Movement training modulates the excitability in several cortical and subcortical areas. Compared to training with a single arm, movement training with both arms yields a greater increase in motor related cortical regions. A short-term session of bimanual training (BMT) enhances cortical activity of motor preparation and execution areas in both hemispheres. The underlying neural mechanisms for this increased activation with BMT are unclear, but may involve interhemispheric connections between homologous primary motor cortex (M1) representations and input from motor preparatory areas (i.e. dorsal premotor cortex (PMd)). Also, it is unclear how selective up-regulation or down-regulation of specific motor-related areas may contribute to changes in M1 excitability when combined with BMT. The work in this thesis investigated modulation of M1 excitability in terms of in-phase versus anti-phase BMT (Study #1), potentially up-regulating the left dorsal premotor cortex (lPMd) via iTBS before BMT (Study #2), theoretically down-regulating contralateral (right) M1 homologous representation before BMT (Study #3), and finally the potential intracortical and interhemispheric cortical adaptations in M1 bilaterally due to the same interventions as Study #2 (Study #4). For Study #1, it was hypothesized that in-phase BMT would lead to an increased excitability in M1. For Studies #2-4, it was hypothesized that modulation of motor-related areas would cause an increase in the excitability of left M1, and this modulation would be greater when combined with BMT. Study #1 found that in-phase, and not anti-phase BMT, lead to increase M1 excitability. Study #2 found that iTBS to lPMd followed by BMT caused a unique increase in M1 excitability, in terms of increased spatial extent and global MEP amplitude. Study #3 found that the combination of cTBS to right M1 with BMT caused greater excitability enhancements than either intervention alone. Finally, Study #4 found distinct modulations of cortical excitability within and across M1 bilaterally due to BMT, iTBS to lPMd and the combination of these interventions that involved long-interval inhibitory circuitry asymmetrically. Overall, this current work found that the modulation of remote cortical areas to M1 (i.e. lPMd and contralateral M1) in combination with movement training led to unique, and at times greater, excitability enhancements of M1 which could be advantageous in enhancing short-term plasticity in damaged M1.

The primary aim of this thesis is to investigate the physiological effects of transcranial direct current stimulation (tDCS) as applied to the primary motor cortex (M1). This research was largely motivated by the need to understand the basic physiological changes of tDCS, in order to evaluate its use as a potential tool in recovery after stroke, as well as its more general applicability as a tool to modulate plasticity. The experiments in this thesis assess the ability of tDCS to modulate the primary motor cortex in healthy controls. The effects of tDCS on cortical GABA and motor resting state functional connectivity were measured with magnetic resonance spectroscopy (MRS) and resting functional MRI (fMRI). Anodal stimulation reduced GABA concentration and increased functional connectivity in the stimulated M1. Testing these changes within the same individuals demonstrated that the magnitude of changes do not correlate across subjects. Novel evidence on the timecourse of GABA change demonstrated that the reduction in GABA is most prominent in the 30-minute period after stimulation. To determine whether the tDCS-induced modulations in inhibition is restricted to the stimulated hemisphere or whether inhibitory changes could be observed in the nonstimulated M1, or in the interhemispheric connections between the M1s, transcranial magnetic stimulation (TMS) was used to measure intracortical inhibition in each M1 and interhemispheric inhibition and facilitation in the contralateral M1. There were no polarity-specifc effects on intracortical inhibition within either M1, and no changes in interhemispheric excitability from the stimulated to non-stimulated M1. Development of a two-voxel MRS method at ultra high field (7 Tesla) allowed for concurrent measurements of cortical neurotransmitters from both M1s with excellent spectral quality and GABA quantifcation. This method was used to demonstrate the timecourse of tDCS-induced changes in neurochemicals concurrently from both M1s. Anodal stimulation reduced GABA in both the anode-targeted and non-stimulated M1. Cathodal stimulation decreased GABA and glutamate in the non-stimulated M1, with no concurrent changes in the cathode-targeted M1. Bilateral stimulation reduced glutamate in both M1 with no change in GABA.

INTRODUÇÃO: O ultrassom transcraniano colorido (UTC) é um eficiente método para avaliação da circulação intracraniana e do fluxo sanguíneo cerebral em diversas condições clínicas incluindo o acidente vascular isquêmico agudo. Uma das principais limitação deste método reside na incapacidade de insonação intracraniana adequada através da janela transtemporal em até 20% dos pacientes. Neste contexto, surge a necessidade do desenvolvimento de uma metodologia estruturada que permitisse caracterizar a qualidade da janela transtemporal de forma mais detalhada e objetiva. No presente estudo, objetivamos: determinar a frequência de visualização dos principais marcos anatômicos pela insonação com UCT utilizando-se a janela transtemporal em pacientes com AVCI agudo; classificar o grau de dificuldade na visualização da primeira porção da artéria cerebral média (ACM) ipsilateral ao lado insonado; determinar a influência da idade, sexo, etnia no na qualidade da janela transtemporal pelo UTC. METODOLOGIA: Avaliamos prospectivamente todos os pacientes adultos, consecutivos, com o primeiro e único episódio de acidente vascular isquêmico no período de julho de 2014 a janeiro de 2015 com um exame de UTC (modo B e Doppler colorido). Dois examinadores classificaram a qualidade da janela transtemporal pelo modo B utilizando uma escore baseado na qualidade da visualização de referencias anatômicas (osso temporal contralateral, asa menor do esfenoide ipsilateral e mesencéfalo) variando de 0 (janela ausente) a 9 (excelente janela). Os preditores independentes de uma boa visualização do sinal da ACM ao UTC foram identificados através de um modelo de regressão logística multivariada selecionado pelo método backward. A acurácia do escore do modo B foi avaliada através dos parâmetro de sensibilidade, especificidade e estatística C (curva ROC). RESULTADOS: entre os 200 paciente incluídos no estudo (55% do sexo masculino e com idade média de 61,17 ± 15,22 anos) o osso temporal contralateral não foi visualizado em 48,5% dos casos, o mesencéfalo foi visualizado em 65% e a asa menor do esfenoide foi visualizada em 66%. A porção proximal da artéria cerebral media (M1) foi visualizada em 62% dos casos. Na análise multivariada, a idade (OR: 0,95; IC95%:0,92 - 0,99; p=0,011) e a pontuação no escore do modo B (OR: 2,97; IC95%:1,93- 4,55; p<0,001) foram preditores independentes de visualização do sinal da ACM ao UTC. A pontuação no escore do modo B mostrou um preditor acudado para subsequente visualização da artéria cerebral médica pelo Doppler colorido com uma área sob a curva ROC de 0,896 (p<0,001). O escore de 2 apresentou uma sensibilidade e especificidade de 80 e 87% para este fim, respectivamente. CONCLUSÃO: O escore do modo B baseado na visualização de referência anatômicas intracranianas pelo modo B do UTC é uma ferramenta útil com boa acurácia para capacidade de visualização do fluxo da artéria cerebral media ipsilateral ao UTC. Este escore permite descrever de forma mais detalhada a qualidade de janela transtemporal ao UTC, em suas diferentes aplicações. / INTRODUCTION: Transcranial Color-Coded Sonography (TCCS) is an widely-used method to assess the intracranial circulation and cerebral blood flow in several clinical conditions including acute ischemic stroke. One of the main limitations of this technic is related to the quality of the transtemporal window, which is poor in about 20% of cases. In this context, it is important to develop an structured approach to better define the quality of the transtemporal window. In this study we aimed to evaluate how frequently the main anatomic landmarks can be adequately visualized by TCCS in acute stroke patients using the transtemporal window; to assess the proportion of patients in which the ipsilateral middle cerebral artery of visualized by TCCS; and to identify the main predictors of a poor transtemporal window on TCCS. METHODS: We examined 200 consecutive acute ischemic stroke (AIS) patients, from July 2014 to January 2015. All patients underwent prospective TCCS evaluation. Visualization of the contralateral temporal bone (CTB), midbrain (MB) and lesser sphenoid wing (LSW) was scored on B-mode images. The resulting B-Mode Score varied from 0 (poor visualization) to 9 (perfect window). A multivariate logistic regression model (backward selection) was used to identify the independent predictors of visualization of the MCA signal by TCCS. The relationship between these B-Mode Score and visualization of the proximal portion of the ipsilateral MCA was assessed in terms of sensitivity, specificity, ROC curve and C statistics. RESULTS: Among 200 AIS patients (male 55%; mean age, 61.17 ± 15,22 years), CTB was invisible\' in 48,5%, the MB was visualized in 65%; and the LSW was seen in 66%. The M1 segment of the MCA was detected in 62% of cases. After multivariate analysis, age (OR: 0.95; 95CI%:0.92-0.99; p=0.011) and B-Mode score (OR: 2.97;95CI%:1.93-4.55; p<0.001) were independente predictors of visualization of MCA signal by TCCS. The BMode Score show good accuracy for the prediction of MCA visualization with an AUC of 0,896. (p<0,001) on the respective ROC curve. A cut-off of 2 on the B-mode score showed a sensitivity of 80% and a specificity of 87% for adequate MCA visualization by TCCS. CONCLUSION: The B-mode Score, which is based on the visualization of intracranial anatomical landmarks on B-Mode, appears to be a reliable way to characterize the quality of the transtemporal window, with a good accuracy as predictor for visualization of the ipsilateral MCA on TCCS. This score may allow more detailed characterization of the transtemporal window for different clinical applications of TCCS.

No description available.

Working memory training improves performance on trained and untrained working memory tasks, but there is little consistent evidence that these gains benefit everyday tasks that rely on working memory. Evidence has shown that transcranial electrical stimulation (tES) may be an effective tool for enhancing cognitive training and promoting transfer. In the first study, participants completed Cogmed working memory training with either active or sham transcranial random noise stimulation (tRNS). Training was associated with substantial gains on the training activities and on transfer measures of working memory with common processing and storage demands to the training tasks. tRNS did not enhance gains on trained or untrained activities. The second study systematically investigated the boundary conditions to training transfer by testing whether gains following backward digit recall (BDR) training transferred within- and across-paradigm to untrained backward recall and n-back tasks with varying degrees of overlap with the training activity. A further aim was to test whether transcranial direct current stimulation (tDCS) enhanced training and transfer. Participants were allocated to one of three conditions: (i) BDR training with active tDCS, (ii) BDR training with sham tDCS, or (iii) visual search control training with sham tDCS. The results indicated that training transfer is constrained by paradigm, but not by stimuli domain or stimuli materials. There was no evidence that tDCS enhanced performance on the training or transfer tasks. The results of Study 1 and Study 2 provide no evidence that tES enhances the benefits of working memory training. The absence of transfer between backward recall training and n-back in Study 2 suggested the tasks might tap into distinct aspects of working memory. Consequently, the final study used a latent variable approach to explore the degree of overlap between different forms of backward recall and n-back tasks containing digits, letters, or spatial locations as stimuli. The best-fitting factor model included two distinct but related (r = .68) constructs corresponding to backward recall and n-back. Both categories of task were linked to a separate fluid reasoning construct, providing evidence that both are valid measures of higher-order complex cognition. Overall, the experiments in this thesis suggest that working memory tasks tap into separate processes and that training may be targeting and improving these distinct processes, explaining the absence of cross-paradigm transfer.

No description available.

Introdução:O Forame Oval Patente (FOP) é a comunicação direita-esquerda (CDE) ou shunt direita-esquerda (SDE) mais comum e frequentemente encontrada em adultos jovens com Acidente Vascular Cerebral (AVC) relacionado ao mecanismo de embolia paradoxal. A Ecocardiografia Transesofágia (ETE) é considerada o padrão para visualização direta do FOP. O Doppler Transcraniano com o teste de microbolhas é frequentemente usado para detectar CDE com boa correlação com o ETE para o diagnóstico de FOP. Mais recentemente, a Ultrassonografia Transcraniana Colorida (TCCS) com inclusão do modo-B e fluxo de cor tem superado o DTC (que é realizado \"as cegas\") em muitas aplicações clínicas mas a acurácia do TCCS para a detecção de CDE e FOP não tem sido sistematicamente avaliada. Objetivo: Determinar se o TCCS é uma ferramenta acurada para identificar tanto FOP quanto CDE. Métodos: Foram recrutados 106 pacientes prospectivamente com Acidente Vascular Cerebral Isquêmico menores de 55 anos admitidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP). Os pacientes foram submetidos aos exames de ETE, DTC e TCCS e todos os exames incluíram a técnica do teste de microbolhas. Os examinadores foram cegos para os resultados desses exames e foi calculado a concordância Kappa de Cohen inter-examinadores para o TCCS e DTC. A acurácia para o TCCS foi calculada em comparação ao ETE. Resultados: Foram detectados CDE em 54 (50.9%) dos pacientes (idade média 43.9 ± 8.2 anos) com Kappa de Cohen de 0.92 (IC 95% 0.78-1.0) quando realizados TCCS e TCD. TEE e TCSS foram positivos em 23/98 (23.4%) e ETE negative em 20/98 (20.4%). Em 30 (28.3%) o ETE revelou FOP. O TCSS teve uma sensibilidade de 88.4%(IC 95% 0.68-0.97) e especificidade de 72.2%(IC 95% 0.60-0.81) e uma razão de verossimilhança positive de 3.18 (IC 95% 2.14-4.73) para o diagnóstico de FOP. Conclusão: TCCS e DTC tiveram excelente concordância. TCCS tem uma boa acurácia para a detecção de FOP e CDE em pacientes jovens com Acidente Vascular Isquêmico / Introduction: Patent Foramen Ovale (PFO) is the most common right-to-left shunt (RLS) and is often found in young patients with stroke related to paradoxical embolism. ContrastEnhanced Transesophageal Echocardiography (TEE) is considered a gold standard to visualize PFO. Transcranial Doppler (TCD) with bubble test is often used to detect RLS with good correlation to TEE for the diagnostic of PFO. More recently, Transcranial Color Coded Sonography (TCCS) which included B-mode and color coded imaging has overcome blind TCD in many clinical applications but the accuracy of TCCS for detection of RLS and PFO has not been systematically evaluated. Hypothesis: To determine if the TCCS is an accurate tool to identify both PFO and RLS. Methods: We investigate 106 patients with ischemic stroke under 55 years-old admitted from 2012 to 2014 in a tertiary academic hospital. Patients were evaluated with TEE, TCD and TCCS, and all exams included a saline bubble test. The examiners were blinded for the other tests results. Kappa agreement was calculated inter-examiners for TCCS and TCD. Accuracy of TCCS was calculated in comparison to TEE. Results: We detected a RLS in 54 (50.9%) patients (age mean 43.9 ± 8.2) with kappa agreement 0.92 (95%CI 0.78-1.0) when performed TCCS and TCD. TEE and TCSS were positive in 23/98 (23.4%) and TEE did not reveal contrast in 20/98 (20.4%). In 30 (28.3%) patients only TEE revealed a PFO. TCSS had a sensitivity of 88.4% (95%CI 0.68-0.97), specificity of 72.2% (95%CI 0.60-0.81) and positive likelihood ratio of 3.18 (2.14-4.73) of the diagnosis of PFO. Conclusion: TCCS and TCD had an excellent agreement. TCCS has a good accuracy for the detection of PFO and RLS in young patients with stroke

O desenvolvimento da estimulação magnética transcraniana (EMT) permitiu o estudo de potenciais evocados motores eliciados pela estimulação direta do córtex cerebral de forma não-invasiva. Foi observado que diferentes paradigmas de estimulação cortical por EMT apresentam diferentes padrões de resposta, que posteriormente foram associados ao funcionamento de circuitos corticais GABAérgicos e glutamatérgicos do córtex motor, compondo assim índices de excitabilidade cortical motora (ECM). Ademais, desvios da normalidade de tais índices foram encontrados em diversas condições clínicas, incluindo transtornos mentais como a esquizofrenia. O uso dessas medidas também auxiliou o desenvolvimento da estimulação transcraniana por corrente contínua (ETCC), técnica que se mostrou capaz de produzir efeitos neuromodulatórios no sistema nervoso central de forma segura e com mínimos efeitos adversos. Tal técnica vem apresentando possibilidades terapêuticas promissoras, como por exemplo, tendo sido observado sua eficácia no alívio de alucinações auditivas de indivíduos com esquizofrenia. O uso de ETCC para tratamento de sintomas negativos da esquizofrenia também pode vir a se mostrar uma abordagem eficaz, e a análise da ECM pode auxiliar no entendimento dos seus mecanismos de ação e atuar como possível preditor de resposta terapêutica. O objetivo do presente estudo é avaliar o perfil de ECM em um grupo de indivíduos com esquizofrenia, e as possíveis influências de um protocolo terapêutico utilizando ETCC sobre essas medidas. Com esse objetivo, foi selecionada uma coorte de sujeitos com esquizofrenia que participou em ensaio clínico randomizado e controlado com placebo (estimulação sham), tendo a ETCC como intervenção ativa alvo. A ECM foi mensurada na avaliação inicial dos sujeitos, assim como após a primeira sessão de ETCC, e quando da avaliação de desfecho primário. O protocolo terapêutico de ETCC envolveu a colocação de 2 eletrodos de área 5x7 cm, pólo anódico aplicado sobre região correspondente ao córtex pré-frontal dorsolateral esquerdo e pólo catódico aplicado sobre córtex de transição temporoparietal esquerdo; com intensidade de corrente de 2 mA, aplicada por 20 minutos. Cada sujeito foi submetido a 10 sessões no total. Encontramos que idade se correlacionou com diminuição da inibição intracortical, reproduzindo resultado previamente encontrado em indivíduos saudáveis. Acerca da modulação da ECM após sessão de ETCC, observamos que sujeitos submetidos à intervenção ativa apresentaram aumento da inibição intracortical no hemisfério estimulado, em oposição à ausência de mudança significativa da ECM nos sujeitos que receberam estimulação placebo. Os resultados sugerem que sessão de ETCC, utilizando os parâmetros aplicados neste estudo, levou ao aumento da inibição intracortical. Devido a evidências prévias de déficit de inibição intracortical em pessoas com esquizofrenia, é possível que o fenômeno observado represente mecanismo terapêutico da ETCC. É necessário verificar se tal efeito sobre a ECM acompanha medidas objetivas de resposta clinica. Caso isto se comprove, a ECM pode se tornar um valioso marcador de resposta terapêutica e evolução clinica em pacientes com esquizofrenia / The development of transcranial magnetic stimulation allowed the study of motor evoked potentials by applying direct stimuli to the brain cortex in a non-invasive fashion. Different stimulation protocols were observed to yield different response patterns, which were later associated with the functioning of cortical GABAergic and glutamatergic circuits, assembled as motor cortex excitability indices. Also, deviations from normality of such indices were observed in several clinical conditions, including mental disorders such as schizophrenia. The use of these measurements also helped the development of transcranial direct current stimulation (tDCS), a technique which was shown to promote neuromodulatory effects in central nervous system, with potential treatment applications. This technique has been used with success in the treatment of auditory hallucinations in patients with schizophrenia. The use of tDCS might also be effective in the treatment of negative symptoms of schizophrenia, and motor cortex excitability analysis might be used to clarify its physiological effects and act as a possible treatment response predictor. The aim of the present study is to evaluate the motor cortical excitability profile of individuals with schizophrenia, as well as possible influences of tDCS over these measurements. With this aim, we selected a cohort of subjects with schizophrenia who participated in a randomized placebo controlled clinical trial using transcranial direct current stimulation (and sham stimulation for placebo), and measuring motor cortical excitability during baseline evaluation, after the first stimulation session, and at the time of the primary outcome evaluation. The transcranial direct current stimulation protocol used in the present study involved the use of 2 electrodes of area 5x7 cm, anode placed over the region corresponding to the left dorsolateral prefrontal cortex, and cathode over the left cortical temporoparietal juntion. A current of 2 mA intensity was applied for 20 minutes. Each subject underwent a total of 10 sessions. We found that age was correlated to reduced intracortical inhibition, as has been previously found in healthy subjects. Regarding changes of motor cortical excitability following a transcranial direct current stimulation session, we observed that subjects that received the active stimulation displayed an increase in intracortical inhibition, as opposed to those who received sham stimulation, which did not present with any significant change. Results suggest that transcranial direct current stimulation session, using the parameters described in this study, led to an increase in intracortical inhibition. Given previous evidence of intracortical inhibition deficit in individuals with schizophrenia, it is possible that the observed phenomenon corresponds to a treatment mechanism of the electrical stimulation in this population. This need to be confirmed by comparing such changes in cortical excitability to objective measurements of clinical improvement. In case that is confirmed, measurement of motor cortical excitability may have a valuable application as a marker of treatment response and clinical outcome for patients with schizophrenia

O desenvolvimento da estimulação magnética transcraniana (EMT) permitiu o estudo de potenciais evocados motores eliciados pela estimulação direta do córtex cerebral de forma não-invasiva. Foi observado que diferentes paradigmas de estimulação cortical por EMT apresentam diferentes padrões de resposta, que posteriormente foram associados ao funcionamento de circuitos corticais GABAérgicos e glutamatérgicos do córtex motor, compondo assim índices de excitabilidade cortical motora (ECM). Ademais, desvios da normalidade de tais índices foram encontrados em diversas condições clínicas, incluindo transtornos mentais como a esquizofrenia. O uso dessas medidas também auxiliou o desenvolvimento da estimulação transcraniana por corrente contínua (ETCC), técnica que se mostrou capaz de produzir efeitos neuromodulatórios no sistema nervoso central de forma segura e com mínimos efeitos adversos. Tal técnica vem apresentando possibilidades terapêuticas promissoras, como por exemplo, tendo sido observado sua eficácia no alívio de alucinações auditivas de indivíduos com esquizofrenia. O uso de ETCC para tratamento de sintomas negativos da esquizofrenia também pode vir a se mostrar uma abordagem eficaz, e a análise da ECM pode auxiliar no entendimento dos seus mecanismos de ação e atuar como possível preditor de resposta terapêutica. O objetivo do presente estudo é avaliar o perfil de ECM em um grupo de indivíduos com esquizofrenia, e as possíveis influências de um protocolo terapêutico utilizando ETCC sobre essas medidas. Com esse objetivo, foi selecionada uma coorte de sujeitos com esquizofrenia que participou em ensaio clínico randomizado e controlado com placebo (estimulação sham), tendo a ETCC como intervenção ativa alvo. A ECM foi mensurada na avaliação inicial dos sujeitos, assim como após a primeira sessão de ETCC, e quando da avaliação de desfecho primário. O protocolo terapêutico de ETCC envolveu a colocação de 2 eletrodos de área 5x7 cm, pólo anódico aplicado sobre região correspondente ao córtex pré-frontal dorsolateral esquerdo e pólo catódico aplicado sobre córtex de transição temporoparietal esquerdo; com intensidade de corrente de 2 mA, aplicada por 20 minutos. Cada sujeito foi submetido a 10 sessões no total. Encontramos que idade se correlacionou com diminuição da inibição intracortical, reproduzindo resultado previamente encontrado em indivíduos saudáveis. Acerca da modulação da ECM após sessão de ETCC, observamos que sujeitos submetidos à intervenção ativa apresentaram aumento da inibição intracortical no hemisfério estimulado, em oposição à ausência de mudança significativa da ECM nos sujeitos que receberam estimulação placebo. Os resultados sugerem que sessão de ETCC, utilizando os parâmetros aplicados neste estudo, levou ao aumento da inibição intracortical. Devido a evidências prévias de déficit de inibição intracortical em pessoas com esquizofrenia, é possível que o fenômeno observado represente mecanismo terapêutico da ETCC. É necessário verificar se tal efeito sobre a ECM acompanha medidas objetivas de resposta clinica. Caso isto se comprove, a ECM pode se tornar um valioso marcador de resposta terapêutica e evolução clinica em pacientes com esquizofrenia / The development of transcranial magnetic stimulation allowed the study of motor evoked potentials by applying direct stimuli to the brain cortex in a non-invasive fashion. Different stimulation protocols were observed to yield different response patterns, which were later associated with the functioning of cortical GABAergic and glutamatergic circuits, assembled as motor cortex excitability indices. Also, deviations from normality of such indices were observed in several clinical conditions, including mental disorders such as schizophrenia. The use of these measurements also helped the development of transcranial direct current stimulation (tDCS), a technique which was shown to promote neuromodulatory effects in central nervous system, with potential treatment applications. This technique has been used with success in the treatment of auditory hallucinations in patients with schizophrenia. The use of tDCS might also be effective in the treatment of negative symptoms of schizophrenia, and motor cortex excitability analysis might be used to clarify its physiological effects and act as a possible treatment response predictor. The aim of the present study is to evaluate the motor cortical excitability profile of individuals with schizophrenia, as well as possible influences of tDCS over these measurements. With this aim, we selected a cohort of subjects with schizophrenia who participated in a randomized placebo controlled clinical trial using transcranial direct current stimulation (and sham stimulation for placebo), and measuring motor cortical excitability during baseline evaluation, after the first stimulation session, and at the time of the primary outcome evaluation. The transcranial direct current stimulation protocol used in the present study involved the use of 2 electrodes of area 5x7 cm, anode placed over the region corresponding to the left dorsolateral prefrontal cortex, and cathode over the left cortical temporoparietal juntion. A current of 2 mA intensity was applied for 20 minutes. Each subject underwent a total of 10 sessions. We found that age was correlated to reduced intracortical inhibition, as has been previously found in healthy subjects. Regarding changes of motor cortical excitability following a transcranial direct current stimulation session, we observed that subjects that received the active stimulation displayed an increase in intracortical inhibition, as opposed to those who received sham stimulation, which did not present with any significant change. Results suggest that transcranial direct current stimulation session, using the parameters described in this study, led to an increase in intracortical inhibition. Given previous evidence of intracortical inhibition deficit in individuals with schizophrenia, it is possible that the observed phenomenon corresponds to a treatment mechanism of the electrical stimulation in this population. This need to be confirmed by comparing such changes in cortical excitability to objective measurements of clinical improvement. In case that is confirmed, measurement of motor cortical excitability may have a valuable application as a marker of treatment response and clinical outcome for patients with schizophrenia

Introdução:O Forame Oval Patente (FOP) é a comunicação direita-esquerda (CDE) ou shunt direita-esquerda (SDE) mais comum e frequentemente encontrada em adultos jovens com Acidente Vascular Cerebral (AVC) relacionado ao mecanismo de embolia paradoxal. A Ecocardiografia Transesofágia (ETE) é considerada o padrão para visualização direta do FOP. O Doppler Transcraniano com o teste de microbolhas é frequentemente usado para detectar CDE com boa correlação com o ETE para o diagnóstico de FOP. Mais recentemente, a Ultrassonografia Transcraniana Colorida (TCCS) com inclusão do modo-B e fluxo de cor tem superado o DTC (que é realizado \"as cegas\") em muitas aplicações clínicas mas a acurácia do TCCS para a detecção de CDE e FOP não tem sido sistematicamente avaliada. Objetivo: Determinar se o TCCS é uma ferramenta acurada para identificar tanto FOP quanto CDE. Métodos: Foram recrutados 106 pacientes prospectivamente com Acidente Vascular Cerebral Isquêmico menores de 55 anos admitidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP). Os pacientes foram submetidos aos exames de ETE, DTC e TCCS e todos os exames incluíram a técnica do teste de microbolhas. Os examinadores foram cegos para os resultados desses exames e foi calculado a concordância Kappa de Cohen inter-examinadores para o TCCS e DTC. A acurácia para o TCCS foi calculada em comparação ao ETE. Resultados: Foram detectados CDE em 54 (50.9%) dos pacientes (idade média 43.9 ± 8.2 anos) com Kappa de Cohen de 0.92 (IC 95% 0.78-1.0) quando realizados TCCS e TCD. TEE e TCSS foram positivos em 23/98 (23.4%) e ETE negative em 20/98 (20.4%). Em 30 (28.3%) o ETE revelou FOP. O TCSS teve uma sensibilidade de 88.4%(IC 95% 0.68-0.97) e especificidade de 72.2%(IC 95% 0.60-0.81) e uma razão de verossimilhança positive de 3.18 (IC 95% 2.14-4.73) para o diagnóstico de FOP. Conclusão: TCCS e DTC tiveram excelente concordância. TCCS tem uma boa acurácia para a detecção de FOP e CDE em pacientes jovens com Acidente Vascular Isquêmico / Introduction: Patent Foramen Ovale (PFO) is the most common right-to-left shunt (RLS) and is often found in young patients with stroke related to paradoxical embolism. ContrastEnhanced Transesophageal Echocardiography (TEE) is considered a gold standard to visualize PFO. Transcranial Doppler (TCD) with bubble test is often used to detect RLS with good correlation to TEE for the diagnostic of PFO. More recently, Transcranial Color Coded Sonography (TCCS) which included B-mode and color coded imaging has overcome blind TCD in many clinical applications but the accuracy of TCCS for detection of RLS and PFO has not been systematically evaluated. Hypothesis: To determine if the TCCS is an accurate tool to identify both PFO and RLS. Methods: We investigate 106 patients with ischemic stroke under 55 years-old admitted from 2012 to 2014 in a tertiary academic hospital. Patients were evaluated with TEE, TCD and TCCS, and all exams included a saline bubble test. The examiners were blinded for the other tests results. Kappa agreement was calculated inter-examiners for TCCS and TCD. Accuracy of TCCS was calculated in comparison to TEE. Results: We detected a RLS in 54 (50.9%) patients (age mean 43.9 ± 8.2) with kappa agreement 0.92 (95%CI 0.78-1.0) when performed TCCS and TCD. TEE and TCSS were positive in 23/98 (23.4%) and TEE did not reveal contrast in 20/98 (20.4%). In 30 (28.3%) patients only TEE revealed a PFO. TCSS had a sensitivity of 88.4% (95%CI 0.68-0.97), specificity of 72.2% (95%CI 0.60-0.81) and positive likelihood ratio of 3.18 (2.14-4.73) of the diagnosis of PFO. Conclusion: TCCS and TCD had an excellent agreement. TCCS has a good accuracy for the detection of PFO and RLS in young patients with stroke