Impact of chronic transcranial random noise stimulation (tRNS) on GABAergic and glutamatergic activity markers in the prefrontal cortex of juvenile mice.

Transcranial random noise stimulation (tRNS), a non-invasive neuromodulatory technique capable of altering cortical activity, has been proposed to improve the signal-to-noise ratio at the neuronal level and the sensitivity of the neurons following an inverted U-function. The aim of this study was to examine the effects of tRNS on vGLUT1 and GAD 65-67 and its safety in terms of pathological changes. For that, juvenile mice were randomly distributed in three different groups: "tRNS 1×" receiving tRNS at the density current used in humans (0.3A/m2, 20min), "tRNS 100×" receiving tRNS at two orders of magnitude higher (30.0A/m2, 20min) and "sham" (0.3A/m2, 15s). Nine tRNS sessions during 5 weeks were administered to the prefrontal cortex of awake animals. No detectable tissue macroscopic lesions were observed after tRNS sessions. Post-stimulation immunohistochemical analysis of GAD 65-67 and vGLUT1 immunoreactivity showed reduced GAD 65-67 immunoreactivity levels in the region directly beneath the electrode for tRNS 1× group with no significant effects in the tRNS 100× nor sham group. The observed results suggest an excitatory effect associated with a decrease in GABA levels in absence of major histopathological alterations providing a novel mechanistic explanation for tRNS effects.

Immediate and after effects of transcranial direct-current stimulation in the mouse primary somatosensory cortex.

Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. On the other hand, 20 min of cathodal stimulation produced significant after-effects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these after effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated versus non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and after effects of tDCS, as well as the asymmetric after effects induced by anodal and cathodal stimulation.

Exploring new transcranial electrical stimulation strategies to modulate brain function in animal models.

Transcranial electrical stimulation (tES) refers to a group of non-invasive brain stimulation techniques to induce changes in the excitability of cortical neurons in humans. In recent years, studies in animal models have been shown to be essential for disentangling the neuromodulatory effects of tES, defining safety limits, and exploring potential therapeutic applications in neurological and neuropsychiatric disorders. Testing in animal models is valuable for the development of new unconventional protocols intended to improve tES administration and optimize the desired effects by increasing its focality and enabling deep-brain stimulation. Successful and controlled application of tES in humans relies on the knowledge acquired from studies meticulously performed in animal models.

Cortical dynamics during the preparation of antisaccadic and prosaccadic eye movements in humans in a gap paradigm.

To compare the cortical dynamics of different oculomotor tasks, EEG and eye movements were recorded in 21 volunteers. Using a comprehensive approach, subjects were asked to perform saccadic tasks, which included a saccadic eye movement to a peripheral target (prosaccadic), a movement to the opposite side (antisaccadic), or maintain the gaze fixed (no-go). In mixed trials, prosaccadic, antisaccadic and no-go tasks were indicated by a color square (S1) present for 1900-2500 ms (instructive period). S1 disappeared for 370 ms (gap) and a black dot at 8 deg at right or left indicated the beginning of the task. Reaction times, amplitude of eye movements and number of errors were greatest in antisaccadic tasks, suggesting a greater difficulty. The EEG showed a contingent negativity variation (CNV) that increased progressively along the instructive period and suddenly during the gap: higher in antisaccadic, followed by prosaccadic and no-go tasks. Principal component analysis (PCA) disentangled fronto-central and occipital CNV-related and fronto-central gap-related components. The instructive period was characterized by fronto-central and occipital beta desynchronization (ERD) higher in antisaccadic than in no-go and parieto-occipital alpha synchronization higher in no-go than in antisaccadic tasks. During the gap, parieto-occipital beta and alpha ERD were higher in antisaccadic compared to no-go. The gap was further characterized by a fronto-central increase of inter-trial coherence in theta: highest during antisaccadic, followed by prosaccadic and no-go tasks. This phase locking in theta was also accompanied by theta ERS, which was significantly higher in antisaccadic than in the other two tasks. In PCA of spectral power two main components had dynamics similar to those extracted from voltage data, suggesting cross-frequency coupling. These results suggest that the more difficult saccadic tasks are associated with top-down control mediated by frontal cortex, while simpler tasks rely more on bottom-up control mediated by posterior cortices.