This thesis has evaluated the use of Independent Component Analysis (ICA) on Surface Electromyography (sEMG), focusing on the biosignal applications. This research has identified and addressed the following four issues related to the use of ICA for biosignals: • The iterative nature of ICA • The order and magnitude ambiguity problems of ICA • Estimation of number of sources based on dependency and independency nature of the signals • Source separation for non-quadratic ICA (undercomplete and overcomplete) This research first establishes the applicability of ICA for sEMG and also identifies the shortcomings related to order and magnitude ambiguity. It has then developed, a mitigation strategy for these issues by using a single unmixing matrix and neural network weight matrix corresponding to the specific user. The research reports experimental verification of the technique and also the investigation of the impact of inter-subject and inter-experimental variations. The results demonstrate that while using sEMG without separation gives only 60% accuracy, and sEMG separated using traditional ICA gives an accuracy of 65%, this approach gives an accuracy of 99% for the same experimental data. Besides the marked improvement in accuracy, the other advantages of such a system are that it is suitable for real time operations and is easy to train by a lay user. The second part of this thesis reports research conducted to evaluate the use of ICA for the separation of bioelectric signals when the number of active sources may not be known. The work proposes the use of value of the determinant of the Global matrix generated using sparse sub band ICA for identifying the number of active sources. The results indicate that the technique is successful in identifying the number of active muscles for complex hand gestures. The results support the applications such as human computer interface. This thesis has also developed a method of determining the number of independent sources in a given mixture and has also demonstrated that using this information, it is possible to separate the signals in an undercomplete situation and reduce the redundancy in the data using standard ICA methods. The experimental verification has demonstrated that the quality of separation using this method is better than other techniques such as Principal Component Analysis (PCA) and selective PCA. This has number of applications such as audio separation and sensor networks.

Dissertation (Ph.D.)--University of South Florida, 2008. / Includes vita. Also available online. Includes bibliographical references (leaves 121-140).

Στην μελέτη μας - που σκοπό είχε την αναζήτηση των ηλεκτροφυσιολογιών παραμέτρων εκείνων οι οποίες πρωϊμώτερα καθίστανται παθολογικές σε αρχόμενη συμπιεστική βλάβη του μέσου νεύρου στον καρπό - εξετάσαμε συνολικά 72 ασθενείς (42 χέρια δεξιά, 30 αριστερά) από τους οποίους οι 66 ήταν γυναίκες και οι 6 άνδρες. Ο μέσος όρος ηλικίας των ασθενών ήταν 49.6±9.8 έτη. Όρος επιλογής των προς μελέτη ασθενών ήταν να παρουσιάζουν συμπτώματα και σημεία τέτοια ώστε κλινικά να τίθεται βάσιμα η υπόνοια συνδρομής καρπιαίου σωλήνα, ταυτόχρονα όμως, στον ηλεκτρονευρογραφικό έλεγχο η τιμή του τελικού κινητικού χρόνου να μην υπερβαίνει τα 4.2 msec, ώστε να εξασφαλίζεται το αρχόμενο - μη προχωρημένο της συμπιεστικής συνδρομής. Στην μελέτη χρησιμοποιήθηκαν και 43 μάρτυρες (19 χέρια δεξιά, 24 χέρια αριστερά). Οι μάρτυρες επελέγησαν με κριτήρια την παντελή απουσία συμπτωμάτων και σημείων από το περιφερικό νευρικό σύστημα και με τον περιορισμό της ουδέποτε λήψης νευροτοξικών ουσιών. Από αυτούς οι 31 ήταν γυναίκες και οι 12 άνδρες, είχαν δε μέσο όρο ηλικίας 41.3±16.4 έτη. Τόσο στους ασθενείς όσο και στους μάρτυρες μελετήθηκαν οι αισθητικές αγωγιμότητες με την ορθοδρομική μέθοδο. Σε κάθε χέρι η μελέτη έγινε με ερεθισμό ένα προς ένα όλων των δακτύλων (1ου, 2ου, 3ου και 4ου) και καταγραφή με επιφανειακό ηλεκτρόδιο στον καρπό από το μέσο νεύρο επιπλέον ερεθίστηκε και ο 5ος δάκτυλος και κατεγράφη το αισθητικό δυναμικό στον καρπό από το ωλένιο νεύρο. Τα αποτελέσματα αυτών των καταγραφών αφορούσαν όλες τις παραμέτρους του αισθητικού δυναμικού (λανθάνων χρόνος, εύρος, διάρκεια) καθώς και αλλοιώσεις της μορφολογίας του, από όλους τους δακτύλους. Στη συνέχεια προχωρήσαμε σε πολλαπλές συσχετίσεις κάθε μιας παραμέτρου σε διαφορετικούς δακτύλους, διαφορετικών παραμέτρων στον ίδιο δάκτυλο, αλλά και σε διαφορετικούς δακτύλους καθώς και στην απαρίθμηση των ανώμαλων κυματομορφών όπου αυτές εμφανίζονταν. Η στατιστική επεξεργασία όλων αυτών των δεδομένων κατέληξε στην συγκρότηση μιας κλίμακος ευαισθησίας ως προς την εγκαιρότερη αλλοίωση ηλεκτροφυσιολογιών παραμέτρων σε αρχόμενη συνδρομή καρπιαίου σωλήνα. Συμπερασματικά από τη μελέτη μας προκύπτουν τα εξής: 1) Η ανάδειξη δικόρυφου δυναμικού ενεργείας σε ερεθισμό είτε του 4ου είτε του 1ου δακτύλου είναι συχνό και ισχυρό εύρημα ως προς την τεκμηρίωση αρχόμενης συνδρομής καρπιαίου σωλήνα. 2) Σε αρχόμενη συνδρομή καρπιαίου σωλήνα πρώιμα παρατείνεται ο λανθάνων χρόνος από 4ο και από 1ο δάκτυλο, αλλοιώνονται όλες οι παράμετροι από τον 4ο δάκτυλο και παρατείνεται ο λανθάνων χρόνος από 3ο δάκτυλο. Δεν υπήρξε διαφοροποίηση των παραπάνω αποτελεσμάτων που να συσχετίζονται με το φύλο ή την ηλικία. / The purpose of the present work was to investigate cases with early median nerve entrapment neuropathy (carpal tunnel syndrome) and to identify the most sensitive neurophysiological parameter by which an early diagnosis of the syndrome can be established. We examined 72 patients (42 right hands and 30 left hands) 66 women and 6 men. The mean age was 49.6±9.8 years. The inclusion criteria were symptoms and signs compatible with the diagnosis of carpal tunnel syndrome and the distal motor latency to be less than 4.2msec. We also examined 43 control subjects (19 right hands and 24 left hands) 31 women and 12 men with a mean age 41.3±16.4 years The control subjects were free of peripheral neurological problems. In all patients and control subjects we studied the sensory conduction parameters using the orthodrom method. In all hands we stimulated all five fingers and we recorded the sensory potentials from the wrist for both nerves (the median nerve for the 4 first fingers and the ulnar nerve for the 5th finger). In all patients and controls median distal motor latency, amplitude and duration of compound sensory nerve action potentials and sensory nerve conduction velocity of all five fingers were measured. The statistical analysis of the results showed the following conclusions. 1. Double peak potentials after stimulation of the 4th finger was the most sensitive test for detecting early carpal tunnel syndrome. Double peak potentials after stimulation of the 1st finger was a less frequent finding. 2. In early carpal tunnel syndrome there is a prolongation of the latency of the 4th and 1st finger Also there are changes in all parameters of the 4th finger potential and there is a prolongation of the latency of 3rd finger. Finally there were no differences between male and female measurements.

The thesis presents a new paradigm for studying the importance of interactions between an organism and its environment using a combination of biology and technology: embodying cultured cortical neurons via robotics. From this platform, explanations of the emergent neural network properties leading to cognition are sought through detailed electrical observation of neural activity. By growing the networks of neurons and glia over multi-electrode arrays (MEA), which can be used to both stimulate and record the activity of multiple neurons in parallel over months, a long-term real-time 2-way communication with the neural network becomes possible. A better understanding of the processes leading to biological cognition can, in turn, facilitate progress in understanding neural pathologies, designing neural prosthetics, and creating fundamentally different types of artificial cognition. Here, methods were first developed to reliably induce and detect neural plasticity using MEAs. This knowledge was then applied to construct sensory-motor mappings and training algorithms that produced adaptive goal-directed behavior. To paraphrase the results, most any stimulation could induce neural plasticity, while the inclusion of temporal and/or spatial information about neural activity was needed to identify plasticity. Interestingly, the plasticity of action potential propagation in axons was observed. This is a notion counter to the dominant theories of neural plasticity that focus on synaptic efficacies and is suggestive of a vast and novel computational mechanism for learning and memory in the brain. Adaptive goal-directed behavior was achieved by using patterned training stimuli, contingent on behavioral performance, to sculpt the network into behaviorally appropriate functional states: network plasticity was not only induced, but could be customized. Clinically, understanding the relationships between electrical stimulation, neural activity, and the functional expression of neural plasticity could assist neuro-rehabilitation and the design of neuroprosthetics. In a broader context, the networks were also embodied with a robotic drawing machine exhibited in galleries throughout the world. This provided a forum to educate the public and critically discuss neuroscience, robotics, neural interfaces, cybernetics, bio-art, and the ethics of biotechnology.

Este estudo teve como objetivo investigar a influência de diferentes estágios de severidade da neuropatia diabética na velocidade de condução das fibras musculares estimada em quatro músculos do membro inferior durante contrações isométricas, utilizando-se eletromiografia de superfície. Oitenta e cinco adultos foram estudados: 16 indivíduos não diabéticos e 69 diabéticos classificados em quatro estágios de neuropatia definidos por um sistema fuzzy: ausente (n=26), leve (n=21), moderada (n=11) e grave (n=11). As velocidades de condução médias das fibras musculares do tibial anterior, gastrocnêmico medial, vasto lateral e bíceps femoral foram avaliadas utilizando uma matriz linear de eletrodos de superfície e foram comparadas entre os grupos estudados por meio de ANOVAs (p < 0,05). As velocidades de condução diminuíram significativamente no grupo com neuropatia moderada para o vasto lateral em relação aos outros grupos (18 a 21% de decréscimo), e foram menores em todos os grupos com diabetes para o tibial anterior em relação ao grupo controle (15 a 20% de decréscimo). Não só a localização anatômica distal do músculo afetou a velocidade de condução, mas também a proporção do tipo de fibras musculares, uma vez que o tibial anterior, com maior proporção de fibras do tipo I, estava com sua velocidade de condução alterada já no grupo ausente, enquanto o vasto lateral, com maior proporção de fibras do tipo II, estava com sua velocidade de condução alterada em estágios mais tardios da doença. De forma geral, os músculos do membro inferior têm diferentes suscetibilidades aos efeitos do diabetes mellitus e da neuropatia e mostram uma redução da velocidade de condução conforme a neuropatia progride / This study aimed at investigating the influence of different stages of diabetic neuropathy in the muscle fiber conduction velocities estimated in four lower limb mucles during isometric maximal voluntary contraction using surface electromyography. Eighty-five adults were studied: 16 non-diabetic individuals and 69 diabetic patients classified into four neuropathy stages, defined by a fuzzy system: absent (n=26), mild (n=21), moderate (n=11) and severe (n=11). Average muscle fiber conduction velocities of gastrocnemius medialis, tibialis anterior, vastus lateralis and biceps femoris were assessed using linear array electrodes, and the studied groups were compared by ANOVAs (p < 0.05). Conduction velocities were significantly decreased in the moderate neuropathy group for the vastus lateralis compared to other groups (from 18 to 21% decrease), and were decreased in all diabetic groups for the tibialis anterior (from 15 to 20% from control group). Not only the distal anatomical localization of the muscle affects the conduction velocity, but also the proportion of muscle fiber type, where the tibialis anterior, with greater type I fiber proportion, is affected already at the absent group while the vastus lateralis with greater type II fiber proportion is affected in later stages of the disease. Generally, the muscles of the lower limb have different responsiveness to the effects of diabetes mellitus and neuropathy and show a reduction in the conduction velocity as the neuropathy progresses

abstract: It is increasingly common to see machine learning techniques applied in conjunction with computational modeling for data-driven research in neuroscience. Such applications include using machine learning for model development, particularly for optimization of parameters based on electrophysiological constraints. Alternatively, machine learning can be used to validate and enhance techniques for experimental data analysis or to analyze model simulation data in large-scale modeling studies, which is the approach I apply here. I use simulations of biophysically-realistic cortical neuron models to supplement a common feature-based technique for analysis of electrophysiological signals. I leverage these simulated electrophysiological signals to perform feature selection that provides an improved method for neuron-type classification. Additionally, I validate an unsupervised approach that extends this improved feature selection to discover signatures associated with neuron morphologies - performing in vivo histology in effect. The result is a simulation-based discovery of the underlying synaptic conditions responsible for patterns of extracellular signatures that can be applied to understand both simulation and experimental data. I also use unsupervised learning techniques to identify common channel mechanisms underlying electrophysiological behaviors of cortical neuron models. This work relies on an open-source database containing a large number of computational models for cortical neurons. I perform a quantitative data-driven analysis of these previously published ion channel and neuron models that uses information shared across models as opposed to information limited to individual models. The result is simulation-based discovery of model sub-types at two spatial scales which map functional relationships between activation/inactivation properties of channel family model sub-types to electrophysiological properties of cortical neuron model sub-types. Further, the combination of unsupervised learning techniques and parameter visualizations serve to integrate characterizations of model electrophysiological behavior across scales. / Dissertation/Thesis / Doctoral Dissertation Applied Mathematics 2020

Horizontal cells (HCs) are retinal interneurons which provide feedback to photoreceptors to produce visual contrast. They are depolarized by glutamate released from photoreceptors, leading to a constant influx of Ca2+ which would be fatal to most neurons. In addition, HCs present spontaneous Ca2+-based action potentials, which are poorly understood and whose function is unknown. Given these unique Ca2+ dynamics, the present thesis sought to define action potentials (APs) and mechanisms of Ca2+ homeostasis in HCs. APs were observed in isolated goldfish HCs with electrophysiology, Ca2+ imaging, and voltage-sensitive dye imaging. Pharmacological inhibition of ion channels suggests APs required extracellular Ca2+ entry via L-type Ca2+ channels, followed by Ca2+-induced Ca2+ release from ryanodine receptors. Next, we developed a novel system to classify all four HC subtypes in vitro, and validated it with immunocytochemistry for a subtype-specific biomarker. All subtypes presented APs, although frequency and duration varied by subtype. APs were also found in HCs of tissue slices prepared from whole retina, where similar trends were found between subtype, frequency, and duration. This highlights subtype-specific differences in Ca2+ dynamics. Lastly, [Ca2+]i was monitored throughout hypoxia in HCs of the hypoxia-tolerant goldfish and the hypoxia-sensitive rainbow trout. In Ca2+ imaging experiments, hypoxia destabilized [Ca2+]i in HCs of trout; but in goldfish, HCs were resistant to the effects of hypoxia. However, when mitochondrial ATP-dependent K+ (mKATP) channels were inhibited, goldfish HCs lost the ability to maintain [Ca2+]i homeostasis during hypoxia. By contrast, in trout HCs, opening of mKATP stabilized [Ca2+]i during hypoxia. Furthermore, in goldfish, hypoxia protected against increases in [Ca2+]i caused by inhibiting glycolysis, showing that hypoxia is not just tolerated, but is actively protective in goldfish HCs. The present thesis includes the first comprehensive description of spontaneous Ca2+-based APs in HCs, and introduces the first cellular model of intrinsic hypoxic neuroprotection in the vertebrate retina.

Introdução. Nos últimos a função motora vem sendo associada com a atenuação sensitiva e de dor, logo antes, durante e apos a contração muscular. No entanto as vias anatômicas e funcionais deste fenômeno não são conhecidas. O objetivo deste estudo é o de criar um modelo animal e investigar o efeito da estimulação subliminar do córtex motor (ECM) no limiar nociceptivo e na atividade neuronal subcortical. Método. O limiar nociceptivo foi avaliado por teste plantar e reflexo de retirada da cauda antes e após o implante dos eletródios epidurais sobre o córtex motor da pata posterior orientado por mapa funcional na mesma cepa de ratos. Os mesmos testes foram repetidos antes, durante e após a ECM. Antagonismo sistêmico do por naloxona foi incluído neste protocolo para investigar a relação com mediação opióide. O registro neuronal multiunitário do núcleo centro mediano (CM) e ventral posterolateral (VPL) do tálamo e da substância periaqüeductal (SPM) foi realizado antes, durante e após ECM ipso e contralateral. Resultados. O implante per se não causou alterações no limiar nociceptivo. ECM induziu significativa antinocicepção seletiva na pata contralateral mas não na ipsolateral. Este efeito não mais foi observado 15 minutos após o término da estimulação. Nenhuma alteração motora e comportamental foi observada nos testes de campo aberto. A mesma estimulação no córtex sensitivo e parietal posterior não causou quaisquer alterações de limiar nociceptivo. Administração sistêmica de naloxone reverteu completamente o efeito antes observado com a ECM. O registro neuronal multiunitário evidenciou diminuição na atividade do CM durante e após a ECM contra e ipsolateral. O ritmo de disparos neuronais no VPL também mostrou diminuição apenas com a ECM ipsolateral. No entanto os neurônios da SPM aumentaram significativamente a freqüência de disparos com ECM ipsolateral e não com a contralateral. Conclusão. A ECM subliminar está relacionada consistentemente com a atenuação sensitiva durante o comportamento, provavelmente mediado por inibição talâmica e ativação da SPM. / Background. The motor function has been associated to sensory and pain attenuation, before during and shortly after the muscle activity. How ever the anatomical and functional basis of this phenomenon is not yet defined. The present study was designed to set an animal model and investigate the effect of subthreshold electrical stimulation of motor cortex (MCS) on pain threshold and neuron activity of thalamus and periaqüedutal gray. Method. Nociceptive thresholds of hind paws and the tail flick reflex were evaluated before and after surgical placement of epidural electrodes; before during and after electrical stimulation of motor cortex. Opioid antagonism was also included in this protocol in order to define neurotransmitter mediation of this process. Multiunit recording of thalamic median center (CM) and ventral posterolateral nuclei (VPL) and lateral periaqüedutal gray (SPM) were performed before and after electrical stimulation of ipso and contralateral motor cortex. Results. The procedure itself did not induce any threshold changes. MCS induced selective antinociception of contralateral paw, but no changes were detected in the nociceptive threshold of the ipsolateral side. This effect disappeared completely 15 minutes after the stimulation was ceased. No behavioral or motor impairment were observed during and after the stimulation session in the open field test. The same stimulation on sensory and posterior parietal cortex did not elicit any changes in behavioral and nociceptive tests. Systemic administration of naloxone completely reversed the previous observed antinociceptive effect. Multiunit recording evidenced decrease in spontaneous neuron firing in CM with short recovery time during ipso and contralateral MCS. Neuron activity in VPL was also significantly decreased during ipsolateral MCS but not with contralateral stimulation. How ever, neuron firing in SPM was significantly increased during and long after ipsolateral MCS but not with contralateral stimulation. Conclusion. Subthreshold MCS is consistently related to sensory attenuation during behavior, probably through thalamic inhibition and SPM activation.

During muscle contraction, electrical signals are generated by the muscle cells. The analysis of those signals is called electromyography (EMG). The EMG signal is mainly determined by physiological factors including so called central factors (central nervous system origin) and peripheral factors (muscle tissue origin). In addition, during the acquisition of EMG signals, technical factors are introduced (measurement equipment origin). The aim of this dissertation was to develop and evaluate methods to estimate physiological properties of the muscles using multichannel surface EMG (MCsEMG) signals. In order to obtain accurate physiological estimates, a method for automatic signal quality estimation was developed. The method’s performance was evaluated using visually classified signals, and the results demonstrated high classification accuracy. A method for estimation of the muscle fibre conduction velocity (MFCV) and the muscle fibre orientation (MFO) was developed. The method was evaluated with synthetic signals and demonstrated high estimation precision at low contraction levels. In order to discriminate between the estimates of MFCV and MFO belonging to single or populations of motor units (MUs), density regions of so called spatial distributions were examined. This method was applied in a study of the trapezius muscle and demonstrated spatial separation of MFCV (as well as MFO) even at high contraction levels. In addition, a method for quantification of MU synchronisation was developed. The performance on synthetic sEMG signals showed high sensitivity on MU synchronisation and robustness to changes in MFCV. The method was applied in a study of the biceps brachii muscle and the relation to force tremor during fatigue. The results showed that MU synchronisation accounted for about 40 % of the force tremor. In conclusion, new sEMG methods were developed to study muscle function and motor control in terms of muscle architecture, muscle fibre characteristics, and processes within the central nervous system.

The work developed in this thesis focusses on the electrical activity of the heart, from the modeling of the action potential originating from cardiac cells and propagating through the heart, as well as its electrical manifestation at the body surface. The study is divided in two main parts: modeling the action potential, and numerical simulations. For modeling the action potential a dimensional and asymptotic analysis is done. The key advance in this part of the work is that this analysis gives the steps to reliably control the action potential. It allows predicting the time/space scales and speed of any action potential that is to say the shape of the action potential and its propagation. This can be done as the explicit relations on all the physiological constants are defined precisely. This method facilitates the integrative modeling of a complete human heart with tissue-specific ionic models. It even proves that using a single model for the cardiac action potential is enough in many situations. For efficient numerical simulations, a numerical method for solving the heart-torso coupling problem is explored according to a level set description of the domains. This is done in the perspective of using directly medical images for building computational domains. A finite element method is then developed to manage meshes not adapted to internal interfaces. Finally, an anisotropic adaptive remeshing methods for unstructured finite element meshes is used to efficiently capture propagating action potentials within complex, realistic two dimensional geometries.