Previous studies suggest that non-invasive transcranial direct current stimulation (tDCS) applied to the prefrontal cortex modulates food choices and calorie intake in obese humans. In a fully randomized, placebo-controlled, within-subject and double-blinded study, we applied single sessions of anodal, cathodal, and sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) and contralateral frontal operculum in 25 hungry obese women and investigated possible influences on food reappraisal abilities as well as calorie intake. We hypothesized that tDCS, (i) improves the ability to regulate the desire for visually presented foods and, (ii) reduces their consumption. We could not confirm an effect of anodal or cathodal tDCS, neither on the ability to modulate the desire for visually presented foods, nor on calorie consumption. The present findings do not support the notion of prefrontal/frontal tDCS as a promising treatment option for obesity.:1. Introduction 1.1 Obejective of investigation 1.1.1 Obesity 1.1.2 Homeostasis versus hedonism? 1.1.3 Regulating the desire to eat 1.1.4 Obesity and the brain 1.2 Previous studies 1.2.1 EEG study 1.2.2 Buffet study 1.3 Transcranial direct current stimulation (TDCS) 1.4 TDCS study 2 Publication 3 Summary of work 3.1 Data Acquisition ans analysis 3.2 Results and discussion 3.2.1 Absence of evidence is not evidence of absence 3.2.2 Multifactorial influence on behavior 3.2.3 Limitations of study design 3.2.4 Limitations of method 3.3 Outlook 4 References 5 Attachments 5.1 Academic contribution 5.2 Erklärung über die eigenständige Abfassung der Arbeit 5.3 Einreichungserklärung 5.4 Curriculum vitae 5.5 Publications 5.6 Acknowledgements

京都大学 / 0048 / 新制・課程博士 / 博士(教育学) / 甲第20127号 / 教博第204号 / 新制||教||167(附属図書館) / 京都大学大学院教育学研究科教育科学専攻 / (主査)准教授 野村 理朗, 教授 齊藤 智, 教授 Emmanuel MANALO / 学位規則第4条第1項該当 / Doctor of Philosophy (Education) / Kyoto University / DGAM

The purpose of this systematic review is to provide insight into the impact traumatic brain injury (TBI) has on the executive function known as the working memory. TBI is a damage to the brain that occurs when the brain is critically injured to the degree that it impacts several brain regions and functions such as the hippocampus, its surrounding areas, the prefrontal cortex, and the performance of the working memory ability. TBI may occur from bleeding or infraction (stroke), lack of oxygen after cardiac arrest (anoxic brain injury), or diseases such as brain tumours or infections in the brain (encephalitis/meningitis). Working memory is the ability that maintains and manipulates information such as judgment and decision-making. TBI impacts several cognitive and executive functions such as the working memory. The implications that TBI has on working memory is that it relatively decreases the activation and connectivity capacity among the main areas of the working memory network which may result in difficulties of attention and concentration. This review summarises five studies about TBI and working memory that uses different working memory task while examiningwith brain imaging techniques. The studies conclude that TBI has a negative impact on working memory since the ability becomes weak.

Maximum voluntary contraction force (MVC) is an important predictor of athletic performance as well as physical fitness throughout life. Many everyday life activities involve multi-joint or whole-body movements that are determined in part through optimized muscle strength. Transcranial direct current stimulation (tDCS) has been reported to enhance muscle strength parameters in single-joint movements after its application to motor cortical areas, although tDCS effects on maximum isometric voluntary contraction force (MIVC) in compound movements remain to be investigated. Here, we tested whether anodal tDCS and/or sham stimulation over primary motor cortex (M1) and cerebellum (CB) improves MIVC during isometric barbell squats (iBS). Our results provide novel evidence that CB stimulation enhances MIVC during iBS. Although this indicates that parameters relating to muscle strength can be modulated through anodal tDCS of the cerebellum, our results serve as an initial reference point and need to be extended. Therefore, further studies are necessary to expand knowledge in this area of research through the inclusion of different tDCS paradigms, for example investigating dynamic barbell squats, as well as testing other whole-body movements.

Transferring a unimanual motor skill to the untrained hand, a phenomenon known as cross-limb transfer, was shown to deteriorate as a function of age. While transcranial direct current stimulation (tDCS) ipsilateral to the trained hand facilitated cross-limb transfer in older adults, little is known about the contribution of the contralateral hemisphere to cross-limb transfer. In the present study, we investigated whether tDCS facilitates cross-limb transfer in older adults when applied over the motor cortex (M1) contralateral to the trained hand. Furthermore, the study aimed at investigating short-term recovery of tDCS-associated cross-limb transfer. In a randomized, doubleblinded, sham-controlled setting, 30 older adults (67.0 4.6 years, 15 female) performed a short grooved-pegboard training using their left hand, while anodal (a-tDCS) or sham-tDCS (s-tDCS) was applied over right M1 for 20 min. Left (LHtrained) - and right-hand (RHuntrained) performance was tested before and after training and in three recovery measures 15, 30 and 45 min after training. LHtrained performance improved during both a-tDCS and s-tDCS and improvements persisted during recovery measures for at least 45 min. RHuntrained performance improved only following a-tDCS but not after s-tDCS and outlasted the stimulation period for at least 45 min. Together, these data indicate that tDCS over the M1 contralateral to the trained limb is capable of enhancing cross-limb transfer in older adults, thus showing that cross-limb transfer is mediated not only by increased bi-hemispheric activation.

No description available.

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

Les Troubles Obsessionnels et Compulsifs (TOC) sont un trouble mental sévère et fréquemment résistant. La physiopathologie du trouble se caractérise par des anomalies au sein des boucle cortico-striato-thalamo-cortical entrainant une hyper-activité du cortex orbito-frontal, du cortex cingulaire antérieur, du putamen. Au cours des dernières années, des anomalies structurales et fonctionnelles du cervelet ont de plus été mise en évidence dans les TOC venant compléter le modèle existant.Nous avons mise au point un protocole de traitement par tDCS ciblant le cortex orbito-frontal gauche et le cervelet droit pour les TOC résistants. Dans une première étude, nous avons étudié la faisabilité de ce protocole de traitement dans une étude ouverte. Cette étude a mis en évidence une réduction significative des symptômes dans une population de patient à haut niveau de résistance. Dans une deuxième étude, nous avons évaluer l’effet de ce traitement dans un protocole randomisé, contrôlé et parallèle contre placebo. Cette étude n’a pas confirmé l’efficacité de ce protocole de traitement. Dans cette même population, nous avons au cours du protocole mesuré les paramètres d’excitabilité corticale au niveau du cortex moteur par stimulation magnétique transrânienne. Nous avons ainsi mis en évidence que la tDCS provoquait une augmentation significative des processus d’inhibition (Short Interval Cortical Inhibition : SICI ) et une diminution non significative des processus de facilitation (Intra Cortical Facilitation : ICF). L’étude des effets cliniques et électro-physiologiques de cette approche thérapeutique novatrice dans les TOC résistants n’a pas permis de confirmer son intérêt clinique malgré un impact de ce protocole sur les modifications de l’excitabilité corticale inhérentes aux troubles. Ces données ont été mise en relation avec la littérature afin de proposer des perspectives d’évolution dans l’utilisation de la tDCS dans les TOC résistants / Obsessive-compulsive disorder (OCD) is a severe mental illness. OCD symptoms are often resistant to available treatments. Neurobiological models of OCD are based on an imbalance between the direct (excitatory) and indirect (inhibitory) pathway within this cortico-striato-thalamo-cortical loops, which causes hyperactivation in the orbito-frontal cortex, the cingular anterior cortex, the putamen. More recently, the role of cerebellum in the OCD physiopathology has been brought to light by studies showing structural and functional abnormalities. We proposed to use tDCS as a therapeutic tool for resistant OCD by targeting the hyperactive left orbito-frontal cortex with cathodal tDCS (assumed to decrease cortical excitability) coupled with anodal cerebellar tDCS. In a first study, we studied the feasibility of this treatment protocol in an open-trial. This study found a significant reduction in symptoms in a population with a high level of resistance. In a second study, we evaluated the effect of this treatment in a randomized-controlled trial. This study did not confirm the effectiveness of this intervention. We have assessed motor cortex cortical excitability parameters by transcranial magnetic stimulation. We thus demonstrated that the tDCS caused a significant increase of inhibition processes (Short Interval Cortical Inhibition: SICI) and a nonsignificant decrease in the facilitation processes (Intra Cortical Facilitation (ICF)). In addition, clinical improvement assessed by Clinical Global Impression at the end of the follow-up period (3 months) was positively correlated with SICI at baseline.tDCS with the cathode placed over the left OFC combined with the anode placed over the right cerebellum decreased hyper-excitability in the motor cortex but was not significantly effective in SSRI- resistant OCD patients. These works were discussed in light of the available literature to create future prospect in the field of tDCS treatment for OCD resistant patients

INTRODUÇÃO: Os episódios depressivos são bastante prevalentes e, potencialmente, incapacitantes ao longo do curso do transtorno bipolar (TB). Todavia, ainda não se dispõe de opções terapêuticas com eficácia e tolerabilidade satisfatórias. A estimulação transcraniana por corrente contínua (ETCC) é uma nova modalidade de estimulação cerebral não-invasiva com poucos eventos adversos, que mostrou resultados promissores na depressão unipolar. OBJETIVO: Avaliar a eficácia e a segurança da ETCC como tratamento aditivo aos psicofármacos na depressão bipolar (DB). MÉTODOS: Foi realizado um ensaio clínico, duplo-cego, randomizado, em ambiente acadêmico. 59 pacientes com transtorno bipolar (TB) tipos I ou II em episódio depressivo maior, em regime farmacológico estável, com escores Hamilton (HDRS-17) superiores a 17. Os dados foram analisados por intenção de tratamento. A ETCC foi aplicada em 2 mA/25cm2, sendo o ânodo e o cátodo posicionados sobre as áreas correspondentes ao córtex dorsolateral pré-frontal esquerdo e direito, respectivamente, por 30 minutos, diários, por dez dias consecutivos, exceto aos finais de semana. Após este período, duas estimulações adicionais foram aplicadas, em semanas alternadas, até o final do estudo (6a semana). A alteração na escala de HDRS -17, na 6a semana, foi o desfecho primário. RESULTADOS: Cinquenta e nove pacientes (40 mulheres), com média de idade de 45,9 anos participaram; 36 (61%) com transtorno bipolar tipo I e 23 (39%) com tipo II foram randomizados e 52 finalizaram o ensaio. Na análise por intenção de tratamento, os pacientes do grupo ETCC ativa apresentaram melhora estatisticamente significativa relação àqueles que receberam ETCC simulada (número necessário para tratar [NNT], 5,8; intervalo de confiança [IC] 95%, 3,3-25,8; p = 0,01). A taxa de resposta cumulativa foi maior no grupo ativo em relação ao simulado (67,6% vs 30,4%, NNT, 2,69; IC 95%, 1,84-4,99; p = 0,01), mas não para taxa de remissão (37,4% vs 19,1%; NNT, 5,46; IC 95%, 3,38-14,2; p = 0,18). Os eventos adversos, incluindo virada maníaca, foram semelhantes entre os grupos; com exceção de vermelhidão na pele, maior no grupo ativo (54% vs 19%; P = 0,01). CONCLUSÃO: Nesse estudo, a ETCC foi uma intervenção eficaz, segura e tolerável para esta pequena amostra de pacientes com depressão bipolar. Todavia, outros estudos são necessários para que se possa examinar a eficácia da ETCC em amostras maiores / INTRODUCTION: More effective, tolerable interventions for bipolar depression treatment are needed. Transcranial direct current stimulation (tDCS) is a novel therapeutic modality virtually devoid of severe adverse effects that showed promising results for unipolar depression. OBJECTVE: To determine the efficacy and safety of tDCS as an add-on treatment for bipolar depression. METHODS: A randomized, sham-controlled, double-blind trial was conducted at an academic setting. Participants included 59 adults with type I or II bipolar disorder in a major depressive episode and receiving a stable pharmacologic regimen with 17-item Hamilton Depression Rating Scale (HDRS-17) scores higher than 17. Data were analyzed in the intention-to-treat sample. Ten daily 30-minute, 2-mA, anodal-left and cathodal-right prefrontal sessions of active or sham tDCS on weekdays and then 1 session every fortnight until week 6. The main outcome was the change in HDRS-17 scores at week 6. RESULTS: 59 patients (40 women), with a mean age of 45.9 years participated; 36 (61%) with bipolar I and 23 (39%) with bipolar II disorder were randomized and 52 finished the trial. In the intention-to-treat analysis, patients in the active tDCS condition showed significantly superior improvement compared with those receiving sham (number needed to treat [NNT], 5.8; 95% confidence interval [CI], 3.3-25.8; p = .01). Cumulative response rates were higher in the active vs sham groups (67.6% vs 30.4%; NNT, 2.69; 95% CI, 1.84-4.99; p = .01), but not remission rates (37.4% vs 19.1%; NNT, 5.46; 95% CI, 3.38-14.2; p = .18). Adverse events, including treatment-emergent affective switches, were similar between groups, except for localized skin redness that was higher in the active group (54% vs 19%; p = .01). CONCLUSION: In this trial, tDCS was an effective, safe, and tolerable add-on intervention for this small bipolar depression sample. Further trials should examine tDCS efficacy in a larger sample

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