Cerebellar direct current stimulation modulates pain perception in humans.

PURPOSE: The cerebellum is involved in a wide number of integrative functions, but its role in pain experience and in the nociceptive information processing is poorly understood. In healthy volunteers we evaluated the effects of transcranial cerebellar direct current stimulation (tcDCS) by studying the changes in the perceptive threshold, pain intensity at given stimulation intensities (VAS:0-10) and laser evoked potentials (LEPs) variables (N1 and N2/P2 amplitudes and latencies). METHODS: Fifteen subjects were studied before and after anodal, cathodal and sham tcDCS. LEPs were obtained using a neodymium:yttrium-aluminium-perovskite (Nd:YAP) laser and recorded from the dorsum of the left hand. VAS was evaluated by delivering laser pulses at two different intensities, respectively two and three times the perceptive threshold. RESULTS: Cathodal polarization dampened significantly the perceptive threshold and increased the VAS score, while the anodal one had opposite effects. Cathodal tcDCS increased significantly the N1 and N2/P2 amplitudes and decreased their latencies, whereas anodal tcDCS elicited opposite effects. Motor thresholds assessed through transcranial magnetic stimulation were not affected by cerebellar stimulation. CONCLUSIONS: tcDCS modulates pain perception and its cortical correlates. Since it is effective on both N1 and N2/P2 components, we speculate that the cerebellum engagement in pain processing modulates the activity of both somatosensory and cingulate cortices. Present findings prompt investigation of the cerebellar direct current polarization as a possible novel and safe therapeutic tool in chronic pain patients.

Cathodal transcutaneous spinal direct current stimulation (tsDCS) improves motor unit recruitment in healthy subjects.

Transcutaneous spinal direct current stimulation (tsDCS) is a new promising technique for modulating spinal cord function in humans. However, its effects on corticospinal pathways and lower motorneuron excitability are poorly understood. We studied the effects of tsDCS on motor unit recruitment by evaluating changes in motor unit number (MUNE) and peripheral silent period (PSP) after sham (s-tsDCS), anodal (a-tsDCS) and cathodal (c-tsDCS) tsDCS applied either over the cervical or the lower thoracic spinal cord in healthy subjects. For the calculation of MUNE we used the multipoint incremental technique recording from either the ulnar nerve innervated abductor digiti minimi (ADM) or the median nerve innervated abductor pollicis brevis (APB) muscle. c-tsDCS dramatically increases MUNE values following cervical polarization, while sham and anodal polarization have no significant effect (APB: F(4,99)=26.4, p<0.001, two-way repeated measures ANOVA with "time" and "stimulation" as factors; ADM: F(4,99)=22.1, p<0.0001). At the same time, c-tsDCS dampened PSP respect to sham and anodal conditions (p<0.0001). Interestingly, also thoracic c-tsDCS significantly improved motor unit recruitment compared with both s-tsDCS and a-tsDCS (APB: F(4,99)=20.1, p<0.0001; ADM: F(4,99)=16.6, p<0.0001). Our data in healthy subjects suggest that tsDCS, possibly also through supraspinal effects, could provide a novel therapeutic tool in managing several pathological conditions characterized by reduced motor unit recruitment, such as stroke and spinal cord injuries.

A novel exon 1 mutation (G10R) in the SOD1 gene in a patient with familial ALS.

Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12-23% of patients with a diagnosis of ALS. Although the mechanism by which mutant SOD1 causes neural death remains elusive, several lines of evidence suggest that ALS is a protein-folding disease. Here we report a novel missense mutation in exon 1 of the SOD1 gene in a 68-year-old female with familial ALS characterized by spinal onset with upper and lower motor neuron signs and early neuroimaging evidence of corticospinal tract involvement. Molecular analysis identified a heterozygous mutation in codon 10, with substitution of a highly conserved glycine with arginine (G10R). Modelling of the mutant SOD1 showed a strong destabilization of the protein secondary structure that could influence the strength of the dimer interface. This property can result in a failure of the protein to fold and generation of toxic intracellular aggregates, suggesting a pathogenic role for the mutation.