Efeitos da estimulação transcraniana por corrente contínua (ETCC) na voz e fala na doença de Parkinson: relato de caso / Effects of transcranial direct current stimulation (tDCS) on voice and speech in Parkinson's disease: a case report

RESUMO Este estudo descreve os resultados de duas intervenções diferentes para a disartria na doença de Parkinson (DP). Trata-se de dois pacientes do sexo masculino com DP e disartria hipocinética que foram submetidos à avaliação fonoaudiológica. O primeiro (S1) recebeu dez sessões de 20 minutos de estimulação transcraniana por corrente contínua (ETCC), enquanto o segundo (S2) recebeu dez sessões de 20 minutos de ETCC e terapia fonoaudiológica. Os pacientes foram reavaliados imediatamente após a intervenção e novamente após 30 dias. A melhora no tempo de fonação, movimento velar e outras medidas de disartria foram mais significativas no S1. De acordo com os parâmetros da análise acústica de fonte glótica, a melhora nas medidas de frequência e Jitter, Shimmer e ruído foi maior no S2 tanto na avaliação pós-intervenção imediata quanto na avaliação 30 dias pós-intervenção, seguida por S1 na avaliação pós-intervenção imediata. S1 apresentou melhores resultados na avaliação perceptivo-auditiva de fala e voz, enquanto S2 obteve melhores escores na análise acústica. Esses achados sugerem que a terapia fonoaudiológica convencional associada à ETCC tem um impacto mais significativo na fala e voz do que a ETCC isolada, demonstrando o potencial da ETCC como tratamento complementar para pacientes com DP.

ABSTRACT This study describes the results of two different interventions for dysarthria in Parkinson's disease (PD). It concerns two male patients with PD and hypokinetic dysarthria who underwent speech and voice assessment. The first (S1) received ten 20-minute sessions of transcranial direct current stimulation (tDCS), while the second (S2) received ten 20-minute sessions of tDCS as well as speech therapy. The patients were re-evaluated immediately after the intervention and again after 30 days. Improvements in phonation time, velar movement, and other measures of dysarthria were more significant in S1. According to the acoustic analysis source parameters, improvements in the frequency measurements and Jitter, Shimmer, and noise measurements were greater in S2 in both the immediate post-intervention and 30-day postintervention assessments, followed by S1 in the immediate post-intervention assessment. S1 showed better results in the auditory-perceptual evaluation of speech and voice, whereas S2 obtained better scores in acoustic analysis. These findings suggest that conventional speech therapy combined with tDCS has a more significant impact on speech and voice than tDCS alone, demonstrating the potential of tDCS as an adjuvant treatment for patients with PD.

Neural Mechanism Underlying Task-Specific Enhancement of Motor Learning by Concurrent Transcranial Direct Current Stimulation / 神经科学通报·英文版

The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm2) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca2+ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.

Clinical Decision on Disorders of Consciousness After Acquired Brain Injury: Stepping Forward / 神经科学通报·英文版

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

Research on electroencephalogram power spectral density of stroke patients under transcranial direct current stimulation / 生物医学工程学杂志

Transcranial direct current stimulation (tDCS) has become a new method of post-stroke rehabilitation treatment and is gradually accepted by people. However, the neurophysiological mechanism of tDCS in the treatment of stroke still needs further study. In this study, we recruited 30 stroke patients with damage to the left side of the brain and randomly divided them into a real tDCS group (15 cases) and a sham tDCS group (15 cases). The resting EEG signals of the two groups of subjects before and after stimulation were collected, then the difference of power spectral density was analyzed and compared in the band of delta, theta, alpha and beta, and the delta/alpha power ratio (DAR) was calculated. The results showed that after real tDCS, delta band energy decreased significantly in the left temporal lobes, and the difference was statistically significant ( P < 0.05); alpha band energy enhanced significantly in the occipital lobes, and the difference was statistically significant ( P < 0.05); the difference of theta and beta band energy was not statistically significant in the whole brain region ( P > 0.05). Furthermore, the difference of delta, theta, alpha and beta band energy was not statistically significant after sham tDCS ( P > 0.05). On the other hand, the DAR value of stroke patients decreased significantly after real tDCS, and the difference was statistically significant ( P < 0.05), and there was no significant difference in sham tDCS ( P > 0.05). This study reveals to a certain extent the neurophysiological mechanism of tDCS in the treatment of stroke.

The measurements of the similarity of dynamic brain functional network / 生物医学工程学杂志

Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.

Terapia de produção audiovisual associada a estimulação por corrente contínua melhora nomeação em paciente com afasia de Broca e doença de Parkinson / Audiovisual production therapy associated with transcranial current stimulation improves naming in a patient with Broca's aphasia and Parkinson's disease

RESUMO A doença de Parkinson (DP) é uma doença neurodegenerativa, caracterizada por disfunções motoras e não motoras. Pacientes com DP também podem apresentar problemas de linguagem, incluindo deficit em tarefas de nomeação. Dificuldade em tarefas de nomeação é uma característica importante da afasia de Broca, transtorno de linguagem associado a lesões pós-acidente vascular cerebral (AVC) no córtex pré-frontal inferior esquerdo (área de Broca). Aqui, apresenta-se o caso de um paciente de 79 anos diagnosticado com DP (estágio 4 na escala de Hoehn e Yahr) e afasia crônica não fluente pós-AVC, com deficit de nomeação severos. O paciente foi tratado com uma nova combinação de terapia audiovisual de produção e estimulação transcraniana por corrente contínua (ETCC), técnica neuromodulatória não invasiva, que tem sido cada vez mais adotada para potencializar terapias fonoaudiológicas. ETCC anodal (2 mA) foi aplicada sobre o córtex pré-frontal inferior esquerdo (F7 no sistema 10/20), durante nove sessões de 20 minutos, ao longo de duas semanas, enquanto o paciente tentava nomear imagens de objetos comuns com o auxílio de vídeos curtos mostrando uma boca articulando os sons do nome do objeto (pista audiovisual). Observou-se aumento significativo nos escores de nomeação entre o pré e o pós-tratamento, tanto para imagens treinadas, quanto para não treinadas, mas fonemicamente similares (generalização). Os resultados apresentaram indícios iniciais de que terapia audiovisual de produção associada à ETCC anodal sobre a área de Broca pode representar uma alternativa viável para pacientes com deficits de nomeação severos.

ABSTRACT Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. PD patients may present language problems, including deficits in confrontation naming. Naming deficits are also an important feature of Broca's aphasia, a condition associated with post-stroke damage to the left inferior prefrontal cortex (Broca's area). We present the case of a 79-year old, male patient diagnosed with both PD (stage 4 in Hoehn and Yahr's scale) and chronic post-stroke, non-fluent aphasia. The patient, with particularly severe naming deficits, was treated with a novel combination of audiovisual production therapy and transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory technique that has been increasingly used to potentiate speech therapy. Anodal tDCS (2 mA) was applied to the left inferior prefrontal cortex (F7 in the 10/20 system) in nine 20-min sessions over two weeks while the patient tried to name pictures of common objects aided by short videos of an articulating mouth (audiovisual cue). We found significant pre- to post-training naming improvement for treated items and for untreated, phonemically similar items (generalization). The results provide initial indication that audiovisual production therapy combined with anodal tDCS over Broca's area may represent a viable treatment alternative for patients with severe naming deficits.

The efficacy and safety of multiple sessions of multisite transcranial random noise stimulation in treating chronic tinnitus / Eficácia e segurança de múltiplas sessões de estimulação transcraniana por ruído aleatório multissítio no tratamento do zumbido crônico

Abstract Introduction: Random noise stimulation was reported as the more effective and safer type of electrical stimulation techniques in relieving tinnitus symptoms. The multisite protocol of transcranial random noise stimulation has shown additional favorable effects. Objective: Here we will discuss the role of applying eight sessions of multisite transcranial random noise stimulation in decreasing tinnitus loudness and annoyance without exerting additional adverse effects. Methods: Twenty-nine subjects (8 female), the mean age of (45.34 ± 9.57) with chronic tinnitus received transcranial random noise stimulation in the multisite protocol, 10 min of auditory-transcranial random noise stimulation applied over the T3, T4 preceded by 10 min of prefrontal-transcranial random noise stimulation applied over F4, FP1. In the first group, only one session was applied and the multiple-sessions group contained eight repeated sessions. Visual analog scale scores for loudness and distress were recorded before and immediately after the treatment. Multivariate repeated measure ANOVA test was used and minimal detectable change calculated. Results: There was a statistically and clinically significant reduction in tinnitus loudness and annoyance in both groups (p < 0.05, effect size (η 2) > 0.8), while the amount of annoyance suppression in the multiple-sessions group was significantly greater than the single-session group. The patients of the multiple-sessions transcranial random noise stimulation group reported an improvement in their sleep and lower tinnitus handicap inventory scores without experiencing any additional adverse effects of the intervention. Conclusions: The results of this study showed a substantial improvement in tinnitus symptoms by using the multiple sessions of transcranial random noise stimulation in the multisite protocol without producing any additional side effects. We suggest further clinical trials with long-term follow-up be investigated.

Resumo Introdução: Tem sido relatado que a estimulação transcraniana por ruído aleatório é um tipo mais eficaz e seguro de técnica de estimulação elétrica no alívio dos sintomas do zumbido. O protocolo multissítio da estimulação transcraniana por ruído aleatório mostrou efeitos favoráveis adicionais. Objetivo: Discutir o papel da aplicação de oito sessões de estimulação transcraniana por ruído aleatório multissítio na diminuição da intensidade (loudness) do som e incômodo (annoyance) do zumbido sem causar efeitos adversos adicionais. Método: Vinte e nove indivíduos com zumbido crônico (oito do sexo feminino), com média de 45,34 ± 9,57 anos, receberam estimulação transcraniana por ruído aleatório no protocolo multissítio, 10 minutos de estimulação transcraniana por ruído aleatório-auditivo aplicado no T3, T4 precedido por 10 min de estimulação transcraniana por ruído aleatório pré-frontal aplicado sobre F4, FP1. No primeiro grupo, apenas uma sessão foi aplicada e o grupo de múltiplas sessões recebeu oito sessões. Os escores da escala visual analógica para a intensidade do som (loudness) e incômodo (annoyance) do zumbido foram registrados antes e imediatamente após o tratamento. O teste Anova multivariada para medidas repetidas foi utilizado e a mudança mínima detectável foi calculada. Resultados: Houve uma redução estatisticamente e clinicamente significante na intensidade e incômodo do zumbido em ambos os grupos (p < 0,05; tamanho do efeito (η2) > 0,8), embora o nível de supressão do incômodo no grupo de sessões múltiplas tenha sido significantemente maior do que no grupo de sessão única. Os pacientes do grupo estimulação transcraniana por ruído aleatório com múltiplas sessões relataram uma melhoria no sono e menores escores no tinnitus handicap inventory, sem experimentar quaisquer efeitos adversos adicionais da intervenção. Conclusão: Os resultados deste estudo mostraram uma melhora substancial nos sintomas do zumbido utilizando múltiplas sessões de estimulação transcraniana por ruído aleatório no protocolo multissítio sem produzir quaisquer efeitos colaterais adicionais. Sugerimos que novos ensaios clínicos com seguimento de longo prazo sejam realizados.

Schizophrenia TreAtment with electRic Transcranial Stimulation (STARTS): design, rationale and objectives of a randomized, double-blinded, sham-controlled trial / Tratamento da esquizofrenia com estimulação transcraniana por corrente contínua (ETCC): fundamentação teórica e objetivos de um ensaio clínico randomizado, duplo-cego, controlado por simulação

Abstract Introduction Schizophrenia is a severe mental disorder. While some antipsychotic medications have demonstrated efficacy in treating positive symptoms, there is no widely recognized treatment for negative symptoms, which can cause significant distress and impairment for patients with schizophrenia. Here we describe the rationale and design of the STARTS study (Schizophrenia TreAtment with electRic Transcranial Stimulation), a clinical trial aimed to test the efficacy of a non-pharmacological treatment known as transcranial direct current stimulation (tDCS) for treating the negative symptoms of schizophrenia Methods The STARTS study is designed as a randomized, sham-controlled, double-blinded trial evaluating tDCS for the treatment of the negative symptoms of schizophrenia. One-hundred patients will be enrolled and submitted to 10 tDCS sessions over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporoparietal junction (cathodal stimulation) over 5 consecutive days. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in the Positive and Negative Syndrome Scale (PANSS) negative subscale score over time and across groups. Biological markers, including blood neurotrophins and interleukins, genetic polymorphisms, and motor cortical excitability, will also be assessed. Results The clinical results will provide insights about tDCS as a treatment for the negative symptoms of schizophrenia, and the biomarker investigation will contribute towards an improved understanding of the tDCS mechanisms of action. Conclusion Our results could introduce a novel therapeutic technique for the negative symptoms of schizophrenia. Clinical trial registration: ClinicalTrials.gov, NCT02535676 .

Resumo Introdução A esquizofrenia é um transtorno mental grave. Embora alguns medicamentos antipsicóticos tenham demonstrado eficácia no tratamento de sintomas positivos, não há tratamento amplamente reconhecido para sintomas negativos, o que pode causar sofrimento e prejuízo significativos para pacientes com esquizofrenia. Aqui descrevemos a fundamentação teórica e o design do estudo STARTS (Schizophrenia TreAtment with electRic Transcranial Stimulation), um ensaio clínico destinado a testar a eficácia de um tratamento não farmacológico conhecido como estimulação transcraniana por corrente contínua (ETCC) para tratar os sintomas negativos da esquizofrenia. Métodos O estudo STARTS foi concebido como um ensaio clínico randomizado, controlado por simulação, duplo-cego, avaliando a ETCC para o tratamento dos sintomas negativos da esquizofrenia. Cem pacientes serão incluídos e submetidos a 10 sessões de ETCC sobre o córtex pré-frontal dorsolateral esquerdo (estimulação anódica) e a junção temporoparietal esquerda (estimulação catodal) durante 5 dias consecutivos. Os participantes serão avaliados através de testes clínicos e neuropsicológicos antes e após a intervenção. O desfecho primário é a mudança na pontuação da subescala negativa da Escala da Síndrome Positiva e Negativa (Positive and Negative Syndrome Scale [PANSS]) ao longo do tempo e entre os grupos. Marcadores biológicos, incluindo neurotrofinas e interleucinas do sangue, polimorfismos genéticos e excitabilidade cortical motora, também serão avaliados. Resultados Os resultados clínicos fornecerão informações sobre a ETCC como um tratamento para os sintomas negativos da esquizofrenia, e a investigação dos biomarcadores contribuirá para uma melhor compreensão dos mecanismos de ação da ETCC. Conclusão Nossos resultados podem trazer uma nova técnica terapêutica para o tratamento dos sintomas negativos da esquizofrenia. Registro do ensaio clínico: ClinicalTrials.gov, NCT02535676.

Safety of transcranial direct current stimulation in a patient with deep brain stimulation electrodes / Segurança da estimulação transcraniana por corrente contínua em uma paciente com implante de eletrodos de estimulação cerebral profunda

ABSTRACT Background: Transcranial direct current stimulation (tDCS) has been investigated in movement disorders, making it a therapeutic alternative in clinical settings. However, there is still no consensus on the most appropriate treatment protocols in most cases, and the presence of deep brain stimulation (DBS) electrodes has been regarded as a contraindication to the procedure. We recently studied the effects of cerebellar tDCS on a female patient already undergoing subthalamic nucleus deep brain stimulation (STN-DBS) for generalized dystonia. She also presented with chronic pain and depression. With STN-DBS, there was improvement of dystonia, and botulinum toxin significantly reduced pain. However, depressive symptoms were worse after STN-DBS surgery. Methods: Neuromodulation with 2 mA anodal cerebellar tDCS was initiated, targeting both hemispheres in each daily 30 minute session: 15 minutes of left cerebellar stimulation followed by 15 minutes of right cerebellar stimulation. The DBS electrodes were in place and functional, but the current was turned off during tDCS. Results: Although our goal was to improve dystonic movements, after 10 tDCS sessions there was also improvement in mood with normalization of Beck Depression Inventory scores. There were no complications in spite of the implanted STN-DBS leads. Conclusion: Our results indicate that tDCS is safe in patients with DBS electrodes and may be an effective add-on neuromodulatory tool in the treatment of potential DBS partial efficacy in patients with movement disorders.

RESUMO Descrição: A estimulação transcraniana por corrente contínua (ETCC) tem sido investigada nos distúrbios de movimento, tornando-a uma alternativa terapêutica no contexto clínico. Contudo, não há consenso quanto aos protocolos mais apropriados na maioria dos casos e a presença de eletrodos de estimulação cerebral profunda (ECP) é geralmente considerada uma contraindicação. Recentemente, estudamos os efeitos da ETCC cerebelar em uma paciente do sexo feminino com implante de eletrodos de estimulação cerebral profunda (ECP) para distonia generalizada. Ela também apresentava dor crônica e depressão. A ETCC foi realizada dois anos após o implante de eletrodos de ECP. Com a ECP houve melhora da distonia e a toxina botulínica reduziu a dor. Contudo, os sintomas depressivos pioraram após a cirurgia de ECP. Métodos: Foi proposta ETCC cerebelar anódica de 2mA, sobre os dois hemisférios em cada sessão de 30min: 15 min de ETCC cerebelar esquerda seguida de 15min de ETCC cerebelar direita. Resultados: Embora o nosso objetivo tenha sido melhorar os movimentos distônicos, após 10 sessões de ETCC houve melhora também do humor da paciente. Não houve nenhuma complicação, apesar da presença de eletrodos de ECP. Conclusão: Nossos resultados apontam para a segurança da tDCS e sua aplicação potencial e efetiva como ferramenta neuromodulatória adicional no tratamento de possíveis sintomas persistentes após a ECP em pacientes com distúrbios de movimento.

Noninvasive brain stimulation in psychiatric disorders: a primer

Objective: Noninvasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), are increasingly being used to treat mental disorders, particularly major depression. The aim of this comprehensive review is to summarize the main advances, limitations, and perspectives of the field. Methods: We searched PubMed and other databases from inception to July 2017 for articles, particularly systematic reviews and meta-analyses, evaluating the use of NIBS in psychiatric disorders. Results: We reviewed the mechanisms of action, safety, tolerability, efficacy, and relevant clinical parameters of NIBS. Repetitive TMS is already an established technique for the treatment of depression, and there is theoretically room for further methodological development towards a high-end therapeutic intervention. In contrast, tDCS is a technically easier method and therefore potentially suitable for wider clinical use. However the evidence of its antidepressant efficacy is less sound, and a recent study found tDCS to be inferior to antidepressant pharmacotherapy. Clinical trials using rTMS for other mental disorders produced mixed findings, whereas tDCS use has not been sufficiently appraised. Conclusion: The most promising results of NIBS have been obtained for depression. These techniques excel in safety and tolerability, although their efficacy still warrants improvement.

Primum non nocere or primum facere meliorem? Hacking the brain in the 21st century / Primum non nocere ou primum facem meliorem? O cérebro pirateado do século 21

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.

A critical review of trials of transcranial direct current stimulation and trigeminal nerve stimulation for depression: the issue of treatment-emergent mania / Revisão crítica da literatura de ensaios clínicos em estimulação transcraniana por corrente contínua e estimulação de nervo trigêmeo para depressão: o problema da mania tratamento-emergente

Abstract Objective: This study is a critical review analyzing occurrence of treatment-emergent mania (TEM) related to transcranial direct current stimulation (tDCS) and trigeminal nerve stimulation (TNS). Method: We present a systematic review of the literature on TEM related to tDCS and TNS treatment for major depressive disorder (MDD), conducted in accordance with the recommendations from Cochrane Group and the PRISMA guidelines. Results: Our search identified few reported episodes of TEM in the literature. In fact, we found 11 trials focused on treatment of MDD (seven controlled trials of tDCS and four trials of TNS, three open label and one controlled). We highlight the need for safety assessment in clinical research settings to establish with precision and in larger samples the risks inherent to the technique under investigation. Conclusion: Safety assessment is of fundamental importance in clinical research. TEM is a very important safety issue in MDD trials. Further and larger controlled trials will help to clarify both the safety and the clinical effects of combinations of pharmacotherapy and tDCS or TNS in daily clinical practice.

Resumo Objetivo: O presente estudo consiste em uma revisão e análise crítica da ocorrência de mania tratamento-emergente (TEM) relacionada a estimulação transcraniana por corrente contínua (ETCC) e estimulação do nervo trigêmeo (TNS). Método: Apresentamos uma revisão sistemática de literatura sobre TEM relacionada a ETCC e TNS no tratamento de transtorno depressivo maior (TDM), conduzida de acordo com as recomendações do Grupo Cochrane e protocolo PRISMA. Resultados: A pesquisa identificou poucos relatos de TEM na literatura. Na verdade, foram encontrados 11 ensaios clínicos com foco no tratamento de TDM (sete estudos controlados de ETCC e quatro de TNS, sendo três abertos e um controlado). Destacamos a necessidade de avaliações de segurança em pesquisas clínicas para se estabelecer com maior precisão e em amostras maiores os riscos inerentes à técnica sob investigação. Conclusão: Avaliação de segurança é fundamental na pesquisa clínica. A TEM é um efeito adverso importante no tratamento do TDM. Maiores ensaios clínicos controlados ajudarão a esclarecer os efeitos clínicos e a segurança da combinação de psicotrópicos e ETCC ou TNS.

Evaluation of different procedure involved in the Transcranial Direct Current Stimulation (tDCS) technique experimental application

Introduction: The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in the central nervous system of animals and humans. Furthermore, tDCS has been suggested as a therapeutic tool for pain management. The aim of this study was to standardize a non-invasive tDCS technique indexed by the nociceptive response of rats submitted to different conditions necessary to the tDCS application. Method: 60-day-old male Wistar rats (n=65), divided into 6 groups: control(C); non-active sham (NAS); active-sham (AS); active-sham restrained (ASR); non-active sham restrained (NASR); active tDCS treatment. Animals received treatment during 30 seconds (sham-active) or 20 minutes (restraint and tDCS)/8 days. Nociceptive threshold was assessed by Hot Plate test at baseline, immediately and 24h after the first session, immediately and 24h after the last session. Variance analysis of repeated measurements followed by Bonferroni was performed for intra-group comparison. Results: Physical restraint and 30 seconds stimulation (sham-tDCS) increased pain sensitivity (P≤0.05), and tDCS treatment was able to prevent the thermal hyperalgesia. Our original tDCS montage is similar to that used in the procedure with humans, because it is not an invasive technique. The electrodes are positioned on the head, and the animals are immobilized during the 20-minute treatment. As this procedure could involve behavior and neurochemical alterations due to stress induced by restriction (thus, it creates a research bias), we hypothesized that a 30-second electrical stimulus application (sham-tDCS) and the physical restriction used during tDCS treatment might alter nociceptive response in rats. Conclusion: There are methodological limitations in the present tDCS-technique. Although active-tDCS treatment is able to prevent these harmful effects, interference of these factors has to be considered during the results' analysis. Future adaptations of the tDCS-technique in rats are required to evaluate its therapeutic effects (AU)

Transcranial magnetic stimulation and transcranial direct current stimulation appear to be safe neuromodulatory techniques useful in the treatment of anxiety disorders and other neuropsychiatric disorders / Uso clínico da estimulação magnética transcraniana e da estimulação transcraniana por corrente direta em transtornos de ansiedade e de transtornos neuropsiquiátricos

ABSTRACT Transcranial magnetic stimulation (TMS) has recently been investigated as a possible adjuvant treatment for many neuropsychiatric disorders, and has already been approved for the treatment of drug-resistant depression in the United States and in Brazil, among other countries. Although its use in other neuropsychiatric disorders is still largely experimental, many physicians have been using it as an off-label add-on therapy for various disorders. More recently, another technique, transcranial direct current stimulation (tDCS), has also become available as a much cheaper and portable alternative to TMS, although its mechanisms of action are different from those of TMS. The use of off-label therapeutic TMS or tDCS tends to occur in the setting of diseases that are notoriously resistant to other treatment modalities. Here we discuss the case of anxiety disorders, namely panic and post-traumatic stress disorders, highlighting the uncertainties and potential problems and benefits of the clinical use of these neuromodulatory techniques at the current stage of knowledge.

RESUMO A estimulação magnética transcraniana (TMS) foi recentemente proposta como um possível tratamento adjuvante para muitos distúrbios neuropsiquiátricos, e já foi aprovada para o tratamento de depressão fármaco-resistente nos Estados Unidos e no Brasil, entre outros países. Apesar do fato de que seu uso em outros transtornos neuropsiquiátricos ainda é em grande parte experimental, muitos médicos têm utilizado essas técnicas como uma terapia off-label em várias doenças. Mais recentemente, uma outra técnica, a estimulação transcraniana por corrente contínua (ETCC), tornou-se também disponível como uma alternativa muito mais barata e portátil do que a TMS, embora os seus mecanismos de ação sejam diferentes daqueles da TMS. O uso off-label de TMS ou ETCC tende a ocorrer no caso de doenças que são notoriamente resistentes a outras modalidades terapêuticas. Aqui nós discutimos o caso dos transtornos de ansiedade, ou seja, transtorno do pânico e estresse pós-traumático, destacando as incertezas, benefícios e problemas potenciais inerentes ao uso clínico dessas técnicas neuromoduladoras no atual estágio do conhecimento.

Motor cortex tDCS does not improve strength performance in healthy subjects / ETCC sobre o córtex motor não aumenta o desempenho de força em sujeitos saudáveis / tDCS en motor corteza no aumenta el rendimiento de fuerza en sujetos sanos

The influence of transcranial direct current stimulation (tDCS) upon maximal strength performance in exercises recruiting large muscle mass has not been established in healthy populations. The purpose of this study was to investigate whether anodal tDCS was able to increase the performance during maximal strength exercise (MSEX) in healthy subjects. Fourteen volunteers (age: 26 ± 4 yrs) performed two MSEX after anodal or sham tDCS (2mA; 20min prior MSEX), involving knee extensors and flexors in concentric isokinetic muscle actions of the dominant limb (3 sets of 10 repetitions). The electrical muscle activity (sEMG) of four recruited muscles was recorded during MSEX. Anodal tDCS was not able to improve force production (i.e., total work and peak torque), fatigue resistance, or electromyographic activity during MSEX when compared to sham condition. In conclusion, anodal tDCS applied upon the contralateral motor cortex was not capable of increasing the strength performance of knee extensors and flexors in young healthy subjects.

A influência da estimulação transcraniana por corrente contínua (ETCC) sobre o desempenho da força muscular em exercícios que recrutam grandes massas musculares ainda não foi estabelecido em populações saudáveis. O objetivo desse estudo foi investigar se a ETCC anódica seria capaz de aumentar o desempenho durante exercício máximo de força (EMF) em sujeitos saudáveis. Catorze voluntários (idade: 26 ± 4 anos) executaram dois EMF com aplicação prévia da ETCC anódica ou placebo (2mA; 20 mim), envolvendo músculos flexores e extensores do joelho dominante em ação concêntrica isocinética (3 séries de 10 repetições). A atividade elétrica muscular (sEMG) de quatro músculos recrutados foi registrada durante o EMF. A ETCC anódica não foi capaz de melhorar a produção de força (trabalho total e pico de torque), resistência à fadiga ou atividade eletromiográfica durante o EMF, quando comparada à condição placebo. Em conclusão, a ETCC anódica aplicada sobre o córtex motor contralateral não foi capaz de aumentar o desempenho de força de flexores e extensores de joelho em jovens saudáveis.

La influencia de estimulación transcraneal de corriente directa (tDCS) en ejercicios de fuerza muscular de rendimiento que reclutan grandes masas musculares no se ha establecido en la población sana. El objetivo de este estudio fue investigar si la ETCC anódica podría mejorar el rendimiento durante el ejercicio máximo de la fuerza (EMF) en sujetos sanos. Catorce voluntarios (26 ± 4 años de edad) realizaron dos EMF con la aplicación previa de ETCC anódica y placebo (2 mA, 20 i) la participación de los flexores y extensores de la rodilla dominante en acción concéntrica (3 series de 10 repeticiones). La actividad eléctrica muscular (sEMG) en cuatro músculos reclutados se registró durante el EMF. La ETCC anódica no fue capaz de mejorar la potencia de salida (trabajo total y pico de torque), la resistencia a la fatiga o la actividad electromiográfica durante el EMF, cuando comparada con la condición placebo. Por lo tanto, la ETCC anódica aplicada a la corteza motora contralateral no fue capaz de aumentar el rendimiento de la fuerza de flexores y extensores de la rodilla en jóvenes sanos.

The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial / Estudo clínico Escitalopram versus Eletroterapia no Tratamento da Depressão (ELECT-TDCS): racional e desenho de estudo de um ensaio de não inferioridade, de três braços, placebo-controlado

CONTEXT AND OBJECTIVE: Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited due to refractoriness and adverse effects. We describe the study rationale and design of ELECT-TDCS (Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study), which is investigating a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). DESIGN AND SETTING: Phase-III, randomized, non-inferiority, triple-arm, placebo-controlled study, ongoing in São Paulo, Brazil. METHODS: ELECT-TDCS compares the efficacy of active tDCS/placebo pill, sham tDCS/escitalopram 20 mg/day and sham tDCS/placebo pill, for ten weeks, randomizing 240 patients in a 3:3:2 ratio, respectively. Our primary aim is to show that tDCS is not inferior to escitalopram with a non-inferiority margin of at least 50% of the escitalopram effect, in relation to placebo. As secondary aims, we investigate several biomarkers such as genetic polymorphisms, neurotrophin serum markers, motor cortical excitability, heart rate variability and neuroimaging. RESULTS: Proving that tDCS is similarly effective to antidepressants would have a tremendous impact on clinical psychiatry, since tDCS is virtually devoid of adverse effects. Its ease of use, portability and low price are further compelling characteristics for its use in primary and secondary healthcare. Multimodal investigation of biomarkers will also contribute towards understanding the antidepressant mechanisms of action of tDCS. CONCLUSION: Our results have the potential to introduce a novel technique to the therapeutic arsenal of treatments for depression. .

CONTEXTO E OBJETIVO: O transtorno depressivo maior (TDM) é uma condição psiquiátrica comum, tratada com medicamentos antidepressivos, os quais são limitados devido à refratariedade e efeitos adversos. Descrevemos o racional e o desenho do Estudo Clínico Escitalopram versus Eletroterapia no Tratamento da Depressão (ELECT-TDCS), que investiga um tratamento não farmacológico, conhecido como estimulação transcraniana por corrente contínua (ETCC). DESENHO E LOCAL: Ensaio de fase III, randomizado, de não inferioridade, de três braços, placebo-controlado, em execução em São Paulo, Brasil. MÉTODOS: O estudo compara a eficácia da ETCC ativa/pílula placebo, ETCC simulada/escitalopram 20 mg/dia e ETCC simulada/pílula placebo durante 10 semanas, randomizando 240 pacientes em uma proporção 3:3:2, respectivamente. O objetivo principal é demostrar que a ETCC não é inferior ao escitalopram com uma margem de não inferioridade de pelo menos 50% do efeito de escitalopram em relação ao placebo. Como objetivos secundários, investigamos biomarcadores como polimorfismos genéticos, marcadores séricos, excitabilidade cortical motora, variabilidade da frequência cardíaca e neuroimagem. RESULTADOS: Provar que ETCC é igualmente eficaz a antidepressivos teria um tremendo impacto na psiquiatria clínica, uma vez que a ETCC é praticamente isenta de efeitos adversos. Sua facilidade de uso, portabilidade e preço baixo são outras características atraentes para uso na atenção primária e secundária de saúde. A investigação multimodal de biomarcadores também contribuirá para a compreensão dos mecanismos de ação antidepressivos da ETCC. CONCLUSÃO: Os nossos resultados podem introduzir uma nova técnica no arsenal terapêutico do tratamento da depressão. .

Neuroprotective effect of epidural hypothermia after spinal cord lesion in rats

OBJECTIVES : To evaluate the neuroprotective effect of epidural hypothermia in rats subjected to experimental spinal cord lesion. METHODS: Wistar rats (n = 30) weighing 320-360 g were randomized to two groups (hypothermia and control) of 15 rats per group. A spinal cord lesion was induced by the standardized drop of a 10-g weight from a height of 2.5 cm, using the New York University Impactor, after laminectomy at the T9-10 level. Rats in the hypothermia group underwent epidural hypothermia for 20 minutes immediately after spinal cord injury. Motor function was assessed for six weeks using the Basso, Beattie and Bresnahan motor scores and the inclined plane test. At the end of the final week, the rats' neurological status was monitored by the motor evoked potential test and the results for the two groups were compared. RESULTS: Analysis of the Basso, Beattie and Bresnahan scores obtained during the six-week period indicated that there were no significant differences between the two groups. There was no significant difference between the groups in the inclined plane test scores during the six-week period. Furthermore, at the end of the study, the latency and amplitude values of the motor evoked potential test were not significantly different between the two groups. CONCLUSION: Hypothermia did not produce a neuroprotective effect when applied at the injury level and in the epidural space immediately after induction of a spinal cord contusion in Wistar rats. .

Transcranial direct current stimulation and repetitive transcranial magnetic stimulation in consultation-liaison psychiatry

Patients with clinical diseases often present psychiatric conditions whose pharmacological treatment is hampered due to hazardous interactions with the clinical treatment and/or disease. This is particularly relevant for major depressive disorder, the most common psychiatric disorder in the general hospital. In this context, nonpharmacological interventions could be useful therapies; and, among those, noninvasive brain stimulation (NIBS) might be an interesting option. The main methods of NIBS are repetitive transcranial magnetic stimulation (rTMS), which was recently approved as a nonresearch treatment for some psychiatric conditions, and transcranial direct current stimulation (tDCS), a technique that is currently limited to research scenarios but has shown promising results. Therefore, our aim was to review the main medical conditions associated with high depression rates, the main obstacles for depression treatment, and whether these therapies could be a useful intervention for such conditions. We found that depression is an important and prevalent comorbidity in a variety of diseases such as epilepsy, stroke, Parkinson's disease, myocardial infarction, cancer, and in other conditions such as pregnancy and in patients without enteral access. We found that treatment of depression is often suboptimal within the above contexts and that rTMS and tDCS therapies have been insufficiently appraised. We discuss whether rTMS and tDCS could have a significant impact in treating depression that develops within a clinical context, considering its unique characteristics such as the absence of pharmacological interactions, the use of a nonenteral route, and as an augmentation therapy for antidepressants.

Brain Stimulation Techniques in Psychiatry.

Some chronic patients remain resistant in spite of using well-advanced pharmacological and non –pharmacological treatments. Some of the severe cases may benefit from treatment with neurosurgical interventions. Besides pharmacological, behavioral, and neurosurgical approaches, different brain stimulation methods-Tran cranial magnetic stimulation, deep brain stimulation, and electro convulsive therapy-have been investigated in treatment-resistant patients with Depression and OCD. The work done in these areas till now, is quite limited in terms of sample size and study design, given the difficulty in conducting standard blinded trials for these procedures. This article is written to know the efficacy and tolerability of these procedures.