Effect of Home-Based Transcranial Direct Current Stimulation on Cognitive Function in Patients with Mild Cognitive Impairment: A Two-Week Intervention.

PURPOSE: Repeated transcranial direct current stimulation (tDCS) is expected to have the potential to improve cognitive function in patients with mild cognitive impairment (MCI). We aimed to evaluate the efficacy and safety of at-home tDCS for elderly patients with MCI. MATERIALS AND METHODS: Patients aged 60-80 years, who maintained normal daily living but reported objective memory impairments, were enrolled. Active or sham stimulations were applied to the dorsal frontal cortex (left: anode; right: cathode) at home for 2 weeks. Changes in cognitive function were assessed using visual recognition tasks and the Mini-Mental State Exam (MMSE), and safety and efficacy were assessed using self-reports and a remote monitoring application. RESULTS: Of the 19 participants enrolled, 12 participants were included in the efficacy analysis. Response times and MMSE scores significantly improved after active stimulation compared to the sham stimulation; however, there were no significant differences in the proportion of correct responses. The mean compliance of the efficacy group was 97.5%±4.1%. Three participants experienced burns, but no permanent sequelae remained. CONCLUSION: This preliminary result suggests that home-based tDCS may be a promising treatment option for MCI patients; however, it requires more attention and technological development to address safety concerns. CLINICAL TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0002721.

Causal roles of prefrontal and temporo-parietal theta oscillations for inequity aversion.

The right temporo-parietal junction (rTPJ) and the right lateral prefrontal cortex (rLPFC) are known to play prominent roles in human social behaviour. However, it remains unknown which brain rhythms in these regions contribute to trading-off fairness norms against selfish interests as well as whether the influence of these oscillations depends on whether fairness violations are advantageous or disadvantageous for a decision maker. To answer these questions, we used non-invasive transcranial alternating current stimulation (tACS) to determine which brain rhythms in rTPJ and rLPFC are causally involved in moderating aversion to advantageous and disadvantageous inequity. Our results show that theta oscillations in rTPJ strengthen the aversion to unequal splits, which is statistically mediated by the rTPJ's role for perspective taking. In contrast, theta tACS over rLPFC enhanced the preference for outcome-maximizing unequal choices more strongly for disadvantageous compared to advantageous outcome distributions. Taken together, we provide evidence that neural oscillations in rTPJ and rLPFC have distinct causal roles in implementing inequity aversion, which can be explained by their involvement in distinct psychological processes.

Increased neural activity of right temporo-parietal junction causes different effect on altruism in situations of advantageous and disadvantageous inequity.

Altruism is defined as the performance of "costly acts that confer economic benefits on other individuals", which is one of the major puzzles in the behavioural sciences today. Altruistic behaviour not only facilitates interpersonal adaptation and harmony but also enhances social welfare and social responsibility. The right temporo-parietal junction (rTPJ) has been proposed as playing a key role in guiding human altruistic behaviour, but its precise functional contribution to altruistic behaviour in situations of advantageous and disadvantageous inequity remains unclear. The purpose of this study was to modulate the activation of the rTPJ through transcranial direct current stimulation (tDCS) in order to clarify the causal role of the rTPJ in altruistic behaviour in situations of advantageous and disadvantageous inequity. A total of 106 participants were randomly assigned to one of three stimulation conditions: anodal tDCS stimulation on the rTPJ; sham tDCS stimulation on the rTPJ and anodal tDCS stimulation on the primary visual cortex (VC)as the control group, and. After 20 min of stimulation, participants undertook a modified dictator game that measured altruistic behaviour. Mixed-effect logistic regressions were applied to statistical analyses in this study. The results indicated that anodal tDCS over the rTPJ increased participants' altruistic tendency by increasing their tendency to choose altruistic options in trials with higher cost, as well as their tendency to behave altruistically in situations of advantageous but not disadvantageous inequity. These results suggested that increased neural activity of the rTPJ leads to different impacts on altruism in these two different inequity situations.

Limited output transcranial electrical stimulation 2023 (LOTES-2023): Updates on engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

The objective and scope of this Limited Output Transcranial Electrical Stimulation 2023 (LOTES-2023) guidance is to update the previous LOTES-2017 guidance. These documents should therefore be considered together. The LOTES provides a clearly articulated and transparent framework for the design of devices providing limited output (specified low-intensity range) transcranial electrical stimulation for a variety of intended uses. These guidelines can inform trial design and regulatory decisions, but most directly inform manufacturer activities - and hence were presented in LOTES-2017 as "Voluntary industry standard for compliance controlled limited output tES devices". In LOTES-2023 we emphasize that these standards are largely aligned across international standards and national regulations (including those in USA, EU, and South Korea), and so might be better understood as "Industry standards for compliance controlled limited output tES devices". LOTES-2023 is therefore updated to reflect a consensus among emerging international standards, as well as best available scientific evidence. "Warnings" and "Precautions" are updated to align with current biomedical evidence and applications. LOTES standards applied to a constrained device dose range, but within this dose range and for different use-cases, manufacturers are responsible to conduct device-specific risk management.

Placebo effect on gait: a way to reduce the dual-task cost in older adults.

The ability to perform two tasks simultaneously is essential for daily activities. In older adults, this ability is markedly reduced, as evidenced by the dual-task cost on gait. Preliminary evidences indicate that the dual-task cost can be influenced by different types of manipulations. Here, we explored the effectiveness of a new approach to reduce the dual-task cost, based on the placebo effect, a psychobiological phenomenon whereby a positive outcome follows the administration of an inert device thought to be effective. Thirty-five healthy older adults were asked to walk on a sensorized carpet (single-task condition) and to walk while counting backward (dual-task condition) in two sessions (pre-test and post-test). A placebo group, randomly selected, underwent sham transcranial direct current stimulation over the supraorbital areas between sessions, along with information about its positive effects on concentration and attention. A control group did not receive any intervention between sessions. The dual-task cost was significantly reduced in the placebo group at the post-test session compared to the pre-test for several gait parameters (Cohen's d > 1.43). At the post-test session, the dual-task cost was also lower in the placebo group than in the control group (d > 0.73). Cognitive (number of subtractions and number of errors) and subjective (perceived mental fatigability) variables remained stable across sessions. The reduced dual-task cost in the placebo group could indicate the ability to re-establish the allocation of attentional resources between tasks. These findings could contribute to the development of cognitive strategies that leverage positive expectations to boost motor control in older adults.

Modulating the Activity of the Right Dorsolateral Prefrontal Cortex Alters Altruism in Situations of Advantageous Inequity.

Altruism is highly valued and cherished by human society. However, human preferences and behavior are sensitive to inequality considerations. Currently, remarkably little is known about the neurobiological mechanisms underlying the process of altruistic acts in inequity situations. Therefore, to clarify the causal role of the right dorsolateral prefrontal cortex (rDLPFC) in altruism during situations of advantageous and disadvantageous inequity, we applied transcranial direct current stimulation (tDCS) to demonstrate the involvement of the rDLPFC in altruism in situations of inequity. A total of 71 participants (38 female and 33 male) received anodal tDCS at 1.5 mA over the rDLPFC (n = 38) or the primary visual cortex (n = 33) and subsequently participated in a modified dictator game that measures altruism. We found that anodal tDCS over the rDLPFC decreased subjects' sensitivity to altruistic efficiency and cost in situations of advantageous inequity. Our results suggested that the rDLPFC plays an important role in overriding self-interest to enforce altruism in situations of advantageous inequity.

The Potential of Transcranial Alternating Current Stimulation to Alleviate Dual-Task Gait Costs in Older Adults: Insights from a Double-Blinded Pilot Study.

BACKGROUND: The performance of an attention-demanding task while walking, i.e., dual-tasking, leads to dual-task costs (e.g., reduced gait speed) in older adults. Previous studies have shown that dual-task costs in gait are associated with future falls and cognitive decline. According to the communication through coherence hypothesis, transcranial alternating current stimulation (tACS) might help alleviate this problem. OBJECTIVE: The aim of this study was to examine the effects of a single session of theta-tACS targeting the left fronto-parietal network (L-FPN) on dual-task walking and cognitive function compared to sham stimulation and transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex, a node within the L-FPN. METHODS: Twenty older adults completed a four-visit, double-blinded, within-subject, cross-over study in which usual-walking, dual-task walking, and cognitive function were evaluated before and immediately after 20 min of tACS, tDCS, or sham (order randomized) stimulation. Dual-task costs to gait speed (primary outcome) and other measures were analyzed. RESULTS: The dual-task cost to gait speed tended to be lower (i.e., better) after tACS (p = 0.067, Cohen's d = 0.433∼small); tDCS significantly reduced this dual-task cost (p = 0.012, Cohen's d = 0.618∼medium), and sham stimulation had no effect (p = 0.467). tACS significantly reduced the dual-task cost to step length (p = 0.037, Cohen's d = 0.502∼medium); a trend was seen after tDCS (p = 0.069, Cohen's d = 0.443∼small). No statistical differences were found for other measures of gait or cognitive function. CONCLUSIONS: The positive effects of tACS on dual-task gait speed and step length were roughly similar to those seen with tDCS. These results suggest that tACS affects the fronto-parietal network and, similar to tDCS, tACS may improve dual-tasking. Nonetheless, to achieve larger benefits and differentiate the effects of tACS and tDCS on brain function and dual-task walking in older adults, other stimulation montages and protocols should be tested.

Distinct roles of the medial prefrontal cortex in advantageous and disadvantageous inequity aversion.

Human beings have a strong preference for the fair distribution of resources in situations of both advantageous and disadvantageous inequity. Neuroimaging studies have shown that the process of advantageous and disadvantageous inequity aversion involves distinct brain regions. However, little is known about the causal roles of the dorsal medial prefrontal cortex (dmPFC) in these two types of inequity aversion. To clarify the roles of the dmPFC in both types of inequity aversion, 70 subjects were recruited and randomly assigned to two anodal transcranial direct current stimulation (tDCS) groups: tDCS over the dmPFC and tDCS over the primary visual cortex. Participants then completed a dictator game, which was used to measure the aversion to inequity. This study found that tDCS over the dmPFC decreased the aversion to disadvantageous inequity, but not that to advantageous inequity, and the treatment effect was modulated by equity cost. These results show that the dmPFC plays different roles in these two types of inequity aversion.

Safety of Special Waveform of Transcranial Electrical Stimulation (TES): In Vivo Assessment.

Intermittent theta burst (iTBS) powered by direct current stimulation (DCS) can safely be applied transcranially to induce neuroplasticity in the human and animal brain cortex. tDCS-iTBS is a special waveform that is used by very few studies, and its safety needs to be confirmed. Therefore, we aimed to evaluate the safety of tDCS-iTBS in an animal model after brain stimulations for 1 h and 4 weeks. Thirty-one Sprague Dawley rats were divided into two groups: (1) short-term stimulation for 1 h/session (sham, low, and high) and (2) long-term for 30 min, 3 sessions/week for 4 weeks (sham and high). The anodal stimulation applied over the primary motor cortex ranged from 2.5 to 4.5 mA/cm2. The brain biomarkers and scalp tissues were assessed using ELISA and histological analysis (H&E staining) after stimulations. The caspase-3 activity, cortical myelin basic protein (MBP) expression, and cortical interleukin (IL-6) levels increased slightly in both groups compared to sham. The serum MBP, cortical neuron-specific enolase (NSE), and serum IL-6 slightly changed from sham after stimulations. There was no obvious edema or cell necrosis seen in cortical histology after the intervention. The short- and long-term stimulations did not induce significant adverse effects on brain and scalp tissues upon assessing biomarkers and conducting histological analysis.

Assessment of Noninvasive Brain Stimulation Interventions for Negative Symptoms of Schizophrenia: A Systematic Review and Network Meta-analysis.

Importance: Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols for relieving negative symptoms remains unclear. Objective: To compare the efficacy and acceptability of different NIBS interventions for treating negative symptoms. Data Sources: The ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, ClinicalTrials.gov, and Web of Science electronic databases were systematically searched from inception through December 7, 2021. Study Selection: A frequentist model network meta-analysis was conducted to assess the pooled findings of trials that evaluated the efficacy of repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation, transcranial random noise stimulation, transcutaneous vagus nerve stimulation, and transcranial direct current stimulation on negative symptoms in schizophrenia. Randomized clinical trials (RCTs) examining NIBS interventions for participants with schizophrenia were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Data were independently extracted by multiple observers. The pair-wise meta-analytic procedures were conducted using a random-effects model. Main Outcomes and Measures: The coprimary outcomes were changes in the severity of negative symptoms and acceptability (ie, dropout rates owing to any reason). Secondary outcomes were changes in positive and depressive symptoms. Results: Forty-eight RCTs involving 2211 participants (mean [range] age, 38.7 [24.0-57.0] years; mean [range] proportion of female patients, 30.6% [0%-70.0%]) were included. Compared with sham control interventions, excitatory NIBS strategies (standardized mean difference [SMD]: high-definition transcranial random noise stimulation, -2.19 [95% CI, -3.36 to -1.02]; intermittent theta-burst stimulation, -1.32 [95% CI, -1.88 to -0.76]; anodal transcranial direct current stimulation, -1.28 [95% CI, -2.55 to -0.02]; high-frequency rTMS, -0.43 [95% CI, -0.68 to -0.18]; extreme high-frequency rTMS, -0.45 [95% CI, -0.79 to -0.12]) over the left dorsolateral prefrontal cortex with or without other inhibitory stimulation protocols in the contralateral regions of the brain were associated with significantly larger reductions in negative symptoms. Acceptability did not significantly differ between the groups. Conclusions and Relevance: In this network meta-analysis, excitatory NIBS protocols over the left dorsolateral prefrontal cortex were associated with significantly large improvements in the severity of negative symptoms. Because relatively few studies were available for inclusion, additional well-designed, large-scale RCTs are warranted.

Does transcranial direct current stimulation enhance cognitive performance in Parkinson's disease mild cognitive impairment? An event-related potentials and neuropsychological assessment study.

BACKGROUND: Parkinson's disease-mild cognitive impairment (PD-MCI) is garnering attention as a key interventional period for cognitive impairment. Currently, there are no approved treatments for PD-MCI and encouraging results of transcranial direct current stimulation (tDCS) combined with other interventions have been proposed, though the efficacy and neural mechanisms of tDCS alone have not been studied in PD-MCI yet. OBJECTIVES: The present double-blind, randomized, sham-controlled study assessed the effects of tDCS over the dorsolateral prefrontal cortex on cognitive functions via neuropsychological and electrophysiological evaluations in individuals with PD-MCI for the first time. METHOD: Twenty-six individuals with PD-MCI were administered 10 sessions of active (n = 13) or sham (n = 13) prefrontal tDCS twice a day, for 5 days. Changes were tested through a comprehensive neuropsychological battery and event-related potential recordings, which were performed before, immediately, and 1 month after the administrations. RESULTS: Neuropsychological assessment showed an improvement in delayed recall and executive functions in the active group. N1 amplitudes in response to targets in the oddball test-likely indexing attention and discriminability and NoGo N2 amplitudes in the continuous performance test-likely indexing cognitive control and conflict monitoring increased in the active group. Active stimulation elicited higher benefits 1 month after the administrations. CONCLUSION: The present findings substantiate the efficacy of tDCS on cognitive control and episodic memory, along with the neural underpinnings of cognitive control, highlighting its potential for therapeutic utility in PD-MCI. TRIAL REGISTRATION: NCT 04,171,804. Date of registration: 21/11/2019.

Transcranial electric stimulation as a neural interface to gain insight on human brain functions: current knowledge and future perspective.

The use of brain stimulation approaches in social and affective science has greatly increased over the last two decades. The interest in social factors has grown along with technological advances in brain research. Transcranial electric stimulation (tES) is a research tool that allows scientists to establish contributory causality between brain functioning and social behaviour, therefore deepening our understanding of the social mind. Preliminary evidence is also starting to demonstrate that tES, either alone or in combination with pharmacological or behavioural interventions, can alleviate the symptomatology of individuals with affective or social cognition disorders. This review offers an overview of the application of tES in the field of social and affective neuroscience. We discuss the issues and challenges related to this application and suggest an avenue for future basic and translational research.

Assessment of treatment resistance criteria in non-invasive brain stimulation studies of schizophrenia.

Novel treatment modalities, such as non-invasive brain stimulation (NIBS), typically focus on patient groups that have failed multiple treatment interventions. Despite its promise, the clinical translation of NIBS in schizophrenia has been limited. One important obstacle to implementation is the inconsistent reporting of treatment resistance in the clinical trial literature contributing to heterogeneity in reported effects. In response, we develop a numerical approach to synthesize quality of assessment of Treatment-Resistant Schizophrenia (TRS) and apply this to studies investigating therapeutic response to NIBS in patients with schizophrenia. Literature search conducted through PubMed database identified 119 studies investigating Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in treating resistant schizophrenia symptoms. A quality score out of 11 was assigned to each study based on adherence to the international consensus guidelines for TRS developed by the Treatment Response and Resistance in Psychosis (TRRIP) group. Results revealed an overall paucity of studies with thorough assessment and/or reporting of TRS phenomenon, as evidenced by a mean quality score of 3.38/11 (SD: 1.01) for trials and 5.16/11 (SD: 1.57) for case reports, though this improved minimally since the publication of consensus criteria. Most studies considered treatment-resistance as a single dimensional construct by reporting resistance of a single symptom, and failed to establish treatment adherence, resistance time course and functional impairment. We conclude that the current NIBS literature in schizophrenia do not reflect its true effects on treatment-resistance. There is an urgent need to improve assessment and reporting standards of clinical trials that target TRS.

Cost-utility analysis of transcranial direct current stimulation therapy with and without virtual illusion for neuropathic pain for adults with spinal cord injury in Canada.

OBJECTIVE: To undertake a cost-utility analysis comparing virtual illusion (VI) and transcranial direct current stimulation (tDCS) combination therapy, tDCS alone and standard pharmacological care in Ontario, Canada from a societal perspective over a three-month time horizon. DESIGN: Cost-utility analysis using Markov model methods. SETTING: Community setting in Ontario, Canada. PARTICIPANTS: Individuals with spinal cord injury and neuropathic pain (NP) resistant to pharmacological therapy. INTERVENTIONS: Virtual illusion and transcranial direct current stimulation, transcranial direct current stimulation alone and standard pharmacological therapy. OUTCOME MEASURES: Incremental costs, quality adjusted life years (QALY) and incremental cost effectiveness ratio. RESULTS: The incremental cost effectiveness ratio of VI and tDCS therapy cost is $3,396 per QALY (2020 Canadian dollars) when compared to standard care. The incremental cost per QALY of tDCS therapy alone is $33,167. VI and tDCS therapy had lower incremental costs (-$519) and higher incremental QALYs (0.026) compared to tDCS alone. From a public healthcare payer perspective, there is a 74% probability that VI and tDCS therapy and 54% probability that tDCS alone would be cost effective at a $50,000 per QALY willingness-to-pay threshold. Our findings remained relatively robust in various scenario analyses. CONCLUSION: Our findings suggest that at three-months after therapy, VI and tDCS combination therapy may be more cost effective than tDCS therapy alone. Based on conventional health technology funding thresholds, VI and tDCS combination therapy merits consideration for the treatment of NP in adults with spinal cord injuries.

Targeted tDCS Mitigates Dual-Task Costs to Gait and Balance in Older Adults.

OBJECTIVE: Among older adults, the ability to stand or walk while performing cognitive tasks (ie, dual-tasking) requires coordinated activation of several brain networks. In this multicenter, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) and the primary sensorimotor cortex (SM1) on dual-task performance "costs" to standing and walking. METHODS: Fifty-seven older adults without overt illness or disease completed 4 separate study visits during which they received 20 minutes of transcranial direct current stimulation (tDCS) optimized to facilitate the excitability of the L-DLPFC and SM1 simultaneously, or each region separately, or neither region (sham). Before and immediately after stimulation, participants completed a dual-task paradigm in which they were asked to stand and walk with and without concurrent performance of a serial-subtraction task. RESULTS: tDCS simultaneously targeting the L-DLPFC and SM1, as well as tDCS targeting the L-DLPFC alone, mitigated dual-task costs to standing and walking to a greater extent than tDCS targeting SM1 alone or sham (p < 0.02). Blinding efficacy was excellent and participant subjective belief in the type of stimulation received (real or sham) did not contribute to the observed functional benefits of tDCS. INTERPRETATION: These results demonstrate that in older adults, dual-task decrements may be amenable to change and implicate L-DPFC excitability as a modifiable component of the control system that enables dual-task standing and walking. tDCS may be used to improve resilience and the ability of older results to walk and stand under challenging conditions, potentially enhancing everyday functioning and reducing fall risks. ANN NEUROL 2021;90:428-439.

Modulating the activity of right temporo-parietal junction increases bidding behavior in lottery contests.

Contest often involves bids that are higher than the Nash equilibrium, and overbidding behaviour closely relates to personal reasoning and judgement. The right temporo-parietal junction (rTPJ) plays an important role in social, cognitive and inference decision-making. In the present study, we investigated the effect of transcranial direct current stimulation (tDCS) of the rTPJ on overbidding behaviour by using a modified model-lottery contests task. Our results showed that participants that received cathodal-stimulation had significantly higher expenditure compared to participants that received anodal and sham stimulation. Cathodal-stimulation may reduce the participants' ability to infer other contestants' intention or may modulate the non-monetary utility of winning. Our data indicate that excitability of the rTPJ may contribute to overbidding behaviour.

Exame de dosagem de anticorpo anti-receptor de acetilcolina para diagnóstico da Miastenia Gravis / Examination of anti-receptor antibody dosage acetylcholine for the diagnosis of Myasthenia Gravis

INTRODUÇÃO: A MG é uma doença autoimune da junção neuromuscular que se apresenta com fraqueza muscular localizada ou generalizada. Na maioria dos casos, a doença é causada por anticorpos contra receptores de acetilcolina (anti-AChR), que estão presentes em cerca de 85% e 50% dos pacientes com as formas generalizadas e ocular, respectivamente. O diagnóstico de MG é definido de acordo com manifestações clínicas, além de provas sorológicas ou eletroneuromiográficas, que apresentam sensibilidade e especificidade variadas de acordo com a apresentação da doença. A estimulação nervosa repetitiva é o estudo eletroneuromiográfico complementar atualmente disponível no Sistema Único de Saúde (SUS) para diagnóstico de MG. TECNOLOGIA: Dosagem de anticorpo anti-receptor de acetilcolina. PERGUNTA: o exame diagnóstico de dosagem de anticorpos anti-acetilcolina pode ser uma alternativa à eletroneuromiografia (estimulação nervosa repetitiva ­ ENR) para o diagnóstico da MG? EVIDÊNCIAS CIENTÍFICAS: Uma revisão sistemática (RS) e dois estudos clínicos prospectivos de avaliação de métodos diagnósticos de MG foram incluídos. A RS incluiu sete estudos de avaliação de anticorpos anti-AChR e sete estudos de avaliação da ENR. As estimativas de acurácia do anti-AChR na RS foram agrupadas de acordo com o delineamento dos estudos, evidenciando sensibilidade de 44% a 66% na MG ocular e de 90% a 96% na MG generalizada, sem variação na especificidade (98% a 99% em ambas as apresentações). Os estudos da ENR foram muitos heterogêneos e evidenciaram sensibilidade entre 11% a 39% no diagnóstico da MG ocular, e entre 32% a 98% na MG generalizada, com especificidade elevada em ambos os casos (94% a 97%). Os estudos individuais evidenciaram sensibilidade de 73% a 74% para MG generalizada e de 38% a 70% para MG ocular para o anti-AChR, e sensibilidade de 80% a 83% para MG generalizada e de 45% a 62% para MG ocular. As avaliações do risco de viés dos estudos incluídos demonstraram alto risco de viés para a RS e baixo risco para a maioria dos domínios avaliados nos estudos de coorte. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A estimativa de custo global anual do exame anti-AChR no cenário base foi de aproximadamente 155 mil reais, com impacto cumulativo em 5 anos de 788 mil reais. Considerando que uma parcela dos indivíduos necessitará submeter-se adicionalmente ao exame eletroneuromiográfico, o que implicaria em aproximadamente 15 mil reais a mais por ano, o custo total do diagnóstico da doença foi de cerca de 170 mil reais a mais por ano, e de cerca de 867 mil reais ao final do quinto ano de incorporação. Na análise de sensibilidade, foram observados valores de custo total de 165 mil reais no cenário mais otimista e acima de 2 milhões de reais no cenário mais pessimista, para o diagnóstico de MG no período de 5 anos. A variável de maior impacto nos resultados foi a população inicial, seguida do custo do exame anti-AChR. CONSIDERAÇÕES FINAIS: A dosagem de anticorpos anti-AChR é um exame confirmatório essencial para diagnóstico de MG. De maneira geral, os estudos evidenciam sensibilidade superior à ENR, tanto no diagnóstico da forma ocular quanto generalizada da doença, com elevada especificidade. Os estudos de ENR foram heterogêneos e evidenciaram diferentes níveis de acurácia de acordo com o número e localização dos estímulos avaliados, o que não ocorre no cenário da dosagem de anticorpos. As avaliações do risco de viés dos estudos incluídos demonstraram alto risco de viés para a RS e baixo risco para a maioria dos domínios avaliados nos estudos de coorte. Não foram identificadas recomendações de diagnóstico de MG em agências de ATS, mas diretrizes internacionais recomendam o exame como etapa inicial no diagnóstico da doença. RECOMENDAÇÃO PRELIMINAR: A Conitec, em sua 93ª reunião ordinária, realizada no dia 08 de dezembro de 2020, deliberou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à incorporação do exame de dosagem de anticorpos anti-acetilcolina para diagnóstico da Miastenia Gravis no Sistema Único de Saúde. Considerouse, entre outros fatores, que, o exame de avaliação de anticorpos anti-AChR possui uma maior sensibilidade diagnóstica em comparação ao exame eletroneuromiográfico, além disso eletroneuromiografia é um exame demorado e requer um treinamento específico para sua realização. Consequentemente, o tratamento precoce da miastenia gravis poderia ser comprometido. CONSULTA PÚBLICA: A consulta pública nº 68 ficou vigente entre os dias 05/01/2021 e 25/01/2021. Foram recebidas nove contribuições, sendo cinco pelo formulário para contribuições técnico-científicas e quatro pelo formulário para contribuições sobre experiência ou opinião. Estas foram provenientes de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. A maioria das contribuições (77,8%) concordou com a recomendação preliminar da Conitec. Uma contribuição foi neutra (nem concorda e nem discorda) e uma contribuição discordou da recomendação preliminar da Conitec, no entanto, ambas estas contribuições não apresentaram justificativa. As contribuições abordaram, principalmente, os pontos positivos da incorporação da dosagem de anticorpos anti-AChR para o diagnóstico de MG. Não foram solicitadas alterações no texto ou apresentadas referências ou anexos. Houve apenas um argumento sobre a possibilidade de inclusão de anti MUSK para melhoria do atendimento dos demais casos negativos do anticorpo anti-receptor de acetilcolina. Porém, como não houve uma demanda ou pergunta de pesquisa priorizada no escopo, a tecnologia não foi avaliada formalmente pela Conitec. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 95ª reunião ordinária, no dia 03 de março de 2021, consideraram que o procedimento possui um corpo de evidências que favorece o exame de dosagem de anticorpos antiacetilcolina para diagnóstico da Miastenia Gravis. Considerou-se a maior sensibilidade e facilidade deste exame comparado à eletroneuromiografia. Diante do exposto, o Plenário deliberou por unanimidade recomendar a incorporação do exame de dosagem de anticorpo anti-receptor de acetilcolina para diagnóstico de Miastenia Gravis. Foi assinado o Registro de Deliberação nº 593/2021. DECISÃO: incorporar o exame de dosagem de anticorpo antirreceptor de acetilcolina para diagnóstico de Miastenia Gravis, do Sistema Único de Saúde - SUS, conforme Portaria nº 11, publicada no Diário Oficial da União nº 74, seção 1, página 235, em 19 de abril de 2021.

Combining transcranial direct current stimulation with a motor-cognitive task: the impact on dual-task walking costs in older adults.

BACKGROUND: The performance of a secondary task while walking increases motor-cognitive interference and exacerbates fall risk in older adults. Previous studies have demonstrated that transcranial direct current stimulation (tDCS) may improve certain types of dual-task performance, and, that tDCS delivered during the performance of a task may augment the benefits of stimulation, potentially reducing motor-cognitive interference. However, it is not yet known if combining multi-target tDCS with the simultaneous performance of a task related to the tDCS targets reduces or increases dual-task walking costs among older adults. The objectives of the present work were (1) To examine whether tDCS applied during the performance of a task that putatively utilizes the brain networks targeted by the neuro-stimulation reduces dual-task costs, and (2) to compare the immediate after-effects of tDCS applied during walking, during seated-rest, and during sham stimulation while walking, on dual-task walking costs in older adults. We also explored the impact on postural sway and other measures of cognitive function. METHODS: A double-blind, 'within-subject' cross-over pilot study evaluated the effects of 20 min of anodal tDCS targeting both the primary motor cortex (M1) and the left dorsolateral prefrontal cortex (lDLPFC) in 25 healthy older adults (73.9 ± 5.2 years). Three stimulation conditions were assessed in three separate sessions: (1) tDCS while walking in a complex environment (tDCS + walking), (2) tDCS while seated (tDCS + seated), and (3) walking in a complex environment with sham tDCS (sham + walking). The complex walking condition utilized virtual reality to tax motor and cognitive abilities. During each session, usual-walking, dual-task walking, quiet standing sway, and cognitive function (e.g., Stroop test) were assessed before and immediately after stimulation. Dual-task costs to gait speed and other measures were computed. RESULTS: The dual-task cost to gait speed was reduced after tDCS + walking (p = 0.004) as compared to baseline values. Neither tDCS + seated (p = 0.173) nor sham + walking (p = 0.826) influenced this outcome. Similar results were seen for other gait measures and for Stroop performance. Sway was not affected by tDCS. CONCLUSIONS: tDCS delivered during the performance of challenging walking decreased the dual-task cost to walking in older adults when they were tested just after stimulation. These results support the existence of a state-dependent impact of neuro-modulation that may set the stage for a more optimal neuro-rehabilitation. TRIAL REGISTRATION: Clinical Trials Gov Registrations Number: NCT02954328.