Brain-machine interfaces (BMIs) are the only currently viable means of communication for many individuals suffering from locked-in syndrome (LIS) – profound paralysis that results in severely limited or total loss of voluntary motor control. By inferring user intent from task-modulated neurological signals and then translating those intentions into actions, BMIs can enable LIS patients increased autonomy. Significant effort has been devoted to developing BMIs over the last three decades, but only recently have the combined advances in hardware, software, and methodology provided a setting to realize the translation of this research from the lab into practical, real-world applications. Non-invasive methods, such as those based on the electroencephalogram (EEG), offer the only feasible solution for practical use at the moment, but suffer from limited communication rates and susceptibility to environmental noise. Maximization of the efficacy of each decoded intention, therefore, is critical. This thesis addresses the challenge of implementing a BMI intended for practical use with a focus on an autonomous assistive robot application. First an adaptive EEG- based BMI strategy is developed that relies upon code-modulated visual evoked potentials (c-VEPs) to infer user intent. As voluntary gaze control is typically not available to LIS patients, c-VEP decoding methods under both gaze-dependent and gaze- independent scenarios are explored. Adaptive decoding strategies in both offline and online task conditions are evaluated, and a novel approach to assess ongoing online BMI performance is introduced. Next, an adaptive neural network-based system for assistive robot control is presented that employs exploratory learning to achieve the coordinated motor planning needed to navigate toward, reach for, and grasp distant objects. Exploratory learning, or “learning by doing,” is an unsupervised method in which the robot is able to build an internal model for motor planning and coordination based on real-time sensory inputs received during exploration. Finally, a software platform intended for practical BMI application use is developed and evaluated. Using online c-VEP methods, users control a simple 2D cursor control game, a basic augmentative and alternative communication tool, and an assistive robot, both manually and via high-level goal-oriented commands.

Objective An electroencephalographic brain–computer interface (BCI) can provide a non-muscular means of communication for people with amyotrophic lateral sclerosis (ALS) or other neuromuscular disorders. We present a novel P300-based BCI stimulus presentation – the checkerboard paradigm (CBP). CBP performance is compared to that of the standard row/column paradigm (RCP) introduced by Farwell and Donchin (1988). Methods Using an 8 × 9 matrix of alphanumeric characters and keyboard commands, 18 participants used the CBP and RCP in counter-balanced fashion. With approximately 9–12 min of calibration data, we used a stepwise linear discriminant analysis for online classification of subsequent data. Results Mean online accuracy was significantly higher for the CBP, 92%, than for the RCP, 77%. Correcting for extra selections due to errors, mean bit rate was also significantly higher for the CBP, 23 bits/min, than for the RCP, 17 bits/min. Moreover, the two paradigms produced significantly different waveforms. Initial tests with three advanced ALS participants produced similar results. Furthermore, these individuals preferred the CBP to the RCP. Conclusions These results suggest that the CBP is markedly superior to the RCP in performance and user acceptability. Significance The CBP has the potential to provide a substantially more effective BCI than the RCP. This is especially important for people with severe neuromuscular disabilities.

Objective: An electroencephalographic brain-computer interface (BCI) can provide a non-muscular means of communication for people with amyotrophic lateral sclerosis (ALS) or other neuromuscular disorders. We present a novel P300-based BCI stimulus presentation - the checkerboard paradigm (CBP). CBP performance is compared to that of the standard row/column paradigm (RCP) introduced by Farwell and Donchin (1988). Methods: Using an 8 × 9 matrix of alphanumeric characters and keyboard commands, 18 participants used the CBP and RCP in counter-balanced fashion. With approximately 9-12 min of calibration data, we used a stepwise linear discriminant analysis for online classification of subsequent data. Results: Mean online accuracy was significantly higher for the CBP, 92%, than for the RCP, 77%. Correcting for extra selections due to errors, mean bit rate was also significantly higher for the CBP, 23 bits/min, than for the RCP, 17 bits/min. Moreover, the two paradigms produced significantly different waveforms. Initial tests with three advanced ALS participants produced similar results. Furthermore, these individuals preferred the CBP to the RCP. Conclusions: These results suggest that the CBP is markedly superior to the RCP in performance and user acceptability. Significance: The CBP has the potential to provide a substantially more effective BCI than the RCP. This is especially important for people with severe neuromuscular disabilities.

Objective: Brain-computer interface (BCI) technology can provide severely disabled people with non-muscular communication. For those most severely disabled, limitations in eye mobility or visual acuity may necessitate auditory BCI systems. The present study investigates the efficacy of the use of six environmental sounds to operate a 6 × 6 P300 Speller. Methods: A two-group design was used to ascertain whether participants benefited from visual cues early in training. Group A (N = 5) received only auditory stimuli during all 11 sessions, whereas Group AV (N = 5) received simultaneous auditory and visual stimuli in initial sessions after which the visual stimuli were systematically removed. Stepwise linear discriminant analysis determined the matrix item that elicited the largest P300 response and thereby identified the desired choice. Results: Online results and offline analyses showed that the two groups achieved equivalent accuracy. In the last session, eight of 10 participants achieved 50% or more, and four of these achieved 75% or more, online accuracy (2.8% accuracy expected by chance). Mean bit rates averaged about 2 bits/min, and maximum bit rates reached 5.6 bits/min. Conclusions: This study indicates that an auditory P300 BCI is feasible, that reasonable classification accuracy and rate of communication are achievable, and that the paradigm should be further evaluated with a group of severely disabled participants who have limited visual mobility. Significance: With further development, this auditory P300 BCI could be of substantial value to severely disabled people who cannot use a visual BCI.

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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.

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