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Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed toward examining post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and Trisomy 21 (T21, Down syndrome). This N-of-1 randomized trial examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) over 10 sessions of anodal tDCS (1.5 mA, 25 cm) over Broca's area with the cathode over the contralateral region was compared to 10 sessions of sham-tDCS and four control sessions in a 20-year-old male individual with T21 presenting moderate-severe childhood apraxia of speech (CAS). The accuracy for NSW production progressively improved (gain of 40%) under tDCS (sham-tDCS and control sessions showed < 20% gain). A decrease in speech severity from moderate-severe to mild-moderate indicated transfer effects in speech production. Speech accuracy under tDCS was correlated with Wernicke's area activation (P3 current source density), which in turn was correlated with the activation of the left supramarginal gyrus and the Sylvian parietal-temporal junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated speech sound acquisition in a young adult with T21 and CAS, possibly through activating brain regions required for phonological working memory.

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ABSTRACT Pelvic floor muscle weakness can lead to urinary incontinence, pelvic organ prolapse, and sexual dysfunction. Although it can be minimized by pelvic floor muscle training (PFMT), its effects are not lasting. Therefore, using combination therapy seems promising. This study aims to evaluate the effect of transcranial direct current stimulation (tDCS) combined with PFMT on intravaginal pressure, pelvic floor muscle strength (PFMS), sexual function (SF), and quality of life (QoL) in healthy women. A total of 32 women, aged from 18 to 45 years, will undergo PFMT (with perineal contractions and relaxation) with the aid of pressure biofeedback associated with active tDCS or sham tDCS. Sessions will last 20 minutes, three times per week, for four weeks, totaling 12 sessions. During the protocol, participants will be instructed to also perform the home-based PFMT daily. The tDCS anodal electrode will be positioned over the supplementary motor area of the dominant cortical hemisphere, whereas the cathodal will be over the contralateral supraorbital region, with a 2mA intensity for 20 minutes. Intravaginal pressure (pressure gauge), PFM strength (measured by digital palpation and the PERFECT scheme), FSFI (Female Sexual Function Index), and QoL (SF-36 questionnaire) will be evaluated before and after the 12 sessions and after a 30-day follow-up.

RESUMEN La debilidad de la musculatura del suelo pélvico puede provocar incontinencia urinaria, prolapso de órganos pélvicos y disfunción sexual, y puede minimizarse mediante el entrenamiento de la musculatura del suelo pélvico (EMSP). Sin embargo, este efecto no es duradero. En este contexto, una terapia combinada puede ser prometedora para mejorar la situación. Este estudio tiene por objetivo evaluar el efecto de la estimulación transcraneal por corriente directa (ETCC) combinada con EMSP sobre la presión intravaginal, la fuerza muscular del suelo pélvico (FMSP), la función sexual (FS) y la calidad de vida (CV) en mujeres sanas. Participarán 32 mujeres, de entre 18 y 45 años, que se someterán a EMSP (contracciones y relajación del perineo) y a Biofeedback asociado a ETCC activa o ETCC sham durante 20 minutos, tres veces por semana, durante 4 semanas, con un total de 12 sesiones. Durante el protocolo, las participantes también se someterán diariamente a EMSP en casa. El electrodo anodal de la ETCC se colocará sobre el área motora suplementaria del hemisferio cortical dominante, y el electrodo catodal sobre la región supraorbital contralateral, a una intensidad de 2 mA, durante 20 minutos. Se evaluarán la presión intravaginal (manómetro), la FMSP (palpación digital, esquema Perfect), la FS (Índice de Función Sexual Femenina) y la CV (cuestionario SF-36) antes y después de las 12 sesiones, así como tras un seguimiento de 30 días.

RESUMO A fraqueza muscular do assoalho pélvico pode gerar incontinência urinária, prolapso de órgãos pélvicos e disfunção sexual, e pode ser minimizada pelo treinamento muscular do assoalho pélvico (TMAP). No entanto, este efeito não é duradouro. Assim, terapia combinada parece ser promissora para a melhora deste quadro. Dessa forma, objetiva-se avaliar o efeito da estimulação transcraniana por corrente contínua (ETCC), combinada ao TMAP, sobre a pressão intravaginal, força muscular do assoalho pélvico (FMAP), função sexual (FS) e qualidade de vida (QV) em mulheres saudáveis. Serão 32 mulheres, entre 18 e 45 anos, que realizaram TMAP (contrações e relaxamento do períneo) e Biofeedback associados a ETCC ativa ou ETCC sham por 20 minutos, três vezes por semana, por 4 semanas, totalizando 12 sessões. Durante o protocolo, as participantes também realizarão diariamente, em domicílio, o TMAP. O eletrodo anodal da ETCC será posicionado sobre a área motora suplementar do hemisfério cortical dominante, e o catodal sobre a região supraorbital contralateral, com intensidade de 2mA, por 20 minutos. A pressão intravaginal (manômetro de pressão), FMAP (palpação digital, esquema Perfect), FS (Índice de Função Sexual Feminina) e QV (questionário SF-36) foram avaliadas antes e depois das 12 sessões, bem como após acompanhamento de 30 dias.

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To the best of our knowledge, neurophysiological markers indicating changes induced by non-invasive brain stimulation (NIBS) on cognitive performance, especially one of the most investigated under these procedures, working memory (WM), are little known. Here, we will briefly introduce frontal midline theta (FM-theta) oscillation (4-8 Hz) as a possible indicator for NIBS effects on WM processing. Electrophysiological recordings of FM-theta oscillation seem to originate in the medial frontal cortex and the anterior cingulate cortex, but they may be driven more subcortically. FM-theta has been acknowledged to occur during memory and emotion processing, and it has been related to WM and sustained attention. It mainly occurs in the frontal region during a delay period, in which specific information previously shown is no longer perceived and must be manipulated to allow a later (delayed) response and observed in posterior regions during information maintenance. Most NIBS studies investigating effects on cognitive performance have used n-back tasks that mix manipulation and maintenance processes. Thus, if considering FM-theta as a potential neurophysiological indicator for NIBS effects on different WM components, adequate cognitive tasks should be considered to better address the complexity of WM processing. Future research should also evaluate the potential use of FM-theta as an index of the therapeutic effects of NIBS intervention on neuropsychiatric disorders, especially those involving the ventral medial prefrontal cortex and cognitive dysfunctions.

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Previously, we demonstrated that acute transcranial direct current stimulation (tDCS) reduced blood pressure (BP) and improved autonomic modulation in hypertensives. We hypothesized that acute and short-term tDCS intervention can promote similar benefits in resistant hypertensive patients (RHT). We assessed the impact of one (acute intervention) and ten (short-term intervention) tDCS or SHAM (20 min, each) sessions on BP, pulse interval (PI) and systolic blood pressure variabilities, humoral mechanisms associated with BP regulation, and cytokines levels. True RHT subjects (n = 13) were randomly submitted to one and ten SHAM and tDCS crossing sessions (1 week of "washout"). Hemodynamic (Finometer®, Beatscope), office BP, and autonomic variables (accessed through spectral analysis of the pulse-to-pulse BP signal, in the time and frequency domain - Fast Fourrier Transform) were measured at baseline and after the short-term intervention. 24 h-ambulatory BP monitoring was measured after acute and short-term protocols. Acute intervention: tDCS reduced BP, cardiac output, and increase high-frequency band of PI (vagal modulation to the heart). Short-term protocol: tDCS did not change BP and cardiac output parameters. In contrast, central systolic BP (-12%), augmentation index (-31%), and pulse wave velocity (34%) were decreased by the short-term tDCS when compared to SHAM. These positive results were accompanied by a reduction in the low-frequency band (-37%) and an increase of the high-frequency band of PI (+62%) compared to SHAM. These findings collectively indicate that short-term tDCS concomitantly improves resting cardiac autonomic control and pulse wave behavior and reduces central BP in RHT patients, https://ensaiosclinicos.gov.br/rg/RBR-8n7c9p.

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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.

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Here, we assessed the impact of one session of transcranial direct current stimulation (tDCS) or SHAM (20 min, each) on ventilatory responses to cardiopulmonary exercise test, central and peripheral blood pressure (BP), and autonomic modulation in resistant hypertensive (RHT) patients. RHT subjects (n = 13) were randomly submitted to SHAM and tDCS crossing sessions (1 week of "washout"). Patients and a technician who set the tDCS/Sham room up were both blind. After brain stimulation, patients were submitted to a cardiopulmonary exercise test to evaluate ventilatory and cardiovascular response to exercise. Hemodynamic (Finometer®, Beatscope), and autonomic variables were measured at baseline (before tDCS/Sham) and after incremental exercise. RESULTS: Our study shows that tDCS condition improved heart rate recovery, VO2 peak, and vagal modulation (after cardiopulmonary exercise test); attenuated the ventilatory variability response, central and peripheral blood pressure well as sympathetic modulation (after cardiopulmonary exercise test) in comparison with SHAM. These data suggest that acute tDCS sessions prevented oscillatory ventilation behavior during the cardiopulmonary exercise test and mitigated the increase of systolic blood pressure in RHT patients. After the exercise test, tDCS promotes better vagal reentry and improved autonomic modulation, possibly reducing central blood pressure and aortic augmentation index compared to SHAM. Brazilian Registry of Clinical Trials (ReBEC): https://ensaiosclinicos.gov.br/rg/RBR-8n7c9p.

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Purpose: Transcranial direct current stimulation (tDCS) seems to positively modulate the autonomic nervous system in different clinical conditions and healthy subjects; however, its effects on hypertensive (HTN) patients are not completely known. This study aimed to evaluate the effects of a tDCS or SHAM session (20 min) on blood pressure (BP) and autonomic variables of HTN patients.Materials and Methods: Subjects (n = 13) were randomly submitted to SHAM and tDCS sessions (1 week of washout). Hemodynamic and autonomic variables were measured at baseline, during, and immediately after tDCS or SHAM stimulation (Finometer®, Beatscope). Ambulatory BP measurement (ABPM) was evaluated after the experimental period.Results: Hemodynamic variables were not changed by tDCS, except for the fall in peripheral vascular resistance (Δ = -1696.51 ± 204.65 dyn.s/cm5). After the tDCS, sympathetic modulation was decreased (-61.47%), and vagal modulation was increased (+38.09%). Such acute autonomic changes may have evoked positive results observed in 24 hs-systolic blood pressure (Δ = -8.4 ± 6.2; P = .0022) and 24hs-diastolic blood pressure (Δ = -5.4 ± 4.2; P = .0010) in tDCS subjects compared with that in SHAM.Conclusion: These findings suggest that the tDCS could promote positive acute adjustments on cardiac autonomic control and reduced values on 24-hs BP of HTN patients. More than a proof-of-concept, these results may point out to the future, where brain stimulation (tDCS) can be used to HTN syndromes, such as refractory HTN.

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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.

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Background: Age is an important factor that impacts the variability of tDCS effects. Objective/Hypothesis: To compare effects of anodal (a)-tDCS over the left dorsolateral prefrontal cortex (DLPFC), and primary motor cortex (M1) in adolescents, adults, and elderly on heat pain threshold (HPT; primary outcome) and the working memory (WM; secondary outcome). We hypothesized that the effect of tDCS on HPT and WM performance would be the largest in adolescents because their pre-frontal cortex is more prone to neuroplasticity. Methods: We included 30 healthy women within the age ranges of 15-16 (adolescents, n = 10), 30-40 (adults, n = 10), and 60-70 (elderly, n = 10) years. In this crossover single-blinded study, participants received three interventions applied over the DLPF and M1. The active stimulation intensity was two mA for 30 min. From 20 min of stimulation onset, the tDCS session was coupled with an online n-back task. The a-tDCS and sham were applied in a random sequence, with a washout time of a minimum 7 days between each trial. HPT was evaluated before and after stimulation. The WM performance with an n-back task was assessed after the tDCS session. Results: A Generalized Estimating Equation (GEE) model revealed a significant effect of the a-tDCS over the left DLPFC to reduce the HPT in adolescents compared with sham. It increased the pain perception significantly [a large effect size (ES) of 1.09)]. In the adults, a-tDCS over M1 enhanced the HPT significantly (a large ES of 1.25) compared to sham. No significant effect for HPT was found in the elderly. Response time for hits was reduced for a-tDCS over the DLPFC in adolescents, as compared to the other two age groups. Conclusions: These findings suggest that a-tDCS modulates pain perception and WM differentially according to age and target area of stimulation. In adolescents, anodal stimulation over the DLPFC increased the pain perception, while in adults, the stimulation over the M1 increased the pain threshold. Thus, they elucidate the impact of tDCS for different age groups and can help to define what is the appropriate intervention according to age in further clinical trials. Clinical Trial Registration: www.ClinicalTrials.gov, Identifier: NCT04328545.

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INTRODUCTION: Transcranial direct-current stimulation (tDCS) has been used to modulate and induce changes in brain function and excitability. tDCS is a promising tool for the treatment of aphasia. OBJECTIVE: To evaluate whether tDCS improves articulatory accuracy and speech production in patients with aphasia after stroke. METHODS AND RESULTS: Twelve right-handed subjects participated in a double-blind, sham-controlled, crossover offline trial. We assessed (1) articulatory accuracy at a naming task, (2) number of words correctly produced, (3) number of syllables repeated correctly, and (4) qualitative assessment of speech. Articulatory accuracy improved when using tDCS over Broca's area in subjects with aphasia post-stroke (p ≤ 0.05). Qualitative improvement in the naming and syllable repetition tasks was observed, but the difference was not statistically significant (respectively, p = 0.15 and p = 0.79). CONCLUSION: The current results corroborate the potential of tDCS to be used as an alternative and complementary treatment for individuals with aphasia.

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Transcranial direct current stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) has been shown to reduce cravings in tobacco addiction; however, results have been somewhat mixed. In this study, we hypothesized that motivation to quit smoking is a critical factor of tDCS effects in smokers. Therefore, we conducted a double-blind, randomized clinical trial to evaluate the effects of both tDCS and motivation to quit on cigarette consumption and the relationship between these two factors. DLPFC tDCS was applied once a day for 5 days. Our primary outcome was the amount of cigarettes smoked per day. We collected this information at baseline (d1), at the end of the treatment period (d5), 2 days later (d7) and at the 4-week follow-up (d35). Visual Analog Scale (VAS) for motivation to quit was collected at the same time-points. 36 subjects (45 ± 11 years old; 24.2 ± 11.5 cigarettes daily smoked, 21 women) were randomized to receive either active or sham tDCS. In our multivariate analysis, as to take into account the mediation and moderation effects of motivation to quit, we found a significant main effect of tDCS, showing that tDCS was associated with a significant reduction of cigarettes smoked per day. We also showed a significant interaction effect of motivation to quit and treatment, supporting our hypothesis that tDCS effects were moderated by motivation to quit, indicating that higher levels of motivation were associated with a larger tDCS response. We found that the participants' motivation to quit alone, both at baseline and at follow-up, does not explain the decrease in the average cigarette consumption. Repetitive prefrontal tDCS coupled with high motivation significantly reduced cigarette consumption up to 4-weeks post-intervention. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov, NCT02146014.

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Phantom limb pain is a chronic neuropathic pain that develops in 45-85% of patients who undergo major amputations of the upper and lower extremities and appears predominantly during two time frames following an amputation: the first month and later about 1 year. Although in most patients the frequency and intensity of pain diminish over time, severe pain persists in about 5-10%. It has been proposed that factors in both the peripheral and central nervous systems play major roles in triggering the development and maintenance of pain associated with extremity amputations. Chronic pain is physically and mentally debilitating, affecting an individual's capacity for self-care, but also diminishing an individual's daily capacity for personal and economic independence. In addition, the pain may lead to depression and feelings of hopelessness. A National Center for Biotechnology Information study found that in the USA alone, the annual cost of dealing with neuropathic pain is more than $600 billion, with an estimated 20 million people in the USA suffering from this condition. Although the pain can be reduced by antiepileptic drugs and analgesics, they are frequently ineffective or their side effects preclude their use. The optimal approach for eliminating neuropathic pain and improving individuals' quality of life is the development of novel techniques that permanently prevent the development and maintenance of neuropathic pain, or that eliminate the pain once it has developed. What is still required is understanding when and where an effective novel technique must be applied, such as onto the nerve stump of the transected peripheral axons, dorsal root ganglion neurons, spinal cord, or cortex to induce the desired influences. This review, the second of two in this journal volume, examines the techniques that may be capable of reducing or eliminating chronic neuropathic pain once it has developed. Such an understanding will improve amputees' quality of life by blocking the mechanisms that trigger and/or maintain PLP and chronic neuropathic pain.

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Abstract Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates cortical excitability. It is devoid of serious adverse events and exerts variable effects on cognition, with several research findings suggesting that it can improve memory, verbal and mathematical skills. Because tDCS devices are low-cost, portable and relatively easy to assemble, they have become available outside of the medical setting and used for non-medical ("cosmetic") purposes by laypersons. In this sense, tDCS has become a popular technique aiming to improve cognition and the achievement of a better performance not only at work, but also in other fields such as sports, leisure activities (video games) and even the military. In spite of these unforeseen developments, there has been a general paralysis of the medical and regulatory agencies to develop guidelines for the use of tDCS for cosmetic purposes. Several challenges are present, most importantly, how to restrict tDCS use outside of the medical setting in face of variable and sometimes conflicting results from scientific research. This article aims to describe the popular use of tDCS, in light of the pillars of neuroethics, a branch of bioethics relative to brain research. Between two possible but extreme solutions - total release or total restriction of tDCS - it is paramount to develop a spectrum of alternatives, which may vary over time and in different cultural backgrounds.

Resumo A estimulação transcraniana por corrente contínua (ETCC) é uma técnica não invasiva de estimulação cerebral que modula a excitabilidade cortical. A ETCC é desprovida de efeitos adversos graves e exerce efeitos variáveis sobre a cognição, com vários achados de pesquisa sugerindo que a técnica pode promover melhora nas habilidades mnêmica, verbal e matemática. Devido ao seu baixo custo, portabilidade e facilidade de montagem, os aparelhos de ETCC tornaram-se disponíveis fora do contexto médico, sendo usados para fins não médicos ("cosméticos") por indivíduos leigos. Nesse sentido, a ETCC tornou-se um procedimento popular para aprimoramento da cognição e a realização de melhor desempenho não somente no ambiente de trabalho, mas também em campos tais como o esporte, atividades de lazer ( video games ) e até no meio militar. Apesar desses acontecimentos imprevisíveis, há uma certa morosidade das agências médicas e regulatórias em desenvolver diretrizes para o uso de ETCC para fins cosméticos. Há muitos desafios presentes, principalmente, como restringir o uso da ETCC fora do contexto médico em face de resultados variáveis, e muitas vezes conflitantes, da pesquisa científica sobre o tema. Este artigo tem como objetivo descrever o uso popular da ETCC sob a luz da neuroética, um ramo da bioética que se dedica ao estudo do cérebro. Entre duas situações possíveis, mas extremas - liberação ou restrição totais da ETCC -, é primordial o desenvolvimento de um espectro de alternativas, que podem variar ao longo do tempo e depender de diversos contextos culturais.

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The cerebellum plays an important role in the planning, initiation and stability of movements, as well as in postural control and balance. Modulation of neural regions underlying balance control may be a potential alternative to treat balance impairments in cerebellar patients. Transcranial direct current stimulation (tDCS) is a noninvasive and safe tool capable to modulate cerebellar activity. We aim to investigate the effects of cerebellar tDCS (ctDCS) on postural balance in healthy individuals. Fifteen healthy and right-handed subjects were submitted to three sessions of ctDCS (anodal, cathodal and sham), separated by at least 48 h. In each session, tests of static (right and left Athlete Single Leg tests) and dynamic balance (Limits of Stability test) were performed using the Biodex Balance System before and immediately after the ctDCS. The results revealed that cathodal ctDCS impaired static balance of healthy individuals, reflected in higher scores on overall stability index when compared to baseline for right (p = 0.034) and left (p = 0.01) Athlete Single Leg test. In addition, we found significant impairment for left Athlete Single Leg test in comparison to sham stimulation (p = 0.04). As far as we know, this is the first study that points changes on balance control after ctDCS in healthy individuals. This finding raises insights to further investigation about cerebellar modulation for neurological patients.

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Both invasive and non-invasive motor cortex stimulation techniques have been successfully employed in the treatment of chronic pain, but the precise mechanism of action of such treatments is not fully understood. It has been hypothesized that a mismatch of normal interaction between motor intention and sensory feedback may result in central pain. Sensory feedback may come from peripheral nerves, vision and also from corollary discharges originating from the motor cortex itself. Therefore, a possible mechanism of action of motor cortex stimulation might be corollary discharge reinforcement, which could counterbalance sensory feedback deficiency. In other instances, primary deficiency in the production of corollary discharges by the motor cortex might be the culprit and stimulation of cortical motor areas might then be beneficial by enhancing production of such discharges. Here we review evidence for a possible role of motor cortex corollary discharges upon both the pathophysiology and the response to motor cortex stimulation of different types of chronic pain. We further suggest that the right dorsolateral prefrontal cortex (DLPC), thought to constantly monitor incongruity between corollary discharges, vision and proprioception, might be an interesting target for non-invasive neuromodulation in cases of chronic neuropathic pain.

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The functional role of the primary motor cortex (M1) in the production of movement parameters, such as length, direction and force, is well known; however, whether M1 is associated with the parametric adjustments in the absolute timing dimension of the task remains unknown. Previous studies have not applied tasks and analyses that could separate the absolute (variant) and relative (invariant) dimensions. We applied transcranial direct current stimulation (tDCS) to M1 before motor practice to facilitate motor learning. A sequential key-pressing task was practiced with two goals: learning the relative timing dimension and learning the absolute timing dimension. All effects of the stimulation of M1 were observed only in the absolute dimension of the task. Mainly, the stimulation was associated with better performance in the transfer test in the absolute dimension. Taken together, our results indicate that M1 is an important area for learning the absolute timing dimension of a motor sequence.

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UNLABELLED: Fibromyalgia is a chronic pain syndrome that is associated with maladaptive plasticity in neural central circuits. One of the neural circuits that are involved in pain in fibromyalgia is the primary motor cortex. We tested a combination intervention that aimed to modulate the motor system: transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) and aerobic exercise (AE). In this phase II, sham-controlled randomized clinical trial, 45 subjects were assigned to 1 of 3 groups: tDCS + AE, AE only, and tDCS only. The following outcomes were assessed: intensity of pain, level of anxiety, quality of life, mood, pressure pain threshold, and cortical plasticity, as indexed by transcranial magnetic stimulation. There was a significant effect for the group-time interaction for intensity of pain, demonstrating that tDCS/AE was superior to AE [F (13, 364) = 2.25, p = 0.007] and tDCS [F (13, 364) = 2.33, p = 0.0056] alone. Post-hoc adjusted analysis showed a difference between tDCS/AE and tDCS group after the first week of stimulation and after 1 month intervention period (p = 0.02 and p = 0.03, respectively). Further, after treatment there was a significant difference between groups in anxiety and mood levels. The combination treatment effected the greatest response. The three groups had no differences regarding responses in motor cortex plasticity, as assessed by TMS. The combination of tDCS with aerobic exercise is superior compared with each individual intervention (cohen's d effect sizes > 0.55). The combination intervention had a significant effect on pain, anxiety and mood. Based on the similar effects on cortical plasticity outcomes, the combination intervention might have affected other neural circuits, such as those that control the affective-emotional aspects of pain. TRIAL REGISTRATION: (www.ClinicalTrials.gov), identifier NTC02358902.