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A brain-machine interface (BMI) is a system that allows the communication between the central nervous system (CNS) and an external device (Wolpaw et al. 2002). Applications of BMIs include the control of external prostheses, cursors and spellers, to name a few. The BMIs developed by various research groups differ in their characteristics (e.g. continuous or discrete, synchronous or asynchronous, degrees of freedom, others) and, in spite of several initiatives towards standardization and guidelines, the cross comparison across studies remains a challenge (Brunner et al. 2015; Thompson et al. 2014). Here, we used a 64-channel EEG equipment to acquire data from 19 healthy participants during three different tasks (SSVEP, P300 and hybrid) that allowed four choices to the user and required no previous neurofeedback training. We systematically compared the offline performance of the three tasks on the following parameters: a) accuracy, b) information transfer rate, c) illiteracy/inefficiency, and d) individual preferences. Additionally, we selected the best performing channels per task and evaluated the accuracy as a function of the number of electrodes. Our results demonstrate that the SSVEP task outperforms the other tasks in accuracy, ITR and illiteracy/inefficiency, reaching an average ITR** of 52,8 bits/min and a maximum ITR** of 104,2 bits/min. Additionally, all participants achieved an accuracy level above 70% (illiteracy/inefficiency threshold) in both SSVEP and P300 tasks. Furthermore, the average accuracy of all tasks did not deteriorate if a reduced set with only the 8 best performing electrodes were used. These results are relevant for the development of online BMIs, including aspects related to usability, user satisfaction and portability. / A interface cérebro-máquina (ICM) é um sistema que permite a comunicação entre o sistema nervoso central e um dispositivo externo (Wolpaw et al., 2002). Aplicações de ICMs incluem o controle de próteses externa, cursores e teclados virtuais, para citar alguns. As ICMs desenvolvidas por vários grupos de pesquisa diferem em suas características (por exemplo, contínua ou discreta, síncrona ou assíncrona, graus de liberdade, outras) e, apesar de várias iniciativas voltadas para diretrizes de padronização, a comparação entre os estudos continua desafiadora (Brunner et al. 2015, Thompson et al., 2014). Aqui, utilizamos um equipamento EEG de 64 canais para adquirir dados de 19 participantes saudáveis ao longo da execução de três diferentes tarefas (SSVEP, P300 e híbrida) que permitiram quatro escolhas ao usuário e não exigiram nenhum treinamento prévio. Comparamos sistematicamente o desempenho \"off-line\" das três tarefas nos seguintes parâmetros: a) acurácia, b) taxa de transferência de informação, c) analfabetismo / ineficiência e d) preferências individuais. Além disso, selecionamos os melhores canais por tarefa e avaliamos a acurácia em função do número de eletrodos. Nossos resultados demonstraram que a tarefa SSVEP superou as demais em acurácia, ITR e analfabetismo/ineficiência, atingindo um ITR** médio de 52,8 bits/min e um ITR** máximo de 104,2 bits/min. Adicionalmente, todos os participantes alcançaram um nível de acurácia acima de 70% (limiar de analfabetismo/ineficiência) nas tarefas SSVEP e P300. Além disso, a acurácia média de todas as tarefas não se deteriorou ao se utilizar um conjunto reduzido composto apenas pelos melhores 8 eletrodos. Estes resultados são relevantes para o desenvolvimento de ICMs \"online\", incluindo aspectos relacionados à usabilidade, satisfação do usuário e portabilidade.

A brain-machine interface (BMI) is a system that allows the communication between the central nervous system (CNS) and an external device (Wolpaw et al. 2002). Applications of BMIs include the control of external prostheses, cursors and spellers, to name a few. The BMIs developed by various research groups differ in their characteristics (e.g. continuous or discrete, synchronous or asynchronous, degrees of freedom, others) and, in spite of several initiatives towards standardization and guidelines, the cross comparison across studies remains a challenge (Brunner et al. 2015; Thompson et al. 2014). Here, we used a 64-channel EEG equipment to acquire data from 19 healthy participants during three different tasks (SSVEP, P300 and hybrid) that allowed four choices to the user and required no previous neurofeedback training. We systematically compared the offline performance of the three tasks on the following parameters: a) accuracy, b) information transfer rate, c) illiteracy/inefficiency, and d) individual preferences. Additionally, we selected the best performing channels per task and evaluated the accuracy as a function of the number of electrodes. Our results demonstrate that the SSVEP task outperforms the other tasks in accuracy, ITR and illiteracy/inefficiency, reaching an average ITR** of 52,8 bits/min and a maximum ITR** of 104,2 bits/min. Additionally, all participants achieved an accuracy level above 70% (illiteracy/inefficiency threshold) in both SSVEP and P300 tasks. Furthermore, the average accuracy of all tasks did not deteriorate if a reduced set with only the 8 best performing electrodes were used. These results are relevant for the development of online BMIs, including aspects related to usability, user satisfaction and portability. / A interface cérebro-máquina (ICM) é um sistema que permite a comunicação entre o sistema nervoso central e um dispositivo externo (Wolpaw et al., 2002). Aplicações de ICMs incluem o controle de próteses externa, cursores e teclados virtuais, para citar alguns. As ICMs desenvolvidas por vários grupos de pesquisa diferem em suas características (por exemplo, contínua ou discreta, síncrona ou assíncrona, graus de liberdade, outras) e, apesar de várias iniciativas voltadas para diretrizes de padronização, a comparação entre os estudos continua desafiadora (Brunner et al. 2015, Thompson et al., 2014). Aqui, utilizamos um equipamento EEG de 64 canais para adquirir dados de 19 participantes saudáveis ao longo da execução de três diferentes tarefas (SSVEP, P300 e híbrida) que permitiram quatro escolhas ao usuário e não exigiram nenhum treinamento prévio. Comparamos sistematicamente o desempenho \"off-line\" das três tarefas nos seguintes parâmetros: a) acurácia, b) taxa de transferência de informação, c) analfabetismo / ineficiência e d) preferências individuais. Além disso, selecionamos os melhores canais por tarefa e avaliamos a acurácia em função do número de eletrodos. Nossos resultados demonstraram que a tarefa SSVEP superou as demais em acurácia, ITR e analfabetismo/ineficiência, atingindo um ITR** médio de 52,8 bits/min e um ITR** máximo de 104,2 bits/min. Adicionalmente, todos os participantes alcançaram um nível de acurácia acima de 70% (limiar de analfabetismo/ineficiência) nas tarefas SSVEP e P300. Além disso, a acurácia média de todas as tarefas não se deteriorou ao se utilizar um conjunto reduzido composto apenas pelos melhores 8 eletrodos. Estes resultados são relevantes para o desenvolvimento de ICMs \"online\", incluindo aspectos relacionados à usabilidade, satisfação do usuário e portabilidade.

The studies in this thesis explored how pain and its relief are represented in the human brain. Pain and relief are important survival signals that motivate escape from danger and search for safety, however, they are often evaluated by subjective descriptions only. Studying how humans learn and adapt to pain and relief allows objective investigation of the information processing and neural circuitry underlying these internal experiences. My research set out to use computational learning models to provide mechanistic explanations for the behavioural and functional neuroimaging data collected in pain/relief learning experiments with independent groups of healthy human participants. With a Pavlovian acute pain conditioning task in Experiment 1, I found that 'associability' (a form of uncertainty signal) had a crucial role in controlling the learning rates of different conditioned responses, and can be used to anatomically dissociate underlying neural systems. Experiment 2 focused on relief learning of terminating a tonic pain stimulus, in which the priority for relief-seeking is in conflict with the general suppression of cognition and attention. I showed that associability during active learning not only controls the relief learning rate, but also correlates with endogenously modulated (reduced) ongoing pain. This finding was confirmed in Experiment 3 using an independent active relief learning paradigm in a complex dynamic environment. Critically, both experiments showed that associability was correlated with responses in the pregenual anterior cingulate cortex (pgACC), a brain region previously implicated in aspects of endogenous pain control related to attention and controllability. This provided a potential computational account of an information-sensitive endogenous analgesic mechanism. In Experiment 4, I explored the implications of endogenous controllability for technology-based pain therapeutics. I designed an adaptive closed-loop system that learned to control pain stimulation using decoded real-time pain representations from the brain. Subjects were shown to actively enhance the discriminability of pain only in the pgACC, and uncertainty during learning again correlated with endogenously modulated pain and were associated with pgACC responses. Together, these studies (i) show the importance of uncertainty in controlling learning during both acute and tonic pain, (ii) describe how uncertainty also flexibly modulates pain to maximise the impact of learning, (iii) illustrate a central role for the pgACC in this process, and (iv) reveal the implications for future technology-based therapeutic systems.

In this work, we present a set of methods aimed at improving the discriminative power of time-varying features of signals that contain noise. These methods use properties of noise signals as well as information theoretic techniques to factor types of noise and support signal inference for electroencephalographic (EEG) based brain-machine interfaces (BMI). EEG data were collected over two studies aimed at addressing Psychophysiological issues involving symmetry and mental rotation processing. The Psychophysiological data gathered in the mental rotation study also tested the feasibility of using dissociations of mental rotation tasks correlated with rotation angle in a BMI. We show the feasibility of mental rotation for BMI by showing comparable bitrates and recognition accuracy to state-of-the-art BMIs. The conclusion is that by using the feature selection methods introduced in this work to dissociate mental rotation tasks, we produce bitrates and recognition rates comparable to current BMIs.

<p>The spinal cord is an information highway continuously transmitting afferent and efferent signals to and from the brain. Although spinal cord stimulation has been used for the treatment of chronic pain for decades, its potential has not been fully explored. Spinal cord stimulation has never been used with the aim to transmit relevant information to the brain. Although, various locations along the sensory pathway have been explored for generating electrical stimulation induced sensory percepts, right from peripheral nerves, to thalamus to primary somatosensory cortex, the role of spinal cord has been largely neglected. In this dissertation, I have attempted to investigate if, electrical stimulation of dorsal columns of spinal cord called as Dorsal Column Stimulation (DCS) can be used as an effective technique to communicate therapeutic and somatosensory information to the brain. </p><p>To study the long term effects of DCS, I employed the 6-hydroxydopamine (6-OHDA) rodent model of Parkinson’s Disease (PD). Twice a week DCS for 30 minutes resulted in a dramatic recovery of weight and behavioral symptoms in rats treated with striatal infusions of 6-OHDA. The improvement in motor symptoms was accompanied by higher dopaminergic innervation in the striatum and increased cell count of dopaminergic neurons in the substantia nigra pars compacta (SNc). These results suggest that DCS has a chronic therapeutic and neuroprotective effect, increasing its potential as a new clinical option for treating PD patients. Thus, I was able to demonstrate the long-term efficacy of DCS, as a technique for therapeutic intervention.</p><p>Subsequently, I investigated if DCS can be used as a technique to transmit artificial somatosensory information to the cortex and trained rats to discriminate multiple artificial tactile sensations. Rats were able to successfully differentiate 4 different tactile percepts generated by varying temporal patterns of DCS. As the rats learnt the task, significant changes in the encoding of this artificial information were observed in multiple brain areas. Finally, I created a Brainet that interconnected two rats: an encoder and a decoder, whereby, cortical signals from the encoder rat were processed by a neural decoder while it performed a tactile discrimination task and transmitted to the spinal cord of the decoder using DCS. My study demonstrated for the first time, a cortico-spinal communication between different organisms. </p><p>My obtained results suggest that DCS, a semi-invasive technique, can be used in the future to send prosthetic somatosensory information to the brain or to enable a healthy brain to directly modulate neural activity in the nervous system of a patient, facilitating plasticity mechanism needed for efficient recovery.</p> / Dissertation

<p>Brain-machine interfaces (BMI) are systems which connect brains directly to machines or computers for communication. BMI-controlled prosthetic devices use algorithms to decode neuronal recordings into movement commands. These algorithms operate using models of how recorded neuronal signals relate to desired movements, called models of tuning. Models of tuning have typically been linear in prior work, due to the simplicity and speed of the algorithms used with them. Neuronal tuning has been shown to slowly change over time, but most prior work do not adapt tuning models to these changes. Furthermore, extracellular electrical recordings of neurons' action potentials slowly change over time, impairing the preprocessing step of spike-sorting, during which the neurons responsible for recorded action potentials are identified.</p> <p></p> <p>This dissertation presents a non-linear adaptive Bayesian filter and an adaptive spike-sorting method for BMI decoding. The adaptive filter consists of the n-th order unscented Kalman filter and Bayesian regression self-training updates. The unscented Kalman filter estimates desired prosthetic movements using a non-linear model of tuning as its observation model. The model is quadratic with terms for position, velocity, distance from center of workspace, and velocity magnitude. The tuning model relates neuronal activity to movements at multiple time offsets simultaneously, and the movement model of the filter is an order n autoregressive model.</p> <p>To adapt the tuning model parameters to changes in the brain, Bayesian regression self-training updates are performed periodically. Tuning model parameters are stored as probability distributions instead of point estimates. Bayesian regression uses the previous model parameters as priors and calculates the posteriors of the regression between filter outputs, which are assumed to be the desired movements, and neuronal recordings. Before each update, filter outputs are smoothed using a Kalman smoother, and tuning model parameters are passed through a transition model describing how parameters change over time. Two variants of Bayesian regression are presented: one uses a joint distribution for the model parameters which allows analytical inference, and the other uses a more flexible factorized distribution that requires approximate inference using variational Bayes.</p> <p>To adapt spike-sorting parameters to changes in spike waveforms, variational Bayesian Gaussian mixture clustering updates are used to update the waveform clustering used to calculate these parameters. This Bayesian extension of expectation-maximization clustering uses the previous clustering parameters as priors and computes the new parameters as posteriors. The use of priors allows tracking of clustering parameters over time and facilitates fast convergence.</p> <p>To evaluate the proposed methods, experiments were performed with 3 Rhesus monkeys implanted with micro-wire electrode arrays in arm-related areas of the cortex. Off-line reconstructions and on-line, closed-loop experiments with brain-control show that the n-th order unscented Kalman filter is more accurate than previous linear methods. Closed-loop experiments over 29 days show that Bayesian regression self-training helps maintain control accuracy. Experiments on synthetic data show that Bayesian regression self-training can be applied to other tracking problems with changing observation models. Bayesian clustering updates on synthetic and neuronal data demonstrate tracking of cluster and waveform changes. These results indicate the proposed methods improve the accuracy and robustness of BMIs for prosthetic devices, bringing BMI-controlled prosthetics closer to clinical use.</p> / Dissertation

This thesis describes a brain-computer interface (BCI) system that was developed to allow direct cortical control of 7 active degrees of freedom in a robotic arm. Two monkeys with chronic microelectrode implants in their motor cortices were able to use the arm to complete an oriented grasping task under brain control. This BCI system was created as a clinical prototype to exhibit (1) simultaneous decoding of cortical signals for control of the 3-D translation, 3-D rotation, and 1-D finger aperture of a robotic arm and hand, (2) methods for constructing cortical signal decoding models based on only observation of a moving robot, (3) a generalized method for training subjects to use complex BCI prosthetic robots using a novel form of operator-machine shared control, and (4) integrated kinematic and force control of a brain-controlled prosthetic robot through a novel impedance-based robot controller. This dissertation describes each of these features individually, how their integration enriched BCI control, and results from the monkeys operating the resulting system.

[pt] Uma interface cérebro-máquina (ICM) é um sistema que permite a um indivíduo, entre outras coisas, controlar um dispositivo robótico por meio de sinais oriundos da atividade cerebral. Entre os diversos métodos para registrar os sinais cerebrais, destaca-se a eletroencefalografia (EEG), principalmente por ter uma rápida resposta temporal e não oferecer riscos ao usuário, além de o equipamento ter um baixo custo relativo e ser portátil. Muitas situações podem fazer com que uma pessoa perca o controle motor sobre o corpo, mesmo preservando todas as funções do cérebro, como doenças degenerativas, lesões medulares, entre outras. Para essas pessoas, uma ICM pode representar a única possibilidade de interação consciente com o mundo externo. Todavia, muitas são as limitações que impossibilitam o uso das ICMs da forma desejada, entre as quais estão as dificuldades de se desenvolver algoritmos capazes de fornecer uma alta confiabilidade em relação ao reconhecimento de padrões dos sinais registrados com EEG. A escolha pelas melhores posições dos eletrodos e as melhores características a serem extraídas do sinal é bastante complexa, pois é altamente condicionada à variabilidade interpessoal dos sinais. Neste trabalho um método é proposto para escolher os melhores eletrodos e as melhores características para pessoas distintas e é testado com um banco de dados contendo registros de sete pessoas. Posteriormente dados são extraídos com um equipamento próprio e uma versão adaptada do método é aplicada visando uma atividade em tempo real. Os resultados mostraram que o método é eficaz para a maior parte das pessoas e a atividade em tempo real forneceu resultados promissores. Foi possível analisar diversos aspectos do algoritmo e da variabilidade inter e intrapessoal dos sinais e foi visto que é possível, mesmo com um equipamento limitado, obter bons resultados mediante análises recorrentes para uma mesma pessoa. / [en] A brain-machine interface (BMI) system allows a person to control robotic devices with brain signals. Among many existing methods for signal acquisition, electroencephalography is the most often used for BCI purposes. Its high temporal resolution, safety to use, portability and low cost are the main reasons for being the most used method. Many situations can affect a person s capability of controlling their body, although brain functions remain healthy. For those people in the extreme case, where there is no motor control, a BCI can be the only way to interact with the external world. Nevertheless, it is still necessary to overcome many obstacles for making the use of BCI systems to become practical, and the most important one is the difficulty to design reliable algorithms for pattern recognition using EEG signals. Inter-subject variability related to the EEG channels and features of the signal are the biggest challenges in the way of making BCI systems a useful technology for restoring function to disabled people. In this paper a method for selecting subject-specific channels and features is proposed and validated with data from seven subjects. Later in the work data is acquired with different EEG equipment and an adapted version of the proposed method is applied aiming online activities. Results showed that the method was efficient for most people and online activities had promising results. It was possible to analyze important aspects concerning the algorithm and inter and intrasubject variability of EEG signals. Also, results showed that it is possible to achieve good results when multiple analyses are performed with the same subject, even with EEG equipment with well known limitations concerning signal quality.