cerebellar syndrome. The aim of this study is to report a patient with a marked postural tremor responding to transcranial cerebello-cerebral direct current stimulation (tCCDCS). METHODS: We applied tCCDCS using anodal stimulation over the cerebellum with a return electrode on the contralateral motor cortex. We performed a clinical rating, accelerometry studies, and recordings of voluntary movements at baseline, after sham, and after active tCCDCS. RESULTS: A dramatic response of postural tremor was observed after tCCDCS, with a major drop of the power spectral density to 26.12% of basal values. DISCUSSION: The postural tremor of cerebellar ataxia associated with ANO10 mutation was highly responsive to tCCDCS in our patient. This case illustrates that tCCDCS is a novel therapeutic option in the treatment of cerebellar deficits and might represent a promising tool to reduce tremor in ARCA3.

Targeting the Cerebellum by Noninvasive Neurostimulation: a Review.

Transcranial magnetic and electric stimulation of the brain are novel and highly promising techniques currently employed in both research and clinical practice. Improving or rehabilitating brain functions by modulating excitability with these noninvasive tools is an exciting new area in neuroscience. Since the cerebellum is closely connected with the cerebral regions subserving motor, associative, and affective functions, the cerebello-thalamo-cortical pathways are an interesting target for these new techniques. Targeting the cerebellum represents a novel way to modulate the excitability of remote cortical regions and their functions. This review brings together the studies that have applied cerebellar stimulation, magnetic and electric, and presents an overview of the current knowledge and unsolved issues. Some recommendations for future research are implemented as well.

tDCS of the Cerebellum: Where Do We Stand in 2016? Technical Issues and Critical Review of the Literature.

Transcranial Direct Current Stimulation (tDCS) is an up-and-coming electrical neurostimulation technique increasingly used both in healthy subjects and in selected groups of patients. Due to the high density of neurons in the cerebellum, its peculiar anatomical organization with the cortex lying superficially below the skull and its diffuse connections with motor and associative areas of the cerebrum, the cerebellum is becoming a major target for neuromodulation of the cerebellocerebral networks. We discuss the recent studies based on cerebellar tDCS with a focus on the numerous technical and open issues which remain to be solved. Our current knowledge of the physiological impacts of tDCS on cerebellar circuitry is criticized. We provide a comparison with transcranial Alternating Current Stimulation (tACS), another promising transcranial electrical neurostimulation technique. Although both tDCS and tACS are becoming established techniques to modulate the cerebellocerebral networks, it is surprising that their impacts on cerebellar disorders remains unclear. A major reason is that the literature lacks large trials with a double-blind, sham-controlled, and cross-over experimental design in cerebellar patients.

Enhancing transcranial direct current stimulation via motor imagery and kinesthetic illusion: crossing internal and external tools.

BACKGROUND: Transcranial direct current stimulation is a safe technique which is now part of the therapeutic armamentarium for the neuromodulation of motor functions and cognitive operations. It is currently considered that tDCS is an intervention that might promote functional recovery after a lesion in the central nervous system, thus reducing long-term disability and associated socio-economic burden. DISCUSSION: A recent study shows that kinesthetic illusion and motor imagery prolong the effects of tDCS on corticospinal excitability, overcoming one of the limitations of this intervention. CONCLUSION: Because changes in excitability anticipate changes in structural plasticity in the CNS, this interesting multi-modal approach might very soon find applications in neurorehabilitation.

The CAM test: a novel tool to quantify the decline in vertical upper limb pointing movements with ageing.

BACKGROUND AND AIM: Although upper limb movements in the vertical plane are very commonly used during the activities of daily life, there is still a lack of a reliable and easy standardized procedure to quantify them. In particular, ageing is associated with a decline in performances of coordinated movements, but a tool to quantify this decline is missing. METHODS: We created a novel portable test called counting arm movement test (CAM test). Participants were asked to perform fast and accurate successive pointing movements towards two fixed targets (mechanical counters) located in a vertical plane in the parasagittal axis during three different time periods (15, 30, 45 s). Each upper limb was assessed separately. The test was evaluated in a group of 63 healthy subjects (mean age ± SD 49.1 ± 19.8 years; F/M 33/30; range 18-87 years). RESULTS: Motor performances (number of clicks) significantly decreased as a function of age for both the dominant side (age effect; linear regression; p < 0.0001 for 15, 30 and 45 s) and the non-dominant side (linear regression; p < 0.0001 for 15, 30 and 45 s). Performances on the dominant and non-dominant side were linearly correlated with the time periods (p < 0.0001 on both sides). The symmetry index (ratio of performance on the dominant side divided by performance on the non-dominant side) was correlated linearly and positively with the duration of the test (y = 0.002x + 1.053; p = 0.0056). We also found a linear relationship between upper limb length and motor performance on the non-dominant side for 15 s (p = 0.023) and 45 s (p = 0.041). The test was characterized by a very high correlation between the results obtained by two investigators during two successive sessions in a subgroup of 7 subjects (Pearson product moment correlation: 0.989 for the dominant side and 0.988 for the non-dominant side). CONCLUSION: The CAM test appears as a robust and low cost tool to quantify upper limb pointing movements. In particular, the test strongly discriminates the effects of age upon motor performances in upper limbs. Future studies are now required to establish the sensitivity, specificity and reliability of this procedure in selected neuromuscular or skeletal diseases affecting the elderly.

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamo-cortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops.

The electronic counting arm movement test (eCAM test).

A novel transportable electronic platform aiming to characterize the performance of successive fast vertical visually guided pointing movements toward two fixed targets (eCAM test: electronic counting arm movement test) is described and one validation test is presented. This platform is based on an Arduino(®) micro-controller and a Processing(®) routine. It records both the pointing performance (number of clicks) and the elapsed time between two successive pointing movements. Using this novel platform, we studied the effects of functional electrical stimulation (FES) applied on the dominant upper limb in 15 healthy volunteers (mean age ± SD: 22.3 ± 4.3 years; 5 males/10 females). The following muscles were stimulated: flexor carpi radialis (FCR), extensor carpi radialis (ECR), biceps brachii (BB), and triceps brachii (TB). The intensities of the stimulation were 2 and 3 mA above the sensory threshold (ST). Movement times were lesser when performed against gravity and pointing performance improved with FES. We provide the first demonstration that low-intensity FES impacts on motor performances during successive vertical goal-directed pointing movements under visual guidance. The eCAM test is currently the sole electronic tool to assess quickly and easily the performances of successive vertical pointing movements. Future potential applications include, in particular, the follow-up of the effects of neurorehabilitation of neurological/neurosurgical disorders associated with hand-eye incoordination, the functional evaluation of upper limb prosthesis or orthosis, and the analysis of the effects of FES in central or peripheral nervous system disorders.

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.

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.