Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications.Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol.Methods: We designed three separate randomized, double-blind, crossover phase I clinical trials in different cohorts of healthy adults using the same stimulation protocol. The primary outcome measure for trial 1 was SVV; trial 2, weight-bearing asymmetry (WBA); and trial 3, electroencephalography power spectral density (EEG-PSD). The HD-tDCS montage comprised a single central, and 3 surround electrodes (HD-tDCS3x1) over the right TPJ. For each study, we tested 3x2 min HD-tDCS3x1 at 1, 2 and 3 mA; with anode center, cathode center, or sham stimulation, in random order across days.Results: We found significant SVV deviation relative to baseline, specific to the cathode center condition, with consistent direction and increasing with stimulation intensity. We further showed significant WBA with direction governed by stimulation polarity (cathode center, left asymmetry; anode center, right asymmetry). EEG-PSD in the gamma band was significantly increased at 3 mA under the cathode.Conclusions: The present series of studies provide converging evidence for focal neuromodulation that can modify physiology and have behavioral consequences with clinical potential.

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Pathologic tilt of subjective visual vertical (SVV) frequently has adverse functional consequences for patients with stroke and vestibular disorders. Repetitive transcranial magnetic stimulation (rTMS) of the supramarginal gyrus can produce a transitory tilt on SVV in healthy subjects. However, the effect of transcranial direct current stimulation (tDCS) on SVV has never been systematically studied. We investigated whether bilateral tDCS over the temporal-parietal region could result in both online and offline SVV misperception in healthy subjects. In a randomized, sham-controlled, single-blind crossover pilot study, thirteen healthy subjects performed tests of SVV before, during and after the tDCS applied over the temporal-parietal region in three conditions used on different days: right anode/left cathode; right cathode/left anode; and sham. Subjects were blind to the tDCS conditions. Montage-specific current flow patterns were investigated using computational models. SVV was significantly displaced towards the anode during both active stimulation conditions when compared to sham condition. Immediately after both active conditions, there were rebound effects. Longer lasting after-effects towards the anode occurred only in the right cathode/left anode condition. Current flow models predicted the stimulation of temporal-parietal regions under the electrodes and deep clusters in the posterior limb of the internal capsule. The present findings indicate that tDCS over the temporal-parietal region can significantly alter human SVV perception. This tDCS approach may be a potential clinical tool for the treatment of SVV misperception in neurological patients.

Objective: Converging evidence supporting an effect of transcranial direct current stimulation (tDCS) on postural control and human verticality perception highlights this strategy as promising for post-stroke rehabilitation. We have previously demonstrated polarity-dependent effects of high-definition tDCS (HD-tDCS) on weight-bearing asymmetry. However, there is no investigation regarding the time-course of effects on postural control induced by HD-tDCS protocols. Thus, we performed a nonlinear time series analysis focusing on the entropy of the ground reaction force as a secondary investigation of our randomized, double-blind, placebo-controlled, crossover clinical trial. Materials and Methods: Twenty healthy right-handed young adults received the following conditions (random order, separate days); anode center HD-tDCS, cathode center HD-tDCS or sham HD-tDCS at 1, 2, and 3 mA over the right temporo-parietal junction (TPJ). Using summarized time series of transfer entropy, we evaluated the exchanging information (causal direction) between both force plates and compared the dose-response across the healthy subjects with a Generalized Linear Hierarchical/Mixed Model (GLMM). Results: We found significant variation during the dynamic information flow (p < 0.001) among the dominant bodyside (and across time). A greater force transfer entropy was observed from the right to the left side during the cathode-center HD-tDCS up to 2 mA, with a causal relationship in the information flow (equilibrium force transfer) from right to left that decreased over time. Conclusions: HD-tDCS intervention induced a dynamic influence over time on postural control entropy. Right hemisphere TPJ stimulation using cathode-center HD-tDCS can induce an asymmetry of body weight distribution towards the ipsilateral side of stimulation. These results support the clinical potential of HD-tDCS for post-stroke rehabilitation.

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