Deep brain stimulation (DBS) is a neurosurgical intervention now established for the treatment of movement disorders. For the treatment of chronic pain refractory to medical therapies, several prospective case series have been reported, but few centres worldwide have published findings from patients treated during the last decade using current standards of technology. This thesis seeks to survey the current clinical status of DBS for pain, investigate its mechanisms and their interactions with autonomic function, its clinical limitations and ablative alternatives. Presented first is a review of the current status of analgesic DBS including contemporary clinical studies. The historical background, scientific rationale, patient selection and assessment methods, surgical techniques and results are described. The clinical outcomes of DBS of the sensory thalamus and periventricular / periaqueductal grey (PAVG) matter in two centres are presented including results from several pain and quality of life measures. A series of translational investigations in human subjects receiving DBS for pain elucidating mechanisms of analgesic DBS and its effects upon autonomic function are then presented. Single photon emission tomography comparing PAVG, VP thalamus and dual target stimulation is described. Somatosensory and local field potential (LFP) recordings suggesting PAVG somatotopy are shown. ABPM results demonstrating changes with PAVG DBS are given and Portapres studies into heart rate variability changes with ventral PAVG DBS are detailed. Investigations using naloxone are then shown to hypothesise separate dorsal opioidergic and ventral parasympathetic analgesic streams in the PAVG. Finally, cingulotomy in lung cancer to relieve pain and dyspnoea results are discussed in the context of altering pain and autonomic function by functional neurosurgery. Pain and autonomic interactions and mechanisms in deep brain surgery for pain are then discussed alongside its limitations with proposals made for optimising treatment and improving outcomes.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and DBS of the pedunculopontine nucleus (PPN) have been shown to be effective surgical therapies for Parkinson’s disease (PD). To better understand the PPN and STN as DBS targets for PD, this research compares the anatomy, electrophysiology, and motor control roles of these nuclei. PPN and STN connections were examined in vivo in human subjects and in the non-human primate using probabilistic diffusion tractography. Both the PPN and STN were connected with each other and with the motor cortex (M1) and basal ganglia. After studying these anatomical connections in primates, their functional significance was further explored in an anesthetized rat model of PD. Examination of the electrophysiological relationship between the PPN and basal ganglia in the presence of slow cortical oscillatory activity suggested that excitatory input from the STN may normally modulate PPN spike timing but that inhibitory oscillatory input from the basal ganglia output nuclei has a greater effect on PPN spike timing in the parkinsonian brain. To examine transmission and modulation of oscillatory activity between these structures at higher frequencies, LFP activity was recorded from the PPN and STN in PD patients performing simple voluntary movements. Movement-related modulation of oscillatory activity predominantly occurred in the α (8-12 Hz) and low β (12-20 Hz) frequencies in the STN but in the high β (20-35 Hz) frequencies in the PPN, supporting observations from rodent studies suggesting that oscillatory activity is not directly transmitted from the STN to the PPN in PD. Finally, to better understand the roles of the STN and PPN in large-scale movement, the effects of STN and PPN DBS on gait abnormalities in PD patients were studied. DBS of the STN appeared to improve gait by optimising executive gait control while DBS of the PPN appeared to restore autonomic gait control. These results have several implications for DBS patient selection, surgical targeting, and for understanding the mechanisms underlying DBS efficacy.

The body of work hereby presented aims at better defining the specific mechanisms underlying cognitive control and flexibility, and to investigate the neural substrates that might support these dynamics. More specifically, the anterior cingulate (ACC), dorsolateral prefrontal (dlPFC) and frontopolar (FPC) cortices have been proposed to play a fundamental role in monitoring and detecting the presence of environmental contingencies that require the recruitment of cognitive control (such as competition between responses in the presence of conflicting information), implementing cognitive control, and supporting higher-order cognitive processing, respectively. This thesis investigates the effects of damage to these regions, and of interference with their activity, on these processes. It also argues for the importance of dissociating possible separate cognitive control components that might differently contribute to behavioural adjustments (such as caution and attention/task-relevant processing), and provides one of the first attempts to quantify them within the parameters of a mathematical model of choice response-time, the Linear Ballistic Accumulator (LBA). The results confirm the crucial role of the dlPFC in modulating behavioural adjustments, as both damage and interference with this region’s activity significantly affect measures of conflict-induced behavioural adaptation. It is hypothesized that dlPFC might drive behavioural adjustments by encoding recent conflict history and/or supporting the automatization of a newly advantageous behavioural strategy during the early stages after a change in conflict levels. When a task does not involve competition between a habit and instructed behaviour, lesions or interference with ACC’s activity do not appear to affect behaviour in a manner that is consistent with the classic conflict-monitoring framework. It is suggested that its role might be better described as a more general monitoring and confirmatory mechanism that evaluates both actual and potential outcomes of an action, in order to proactively guide adjustments away from contextually disadvantageous responses. Finally, lesions to the FPC do not affect abstract-rule integration, but do impair the early stages of acquisition of a new abstract rule, when a previously rewarded rule stops being rewarded, and specifically when acquisition is dependent on self-initiated exploration. This suggests a role for FPC in the evaluation of multiple concurrent options in order to aid the development of new behavioural strategies.

This thesis is concerned with the neurocircuitry that underpins the cardiovascular response to exercise, which has thus far remained incompletely understood. Small animal studies have provided clues, but with the advent of functional neurosurgery, it has now been made possible to translate these findings to humans. Chapter One reviews the background to the studies in this thesis. Our current understanding of the cardiovascular response to exercise is considered, followed by a discussion on the anatomy and function of various brain nuclei. In particular, the rationale for targeting the periaqueductal grey (PAG) and the subthalamic nucleus (STN) is reviewed. Chapter Two reviews the use of deep brain stimulation (DBS), in which deep brain stimulating electrodes are implanted into various brain nuclei in humans, in order to treat chronic pain and movement disorders. This technique not only permits direct electrical stimulation of the human brain, but also gives the opportunity to record the neural activity from different brain regions during a variety of cardiovascular experiments. This chapter also gives a detailed methodological description of the experimental techniques performed in the studies in this thesis. Chapter Three identifies the cardiovascular neurocircuitry involved in the exercise pressor reflex in humans using functional neurosurgery. It shows for the first time in humans that the exercise pressor reflex is associated with significantly increased neural activity in the dorsal PAG. The other sites investigated, which had previously been identified as cardiovascular active in both animals and humans, seem not to have a role in the integration of this reflex. Chapter Four investigates whether changes in exercise intensity affect the neurocircuitry involved in the exercise pressor reflex. It demonstrates that the neural activity in the PAG is graded to increases in exercise intensity and corresponding increases in arterial blood pressure. This chapter also provides evidence to suggest that neural activity in the STN corresponds to the cardiovascular changes evoked by the remote ischaemic preconditioning stimulus in humans. Chapter Five identifies the cardiovascular neurocircuitry involved during changes in central command during isometric exercise at constant muscle tension using muscle vibration. It shows that, in humans, central command is associated with significantly decreased neural activity in the STN. Furthermore, the STN is graded to the perception of the exercise task, i.e. the degree of central command. The other sites investigated appear not to have as significant a role in the integration of central command during the light exercise task that was undertaken. Chapter Six studies the changes in muscle sympathetic nerve activity (MSNA) during stimulation of various brain nuclei in humans. Regrettably, the results presented in this chapter are not convincing enough to support the hypothesis that stimulation of particular subcortical structures corresponds to changes in MSNA. However, the cardiovascular changes that were recorded during stimulation of the different subcortical structures are congruous with previous studies in both animals and humans. Chapter Seven presents a brief summary of the findings in this thesis.

Parkinson's Disease affects more than 1 million people in the United States with 60,000 new cases being diagnosed each year. Currently, there is no cure for Parkinson's Disease, but there are several treatment options available. Currently the most popular surgical option is Deep Brain Stimulation. Microelectrode recording helps identify nuclei as the microelectrode passes through them. While the firing frequencies of the target nuclei are well defined, other nuclei are not. This study will attempt to characterize the Zona Incerta, which is the structure directly above the Subthalamic Nucleus, a target nucleus. Characterization of the firing frequency of the Zona Incerta will help aid Deep Brain Stimulation procedures. Looking at the Interspike Intervals for 25 files showed that the average firing frequency is 11.6Hz. A file recorded in the STN was used for comparison and to validate the methods used. This yielded an average firing frequency of 37.5Hz.

L’efficacité de la stimulation cérébrale profonde subthalamique dans certains cas de maladie de Parkinson est maintenant bien établie. Toutefois, des progrès restent possibles, à la fois en terme de contrôle du geste chirurgical et en terme de définition de la cible chirurgicale. Dans la première partie de ce travail, nous nous sommes intéressés à l’optimisation du contrôle de l’implantation des électrodes de stimulation cérébrale profonde. Nous avons tout d’abord analysé rétrospectivement les résultats obtenus en réalisant une imagerie tridimensionnelle per-opératoire pour le contrôle de positionnement des électrodes. Nous nous sommes ensuite intéressés à la possibilité d’utiliser un repère de visée radiologique per-opératoire. Nous avons revu pour cela une série de patients ayant subi une réimplantation d’électrodes, pour lesquels l’électrode déjà en place était utilisée comme point de repère à la fois pour définir la cible de la réimplantation et pour contrôler radiologiquement l’implantation de la nouvelle électrode. Dans la seconde partie, nous avons travaillé à l’optimisation de la cible subthalamique. Nous avons tout d’abord évalué la pertinence du repérage du faisceau mamillo-thalamique sur des coupes IRM axiales comme marqueur de la coordonnée y du bord antérieur du noyau subthalamique. Ensuite, nous avons tâché de proposer une normalisation tridimensionnelle de l’espace stéréotaxique à partir de données recueillies dans une série de volontaires sains. Enfin, pour une série de patients opérés avec un bon résultat, nous avons cherché à corréler la position des contacts actifs en stimulation chronique avec des points de repères profonds visibles en IRM. Nous avons pu proposer ainsi une cible normalisée dont les coordonnées sont : x = 0,44xbord latéral du V3 + 10,71mm; y = 0,69xfaisceau mamillothalamique + 1,62 mm ou 0,34 distance CACP + 2,52 mm; z = 0,72 hauteur du thalamus – 16 mm. Cette cible sera évaluée dans une future étude prospective. / The clinical efficacy of subthalamic deep brain stimulation is now well established. Nevertheless, progress is possible, regarding especially (1) the accuracy of electrodes implantation and (2) the definition of the surgical target. In the first part of this work, we worked on the optimization of DBS electrodes implantation. First, we analyzed retrospectively the results obtained by using intra-operative 3D imaging for the control of microelectrodes and definite leads placement. Thereafter, we considered the possibility to use a radiological landmark for intraoperative controls. To this end, we studied the cases of patients who underwent reimplantation of DBS electrodes. The initial electrode (still implanted) was used as a landmark: (1) for the deifntion of the reimplantation target and (2) for the radiological control of the new lead positioning. In the second part, we worked on the optimization of the surgical target. First, we assessed the interest of the mamillothalamic tract as a landmark of the anteroposterior coordinate of the anterior border of the STN in MR axial images. Thereafter, we tried to identify MR landmarks for tridimensionnal normalization of the stereotactic space. Finally, we tried to correlate the coordinates of active contacts with MR-defined landmarks in a series of patients that had been operated with good clinical results. Based on our results, we can propose the following coordinates for a new normalized subthalamic target : x = 0.44xlat edge 3rd ventricle + 10.71mm; y = 0.69xmamillo-thalamic tract + 1.62 mm or 0.34 ACPC length + 2.52 mm; z = 0.72xthalamus height – 16 mm. We will assess this target in a future prospective study.

A Doença de Parkinson (DP) é causada pela degeneração progressiva de neurônios no sistema nervoso central, principalmente os neurônios dopaminérgicos nigroestriatais, levando a sintomas motores como a bradicinesia, rigidez e tremor. Os sintomas não motores (SNM), como a dor, estão presentes em muitos doentes e representam um impacto negativo na qualidade de vida. A estimulação encefálica profunda é um tratamento bem estabelecido para o tratamento dos sintomas motores da DP. Entretanto, o seu impacto sobre os sintomas não motores ainda é bastante desconhecido. O objetivo do presente estudo foi avaliar os efeitos da EEP sobre as diferentes características da dor e sensibilidade, e de outros SNM nos indivíduos com DP. Foram avaliados 41 indivíduos com diagnóstico de DP (14 do sexo feminino), idade de 60 ± 10,4 anos, com 15 ± 7,6 anos da duração da doença e estágio intermediário de evolução (Escala de Hoehn & Yahr = 2,80 ± 0,64). Os doentes foram submetidos a implante de sistema de estimulação bilateral do núcleo subtalâmico guiado por eletrofisiologia intraoperatória. Foram avaliados, prospectivamente, antes e um ano após, o procedimento de forma encoberta. O desfecho principal foi a mudança da prevalência da dor após a cirurgia. Os desfechos secundários incluíam mudanças nos sintomas motores (UPDRS parte III), na qualidade de vida (escala SF-36), na avaliação de humor (Escala Hospitalar de Ansiedade e Depressão [EHAD]), nos outros sintomas não motores (Escala dos sintomas não motores [ESNM]) e nas características da dor. Foram avaliadas as dimensões da dor (questionário de McGill), a intensidade e o impacto nas atividades de vida diária da dor (escala visual analógica da dor [EVA], inventário breve da dor [IBD]), a presença de dor neuropática (Douleur Neuropathique-4 Questionnaire [DN-4]) e o perfil dos sintomas neuropáticos (inventário de sintomas de dor neuropática (ISDN), o perfil de catastrofismo da dor (Escala catastrófica da dor [ECD]) e os limiares de sensitivos por meio da análise quantificada dos limiares de sensibilidade. Houve redução de prevalência da dor de 70% para 21% após a cirurgia (p < 0,05). Houve melhora na intensidade (EVA: antes = 80 ± 13,2; depois = 42,2 ± 17,8, p = 0,007) e nos diferentes aspectos da dor, além de outros sintomas não motores (ESNM: antes = 114,80 ± 59,89; depois = 62,68 ± 22,76; p < 0,001), como a cognição, humor, atenção, alucinação e trato gastrointestinal. Houve melhora na detecção de estímulos térmicos e mecânicos após a cirurgia, além de redução da sensibilidade aos limiares de dor (p < 0,05). A melhora na intensidade da dor foi fortemente relacionada com a melhora na qualidade vida (r = 0,708; p < 0,005). Não houve correlação entre a melhora da dor e a resposta à dopamina pré-operatória ou a melhora motora após a cirurgia (r = 0,247; p = 0,197 e r = 0,249; p = 0,193, respectivamente). Concluise que a ECP do núcleo subtalâmico diminui a prevalência e diferentes aspectos da dor após a cirurgia, e essa melhora está diretamente associada à melhora da qualidade de vida. A melhora motora ou dos outros SNM não foi relacionada à melhora da dor, sugerindo que a ECP apresenta diferentes mecanismos de ação sobre os sintomas nos indivíduos com DP / Parkinson disease (PD) is caused by progressive degeneration of neurons throughout the nervous system, especially the dopamine neurons, leading to motor symptoms as bradykinesia, rigidity and tremor. Non-motor symptoms (NMS), such as pain, are present in a large proportion of Parkinson\'s disease patients and have a major negative impact on patients quality of life. Subthalamic deep brain stimulation has gained general use in the management of motor symptoms in these patients. However, its impact on non-motor symptoms remains largely unknown. The aim of this study was to evaluate the effect of subthalamic deep brain stimulation (STN-DBS) on the different characteristics of pain, sensibility and other NMS in patients with PD. Forty-one patients with PD were evaluated (14 female), mean age 60 ± 10,4 years. The mean duration of the disease was 15 ± 7.6 years, and the Hoehn & Yahr off-medication score was 2.80 ± 0.64. The patients underwent stereotactic implantation of bilateral subthalamic nucleus stimulation system guided by intraoperative electrophysiology. They were evaluated before and 01 year after surgery. The primary outcome was change in pain prevalence after surgery. Secondary outcome measures were changes in motor function (PDRS part III), quality of life (SF-36 scale), presence of NMS (Non-motor symptoms scale [NMSS] and Hospital Anxiety and Depression Scale [HADS]), and characteristics of pain. We evaluated pain dimensions (Short Form of McGill Pain Questionnaire [MPQ]), pain intensity and impact of pain in daily activities (Brief Pain Inventory [BPI] and Visual Analogic Scale [VAS]), presence of neuropathic pain (Douleur Neuropathique-4 Questionnaire [DN-4]) and its symptom profile (Neuropathic Pain Symptom Inventory [NPSI]), catastrophizing (Pain Catatrosphizing Scale [PCS]) and the sensory thresholds throught the quantitative sensory threshold test. The prevalence of pain changed from 70% to 21% after surgery (p < 0.001). There were also significant improvements in pain intensity (VAS: before = 80 ± 13.2; after = 42.2 ± 17.8, p = 0.007), in different aspects of pain and NMS (before = 114.80 ± 59.89; after = 62.68 ± 22.76; p < 0.001) as cognition, attention, mood and gastrointestinal function. There was improvement on cold and heat detection thresholds (p < 0.05). There was a strong correlation between the change in pain intensity and the improvement in quality of life (r = 0.708; p < 0.005). No correlation was found between pain improvement and preoperative response to levodopa or motor improvement during stimulation (r = 0.247; p = 0.197 and r = 0.249; p = 0.193, respectively) or with changes in other non-motor symptoms. In conclusion, STN-DBS decreased pain intensity. The pain relief was directly associated with improvement in quality of life. Motor and NMS improvements after STN-DBS did not correlate with pain relief, suggesting differents mechanisms of DBS action in PD patients

Introdução: A disfunção da marcha é um dos maiores comprometimentos funcionais do paciente com a doença de Parkinson (DP). A estimulação cerebral profunda do núcleo subtalâmico tem mostrado melhora da marcha e equilíbrio. Esse efeito pode ser mantido e potencializado por programas de reabilitação motora específicos, como o treino em esteira sem e com suporte de peso corporal. No entanto, faltam estudos desses treinos em pacientes com a DP em uso desta estimulação. Objetivo: Comparar parâmetros cinemáticos lineares e angulares da marcha de pacientes com a DP em uso de estimulação cerebral profunda bilateral do núcleo subtalâmico, antes e após dois treinamentos: esteira sem e com suporte de peso corporal, associados à cinesioterapia convencional. Métodos: 12 pacientes (60,9 ± 10,6 anos; 20 ± 7 anos de doença e 20 ± 4 meses de tempo de cirurgia) completaram ambos os treinos em estudo cruzado fixo. Os pacientes passaram por 8 semanas de treino de marcha em esteira sem suporte de peso corporal e programa de cinesioterapia convencional, seguidas por 6 semanas de período sem intervenção. Posteriormente, realizaram 8 semanas de treino de marcha em esteira com suporte de peso corporal e o mesmo programa de cinesioterapia regular. As intervenções tiveram frequência de duas vezes por semana e duração de 90 minutos por sessão. A análise cinemática da marcha envolveu oito câmeras infravermelhas que detectaram 19 marcadores reflexivos nos membros inferiores dos pacientes. A análise estatística utilizou o teste Wilcoxon e foi adotado valor de p <= 0,05 como estatisticamente significante. Resultados: Ambos os treinos não mostraram diferenças significativas nos parâmetros lineares. Após o treino com suporte, observou-se aumento significativo dos seguintes parâmetros angulares: amplitude de movimento da pelve (inclinação, obliquidade e rotação); amplitude de movimento do quadril (abduçãoadução e rotação); % da fase de balanço que corresponde à flexão máxima do joelho e amplitude de movimento da progressão do pé. Conclusão: O treino em esteira com suporte de peso corporal mostrou capacidade de promover mudanças em parâmetros cinemáticos angulares da marcha. As implicações do treino em suspensão podem ter sido somadas aos efeitos neurofisiológicos da estimulação cerebral profunda e então desencadeado a melhora da mobilidade dos membros inferiores durante a marcha / Introduction: Gait disturbance is one of the hallmark features of Parkinson\'s disease (PD). Subthalamic nucleus deep brain stimulation (DBS) has shown improvements in gait and balance, and this effect can be maintained and enhanced by specific motor rehabilitation programs, such treadmill training without and with body weight support. However, at present there is a paucity of research on these combined interventions in PD with of this stimulation. Objective: To compare training-induced changes in gait linear and angular kinematic parameters among patients with PD who have used bilateral subthalamic nucleus DBS, and a combined intervention of conventional physical therapy with either treadmill training with body weight support or without support. Methods: 12 patients (age: 60.9 ± 10.6 years; disease duration: 20 ± 7 years; and time since DBS surgery: 20 ± 4 months) completed both training protocols in a fixed cross-over design. All patients received 8 weeks of treadmill training without body weight support in conjunction with conventional physical therapy, followed by a 6 weeks wash out period of no training. Thereafter, all patients received 8 weeks of body weight support treadmill training, in conjunction with the same conventional physical therapy. Both interventions had a frequency of two times per week, and duration of 90 minutes per session. Gait kinematic analysis involved eight infrared cameras that detected 19 reflective spherical markers attached to the limb lower of patients. Statistical analysis used the Wilcoxon and was adopted the value of p <= 0,05 as statistically significant. Results: Both the training no showed significant differences in linear parameters. After the body weight support training, observed there was a significant increase in following angular parameters: pelvis\' range of motion (tilt, obliquity, rotation); hip\'s range of motion (abduction-adduction and rotation); % Knee maximal flexion on Swing phase and foot progression\' range of motion. Conclusion: Treadmill training with body weight support showed an ability to promote changes in gait angular kinematic parameters. The implications of this training may have been added to the neurophysiological effects of DBS and then triggered the improved of mobility of lower limbs during gait

Introdução: Após a cirurgia de Estimulação Cerebral Profunda (DBS), pacientes com doença de Parkinson (DP) ainda apresentam alterações posturais e da marcha. Assim, intervenções adicionais são necessárias para reduzir a instabilidade postural e quedas. O treino de marcha em esteira é conhecido por melhorar parâmetros do equilíbrio e marcha de pacientes com DP; no entanto, o que ainda não se sabe é se há diferença entre o treino com e sem suspensão do peso corporal e se esses tipos de treinamento são capazes de potencializar os efeitos da DBS. Objetivo: A proposta deste estudo foi comparar os efeitos do treino em esteira, com e sem supensão do peso corporal, em aspectos do equilíbrio de pacientes com DP após DBS. Métodos: Homens (n=6) e Mulheres (n=5) com DP (60.9± 10.6 anos) em uso de DBS bilateral em Núcleo Subtalâmico foram avaliados quanto o equilíbrio e mobilidade antes e após o tratamento, usando o Time Up and Go test (TUG) em três condições: convencional, cognitiva e motora; assim como, a Escala de Berg e a Posturografia Estática. Na fase 1, todos os sujeitos participaram de um programa de fisioterapia convencional associado à treino em esteira por 8 semanas (16 sessões). Após 6 semanas de período de wash-out, cada participante realizou o mesmo treino durante 8 semanas porém, o treino em esteira foi realizado com suspensão do peso corporal. Resultados: Após a fase 1 de treino em esteira sem suspensão, houve melhoras na performance do TUG cognitivo (pré: 15.7±1,8 s versus pós: 13.7±3.1 s; p=0.01) e um aumento do deslocamento corporal ântero-posterior e médio-lateral com os olhos fechados. Após a fase 2 de treino em esteira com suspensão do peso corporal, houve melhoras do TUG convencional (pré: 12.3±2.0 s versus pós: 10.7±1.7 s; p=0.01) e cognitivo (pré: 14.6±3.5 s versus pós: 12.5±1.6 s; p < 0.05). Não houve mudanças significantes nos escores da Escala de Berg após ambas as fases. Conclusão: O treino de marcha em esteira com ou sem suspensão do peso corporal promove melhora do equilíbrio estático e dinâmico em pacientes com DP após a cirurgia de DBS. Ambos os métodos tem resultados similares; No entanto, o treino de marcha com suspensão do peso corporal parece ser uma opção potencialmente superior, uma vez que pacientes sentem-se mais seguros, e isso pode levar à um tipo de treino mais viável / Background: After deep brain stimulation (DBS) surgery, patients with Parkinson`s disease (PD) typically still present significant gait and postural stability problems, and thus additional interventions are needed to reduce slip and fall accidents and injuries. Treadmill training is known to improve balance and gait parameters in PD; however, what remains to be determined is the comparative effectiveness of treadmill training with support versus without and if they could potentiate DBS effects. Objective: The purpose of this study was to evaluate the comparative effectiveness of treadmill training, with and without body weight support, on balance outcomes among patients with PD after DBS. Methods: Male (n=6) and female (n=5) patients with PD (60.9± 10.6 years old) that were using bilateral subthalamic nucleus DBS were evaluated for balance and mobility prior to and following treatments, using Time Up and Go test (TUG) in three conditions: conventional, cognitive and motor, as well as the Berg Balance Scale and Static Posturography. In phase 1, all subjects participated in 8-weeks (16 sessions) of treadmill training in conjunction with conventional physiotherapy. After a six weeks period of wash-out, each patient then participated in a subsequent 8-weeks of treadmill training with partial body weight support. Results: After the phase 1 unsupported treadmill training, there were improvements on the cognitive TUG performance (pre: 15.7±1,8 sec versus post: 13.7±3.1 sec; p=0. 01) and an increase of anteroposterior and medio-lateral body oscillation with eyes closed. After the phase 2 body weight supported treadmill training, there were improvements in conventional (pre: 12.3±2.0 sec versus post: 10.7±1.7 sec; p=0. 01) and cognitive (pre: 14.6±3.5 sec versus post: 12.5±1.6 sec; p < 0. 05) TUG performances. There were no significant changes in the Berg Balance Scale following either training protocol. Conclusions: Both unsupported and supported treadmill training improved static and dynamic balance in patients with PD after DBS surgery. Both methods had similar results; however, supported treadmill training seemed to be a potentially superior option, as patients tended to feel safer, and thus it may prove to be a more viable means of training

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