Effect of transcranial direct current stimulation and transcranial magnetic stimulation on the cognitive function of individuals with Alzheimer's disease: a systematic review with meta-analysis and meta-regression.

OBJECTIVE: To analyze the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) on the cognitive function of individuals with Alzheimer's disease (AD). METHODS: This systematic review with meta-analysis and meta-regression included randomized clinical trials published until 05/2022. We included studies conducted with individuals with AD of both sexes, aged between 55 and 85 years, treated with tDCS, TMS, or both. RESULTS: Twenty-one studies were included in the systematic review and sixteen in the meta-analysis. Meta-regression suggested a significant influence of anodic tDCS with current intensity of 1.5 mA on cognitive function. Significant results were found with treatment frequencies of three and five days a week for two weeks. Subgroup analysis found that anodic tDCS influences cognitive function, regardless of AD stage. Similar was observed for TMS using a frequency of 20 Hz and current intensity of 90% of the resting motor threshold. DISCUSSION: Anodal tDCS and 20 Hz TMS have demonstrated the ability to improve cognitive function in AD by modulating neural activity. These therapies are safe and well-tolerated, offering promise as adjuncts to available pharmacological treatments. Studies with greater methodological rigor and parameter standardization are warranted. Comprehensive investigations involving neuroimaging techniques may provide a better understanding of the interaction between induced electrical fields and the complex neural networks affected in AD, paving the way for more personalized and effective neurostimulation approaches.

Identifying biomarkers for tDCS treatment response in Alzheimer's disease patients: a machine learning approach using resting-state EEG classification.

Background: Transcranial direct current stimulation (tDCS) is a promising treatment for Alzheimer's Disease (AD). However, identifying objective biomarkers that can predict brain stimulation efficacy, remains a challenge. The primary aim of this investigation is to delineate the cerebral regions implicated in AD, taking into account the existing lacuna in comprehension of these regions. In pursuit of this objective, we have employed a supervised machine learning algorithm to prognosticate the neurophysiological outcomes resultant from the confluence of tDCS therapy plus cognitive intervention within both the cohort of responders and non-responders to antecedent tDCS treatment, stratified on the basis of antecedent cognitive outcomes. Methods: The data were obtained through an interventional trial. The study recorded high-resolution electroencephalography (EEG) in 70 AD patients and analyzed spectral power density during a 6 min resting period with eyes open focusing on a fixed point. The cognitive response was assessed using the AD Assessment Scale-Cognitive Subscale. The training process was carried out through a Random Forest classifier, and the dataset was partitioned into K equally-partitioned subsamples. The model was iterated k times using K-1 subsamples as the training bench and the remaining subsample as validation data for testing the model. Results: A clinical discriminating EEG biomarkers (features) was found. The ML model identified four brain regions that best predict the response to tDCS associated with cognitive intervention in AD patients. These regions included the channels: FC1, F8, CP5, Oz, and F7. Conclusion: These findings suggest that resting-state EEG features can provide valuable information on the likelihood of cognitive response to tDCS plus cognitive intervention in AD patients. The identified brain regions may serve as potential biomarkers for predicting treatment response and maybe guide a patient-centered strategy. Clinical Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT02772185?term=NCT02772185&draw=2&rank=1, identifier ID: NCT02772185.

A Novel Exploratory Graph-Based Analytical Tool for Functional Near-Infrared Spectroscopy in Naturalistic Experiments: An Illustrative Application in Typically Developing Children.

Naturalistic paradigms are being increasingly applied to investigate human brain function. Compared with resting-state and task-based paradigms in neuroimaging, naturalistic stimuli and situations can be potentially more readily translated to daily-life applications. Among neuroimaging modalities, functional near-infrared spectroscopy (fNIRS) is particularly suitable for naturalistic investigations and applications. However, specific and tailored statistical analysis to interrogate brain function using naturalistic fNIRS is warranted. Here, we describe an exploratory graph-centrality-based approach to investigating participants' spatiotemporal similarities from the fNIRS signal. We illustrate the usefulness of our approach in a sample of typically developing children (10 males and 9 females; mean age of 5.2 years old; sd = 0.78) while they watch the Inscapes movie designed for neuroimaging acquisition. A node in the left dorsal prefrontal cortex presented similar responses across children, and those fNIRS responses were in line with scene transitions in the movie stimulus. Our results suggest the feasibility of applying centrality graph-based measures to investigate brain function in naturalistic fNIRS during development.

Effects of transcranial direct current stimulation on lower limb function, balance and quality of life after stroke: a systematic review and meta-analysis.

OBJECTIVE: This systematic review with meta-analysis aimed to evaluate the effectiveness of tDCS on lower limb function, balance and quality of life in stroke patients. METHODS: The search included PubMed, CENTRAL, PEDro, Web of Science, SCOPUS, PsycINFO Ovid, CINAHL EBSCO, EMBASE, ScienceDirect, reference lists of relevant reviews, clinical trials registries and academic google, in June and July 2021. Randomized controlled trials were selected, which present the effect of tDCS on lower limb motor function recovery in stroke patients, comparing any type of active tDCS versus sham; parallel or crossover study design; adult patients; stimulation on the primary motor cortex; articles published in any language; without restriction of publication period. RESULTS: Nineteen studies were included. The treatment with active tDCS did not improve motor function (Chi2 = 32,87, I2 = 76%, SMD = 0,36 e 95% CI -0,18-0,90). Subgroup analyzes showed a significant effect favorable to tDCS, in relation to motor function, in the acute and subacute post stroke phases. However, the quality of evidence for this outcome was very low. Regarding balance outcome, a meta-analysis showed a significant difference in favor of active tDCS, but the quality of the evidence was considered very low. As for the quality of life outcome, no statistically significant difference was found in favor of tDCS. DISCUSSION: There is a lack of evidence in recommending the use of tDCS in isolation in the treatment of patients after stroke, aiming at improving motor function, balance and quality of life. However, it is possible that tDCS can be beneficial when associated with other therapies or interventions.

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

OBJECTIVES: This study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD. METHODS: This cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes-closed and eyes-open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD. RESULTS: The PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose). CONCLUSION: Alterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.

Effects on pain and cognition of transcranial direct current stimulation over the dorsolateral prefrontal cortex in women with chronic migraine.

We compared the effects of one versus two daily sessions of anodal transcranial direct current stimulation (a-tDCS) delivered to the left dorsolateral prefrontal cortex (DLPFC) for 10 days in a cohort of 30 women (mean age 28.0±6.92) with chronic migraine (CM, disease duration: 37.8±48.41 month). Participants were randomly allocated to three groups: a-tDCS 1-s Group received one daily a-tDCS session; a-tDCS 2-s Group received two daily a-tDCS sessions; Group SHAM received one daily session with a simulated (placebo) current. All participants were assessed before, after and one month after treatment, using the Migraine Disability Assessment, Montreal Cognitive Assessment, d2 Test of Attention, Trail Making Test (part B), Sequence of Letters and Numbers of the Wechsler Adult Intelligence Scale - III, and Nine Hole Peg Test. We found no difference between groups in the cognitive measures and motor dexterity. However, after treatment, a significant decrease in migraine-related disability was found for the a-tDCS 1-s Group. For all variables, no cumulative effects were observed in a-tDCS 2-s compared to the a-tDCS 1-s Group. The study findings provide preliminary results for future clinical trials designed to compare different intervals between tDCS sessions in CM.

Efficacy and safety of HD-tDCS and respiratory rehabilitation for critically ill patients with COVID-19 The HD-RECOVERY randomized clinical trial.

BACKGROUND AND PURPOSE: Acute Respiratory Distress Syndrome (ADRS) due to coronavirus disease 2019 (COVID-19) has been associated with muscle fatigue, corticospinal pathways dysfunction, and mortality. High-Definition transcranial Direct Current Stimulation (HD-tDCS) may be used to attenuate clinical impairment in these patients. The HD-RECOVERY randomized clinical trial was conducted to evaluate the efficacy and safety of HD-tDCS with respiratory rehabilitation in patients with moderate to severe ARDS due to COVID-19. METHODS: Fifty-six critically ill patients were randomized 1:1 to active (n = 28) or sham (n = 28) HD-tDCS (twice a day, 30-min, 3-mA) plus respiratory rehabilitation for up to 10 days or until intensive care unit discharge. The primary outcome was ventilator-free days during the first 28 days, defined as the number of days free from mechanical ventilation. Furthermore, secondary outcomes such as delirium, organ failure, hospital length of stay and adverse effects were investigated. RESULTS: Active HD-tDCS induced more ventilator-free days compared to sham HD-tDCS. Patients in the active group vs in the sham group experienced lower organ dysfunction, delirium, and length of stay rates over time. In addition, positive clinical response was higher in the active vs sham group. There was no significant difference in the prespecified secondary outcomes at 5 days. Adverse events were similar between groups. CONCLUSIONS: Among patients with COVID-19 and moderate to severe ARDS, use of active HD-tDCS compared with sham HD-tDCS plus respiratory rehabilitation resulted in a statistically significant increase in the number of ventilator-free days over 28 days. HD-tDCS combined with concurrent rehabilitation therapy is a safe, feasible, potentially add-on intervention, and further trials should examine HD-tDCS efficacy in a larger sample of patients with COVID-19 and severe hypoxemia.

Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: A double-blind randomized clinical trial.

OBJECTIVES: We aimed to examine the effects of multisite anodal transcranial direct current stimulation (tDCS) combined with cognitive stimulation (CS) over 2 months on cognitive performance and brain activity, and the relationship between them, in patients with Alzheimer's disease (AD). METHODS: Patients with AD were randomly assigned to an active tDCS+CS (n=18) or a sham tDCS+CS (n=18) group. Cognitive performance was assessed using the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain activity using EEG (spectral power and coherence analysis) before and after the intervention. Multisite anodal tDCS (2 mA, 30 min) was applied over six brain regions [left and right dorsolateral prefrontal cortex (F3 and F4), Broca's area (F5), Wernicke's area (CP5), left and right somatosensory association cortex (P3 and P4)] for 24 sessions (three times a week). Both groups performed CS during tDCS. RESULTS: Anodal tDCS+CS delays cognitive decline (ADAS-cog change) to a greater extent than sham tDCS+CS (-3.4±1.1 vs. -1.7±0.4; p=.03). Bilateral EEG coherence at high and low frequencies was greater for the active tDCS+CS than sham+CS group for most electrode pairs assessed (p < .05). The post-intervention ADAS-cog change score was predictive for EEG coherence at different sites (R²=.59 to .68; p < .05) in the active but not in the sham tDCS+CS group. CONCLUSION: Anodal tDCS+CS improved overall cognitive function and changed EEG brain activity compared to sham tDCS+CS. Changes in cognitive performance were associated with changes in EEG measures of brain activity. Anodal tDCS+CS appears to be a promising therapeutic strategy to modulate cortical activity and improve cognitive function in patients with AD.

The Effects of Non-Invasive Brain Stimulation on Quantitative EEG in Patients With Parkinson's Disease: A Systematic Scoping Review.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, aside from alterations in the electroencephalogram (EEG) already registered. Non-invasive brain stimulation (NIBS) techniques have been suggested as an alternative rehabilitative therapy, but the neurophysiological changes associated with these techniques are still unclear. We aimed to identify the nature and extent of research evidence on the effects of NIBS techniques in the cortical activity measured by EEG in patients with PD. A systematic scoping review was configured by gathering evidence on the following bases: PubMed (MEDLINE), PsycINFO, ScienceDirect, Web of Science, and cumulative index to nursing & allied health (CINAHL). We included clinical trials with patients with PD treated with NIBS and evaluated by EEG pre-intervention and post-intervention. We used the criteria of Downs and Black to evaluate the quality of the studies. Repetitive transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), electrical vestibular stimulation, and binaural beats (BBs) are non-invasive stimulation techniques used to treat cognitive and motor impairment in PD. This systematic scoping review found that the current evidence suggests that NIBS could change quantitative EEG in patients with PD. However, considering that the quality of the studies varied from poor to excellent, the low number of studies, variability in NIBS intervention, and quantitative EEG measures, we are not yet able to use the EEG outcomes to predict the cognitive and motor treatment response after brain stimulation. Based on our findings, we recommend additional research efforts to validate EEG as a biomarker in non-invasive brain stimulation trials in PD.

Effects of rTMS and tDCS on neuropathic pain after brachial plexus injury: a randomized placebo-controlled pilot study.

Neuropathic pain after brachial plexus injury (NPBPI) is a highly disabling clinical condition and is increasingly prevalent due to increased motorcycle accidents. Currently, no randomized controlled trials have evaluated the effectiveness of non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in patients suffering from NPBPI. In this study, we directly compare the efficacy of 10-Hz rTMS and anodal 2 mA tDCS techniques applied over the motor cortex (5 daily consecutive sessions) in 20 patients with NPBPI, allocated into 2 parallel groups (active or sham). The order of the sessions was randomised for each of these treatment groups according to a crossover design and separated by a 30-day interval. Scores for "continuous" and "paroxysmal" pain (primary outcome) were tabulated after the last stimulation day and 30 days after. Secondary outcomes included the improvement in multidimensional aspects of pain, anxiety state and quality of life from a qualitative and quantitative approach. Active rTMS and tDCS were both superior to sham in reducing continuous (p < 0.001) and paroxysmal (p = 0.002; p = 0.02) pain as well as in multidimensional aspects of pain (p = 0.001; p = 0.002) and anxiety state (p = < 0.001; p = 0.005). Our results suggest rTMS and tDCS are able to treat NPBPI with little distinction in pain and anxiety state, which may promote the use of tDCS in brachial plexus injury pain management, as it constitutes an easier and more available technique.Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/, RBR-5xnjbc - Sep 3, 2018.

Effects of Synergism of Mindfulness Practice Associated With Transcranial Direct-Current Stimulation in Chronic Migraine: Pilot, Randomized, Controlled, Double-Blind Clinical Trial.

Chronic migraine is a difficult disease to diagnose, and its pathophysiology remains undefined. Its symptoms affect the quality of life and daily living tasks of the affected person, leading to momentary disability. This is a pilot, randomized, controlled, double-blind clinical trial study with female patients between 18 and 65 years old with chronic migraine. The patients underwent twelve mindfulness sessions paired with anodal transcranial direct-current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC), with current intensity of 2 mA applied for 20 min, three times a week for 4 weeks. In addition, 20 min of mindfulness home practices were performed by guided meditation audio files. A total of 30 participants were evaluated after the treatment, and these were subdivided into two groups-active tDCS and sham tDCS, both set to mindfulness practice. The FFMQ-BR (Five Facet of Mindfulness Questionnaire), MIDAS (Migraine Disability Assessment), and HIT-6 (Headache Impact Test) questionnaires were used to evaluate the outcomes. After the treatment, the active mindfulness and tDCS group showed better results in all outcomes. The sham group also showed improvements, but with smaller effect sizes compared to the active group. The only significant difference in the intergroup analysis was the outcome evaluated by HIT-6 in the post treatment result. Our results provide the first therapeutic evidence of mindfulness practices associated with left DLPFC anodal tDCS with a consequent increase in the level of full attention and analgesic benefits in the clinical symptoms of patients with chronic migraine.

Multisite non-invasive brain stimulation in Parkinson's disease: A scoping review.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by cardinal motor symptoms in addition to cognitive impairment. New insights concerning multisite non-invasive brain stimulation effects have been gained, which can now be used to develop innovative treatment approaches. OBJECTIVE: Map the researchs involving multisite non-invasive brain stimulation in PD, synthesize the available evidence and discuss future directions. METHODS: The databases PubMed, PsycINFO, CINAHL, LILACS and The Cochrane Library were searched from inception until April 2020, without restrictions on the date of publication or the language in which it was published. The reviewers worked in pairs and sequentially evaluated the titles, abstracts and then the full text of all publications identified as potentially relevant. RESULTS: Twelve articles met the inclusion criteria. The target brain regions included mainly the combination of a motor and a frontal area, such as stimulation of the primary motor córtex associated with the dorsolateral prefrontal cortex. Most of the trials showed that this modality was only more effective for the motor component, or for the cognitive and/or non-motor, separately. CONCLUSIONS: Despite the results being encouraging for the use of the multisite aproach, the indication for PD management should be carried out with caution and deserves scientific deepening.

A guide for the use of fNIRS in microcephaly associated to congenital Zika virus infection.

Congenital Zika Syndrome (CZS) is characterized by changes in cranial morphology associated with heterogeneous neurological manifestations and cognitive and behavioral impairments. In this syndrome, longitudinal neuroimaging could help clinicians to predict developmental trajectories of children and tailor treatment plans accordingly. However, regularly acquiring magnetic resonance imaging (MRI) has several shortcomings besides cost, particularly those associated with childrens' clinical presentation as sensitivity to environmental stimuli. The indirect monitoring of local neural activity by non-invasive functional near-infrared spectroscopy (fNIRS) technique can be a useful alternative for longitudinally accessing the brain function in children with CZS. In order to provide a common framework for advancing longitudinal neuroimaging assessment, we propose a principled guideline for fNIRS acquisition and analyses in children with neurodevelopmental disorders. Based on our experience on collecting fNIRS data in children with CZS we emphasize the methodological challenges, such as clinical characteristics of the sample, desensitization, movement artifacts and environment control, as well as suggestions for tackling such challenges. Finally, metrics based on fNIRS can be associated with established clinical metrics, thereby opening possibilities for exploring this tool as a long-term predictor when assessing the effectiveness of treatments aimed at children with severe neurodevelopmental disorders.

Transcranial Direct Current Stimulation on Parkinson's Disease: Systematic Review and Meta-Analysis.

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson's disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD. Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms. Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were included. Results: Ten studies (n = 236) were included in meta-analysis and 25 studies (n = 405) in qualitative synthesis. The most frequently stimulated targets were dorsolateral prefrontal cortex and primary motor cortex. No significant effect was found among single targets on motor outcomes: Unified Parkinson's Disease Rating Scale (UPDRS) III - motor aspects (MD = -0.98%, 95% CI = -10.03 to 8.07, p = 0.83, I 2 = 0%), UPDRS IV - dyskinesias (MD = -0.89%, CI 95% = -3.82 to 2.03, p = 0.55, I 2 = 0%) and motor fluctuations (MD = -0.67%, CI 95% = -2.45 to 1.11, p = 0.46, I 2 = 0%), timed up and go - gait (MD = 0.14%, CI 95% = -0.72 to 0.99, p = 0.75, I 2 = 0%), Berg Balance Scale - balance (MD = 0.73%, CI 95% = -1.01 to 2.47, p = 0.41, I 2 = 0%). There was no significant effect of single vs. multiple targets in: UPDRS III - motor aspects (MD = 2.05%, CI 95% = -1.96 to 6.06, p = 0.32, I 2 = 0%) and gait (SMD = -0.05%, 95% CI = -0.28 to 0.17, p = 0.64, I 2 = 0%). Simple univariate meta-regression analysis between treatment dosage and effect size revealed that number of sessions (estimate = -1.7, SE = 1.51, z-score = -1.18, p = 0.2, IC = -4.75 to 1.17) and cumulative time (estimate = -0.07, SE = 0.07, z-score = -0.99, p = 0.31, IC = -0.21 to 0.07) had no significant association. Conclusion: There was no significant tDCS alone short-term effect on motor function, balance, gait, dyskinesias or motor fluctuations in Parkinson's disease, regardless of brain area or targets stimulated.

Transcranial Direct Current Stimulation and Mirror Therapy for Neuropathic Pain After Brachial Plexus Avulsion: A Randomized, Double-Blind, Controlled Pilot Study.

Introduction: Although transcranial direct current stimulation (tDCS) and mirror therapy (MT) have benefits in combating chronic pain, there is still no evidence of the effects of the simultaneous application of these techniques in patients with neuropathic pain. This study aims to assess the efficacy of tDCS paired with MT in neuropathic pain after brachial plexus injury. Methods: In a sham controlled, double-blind, parallel-group design, 16 patients were randomized to receive active or sham tDCS administered during mirror therapy. Each patient received 12 treatment sessions, 30 min each, during a period of 4 weeks over M1 contralateral to the side of the injury. Outcome variables were evaluated at baseline and post-treatment using the McGill questionnaire, Brief Pain Inventory, and Medical Outcomes Study 36-Item Short-Form Health Survey. Long-term effects of treatment were evaluated at a 3-month follow-up. Results: An improvement in pain relief and quality of life were observed in both groups (p ≤ 0.05). However, active tDCS and mirror therapy resulted in greater improvements after the endpoint (p ≤ 0.02). No statistically significant differences in the outcome measures were identified among the groups at follow-up (p ≥ 0.12). A significant relationship was found between baseline pain intensity and outcome measures (p ≤ 0.04). Moreover, the results showed that state anxiety is closely linked to post-treatment pain relief (p ≤ 0.05). Conclusion: Active tDCS combined with mirror therapy has a short-term effect of pain relief, however, levels of pain and anxiety at the baseline should be considered. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04385030.

Transcranial direct current stimulation improves tinnitus perception and modulates cortical electrical activity in patients with tinnitus: A randomized clinical trial.

OBJECTIVES: This study aims to determine whether transcranial direct current stimulation (tDCS): a) is effective in the treatment of tinnitus by decreasing its annoyance and severity; b) modulates the cortical electrical activity of such individuals. METHODS: A double-blind, placebo-controlled clinical trial was conducted with 24 patients with tinnitus, randomized into two groups: Group 1 (n = 12) received anodal tDCS over the left temporoparietal area (LTA) and cathodal tDCS over the right dorsolateral prefrontal cortex (DLPFC) and Group 2 (n = 12) received placebo intervention. Tinnitus perception using a visual analog scale (VAS) and the Tinnitus Handicap Inventory (THI) questionnaire, in addition to electroencephalogram (EEG) was measured with eyes opened and closed at baseline and after the intervention. For the treatment, patients were subjected to five consecutive sessions of tDCS with the anodal electrode over the LTA and cathodal electrode over the right DLPFC (7 × 5 cm, 2 mA for 20 min). tDCS was turned off after 30 s in the sham group. RESULTS: Active tDCS significantly improved tinnitus annoyance and severity. It was associated with decreased beta and theta EEG frequency bands with eyes opened and decreased alpha frequency with eyes closed. sLORETA identified changes in frequency bands in the frontal, temporoparietal, and limbic regions. Finally, there were negative correlations between baseline EEG frequency bands and tDCS-induced change in tinnitus annoyance and severity. CONCLUSIONS: These results demonstrate that tDCS modulates the EEG activity and alleviates tinnitus perception. This effect may be related to baseline EEG activity.

Neurostimulation Combined With Cognitive Intervention in Alzheimer's Disease (NeuroAD): Study Protocol of Double-Blind, Randomized, Factorial Clinical Trial.

Despite advances in the treatment of Alzheimer's disease (AD), there is currently no prospect of a cure, and evidence shows that multifactorial interventions can benefit patients. A promising therapeutic alternative is the use of transcranial direct current stimulation (tDCS) simultaneously with cognitive intervention. The combination of these non-pharmacological techniques is apparently a safe and accessible approach. This study protocol aims to compare the efficacy of tDCS and cognitive intervention in a double-blind, randomized and factorial clinical trial. One hundred participants diagnosed with mild-stage AD will be randomized to receive both tDCS and cognitive intervention, tDCS, cognitive intervention, or placebo. The treatment will last 8 weeks, with a 12-month follow-up. The primary outcome will be the improvement of global cognitive functions, evaluated by the AD Assessment Scale, cognitive subscale (ADAS-Cog). The secondary outcomes will include measures of functional, affective, and behavioral components, as well as a neurophysiological marker (Brain-derived neurotrophic factor, BDNF). This study will enable us to assess, both in the short and long term, whether tDCS is more effective than the placebo and to examine the effects of combined therapy (tDCS and cognitive intervention) and isolated treatments (tDCS vs. cognitive intervention) on patients with AD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02772185-May 5, 2016.

Colour discrimination thresholds in type 1 Bipolar Disorder: a pilot study.

Although some studies have reported perceptual changes in psychosis, no definitive conclusions have been drawn about visual disturbances that are related to bipolar disorder (BPD). The purpose of the present study was to evaluate colour vision in BPD patients. Data were recorded from 24 participants: healthy control group (n = 12) and type 1 BPD group (n = 12). The participants were 20-45 years old and they were free from neurological disorders and identifiable ocular disease and had normal or corrected-to-normal visual acuity. Colour discrimination was evaluated using the Lanthony D-15d, Trivector and Ellipse tests, using a psychophysical forced-choice method. The relationship of visual measures to mood state and cognitive function was also investigated. The results showed that BPD patients had higher colour discrimination thresholds in the D15d (p < 0.001), Trivector (p < 0.001) and Ellipse (p < 0.01) tests compared with healthy controls. Linear regression analysis showed that mood state was related to colour discrimination. BPD individuals were not impaired in cognitive tasks. The present study provided new evidence of potential links between type 1 BPD and visual processing impairments. This research suggests a new direction for studies and the need for research in this field of study.

Effects of different montages of transcranial direct current stimulation on the risk of falls and lower limb function after stroke.

BACKGROUND: Stroke is associated with high rates of falling and severe impairment of lower limb in patients who survive. OBJECTIVE: The aim of this study was to analyze the effectiveness of different montages of transcranial direct current stimulation (tDCS) on reducing falls and on lower limb function after acute stroke. METHODS: Sixty participants with acute stroke were randomly allocated into four groups with different electrode's setups: anodal, cathodal, bilateral and sham tDCS. Each patient received 10 stimulation sessions (five consecutive days for two weeks). Four Square Step Test, Occurrence of Falling Index, Overall Stability Index, Falls Efficacy Scale - International, Berg Balance Scale, Six-minute walk test and Sit to Stand Test were measured at baseline, post-treatment, and at one- and three-month follow-up. RESULTS: At baseline, no differences between the groups in terms of clinical and demographic characteristics were found. However, after treatment and during follow up, all the groups that received active stimulation showed greater reduction in the risk of falls and improved performance of the lower limb's motor skills when compared to the sham group. No significant differences were found between the three types of active montages in relation to the risk of falling. In relation to lower limb function, bilateral stimulation provided a higher improvement when compared to anodal and cathodal tDCS. CONCLUSIONS: This is the first trial with different setups of tDCS on acute stroke patients. tDCS presents as an effective treatment strategy in reducing the risk of falls and improving lower limb function after a stroke. ClinicalTrials.gov (NCT 02422173).