Dataset of middle cerebral artery blood flow stability in response to high-definition transcranial electrical stimulation.

This supplementary dataset is supportive of the randomized sham-controlled, double-blind, crossover clinical trial investigating polarity- and intensity-dependent effects of high-definition transcranial electrical stimulation (HD-tDCS) applied over the right temporo-parietal junction on mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally. Data of eleven healthy right-handed adults (6 women, 5 men; mean age 31 ± 5.6 years old) were analyzed for MCA-BFv, assessed using transcranial doppler ultrasound on the stimulated and the contralateral hemisphere concomitantly, during and after 3 blocks of 2 min HD-tDCS at 1, 2, and 3 mA. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) randomly ordered across different days. The collected data is publicly available at Mendeley Data. This article and the data will inform future related investigations and safety analysis of transcranial non-invasive brain stimulation.

Middle cerebral artery blood flow stability in response to high-definition transcranial electrical stimulation: A randomized sham-controlled clinical trial.

Since neuronal activity is coupled with neurovascular activity, we aimed to analyze the cerebral blood flow hemodynamics during and following high-definition transcranial direct current stimulation (HD-tDCS). We assessed the mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally using transcranial doppler ultrasound, during and after HD-tDCS, in eleven right-handed healthy adult participants (6 women, 5 men; mean age 31 ± 5.6 years old), with no evidence of brain or cardiovascular dysfunction. The HD-tDCS electrode montage was centered over the right temporo-parietal junction. The stimulation protocol comprised 3 blocks of 2 min at each current intensity (1, 2, and 3 mA) and an inter-stimulus interval of 5 min between blocks. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) on three different days, with an interval of at least 24 h. Stimulation was well tolerated across HD-tDCS conditions tested, and the volunteers reported no significant discomfort related to stimulation. There was no significant difference in the right or the left MCA-BFv during or after the stimulation protocol across all stimulation conditions. We conclude that at a range of intensities, vascular reaction assessed using middle cerebral artery blood flow is not significantly altered during or after HD-tDCS both locally and remotely, which provides further evidence for the safety of HD-tDCS.

BrainWave Nets: Are Sparse Dynamic Models Susceptible to Brain Manipulation Experimentation?

Sparse time series models have shown promise in estimating contemporaneous and ongoing brain connectivity. This paper was motivated by a neuroscience experiment using EEG signals as the outcome of our established interventional protocol, a new method in neurorehabilitation toward developing a treatment for visual verticality disorder in post-stroke patients. To analyze the [complex outcome measure (EEG)] that reflects neural-network functioning and processing in more specific ways regarding traditional analyses, we make a comparison among sparse time series models (classic VAR, GLASSO, TSCGM, and TSCGM-modified with non-linear and iterative optimizations) combined with a graphical approach, such as a Dynamic Chain Graph Model (DCGM). These dynamic graphical models were useful in assessing the role of estimating the brain network structure and describing its causal relationship. In addition, the class of DCGM was able to visualize and compare experimental conditions and brain frequency domains [using finite impulse response (FIR) filter]. Moreover, using multilayer networks, the results corroborate with the susceptibility of sparse dynamic models, bypassing the false positives problem in estimation algorithms. We conclude that applying sparse dynamic models to EEG data may be useful for describing intervention-relocated changes in brain connectivity.

Fractional Anisotropy of Thalamic Nuclei Is Associated With Verticality Misperception After Extra-Thalamic Stroke.

Verticality misperception after stroke is a frequent neurological deficit that leads to postural imbalance and a higher risk of falls. The posterior thalamic nuclei are described to be involved with verticality perception, but it is unknown if extra-thalamic lesions can have the same effect via diaschisis and degeneration of thalamic nuclei. We investigated the relationship between thalamic fractional anisotropy (FA, a proxy of structural integrity), and verticality perception, in patients after stroke with diverse encephalic extra-thalamic lesions. We included 11 first time post-stroke patients with extra-thalamic primary lesions, and compared their region-based FA to a group of 25 age-matched healthy controls. For the patient sample, correlation and regression analyses evaluated the relationship between thalamic nuclei FA and error of postural vertical (PV) and haptic vertical (HV) in the roll (PVroll/HVroll) and pitch planes (PVpitch/HVpitch). Relative to controls, patients showed decreased FA of anterior, ventral anterior, ventral posterior lateral, dorsal, and pulvinar thalamic nuclei, despite the primary lesions being extra-thalamic. We found a significant correlation between HVroll, and FA in the anterior and dorsal nuclei, and PVroll with FA in the anterior nucleus. FA in the anterior, ventral anterior, ventral posterior lateral, dorsal and pulvinar nuclei predicted PV, and FA in the ventral anterior, ventral posterior lateral and dorsal nuclei predicted HV. While prior studies indicate that primary lesions of the thalamus can result in verticality misperception, here we present evidence supporting that secondary degeneration of thalamic nuclei via diaschisis can also be associated with verticality misperception after stroke.

Entropy Analysis of High-Definition Transcranial Electric Stimulation Effects on EEG Dynamics.

A foundation of medical research is time series analysis-the behavior of variables of interest with respect to time. Time series data are often analyzed using the mean, with statistical tests applied to mean differences, and has the assumption that data are stationary. Although widely practiced, this method has limitations. Here we present an alternative statistical approach with sample analysis that provides a summary statistic accounting for the non-stationary nature of time series data. This work discusses the use of entropy as a measurement of the complexity of time series, in the context of Neuroscience, due to the non-stationary characteristic of the data. To elucidate our argument, we conducted entropy analysis on a sample of electroencephalographic (EEG) data from an interventional study using non-invasive electrical brain stimulation. We demonstrated that entropy analysis could identify intervention-related change in EEG data, supporting that entropy can be a useful "summary" statistic in non-linear dynamical systems.

Manipulation of Human Verticality Using High-Definition Transcranial Direct Current Stimulation.

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.

Normative data for human postural vertical: A systematic review and meta-analysis.

Perception of verticality is required for normal daily function, yet the typical human detection error range has not been well characterized. Vertical misperception has been correlated with poor postural control and functionality in patients after stroke and after vestibular disorders. Until now, all the published studies that assessed Subjective Postural Vertical (SPV) in the seated position used small groups to establish a reference value. However, this sample size does not represent the healthy population for comparison with conditions resulting in pathological vertical. Therefore, the primary objective was to conduct a systematic review with meta-analyses of Subjective Postural Vertical (SPV) data in seated position in healthy adults to establish the reference value with a representative sample. The secondary objective was to investigate the methodological characteristics of different assessment protocols of SPV described in the literature. A systematic literature search was conducted using Medline, EMBASE, and Cochrane libraries. Mean and standard deviation of SPV in frontal and sagittal planes were considered as effect size measures. Sixteen of 129 identified studies met eligibility criteria for our systematic review (n = 337 subjects in the frontal plane; n = 187 subjects in sagittal plane). The meta-analyses measure was estimated using the pooled mean as the estimator and its respective error. Mean reference values were 0.12°±1.49° for the frontal plane and 0.02°±1.82° for the sagittal plane. There was a small variability of the results and this systematic review resulted in representative values for SPV. The critical analysis of the studies and observed homogeneity in the sample suggests that the methodological differences used in the studies did not influence SPV assessment of directional bias in healthy subjects. These data can serve as a reference for clinical studies in disorders of verticality.

Spared Primary Motor Cortex and The Presence of MEP in Cerebral Palsy Dictate the Responsiveness to tDCS during Gait Training.

The current priority of investigations involving transcranial direct current stimulation (tDCS) and neurorehabilitation is to identify biomarkers associated with the positive results of the interventions such that respondent and non-respondent patients can be identified in the early phases of treatment. The aims were to determine whether: (1) present motor evoked potential (MEP); and (2) injuries involving the primary motor cortex, are associated with tDCS-enhancement in functional outcome following gait training in children with cerebral palsy (CP). We reviewed the data from our parallel, randomized, sham-controlled, double-blind studies. Fifty-six children with spastic CP received gait training (either treadmill training or virtual reality training) and tDCS (active or sham). Univariate and multivariate logistic regression analyses were employed to identify clinical, neurophysiologic and neuroanatomic predictors associated with the responsiveness to treatment with tDCS. MEP presence during the initial evaluation and the subcortical injury were associated with positive effects in the functional results. The logistic regression revealed that present MEP was a significant predictor for the six-minute walk test (6MWT; p = 0.003) and gait speed (p = 0.028), whereas the subcortical injury was a significant predictor of gait kinematics (p = 0.013) and gross motor function (p = 0.021). In this preliminary study involving children with CP, two important prediction factors of good responses to anodal tDCS combined with gait training were identified. Apparently, MEP (integrity of the corticospinal tract) and subcortical location of the brain injury exerted different influences on aspects related to gait, such as velocity and kinematics.

Polarity-Dependent Misperception of Subjective Visual Vertical during and after Transcranial Direct Current Stimulation (tDCS).

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.

Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. METHODS: We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. MAIN FINDINGS/DISCUSSION: We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.

Transcranial DC stimulation coupled with TENS for the treatment of chronic pain: a preliminary study.

OBJECTIVE: Based on evidence showing that electrical stimulation of the nervous system is an effective method to decrease chronic neurogenic pain, we aimed to investigate whether the combination of 2 methods of electrical stimulation-a method of peripheral stimulation [transcutaneous electrical nerve stimulation (TENS)] and a method of noninvasive brain stimulation [transcranial direct current stimulation (tDCS)]-induces greater pain reduction as compared with tDCS alone and sham stimulation. METHODS: We performed a preliminary, randomized, sham-controlled, crossover, clinical study in which 8 patients were randomized to receive active tDCS/active TENS ("tDCS/TENS" group), active tDCS/sham TENS ("tDCS" group), and sham tDCS/sham TENS ("sham" group) stimulation. Assessments were performed immediately before and after each condition by a blinded rater. RESULTS: The results showed that there was a significant difference in pain reduction across the conditions of stimulation (P=0.006). Post hoc tests showed significant pain reduction as compared with baseline after the tDCS/TENS condition [reduction by 36.5% (+/-10.7), P=0.004] and the tDCS condition [reduction by 15.5% (+/-4.9), P=0.014], but not after sham stimulation (P=0.35). In addition, tDCS/TENS induced greater pain reduction than tDCS (P=0.02). CONCLUSIONS: The results of this pilot study suggest that the combination of TENS with tDCS has a superior effect compared with tDCS alone.