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.

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.

Cerebellum: links between development, developmental disorders and motor learning.

The study of the links and interactions between development and motor learning has noticeable implications for the understanding and management of neurodevelopmental disorders. This is particularly relevant for the cerebellum which is critical for sensorimotor learning. The olivocerebellar pathway is a key pathway contributing to learning of motor skills. Its developmental maturation and remodeling are being unraveled. Advances in genetics have led to major improvements in our appraisal of the genes involved in cerebellar development, especially studies in mutant mice. Cerebellar neurogenesis is compartmentalized in relationship with neurotransmitter fate. The Engrailed-2 gene is a major actor of the specification of cerebellar cell types and late embryogenic morphogenesis. Math1, expressed by the rhombic lip, is required for the genesis of glutamatergic neurons. Mutants deficient for the transcription factor Ptf1a display a lack of Purkinje cells and gabaergic interneurons. Rora gene contributes to the developmental signaling between granule cells and Purkinje neurons. The expression profile of sonic hedgehog in postnatal stages determines the final size/shape of the cerebellum. Genes affecting the development impact upon the physiological properties of the cerebellar circuits. For instance, receptors are developmentally regulated and their action interferes directly with developmental processes. Another field of research which is expanding relates to very preterm neonates. They are at risk for cerebellar lesions, which may themselves impair the developmental events. Very preterm neonates often show sensori-motor deficits, highlighting another major link between impaired developments and learning deficiencies. Pathways playing a critical role in cerebellar development are likely to become therapeutical targets for several neurodevelopmental disorders.

Respective implications of glutamate decarboxylase antibodies in stiff person syndrome and cerebellar ataxia.

BACKGROUND: To investigate whether Stiff-person syndrome (SPS) and cerebellar ataxia (CA) are associated with distinct GAD65-Ab epitope specificities and neuronal effects. METHODS: Purified GAD65-Ab from neurological patients and monoclonal GAD65-Ab with distinct epitope specificities (b78 and b96.11) were administered in vivo to rat cerebellum. Effects of intra-cerebellar administration of GAD65-Ab were determined using neurophysiological and neurochemical methods. RESULTS: Intra-cerebellar administration of GAD65-Ab from a SPS patient (Ab SPS) impaired the NMDA-mediated turnover of glutamate, but had no effect on NMDA-mediated turnover of glycerol. By contrast, GAD65-Ab from a patient with cerebellar ataxia (Ab CA) markedly decreased the NMDA-mediated turnover of glycerol. Both GAD65-Ab increased the excitability of the spinal cord, as assessed by the F wave/M wave ratios. The administration of BFA, an inhibitor of the recycling of vesicles, followed by high-frequency stimulation of the cerebellum, severely impaired the cerebello-cortical inhibition only when Ab CA was used. Moreover, administration of transcranial direct current stimulation (tDCS) of the motor cortex revealed a strong disinhibition of the motor cortex with Ab CA. Monoclonal antibodies b78 and b96.11 showed distinct effects, with greater effects of b78 in terms of increase of glutamate concentrations, impairment of the adaptation of the motor cortex to repetitive peripheral stimulation, disinhibition of the motor cortex following tDCS, and increase of the F/M ratios. Ab SPS shared antibody characteristics with b78, both in epitope recognition and ability to inhibit enzyme activity, while Ab CA had no effect on GAD65 enzyme activity. CONCLUSIONS: These results suggest that, in vivo, neurological impairments caused by GAD65-Ab could vary according to epitope specificities. These results could explain the different neurological syndromes observed in patients with GAD65-Ab.

Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits.

OBJECTIVE: The study objective was to determine the eventual consequences (falls, unsteadiness, and cognitive impairment) of mild chronic hyponatremia, which is generally considered as asymptomatic. METHODS: In a case-control study, we focused on the incidence of falls among 122 patients (mean age 72+/-13 years) with asymptomatic chronic hyponatremia (mean serum sodium concentration [SNa] 126+/-5 mEq/L), who were admitted to the medical emergency department, compared with 244 matched controls. To explore the mechanisms of the excess of falls, we prospectively asked 16 comparable patients (mean age 63+/-15 years; SNa+/-2 mEq/L) to perform 8 attention tests and a gait test consisting of 3 steps "in tandem," in which we measured the "total traveled way" by the center of pressure or total traveled way. Thereafter, the patients were treated and tested again (50% of the patients were tested first with normal SNa to avoid learning biases). RESULTS: Epidemiology of falls: Twenty-six patients (21.3%) of 122 were admitted for falls, compared with only 5.3% of the control patients (adjusted odds ratio: 67; 95% confidence: 7.5-607; P <.001). The frequency of falls was the same regardless of the level of hyponatremia. Gait: The total traveled way by the center of pressure significantly increased in hyponatremia (1336+/-320 mm vs 1047+/-172 mm with normal SNa; P=.003). Attention tests: The mean response time was 673+/-182 milliseconds in hyponatremia and 615+/-184 milliseconds in patients with normal SNa (difference: 58 milliseconds, P <.001). The total error number in hyponatremia increased 1.2-fold (P=.001). These modifications were comparable to those observed after alcohol intake in 10 volunteers. CONCLUSIONS: Mild chronic hyponatremia induces a high incidence of falls possibly as the result of marked gait and attention impairments. Treating these patients might prevent a considerable number of hospitalizations.