Introdução: Climatério é definido como o período de tempo onde ocorre a mudança de vida reprodutiva para não reprodutiva, com extensão de duração variável. Durante esse período e após o estabelecimento da menopausa, é comum o surgimento de diversos sintomas que expressam o esgotamento dos folículos ovarianos. Dentre os sintomas, o mais comumente relatado pelas mulheres são os sintomas vasomotores ou fogachos. Além da Terapia de Reposição Hormonal (TRH), outras medicações como os Inibidores Seletivos da Recaptação da Serotonina (ISRS) têm sido empregadas na tentativa de melhorá-los. Justificativa: TRH não pode ser aplicado a todas as mulheres com sintomas. As medicações não hormonais, apesar de apresentarem melhores respostas que placebo, ainda demonstram pouco impacto clínico na redução dos sintomas vasomotores. Esta lacuna permite avaliar outras alternativas terapêuticas, como a Estimulação Transcraniana por Corrente Direta (ou tDCS, do inglês transcranial direct current stimulation). O racional para estudar o efeito desta técnica neste contexto, é o seu possível efeito modulatório autonômico. O que reforça a escolha desta técnica é o fato de ter eficácia demonstrada em outras patologias como depressão, dor, doença Parkinson dentre outras. A tDCS é um método de neuromodulação transcraniana não invasivo, que se baseia na aplicação de correntes contínuas de baixa intensidade, através de eletrodos colocados sobre o escalpo, de forma simples e indolor. Objetivo: Avaliar o efeito da tDCS (tratamento ativo) comparada ao tDCS-sham (placebo) nos sintomas vasomotores de mulheres na pós- menopausa como objetivo primário; e como objetivo secundário, seus efeitos na qualidade de vida. Método: Ensaio Clínico Randomizado realizado em 30 pacientes pós-menopáusicas com queixa de pelo menos 05 episódios de fogachos/dia. Participantes foram selecionadas no ambulatório de Climatério do Serviço de Ginecologia e Obstetrícia do Hospital de Clínicas de Porto Alegre e via chamamento de jornal. Estas foram randomizadas para um dos grupos: tDCS ou placebo-sham. A intervenção consistiu na aplicação de sessões diárias de estimulação com corrente elétrica de 02 mili Ampere, pelo período de 10 dias consecutivos, à exceção dos finais de semana. Por uma semana anterior à intervenção e por 30 dias após, as participantes registravam o número e intensidade dos fogachos ao dia. Responderam ao Women´s Health Questionaire (WHQ) antes e ao termino da intervenção. Resultados: A média de fogachos/dia se comportou de forma semelhante nos dois grupos havendo uma redução do número de fogachos nas três primeiras semanas após intervenção com retorno ao basal a partir da quarta semana pós-aplicação. No grupo tDCS, se observou uma tendência a uma transferência dos fogachos intensos para leves sugerindo uma melhora clínica. Os resultados, apesar de não apresentarem significância estatística, reforçam a ideia de ampliar a investigação, com maior número de pacientes e com maior tempo de duração além do caráter inovador da pesquisa. / Introduction: Menopause is defined as a period where there is a change from the reproductive stage to a nonreproductive phase, with variable duration. During this period and following the establishment of menopause, there is usually an onset of several symptoms indicating the depletion of ovarian follicles. Among the symptoms, the ones that are more frequently reported by women are vasomotor symptoms or hot flashes. In addition to Hormone Replacement Therapy (HRT), other medications such as Selective Serotonin Reuptake Inhibitors (SSRIs) have been employed to treat them. Justification: HRT may not be applied to all women with symptoms. Non-hormonal medications, despite having better responses than placebo, have still shown little clinical impact on the reduction of vasomotor symptoms. This gap allows other therapeutic alternatives to be considered, such as Transcranial Direct Current Stimulation (tDCS). The rationale for studying the effect of this technique in this context is its possible autonomic modulatory effect. What reinforces the choice of this technique is the efficacy which it has demonstrated in other disorders such as depression, pain, Parkinson's disease, among others. tDCS is a non-invasive transcranial neuromodulation method based on the application of continuous low-intensity currents through electrodes placed to the scalp, in a simple and painless way. Goal: To evaluate the effect of tDCS (active treatment) compared to tDCS-sham (placebo) on vasomotor symptoms in postmenopausal women as a primary endpoint and its effects on quality of life as a secondary endpoint. Method: Randomized Clinical Trial conducted in 30 postmenopausal patients complaining of at least five episodes of hot flashes per day. Participants were selected at the Gynecology and Obstetrics Service Menopause Outpatient Clinic, Hospital de Clínicas de Porto Alegre and via a newspaper call. These were randomized to one of the groups: tDCS or placebo-sham. The intervention consisted of daily sessions in which stimulation was applied with an electric current of 02 milliamperes for 10 consecutive days, except on weekends. Participants recorded the number and intensity of hot flashes per day for one week before and for 30 days after the intervention. They answered the Women’s Health Questionnaire (WHQ) before and after the intervention completion. Results: The mean of hot flashes/day behaved in a similar way in both groups, and there was a reduction in hot flashes in the first three weeks following the intervention with a return to baseline starting in the fourth week after the administration. In the tDCS group, a trend towards a conversion of intensive hot flashes into mild ones was noted, which suggested a clinical improvement. The results, despite not showing statistical significance, supported the idea of extending the investigation with a larger number of patients and longer duration, in addition to the innovating nature of the research.

Transcranial direct current stimulation (TDCS) allows for the noninvasive modulation of cortical activity. In this study, the effects of cathodal and anodal TDCS treatment on baseline activity in the motor cortex of rats were investigated via translaminar electroencephalogram (EEG) recording and power spectral density analysis. Treatment with low intensity anodal TDCS for five minutes was found to increase delta and theta frequency cortical activity during and for up to five minutes following treatment. This study also assessed the interaction of TDCS with the phenomenon of cortical spreading depression (CoSD), which has been implicated in numerous disease states, including migraine and stroke. TDCS treatment was given concurrently with induction of CoSD via administration of potassium chloride to the surface of the dura. The presence of the spreading depression event, a characteristic low frequency wave observed to travel outwards from the point of CoSD induction and downwards through the cortex, was used as a proxy measure for the occurrence of CoSD. It was observed that animals treated with cathodal TDCS exhibited fewer spreading depression events relative to those treated with anodal TDCS or those receiving sham treatment. In this study, animals were segregated into groups that exhibited stimulus artifact during TDCS treatment and those that did not. Stimulus artifact was defined as a characteristic alpha and/or beta frequency activity spike lasting throughout and not longer than the period of stimulation. Those animals receiving TDCS without exhibiting stimulus artifact were considered for the purposes of this study to not have received proper TDCS treatment, and acted as a sham treatment group. Because salient differences emerged between the stimulus artifact positive and stimulus artifact negative groups, this study suggests that the presence of stimulus artifact could be used as a proxy measure for successful TDCS dosage.

TDCS is a form of non-invasive neurostimulation that is comprised of injection of current via strategically placed scalp electrodes into targeted areas of the brain. TDCS has shown therapeutic benefit for numerous clinical applications. This technique has not however been widely adopted due to high variability of response to the stimulation. Current state of the art methods for optimizing tDCS are based on FEM models that generally model tissue as isotropic and homogeneous and do not take into account inter subject variability of head tissue electrical properties. We therefore develop an in-vivo method of measuring and analyzing bioimpedance spectroscopy measurements of the head to estimate change to tDCS dose in neural tissues for different subjects. Finite element simulations are implemented on a realistic MRI derived head model. 5\% random Gaussian noise is added. Experimental bioimpedance measurements are taken of the heads of 8 subjects. We simulate sensitivity distribution and impedance for a variety of 2 and 4 electrode configurations over a wide frequency range. We also extract Cole parameters and implement PCA on simulated and experimental impedance. We demonstrate that the Cole model of the head can be accurately approximated by the sum in series of Cole systems of each tissue. Comparison of Cole parameters from various simulated electrode configurations show statistical differences (paired t test $p<.05$). PCA shows that close to 100\% of the variance between two impedance spectra is described along a single principal component. Variation described by the second principal component increases as a function of increasing inter electrode gap which may be related to changes in dose. FEM and experimentally derived Cole parameters show different trends for various electrode configurations, good agreement is however shown for the PCA results. The outcome of this research may lead to a higher tDCS efficacy by improving standardization and control of stimulation by relation of dose and bioimpedance spectra characteristics.

Locomotion requires visuospatial attention. However, the role and cortical control of visuospatial attention during locomotion remain unclear. Four experiments were conducted in this study to examine the role and cortical control of visuospatial attention during locomotion in healthy young adults. In the first experiment, we employed a visuospatial attention task at different phases of obstacle crossing during gait. The results suggested that toe-obstacle clearance was significantly reduced for the trailing limb when distraction interfered with visuospatial attention during the approaching phase of obstacle crossing. In the second experiment, subjects performed a visual Stroop task while approaching and crossing an obstacle during gait. The results for the second experiment indicated toe-obstacle clearance was significantly increased for the leading and trailing limbs. Taken together, it was found that different visual attention tasks lead to distinct modifications on obstacle crossing behaviors. In the third and fourth experiments, anodal transcranial direct current stimulation (tDCS) was applied over the right posterior parietal cortex (PPC) to examine the aftereffects on attention function and locomotor behavior. The results suggested that the orienting attention was significantly improved after anodal tDCS. In addition, the aftereffects of anodal tDCS potentially enhanced cognitive and motor performance while interacting with a challenging obstacle-crossing task in young healthy adults, suggesting that the right PPC contributes to attending visuospatial information during locomotion. This study demonstrated that visuospatial attention is critical for planning during locomotion and the right PPC contributes to this interplay of the neural processing of visuospatial attention during locomotion. This dissertation includes previously published and unpublished co-authored material.

Introdução: Climatério é definido como o período de tempo onde ocorre a mudança de vida reprodutiva para não reprodutiva, com extensão de duração variável. Durante esse período e após o estabelecimento da menopausa, é comum o surgimento de diversos sintomas que expressam o esgotamento dos folículos ovarianos. Dentre os sintomas, o mais comumente relatado pelas mulheres são os sintomas vasomotores ou fogachos. Além da Terapia de Reposição Hormonal (TRH), outras medicações como os Inibidores Seletivos da Recaptação da Serotonina (ISRS) têm sido empregadas na tentativa de melhorá-los. Justificativa: TRH não pode ser aplicado a todas as mulheres com sintomas. As medicações não hormonais, apesar de apresentarem melhores respostas que placebo, ainda demonstram pouco impacto clínico na redução dos sintomas vasomotores. Esta lacuna permite avaliar outras alternativas terapêuticas, como a Estimulação Transcraniana por Corrente Direta (ou tDCS, do inglês transcranial direct current stimulation). O racional para estudar o efeito desta técnica neste contexto, é o seu possível efeito modulatório autonômico. O que reforça a escolha desta técnica é o fato de ter eficácia demonstrada em outras patologias como depressão, dor, doença Parkinson dentre outras. A tDCS é um método de neuromodulação transcraniana não invasivo, que se baseia na aplicação de correntes contínuas de baixa intensidade, através de eletrodos colocados sobre o escalpo, de forma simples e indolor. Objetivo: Avaliar o efeito da tDCS (tratamento ativo) comparada ao tDCS-sham (placebo) nos sintomas vasomotores de mulheres na pós- menopausa como objetivo primário; e como objetivo secundário, seus efeitos na qualidade de vida. Método: Ensaio Clínico Randomizado realizado em 30 pacientes pós-menopáusicas com queixa de pelo menos 05 episódios de fogachos/dia. Participantes foram selecionadas no ambulatório de Climatério do Serviço de Ginecologia e Obstetrícia do Hospital de Clínicas de Porto Alegre e via chamamento de jornal. Estas foram randomizadas para um dos grupos: tDCS ou placebo-sham. A intervenção consistiu na aplicação de sessões diárias de estimulação com corrente elétrica de 02 mili Ampere, pelo período de 10 dias consecutivos, à exceção dos finais de semana. Por uma semana anterior à intervenção e por 30 dias após, as participantes registravam o número e intensidade dos fogachos ao dia. Responderam ao Women´s Health Questionaire (WHQ) antes e ao termino da intervenção. Resultados: A média de fogachos/dia se comportou de forma semelhante nos dois grupos havendo uma redução do número de fogachos nas três primeiras semanas após intervenção com retorno ao basal a partir da quarta semana pós-aplicação. No grupo tDCS, se observou uma tendência a uma transferência dos fogachos intensos para leves sugerindo uma melhora clínica. Os resultados, apesar de não apresentarem significância estatística, reforçam a ideia de ampliar a investigação, com maior número de pacientes e com maior tempo de duração além do caráter inovador da pesquisa. / Introduction: Menopause is defined as a period where there is a change from the reproductive stage to a nonreproductive phase, with variable duration. During this period and following the establishment of menopause, there is usually an onset of several symptoms indicating the depletion of ovarian follicles. Among the symptoms, the ones that are more frequently reported by women are vasomotor symptoms or hot flashes. In addition to Hormone Replacement Therapy (HRT), other medications such as Selective Serotonin Reuptake Inhibitors (SSRIs) have been employed to treat them. Justification: HRT may not be applied to all women with symptoms. Non-hormonal medications, despite having better responses than placebo, have still shown little clinical impact on the reduction of vasomotor symptoms. This gap allows other therapeutic alternatives to be considered, such as Transcranial Direct Current Stimulation (tDCS). The rationale for studying the effect of this technique in this context is its possible autonomic modulatory effect. What reinforces the choice of this technique is the efficacy which it has demonstrated in other disorders such as depression, pain, Parkinson's disease, among others. tDCS is a non-invasive transcranial neuromodulation method based on the application of continuous low-intensity currents through electrodes placed to the scalp, in a simple and painless way. Goal: To evaluate the effect of tDCS (active treatment) compared to tDCS-sham (placebo) on vasomotor symptoms in postmenopausal women as a primary endpoint and its effects on quality of life as a secondary endpoint. Method: Randomized Clinical Trial conducted in 30 postmenopausal patients complaining of at least five episodes of hot flashes per day. Participants were selected at the Gynecology and Obstetrics Service Menopause Outpatient Clinic, Hospital de Clínicas de Porto Alegre and via a newspaper call. These were randomized to one of the groups: tDCS or placebo-sham. The intervention consisted of daily sessions in which stimulation was applied with an electric current of 02 milliamperes for 10 consecutive days, except on weekends. Participants recorded the number and intensity of hot flashes per day for one week before and for 30 days after the intervention. They answered the Women’s Health Questionnaire (WHQ) before and after the intervention completion. Results: The mean of hot flashes/day behaved in a similar way in both groups, and there was a reduction in hot flashes in the first three weeks following the intervention with a return to baseline starting in the fourth week after the administration. In the tDCS group, a trend towards a conversion of intensive hot flashes into mild ones was noted, which suggested a clinical improvement. The results, despite not showing statistical significance, supported the idea of extending the investigation with a larger number of patients and longer duration, in addition to the innovating nature of the research.

Introdução: Climatério, ou transição menopáusica, é definido como o período onde ocorre a mudança de vida reprodutiva para não reprodutiva, com extensão de duração variável. Durante esse período, e após o estabelecimento da menopausa, é comum o surgimento de diversos sintomas que expressam o esgotamento dos folículos ovarianos; sendo os sintomas vasomotores, ou fogachos, os mais comumente relatados pelas mulheres. Atualmente, Terapia Hormonal, bem como os Inibidores Seletivos da Recaptação da Serotonina, têm sido empregadas na tentativa de melhorar estes sintomas. As medicações não hormonais, apesar de apresentarem melhores respostas que placebo, ainda demonstram pouco impacto clínico na redução dos sintomas vasomotores. Esta lacuna permite avaliar outras alternativas terapêuticas, como a Estimulação Transcraniana por Corrente Direta (ou tDCS, do inglês transcranial direct current stimulation). Objetivo: avaliar a diminuição no número de episódios de sintomas vasomotores em pacientes tratadas com aplicação de tDCS e placebo-sham, além de testar os efeitos do tDCS sobre o processo de neuroplasticidade, através da medida sérica de BDNF. Métodos: foram selecionadas nove pacientes pós-menopausicas com queixa de ao menos 5 episódios diários de sintomas vasomotores. Estas pacientes foram randomizadas para um dos grupos, tDCS (tratamento ativo) ou placebo-sham. O tratamento consistiu na aplicação de sessões diárias de estimulação com corrente elétrica de 02 mili Ampere, pelo período de dez dias consecutivos. Após uma semana e um mês de tratamento, as pacientes registravam o número de fogachos ao dia, e respondiam ao Women´s Health Questionaire (WHQ). No primeiro e no último dia de tratamento, foram coletadas amostras sanguíneas para dosagem de BDNF. Resultados: comparando o número médio de sintomas vasomotores (fogachos) ao dia, durante o período de sete dias, não houve diferença significativa entre os dois grupos, assim como nos níveis de BDNF e no WHQ. Conclusão: no momento, não podemos descartar o uso de tDCS no tratamento dos sintomas vasomotores, em virtude de pequeno número de pacientes avaliadas nesta pesquisa. Será mantido o acompanhamento das pacientes avaliadas até esse momento, e o tratamento será aplicado em novas mulheres com sintomas vasomotores. / Background: Climacteric or Menopausal Transition is defined as the time period where there is a change to non-reproductive reproductive life, with extension of variable length. During this period, and after the establishment of Menopause and non-functioning ovarian, the appearance of various symptoms that express the depletion of ovarian follicles is common; among these symptoms, the most frequently reported by women are vasomotor symptoms or hot flashes. In addition to hormonal therapy, other medications have been employed in an attempt to improve these symptoms; although they present better results than placebo, yet have little clinical impact in reducing vasomotor symptoms. Therefore, this gap allows the evaluation of alternative therapies, such as Transcranial Direct Current Stimulation (tDCS). Objective: evaluate the decrease in the number of episodes of vasomotor symptoms in patients treated with tDCS and placebo –sham, beyond testing the effects of tDCS on the neuroplasticity process through measurement of serum BDNF. Methods: nine post-menopausal women with at least 5 episodes of hot flashes/day were selected. These patients were randomized to one of the groups, tDCS (active treatment) or placebo-sham. The treatment consisted in daily application sessions of stimulation with electrical current of 02 mA, for ten consecutive days. After one week and one month of treatment, patients recorded the number of hot flashes per day, and answered the Women's Health Questionnaire (WHQ). In the first and in the last day of treatment, blood samples were collected for measurement of BDNF. Results: Comparing the average number of vasomotor symptoms (hot flashes) per day during the period of seven days, there was no significant difference between the two groups, and there were no differences in the levels of BDNF and WHQ. Conclusion: we can not rule out the use of tDCS in the treatment of vasomotor symptoms, because of the small number of patients evaluated in this study. Monitoring of these patients will be kept, and treatment will be applied to other women with vasomotor symptoms.

Introdução: Climatério, ou transição menopáusica, é definido como o período onde ocorre a mudança de vida reprodutiva para não reprodutiva, com extensão de duração variável. Durante esse período, e após o estabelecimento da menopausa, é comum o surgimento de diversos sintomas que expressam o esgotamento dos folículos ovarianos; sendo os sintomas vasomotores, ou fogachos, os mais comumente relatados pelas mulheres. Atualmente, Terapia Hormonal, bem como os Inibidores Seletivos da Recaptação da Serotonina, têm sido empregadas na tentativa de melhorar estes sintomas. As medicações não hormonais, apesar de apresentarem melhores respostas que placebo, ainda demonstram pouco impacto clínico na redução dos sintomas vasomotores. Esta lacuna permite avaliar outras alternativas terapêuticas, como a Estimulação Transcraniana por Corrente Direta (ou tDCS, do inglês transcranial direct current stimulation). Objetivo: avaliar a diminuição no número de episódios de sintomas vasomotores em pacientes tratadas com aplicação de tDCS e placebo-sham, além de testar os efeitos do tDCS sobre o processo de neuroplasticidade, através da medida sérica de BDNF. Métodos: foram selecionadas nove pacientes pós-menopausicas com queixa de ao menos 5 episódios diários de sintomas vasomotores. Estas pacientes foram randomizadas para um dos grupos, tDCS (tratamento ativo) ou placebo-sham. O tratamento consistiu na aplicação de sessões diárias de estimulação com corrente elétrica de 02 mili Ampere, pelo período de dez dias consecutivos. Após uma semana e um mês de tratamento, as pacientes registravam o número de fogachos ao dia, e respondiam ao Women´s Health Questionaire (WHQ). No primeiro e no último dia de tratamento, foram coletadas amostras sanguíneas para dosagem de BDNF. Resultados: comparando o número médio de sintomas vasomotores (fogachos) ao dia, durante o período de sete dias, não houve diferença significativa entre os dois grupos, assim como nos níveis de BDNF e no WHQ. Conclusão: no momento, não podemos descartar o uso de tDCS no tratamento dos sintomas vasomotores, em virtude de pequeno número de pacientes avaliadas nesta pesquisa. Será mantido o acompanhamento das pacientes avaliadas até esse momento, e o tratamento será aplicado em novas mulheres com sintomas vasomotores. / Background: Climacteric or Menopausal Transition is defined as the time period where there is a change to non-reproductive reproductive life, with extension of variable length. During this period, and after the establishment of Menopause and non-functioning ovarian, the appearance of various symptoms that express the depletion of ovarian follicles is common; among these symptoms, the most frequently reported by women are vasomotor symptoms or hot flashes. In addition to hormonal therapy, other medications have been employed in an attempt to improve these symptoms; although they present better results than placebo, yet have little clinical impact in reducing vasomotor symptoms. Therefore, this gap allows the evaluation of alternative therapies, such as Transcranial Direct Current Stimulation (tDCS). Objective: evaluate the decrease in the number of episodes of vasomotor symptoms in patients treated with tDCS and placebo –sham, beyond testing the effects of tDCS on the neuroplasticity process through measurement of serum BDNF. Methods: nine post-menopausal women with at least 5 episodes of hot flashes/day were selected. These patients were randomized to one of the groups, tDCS (active treatment) or placebo-sham. The treatment consisted in daily application sessions of stimulation with electrical current of 02 mA, for ten consecutive days. After one week and one month of treatment, patients recorded the number of hot flashes per day, and answered the Women's Health Questionnaire (WHQ). In the first and in the last day of treatment, blood samples were collected for measurement of BDNF. Results: Comparing the average number of vasomotor symptoms (hot flashes) per day during the period of seven days, there was no significant difference between the two groups, and there were no differences in the levels of BDNF and WHQ. Conclusion: we can not rule out the use of tDCS in the treatment of vasomotor symptoms, because of the small number of patients evaluated in this study. Monitoring of these patients will be kept, and treatment will be applied to other women with vasomotor symptoms.

Made available in DSpace on 2016-03-15T19:40:37Z (GMT). No. of bitstreams: 1 Alexandre Tadeu Fae Rosa.pdf: 3127122 bytes, checksum: 7cc2fee5f67c75093575447bd7628184 (MD5) Previous issue date: 2009-01-22 / Fundo Mackenzie de Pesquisa / Transcranial Direct Current Stimulation (tDCS) is a technique which is able to modulate cortical excitability in a safe, painless and non-invasive way. The effects of increasing and reduction of the excitability obtained after application of tDCS depend on the polarity which has been used (anodal or cathodal). This dissertation aims at investigating the effects of tDCS on the preparation of saccadic movements in reading. In the experiment, healthy volunteers performed a word-reading task after being exposed to anodal, cathodal or sham tDCS over the right frontal eye field (FEF). The results show that anodal tDCS applied over the right FEF has a delay effect on the performance of the subjects while making the first saccadic movement during reading. Besides, the results show a significant increase of the condition of cathodal stimulation when compared to sham and anodal stimulation related to time in which the subject looks at a fixation mark at the left side after the words appear on the screen. Also, concerning the average reading time of the whole set of words, there was not any significant difference on the main effects or interaction. / A estimulação transcraniana por corrente contínua (ETCC) é uma técnica capaz de modular a excitabilidade cortical de maneira segura, indolor e não-invasiva. Os efeitos de aumento ou diminuição da excitabilidade obtidos após a aplicação da ETCC dependem da polaridade utilizada (anódica ou catódica). Esta dissertação tem como objetivo investigar os efeitos produzidos pela ETCC na preparação de movimentos sacádicos durante a leitura. No experimento realizado, voluntários saudáveis realizaram uma tarefa de leitura de palavras após terem recebido ETCC anódica, catódica ou placebo em campo visual frontal (CVF) direito. Os resultados mostram que a ETCC catódica em CVF direito piora o desempenho dos sujeitos na realização do primeiro movimento sacádico durante a leitura. Além disso, os resultados revelaram aumento significativo da condição de estimulação catódica em comparação com o placebo e da estimulação catódica em comparação com a anódica com relação ao tempo em que o sujeito fixa o olhar no ponto de referência à esquerda depois do aparecimento dos itens a serem lidos. Ainda, com relação ao tempo médio de leitura de todo o conjunto de palavras, não houve nenhuma diferença significativa para os efeitos principais ou interação.

Background: While pain is essential for physiological functioning, chronic or pathologic pain is responsible for a major burden of disease in society. Novel approaches to treating acute and chronic pain have employed neuromodulatory tools to target the central and peripheral neural structures that mediate pain. Transcranial direct current stimulation (tDCS), for example, is a safe, non-invasive brain stimulation technique that has been shown in preliminary studies to reduce chronic pain when applied to the primary motor cortex. In contrast to this exogenous neuromodulatory approach, diffuse noxious inhibitory controls (DNIC) refers to endogenous pain regulatory mechanisms that decrease pain following introduction of heterotopic noxious stimuli. This thesis explores whether combining these exogenous and endogenous pain modulation approaches synergistically increases the threshold at which pain is perceived. Methods: We conducted a double-blinded, randomized, placebo-controlled trial with a crossover design to investigate the effects of tDCS and DNIC on pain thresholds in 15 healthy human subjects. Pain thresholds were assessed prior to and following administration of active tDCS, sham tDCS, cold-water-induced DNIC, and combined active tDCS and DNIC. Using magnetic resonance spectroscopy, we examined whether baseline concentrations of brain metabolites such as N-acetylaspartate in pain-related regions of interest were associated with responses to the varying neuromodulatory conditions. Results: Pain thresholds significantly increased following both active tDCS and the DNIC paradigm. These modulatory approaches appeared to have additive effects when combined. Pain threshold increases after active tDCS were positively correlated with baseline levels of N-acetylaspartate, a marker of good neural function, in the anterior cingulate cortex and negatively correlated with baseline levels of glutamine in the thalamus. Conclusions: Combining endogenous pain regulatory mechanisms with exogenous stimulation of the motor cortex can more effectively increase pain thresholds in healthy humans. Future studies should examine whether existing pain therapies may be enhanced with noninvasive brain stimulation and activation of DNIC. They should also assess whether brain metabolite levels can be utilized to predict clinical response to therapeutic interventions.

Schizophrenia is a severe neuropsychiatric disorder characterized by delusions, hallucinations, behavioral symptoms, and cognitive deficits. Roughly, 70%-80% of schizophrenia patients experience auditory verbal hallucinations (AVHs), with 25%-30% demonstrating resistance to conventional antipsychotic medications. Studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in the treatment of medication-refractory AVHs. The mechanisms through which tDCS could be therapeutic in such cases are unclear, but possibly involve neuroplastic effects. In recent years, functional near-infrared spectroscopy (fNIRS) has been used successfully to study tDCS-induced neuroplastic changes. In a double-blind, sham-controlled design, we applied fNIRS to measure task-dependent cerebral blood flow (CBF) changes as a surrogate outcome of single session tDCS-induced effects on neuroplasticity in a schizophrenia patient with persistent auditory hallucinations. The observations are discussed in this case report.