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.

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 Rehabilitation top‐down techniques based on brain stimulation present variable outcomes in unilateral spatial neglect (USN) after stroke. This study aimed to examine the effects of physical therapy after anodal and cathodal transcranial direct current stimulation (A‐tDCS and C‐tDCS, respectively) to improve visuospatial and functional impairments in individuals with USN after stroke. Methods This double‐blinded, pilot randomized clinical trial enrolled patients with USN after ischemic stroke. Randomization was stratified according to the Behavior Inattention Test–Conventional (BIT‐C) and Catherine Bergego Scale (CBS). Outpatient physical therapy was conducted for 7.5 weeks after 20 minutes of tDCS. The primary outcome was the USN degree evaluated by the BIT‐C. Secondary outcomes were the difference in CBS score, stroke severity (National Institutes of Health Stroke Scale [NIHSS]), disability (modified Rankin Scale), autonomy (Barthel Index, Functional Independence Measure), and quality of life (EuroQol Group 5‐Dimension Self‐Report Questionnaire). Outcomes were analyzed using an analysis of covariance model corrected by age, baseline NIHSS, and baseline BIT‐C. Pairwise post hoc comparisons were performed using Bonferroni correction. Results In the primary outcomes, A‐tDCS led to greater improvement in BIT‐C after intervention (mean difference [MD] = 18.4, 95% confidence interval [CI] = 3.9–32.8, p = 0.008) compared to sham. However, no significant differences were observed between A‐tDCS and C‐tDCS (MD = 13.9, 95% CI = −0.3 to 28.1, p = 0.057), or C‐tDCS and sham (MD = 4.5, 95% CI = −9.7 to 18.8, p = 0.99). There were no significant differences between groups in terms of secondary outcomes. Interpretation A‐tDCS associated with physical therapy can decrease the severity of USN after stroke. However, these preliminary findings must be confirmed by collecting additional evidence in a larger phase 3 trial. ANN NEUROL 2022;92:400–410

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

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.

Background: Few Brazilian studies investigated risk factors for dysphagia and associated complications in a large cohort. Objective: To investigate frequency, predictors, and associated outcomes of dysphagia in patients up to three months post-stroke. Methods: Prospective cohort study of consecutively admitted patients in a specialized center for acute stroke. Patients with a transient ischemic attack, subarachnoid hemorrhage, cerebral venous thrombosis, hemorrhagic stroke with secondary cause, non-acute stroke, or those who did not consent to participate were excluded. Swallowing was evaluated by speech language pathologists using Volume-Viscosity Swallow Test. General function at three months post-stroke was assessed using the following instruments: Modified Rankin scale, Barthel Index and Functional Independence Measure. Results: A total of 831 patients were admitted and 305 patients were included according to the inclusion and exclusion criteria. The mean age of patients was 63.6±13.3 years, mean time from stroke to swallowing assessment was 4.2±4.1 days, and 45.2% of the patients had dysphagia. Age (OR=1.02; 95%CI 1.00-1.04; p=0.017), known medical history of obstructive sleep apnea (OR=5.13; 95%CI 1.74-15.15; p=0.003), and stroke severity at hospital admission (OR=1.10; 95%CI 1.06-1.15; p<0.001) were independently associated with dysphagia. Dysphagia (OR=3.78; 95%CI 2.16-6.61; p<0.001) and stroke severity (OR=1.05; 95%CI 1.00-1.09; p=0.024) were independently associated with death or functional dependence at three months. Conclusions: Dysphagia was present in almost half of stroke patients. Age, obstructive sleep apnea, and stroke severity were predictors of dysphagia, which was independently associated with death or functional dependence at three months.

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