Efeitos da estimulação transcraniana de corrente contínua no processamento sensorial e na memória de trabalho em diferentes faixas etárias

A estimulação transcraniana por corrente contínua (ETCC) é uma técnica neuromodulatória com potencial para auxiliar no tratamento da dor crônica e outras condições clínicas. O efeito da ETCC, no entanto, está associado com a plasticidade cerebral, de modo que fatores que influenciam nesta plasticidade podem alterar os resultados obtidos com a estimulação gerando variabilidade nos resultados da técnica. A idade é um fator importante que modula a plasticidade, de modo que especificar a idade em protocolos de ETCC pode elevar a eficácia do método, possibilitando o uso mais assertivo em protocolos de pesquisa, como também em tratamentos clínicos. No primeiro estudo apresentamos uma revisão sistemática e meta-análise sobre o feito da ETCC nas medidas de dor em crianças, adolescentes e idosos, com a finalidade de compilar evidências sobre o impacto da idade na resposta à ETCC aplicada em montagens de importância no estudo da dor: córtex motor primário (M1) e córtex pré-frontal dorsolateral (DLPFC). Métodos: Realizamos uma revisão sistemática pesquisando os seguintes bancos de dados: PubMed, EMBASE e Science Direct usando os termos de pesquisa que foram adaptados de acordo com MeSh ou Entree: [(“Adolescent” OR “Children” OR “Elderly” ) AND (“tDCS” ) AND (“Pain” OR “Pain threshold”) AND ( “dorsolateral prefrontal cortex” OR “Motor cortex)]. Pré-selecionamos 228 artigos, 13 foram incluídos na revisão sistemática. A meta-análise incluiu 4 estudos para desfechos de nível de dor e 3 estudos pra limiar de dor, que foram classificados como baixo risco de viés. Apenas estudos com idosos foram incluídos na meta-análise. Resultados: Para desfecho de nível de dor os dados apresentaram considerável heterogeneidade (I2 = 60%), foi então aplicado um modelo de efeitos aleatórios. Um total de 96 pacientes recebeu estimulação ativa e a maioria dos estudos favorece a ETCC ativa, mostrando uma redução significativa (P = 0,002) dos níveis de dor quando comparada à sham. A diferença de média padronizada foi de -0,76 (IC 95% = -1,24, -0,28). Para desfecho de limiar de dor 88 idosos receberam ETCC ativa, mas a análise combinada dos estudos não mostrou diferença quando comparado a sham. Apenas dois estudos foram incluídos para o efeito da ETCC na dor em adolescentes. Os estudos foram divergentes em suas conclusões: um estudo com o uso de ETCC anodal sobre córtex pré-frontal relatou redução de escores de dor, enquanto o outro estudo relatou aumento da sensibilidade à dor. Conclusão: Nossos achados sugerem um efeito favorável da ETCC na redução da dor em idosos. No entanto, o número de estudos 9 incluídos foi pequeno e houve heterogeneidade de protocolos e condições clínicas da população do estudo. O segundo estudo teve como objetivo comparar os efeitos da ETCC anodal sobre o DLPFC e o M1 em adolescentes, adultas e idosas. O desfecho primário foi o limiar de dor pelo calor (HPT), enquanto os desfechos secundários foram o desempenho na tarefa de memória de trabalho (WM), dor moderada ao estímulo térmico e a tolerância ao estímulo térmico. Nossa hipótese foi que o efeito da ETCC seria de maior magnitude em adolescentes, quando a ETCC fosse realizada sobre o DLPFC. Métodos: Foram incluídas 30 mulheres saudáveis, destras, com idade entre 15 e 16 anos (adolescentes, n = 10), 30 a 40 anos (adultas, n = 10) e 60 a 70 anos (idosas, n = 10). Neste estudo cruzado e cego, as participantes receberam três sessões de intervenção: ETCC sobre o DLPFC esquerdo, ETCC sobre M1 esquerdo e estimulação simulada. O intervalo entre as sessões foi de pelo menos 7 dias e com alocação randomizada. Durante a estimulação as participantes realizaram tarefas online de WM. A intensidade e duração da estimulação ativa foi de 2 mA por 30 min. O HPT foi avaliado antes e após a estimulação. As participantes realizaram n-back, uma tarefa de avaliação de WM, durante e também após a ETCC. Para medidas de desfecho foi avaliada a variação percentual do HPT do pré para o pós ETCC e para o desempenho da WM foi avaliado pela tarefa de n-back após a estimulação. Resultados: Um modelo de Generalized Estimating Equation (GEE) revelou que a ETCC anodal sobre o DLPFC reduziu o HPT em adolescentes em 3,5%. Em adultos jovens, a ETCC anodal sobre M1, mas não sobre o DLPFC, aumentou o HPT significativamente em comparação com ETCC simulada. Nenhum efeito significativo para HPT foi encontrado no grupo de idosas. Para memória de trabalho o tempo de resposta para acertos foi reduzido para ETCC anodal sobre o DLPFC em adolescentes, em comparação com os outros dois grupos. Conclusão: Esses achados sugerem que a ETCC anodal modula a percepção da dor e as funções cognitivas de forma diferenciada de acordo com a idade e a área de estimulação, com maiores efeitos em adolescentes alcançados via ETCC sobre o DLPFC. A partir dos estudos realizados concluímos que a ETCC modula sensibilidade à dor de maneira distinta para adolescentes, adultos e idosos. No entanto, também a montagem de ETCC apresenta interação com o fator idade para os resultados da estimulação. Na literatura, no entanto há poucos estudos que abordam o uso da ETCC em medidas de dor para crianças, adolescentes ou idosos. Assim, estudos com rigor 10 metodológico devem ser buscados nestas faixas etárias para melhor elucidar o efeito da ETCC no nível de dor e possível impacto no ambiente clínico.Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that has potential to aid in the treatment of chronic pain and other clinical conditions. However tDCS has large variability of effects, what brings inconsistency to the method. Since the effect of tDCS is associated with brain plasticity, factors that influence this plasticity, such as chronological age, modify the response to the method and must be addressed in clinical and research protocols. Individualizing age can improve tDCS protocols efficacy, allowing the proper use of the technique in research and in clinical setting. In the first study, we evaluated in a systematic review and meta-analysis the existing literature on the effect of tDCS on pain level for children, adolescents and elderly. We aimed to review the knowledge of tDCS effect on pain scores for these particular age groups to elucidate tDCS effect on pain outcomes considering age as a influence factor on two tDCS montages used for the study of pain: primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC). Methods: We have conducted a systematic review searching the following databases: PubMed, EMBASE, and Science Direct using the following search terms which were adapted according to MeSh or Entree: [(“Adolescent” OR “Children” OR “Elderly”) AND (“tDCS”) AND (“Pain” OR “Pain threshold”) AND (“dorsolateral prefrontal cortex” OR “Motor cortex)] up to April 20th, 2020. We preselected 228 articles, 13 of which were included in the systematic review, only two studies included adolescents, and none was retrieved with children. The meta-analysis included five studies that showed a lower risk of bias, only studies with elderly. First, we analyzed studies with pain score outcomes (n=4), and the second we analyzed studies that the outcome was the pain threshold (n=3). Results: A random-effects model was applied due to data having considerable heterogeneity (I2 = 60% for pain score). A total of 96 subjects received active stimulation, and most of the studies indicate a favorable effect for active tDCS to reduce the pain score compared to sham tDCS (P =0.002). The standardized mean difference was −0.76 (CI 95% = −1.24 to −0.28). For the pain threshold, 88 elderly received active tDCS. However, the analysis of combined data did not present statistical differences. We included two studies with adolescents, that were divergent in their conclusions: one study using anodal tDCS over the prefrontal cortex reported a reduction in pain scores, contrarily the second study reported an increase in pain sensitivity. Conclusion: Our findings suggest a favorable effect of a-tDCS to reduce pain for elderly. Nevertheless the number of included studies was small, and heterogeneity for clinical condition and protocols was present. The objective of the second study was to compare effects of anodal (a)-tDCS over the left dorsolateral prefrontal cortex (DLPFC), and primary motor cortex (M1) in adolescents, young adults and elderly . Primary outcome was heat pain threshold (HPT),and secondary outcomes were working memory (WM) performance, heat moderate pain and heat pain tolerance. We hypothesized that the effect of tDCS would be the largest in adolescents for the DLPFC tDCS. Methods: We included 30 healthy women within the age ranges of 15 to 16 (adolescents, n= 10), 30 to 40 (young adults, n=10), and 60 to 70 (elderly, n=10) years. In this crossover single-blinded study, participants received three intervention sessions (a-tDCS over the left DLPFC, a-tDCS over left M1, and sham stimulation), separated by at least 7 days coupled with WM online task performance in randomized order. Active stimulation intensity and duration were 2 mA and 30 min, respectively. HPT was evaluated before and after stimulation. Participants performed an n-back WM task during, and also after tDCS. For outcome measures, WM performance after stimulation was evaluated. Results: Generalized Estimating Equation (GEE) revealed that 12 a-tDCS over the DLPFC reduced HPT in adolescents (3.5%). In young adults, a-tDCS over M1, but not the DLPFC, enhanced HPT significantly compared to sham. No significant effect for HPT was found in the elderly group. Response time for hits was reduced for a-tDCS over the DLPFC in adolescents, as compared to the other two groups. Conclusions: These findings suggest that a-tDCS modulates pain perception and cognitive functions differentially according to age and target area of stimulation, with larger effects in adolescents achieved via tDCS over the DLPFC. From the studies we have developed, we concluded that tDCS modulates sensitivity to pain in a different way for adolescents, adults and the elderly. However, the tDCS montage also presents interaction with the age factor for the results of stimulation. In the literature, however, there are few studies that address the use of tDCS for pain measures in children, adolescents or elderly. Thus, further studies with methodological rigor should be sought in these age groups to better elucidate the effect of tDCS on pain and the possible impact on the clinical setting

Impact of age on tDCS effects on pain threshold and working memory : results of a proof of concept cross-over randomized controlled study

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

Efeitos da estimulação transcraniana de corrente contínua no processamento sensorial e na memória de trabalho em diferentes faixas etárias

A estimulação transcraniana por corrente contínua (ETCC) é uma técnica neuromodulatória com potencial para auxiliar no tratamento da dor crônica e outras condições clínicas. O efeito da ETCC, no entanto, está associado com a plasticidade cerebral, de modo que fatores que influenciam nesta plasticidade podem alterar os resultados obtidos com a estimulação gerando variabilidade nos resultados da técnica. A idade é um fator importante que modula a plasticidade, de modo que especificar a idade em protocolos de ETCC pode elevar a eficácia do método, possibilitando o uso mais assertivo em protocolos de pesquisa, como também em tratamentos clínicos. No primeiro estudo apresentamos uma revisão sistemática e meta-análise sobre o feito da ETCC nas medidas de dor em crianças, adolescentes e idosos, com a finalidade de compilar evidências sobre o impacto da idade na resposta à ETCC aplicada em montagens de importância no estudo da dor: córtex motor primário (M1) e córtex pré-frontal dorsolateral (DLPFC). Métodos: Realizamos uma revisão sistemática pesquisando os seguintes bancos de dados: PubMed, EMBASE e Science Direct usando os termos de pesquisa que foram adaptados de acordo com MeSh ou Entree: [(“Adolescent” OR “Children” OR “Elderly” ) AND (“tDCS” ) AND (“Pain” OR “Pain threshold”) AND ( “dorsolateral prefrontal cortex” OR “Motor cortex)]. Pré-selecionamos 228 artigos, 13 foram incluídos na revisão sistemática. A meta-análise incluiu 4 estudos para desfechos de nível de dor e 3 estudos pra limiar de dor, que foram classificados como baixo risco de viés. Apenas estudos com idosos foram incluídos na meta-análise. Resultados: Para desfecho de nível de dor os dados apresentaram considerável heterogeneidade (I2 = 60%), foi então aplicado um modelo de efeitos aleatórios. Um total de 96 pacientes recebeu estimulação ativa e a maioria dos estudos favorece a ETCC ativa, mostrando uma redução significativa (P = 0,002) dos níveis de dor quando comparada à sham. A diferença de média padronizada foi de -0,76 (IC 95% = -1,24, -0,28). Para desfecho de limiar de dor 88 idosos receberam ETCC ativa, mas a análise combinada dos estudos não mostrou diferença quando comparado a sham. Apenas dois estudos foram incluídos para o efeito da ETCC na dor em adolescentes. Os estudos foram divergentes em suas conclusões: um estudo com o uso de ETCC anodal sobre córtex pré-frontal relatou redução de escores de dor, enquanto o outro estudo relatou aumento da sensibilidade à dor. Conclusão: Nossos achados sugerem um efeito favorável da ETCC na redução da dor em idosos. No entanto, o número de estudos 9 incluídos foi pequeno e houve heterogeneidade de protocolos e condições clínicas da população do estudo. O segundo estudo teve como objetivo comparar os efeitos da ETCC anodal sobre o DLPFC e o M1 em adolescentes, adultas e idosas. O desfecho primário foi o limiar de dor pelo calor (HPT), enquanto os desfechos secundários foram o desempenho na tarefa de memória de trabalho (WM), dor moderada ao estímulo térmico e a tolerância ao estímulo térmico. Nossa hipótese foi que o efeito da ETCC seria de maior magnitude em adolescentes, quando a ETCC fosse realizada sobre o DLPFC. Métodos: Foram incluídas 30 mulheres saudáveis, destras, com idade entre 15 e 16 anos (adolescentes, n = 10), 30 a 40 anos (adultas, n = 10) e 60 a 70 anos (idosas, n = 10). Neste estudo cruzado e cego, as participantes receberam três sessões de intervenção: ETCC sobre o DLPFC esquerdo, ETCC sobre M1 esquerdo e estimulação simulada. O intervalo entre as sessões foi de pelo menos 7 dias e com alocação randomizada. Durante a estimulação as participantes realizaram tarefas online de WM. A intensidade e duração da estimulação ativa foi de 2 mA por 30 min. O HPT foi avaliado antes e após a estimulação. As participantes realizaram n-back, uma tarefa de avaliação de WM, durante e também após a ETCC. Para medidas de desfecho foi avaliada a variação percentual do HPT do pré para o pós ETCC e para o desempenho da WM foi avaliado pela tarefa de n-back após a estimulação. Resultados: Um modelo de Generalized Estimating Equation (GEE) revelou que a ETCC anodal sobre o DLPFC reduziu o HPT em adolescentes em 3,5%. Em adultos jovens, a ETCC anodal sobre M1, mas não sobre o DLPFC, aumentou o HPT significativamente em comparação com ETCC simulada. Nenhum efeito significativo para HPT foi encontrado no grupo de idosas. Para memória de trabalho o tempo de resposta para acertos foi reduzido para ETCC anodal sobre o DLPFC em adolescentes, em comparação com os outros dois grupos. Conclusão: Esses achados sugerem que a ETCC anodal modula a percepção da dor e as funções cognitivas de forma diferenciada de acordo com a idade e a área de estimulação, com maiores efeitos em adolescentes alcançados via ETCC sobre o DLPFC. A partir dos estudos realizados concluímos que a ETCC modula sensibilidade à dor de maneira distinta para adolescentes, adultos e idosos. No entanto, também a montagem de ETCC apresenta interação com o fator idade para os resultados da estimulação. Na literatura, no entanto há poucos estudos que abordam o uso da ETCC em medidas de dor para crianças, adolescentes ou idosos. Assim, estudos com rigor 10 metodológico devem ser buscados nestas faixas etárias para melhor elucidar o efeito da ETCC no nível de dor e possível impacto no ambiente clínico.Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that has potential to aid in the treatment of chronic pain and other clinical conditions. However tDCS has large variability of effects, what brings inconsistency to the method. Since the effect of tDCS is associated with brain plasticity, factors that influence this plasticity, such as chronological age, modify the response to the method and must be addressed in clinical and research protocols. Individualizing age can improve tDCS protocols efficacy, allowing the proper use of the technique in research and in clinical setting. In the first study, we evaluated in a systematic review and meta-analysis the existing literature on the effect of tDCS on pain level for children, adolescents and elderly. We aimed to review the knowledge of tDCS effect on pain scores for these particular age groups to elucidate tDCS effect on pain outcomes considering age as a influence factor on two tDCS montages used for the study of pain: primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC). Methods: We have conducted a systematic review searching the following databases: PubMed, EMBASE, and Science Direct using the following search terms which were adapted according to MeSh or Entree: [(“Adolescent” OR “Children” OR “Elderly”) AND (“tDCS”) AND (“Pain” OR “Pain threshold”) AND (“dorsolateral prefrontal cortex” OR “Motor cortex)] up to April 20th, 2020. We preselected 228 articles, 13 of which were included in the systematic review, only two studies included adolescents, and none was retrieved with children. The meta-analysis included five studies that showed a lower risk of bias, only studies with elderly. First, we analyzed studies with pain score outcomes (n=4), and the second we analyzed studies that the outcome was the pain threshold (n=3). Results: A random-effects model was applied due to data having considerable heterogeneity (I2 = 60% for pain score). A total of 96 subjects received active stimulation, and most of the studies indicate a favorable effect for active tDCS to reduce the pain score compared to sham tDCS (P =0.002). The standardized mean difference was −0.76 (CI 95% = −1.24 to −0.28). For the pain threshold, 88 elderly received active tDCS. However, the analysis of combined data did not present statistical differences. We included two studies with adolescents, that were divergent in their conclusions: one study using anodal tDCS over the prefrontal cortex reported a reduction in pain scores, contrarily the second study reported an increase in pain sensitivity. Conclusion: Our findings suggest a favorable effect of a-tDCS to reduce pain for elderly. Nevertheless the number of included studies was small, and heterogeneity for clinical condition and protocols was present. The objective of the second study was to compare effects of anodal (a)-tDCS over the left dorsolateral prefrontal cortex (DLPFC), and primary motor cortex (M1) in adolescents, young adults and elderly . Primary outcome was heat pain threshold (HPT),and secondary outcomes were working memory (WM) performance, heat moderate pain and heat pain tolerance. We hypothesized that the effect of tDCS would be the largest in adolescents for the DLPFC tDCS. Methods: We included 30 healthy women within the age ranges of 15 to 16 (adolescents, n= 10), 30 to 40 (young adults, n=10), and 60 to 70 (elderly, n=10) years. In this crossover single-blinded study, participants received three intervention sessions (a-tDCS over the left DLPFC, a-tDCS over left M1, and sham stimulation), separated by at least 7 days coupled with WM online task performance in randomized order. Active stimulation intensity and duration were 2 mA and 30 min, respectively. HPT was evaluated before and after stimulation. Participants performed an n-back WM task during, and also after tDCS. For outcome measures, WM performance after stimulation was evaluated. Results: Generalized Estimating Equation (GEE) revealed that 12 a-tDCS over the DLPFC reduced HPT in adolescents (3.5%). In young adults, a-tDCS over M1, but not the DLPFC, enhanced HPT significantly compared to sham. No significant effect for HPT was found in the elderly group. Response time for hits was reduced for a-tDCS over the DLPFC in adolescents, as compared to the other two groups. Conclusions: These findings suggest that a-tDCS modulates pain perception and cognitive functions differentially according to age and target area of stimulation, with larger effects in adolescents achieved via tDCS over the DLPFC. From the studies we have developed, we concluded that tDCS modulates sensitivity to pain in a different way for adolescents, adults and the elderly. However, the tDCS montage also presents interaction with the age factor for the results of stimulation. In the literature, however, there are few studies that address the use of tDCS for pain measures in children, adolescents or elderly. Thus, further studies with methodological rigor should be sought in these age groups to better elucidate the effect of tDCS on pain and the possible impact on the clinical setting

Age as a mediator of tDCS effects on pain : an integrative systematic review and meta-analysis

Introduction: The transcranial direct current stimulation (tDCS) is a neuromodulatory technique with the potential to decrease pain scores and to improve chronic pain treatment. Although age is an essential factor that might impact the tDCS effect, most studies are solely conducted in adults. Therefore, the age limitation presents a critical research gap in this field and can be shown by only a handful of studies that have included other age groups. To examine the evidence upon the tDCS effect on pain scores on children, adolescents, or elderly, and indirectly, to infer the age-dependent impact on tDCS effects, we conducted a systematic review and meta-analysis. Methods: A systematic review searching the following databases: PubMed, EMBASE, and Science Direct using the following search terms adapted according to MeSh or Entree: [(“Adolescent” OR “Children” OR “Elderly”) AND (“tDCS”) AND (“Pain” OR “Pain threshold”) AND (“dorsolateral prefrontal cortex” OR “Motor cortex)] up to April 20th, 2020. We retrieved 228 articles, 13 were included in the systematic review, and five studies with elderly subjects that had their outcomes assessed by pain score or pain threshold were included in the meta-analysis. Results: For the analysis of pain score, 96 individuals received active stimulation, and we found a favorable effect for active tDCS to reduce pain score compared to sham (P = 0.002). The standardized difference was −0.76 (CI 95% = −1.24 to −0.28). For the pain threshold, the analysis showed no significant difference between active and sham tDCS. We reviewed two studies with adolescents: one study using anodal tDCS over the prefrontal cortex reported a reduction in pain scores. However, the second study reported an increase in pain sensitivity for the dorsolateral prefrontal cortex (DLPFC) stimulation. Conclusion: Our findings suggest tDCS may reduce pain levels in the elderly group. Nevertheless, the small number of studies included in this review—and the considerable heterogeneity for clinical conditions and protocols of stimulation present—limits the support of tDCS use for pain treatment in elderly people. Larger studies on the tDCS effect on pain are needed to be conducted in elderly and adolescents, also evaluating different montages and electrical current intensity

我國輸出入銀行績效考核制度之研究

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