Computational and Imaging Methods for Studying Neuronal Populations during Behavior

One of the central questions in neuroscience is how the nervous system generates and regulates behavior. To understand the neural code for any behavior, an ideal experiment would entail (i) quantitatively defining that behavior, (ii) recording neuronal activity in relevant brain regions to identify the underlying neuronal circuits and eventually (iii) manipulating them to test their function. Novel methods in neuroscience have greatly advanced our abilities to conduct such experiments but are still insufficient. In this thesis, I developed methods for these three goals. In Chapter 2, I describe an automatic behavior identification and classification method for the cnidarian Hydra vulgaris using machine learning. In Chapter 3, I describe a fast volumetric two-photon microscope with dual-color laser excitation that can image in 3D the activity of populations of neurons from visual cortex of awake mice. In Chapter 4, I present a machine learning method that identifies cortical ensembles and pattern completion neurons in mouse visual cortex, using two-photon calcium imaging data. These methods advance current technologies, providing opportunities for new discoveries

Non-Penetrating Microelectrode Interfaces for Cortical Neuroprosthetic Applications with a Focus on Sensory Encoding: Feasibility and Chronic Performance in Striate Cortex

abstract: Growing understanding of the neural code and how to speak it has allowed for notable advancements in neural prosthetics. With commercially-available implantable systems with bi- directional neural communication on the horizon, there is an increasing imperative to develop high resolution interfaces that can survive the environment and be well tolerated by the nervous system under chronic use. The sensory encoding aspect optimally interfaces at a scale sufficient to evoke perception but focal in nature to maximize resolution and evoke more complex and nuanced sensations. Microelectrode arrays can maintain high spatial density, operating on the scale of cortical columns, and can be either penetrating or non-penetrating. The non-penetrating subset sits on the tissue surface without puncturing the parenchyma and is known to engender minimal tissue response and less damage than the penetrating counterpart, improving long term viability in vivo. Provided non-penetrating microelectrodes can consistently evoke perception and maintain a localized region of activation, non-penetrating micro-electrodes may provide an ideal platform for a high performing neural prosthesis; this dissertation explores their functional capacity. The scale at which non-penetrating electrode arrays can interface with cortex is evaluated in the context of extracting useful information. Articulate movements were decoded from surface microelectrode electrodes, and additional spatial analysis revealed unique signal content despite dense electrode spacing. With a basis for data extraction established, the focus shifts towards the information encoding half of neural interfaces. Finite element modeling was used to compare tissue recruitment under surface stimulation across electrode scales. Results indicated charge density-based metrics provide a reasonable approximation for current levels required to evoke a visual sensation and showed tissue recruitment increases exponentially with electrode diameter. Micro-scale electrodes (0.1 – 0.3 mm diameter) could sufficiently activate layers II/III in a model tuned to striate cortex while maintaining focal radii of activated tissue. In vivo testing proceeded in a nonhuman primate model. Stimulation consistently evoked visual percepts at safe current thresholds. Tracking perception thresholds across one year reflected stable values within minimal fluctuation. Modulating waveform parameters was found useful in reducing charge requirements to evoke perception. Pulse frequency and phase asymmetry were each used to reduce thresholds, improve charge efficiency, lower charge per phase – charge density metrics associated with tissue damage. No impairments to photic perception were observed during the course of the study, suggesting limited tissue damage from array implantation or electrically induced neurotoxicity. The subject consistently identified stimulation on closely spaced electrodes (2 mm center-to-center) as separate percepts, indicating sub-visual degree discrete resolution may be feasible with this platform. Although continued testing is necessary, preliminary results supports epicortical microelectrode arrays as a stable platform for interfacing with neural tissue and a viable option for bi-directional BCI applications.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

Systematic Review of Intelligent Algorithms in Gait Analysis and Prediction for Lower Limb Robotic Systems

The rate of development of robotic technologies has been meteoric, as a result of compounded advancements in hardware and software. Amongst these robotic technologies are active exoskeletons and orthoses, used in the assistive and rehabilitative fields. Artificial intelligence techniques are increasingly being utilised in gait analysis and prediction. This review paper systematically explores the current use of intelligent algorithms in gait analysis for robotic control, specifically the control of active lower limb exoskeletons and orthoses. Two databases, IEEE and Scopus, were screened for papers published between 1989 to May 2020. 41 papers met the eligibility criteria and were included in this review. 66.7% of the identified studies used classification models for the classification of gait phases and locomotion modes. Meanwhile, 33.3% implemented regression models for the estimation/prediction of kinematic parameters such as joint angles and trajectories, and kinetic parameters such as moments and torques. Deep learning algorithms have been deployed in ∼15% of the machine learning implementations. Other methodological parameters were reviewed, such as the sensor selection and the sample sizes used for training the models

Recent Applications in Graph Theory

Graph theory, being a rigorously investigated field of combinatorial mathematics, is adopted by a wide variety of disciplines addressing a plethora of real-world applications. Advances in graph algorithms and software implementations have made graph theory accessible to a larger community of interest. Ever-increasing interest in machine learning and model deployments for network data demands a coherent selection of topics rewarding a fresh, up-to-date summary of the theory and fruitful applications to probe further. This volume is a small yet unique contribution to graph theory applications and modeling with graphs. The subjects discussed include information hiding using graphs, dynamic graph-based systems to model and control cyber-physical systems, graph reconstruction, average distance neighborhood graphs, and pure and mixed-integer linear programming formulations to cluster networks

Brain-Computer Interface

Brain-computer interfacing (BCI) with the use of advanced artificial intelligence identification is a rapidly growing new technology that allows a silently commanding brain to manipulate devices ranging from smartphones to advanced articulated robotic arms when physical control is not possible. BCI can be viewed as a collaboration between the brain and a device via the direct passage of electrical signals from neurons to an external system. The book provides a comprehensive summary of conventional and novel methods for processing brain signals. The chapters cover a range of topics including noninvasive and invasive signal acquisition, signal processing methods, deep learning approaches, and implementation of BCI in experimental problems

Novel Bidirectional Body - Machine Interface to Control Upper Limb Prosthesis

Objective. The journey of a bionic prosthetic user is characterized by the opportunities and limitations involved in adopting a device (the prosthesis) that should enable activities of daily living (ADL). Within this context, experiencing a bionic hand as a functional (and, possibly, embodied) limb constitutes the premise for mitigating the risk of its abandonment through the continuous use of the device. To achieve such a result, different aspects must be considered for making the artificial limb an effective support for carrying out ADLs. Among them, intuitive and robust control is fundamental to improving amputees’ quality of life using upper limb prostheses. Still, as artificial proprioception is essential to perceive the prosthesis movement without constant visual attention, a good control framework may not be enough to restore practical functionality to the limb. To overcome this, bidirectional communication between the user and the prosthesis has been recently introduced and is a requirement of utmost importance in developing prosthetic hands. Indeed, closing the control loop between the user and a prosthesis by providing artificial sensory feedback is a fundamental step towards the complete restoration of the lost sensory-motor functions. Within my PhD work, I proposed the development of a more controllable and sensitive human-like hand prosthesis, i.e., the Hannes prosthetic hand, to improve its usability and effectiveness. Approach. To achieve the objectives of this thesis work, I developed a modular and scalable software and firmware architecture to control the Hannes prosthetic multi-Degree of Freedom (DoF) system and to fit all users’ needs (hand aperture, wrist rotation, and wrist flexion in different combinations). On top of this, I developed several Pattern Recognition (PR) algorithms to translate electromyographic (EMG) activity into complex movements. However, stability and repeatability were still unmet requirements in multi-DoF upper limb systems; hence, I started by investigating different strategies to produce a more robust control. To do this, EMG signals were collected from trans-radial amputees using an array of up to six sensors placed over the skin. Secondly, I developed a vibrotactile system to implement haptic feedback to restore proprioception and create a bidirectional connection between the user and the prosthesis. Similarly, I implemented an object stiffness detection to restore tactile sensation able to connect the user with the external word. This closed-loop control between EMG and vibration feedback is essential to implementing a Bidirectional Body - Machine Interface to impact amputees’ daily life strongly. For each of these three activities: (i) implementation of robust pattern recognition control algorithms, (ii) restoration of proprioception, and (iii) restoration of the feeling of the grasped object's stiffness, I performed a study where data from healthy subjects and amputees was collected, in order to demonstrate the efficacy and usability of my implementations. In each study, I evaluated both the algorithms and the subjects’ ability to use the prosthesis by means of the F1Score parameter (offline) and the Target Achievement Control test-TAC (online). With this test, I analyzed the error rate, path efficiency, and time efficiency in completing different tasks. Main results. Among the several tested methods for Pattern Recognition, the Non-Linear Logistic Regression (NLR) resulted to be the best algorithm in terms of F1Score (99%, robustness), whereas the minimum number of electrodes needed for its functioning was determined to be 4 in the conducted offline analyses. Further, I demonstrated that its low computational burden allowed its implementation and integration on a microcontroller running at a sampling frequency of 300Hz (efficiency). Finally, the online implementation allowed the subject to simultaneously control the Hannes prosthesis DoFs, in a bioinspired and human-like way. In addition, I performed further tests with the same NLR-based control by endowing it with closed-loop proprioceptive feedback. In this scenario, the results achieved during the TAC test obtained an error rate of 15% and a path efficiency of 60% in experiments where no sources of information were available (no visual and no audio feedback). Such results demonstrated an improvement in the controllability of the system with an impact on user experience. Significance. The obtained results confirmed the hypothesis of improving robustness and efficiency of a prosthetic control thanks to of the implemented closed-loop approach. The bidirectional communication between the user and the prosthesis is capable to restore the loss of sensory functionality, with promising implications on direct translation in the clinical practice

Biomedical signal filtering for noisy environments

 Luke\u27s work addresses issue of robustly attenuating multi-source noise from surface EEG signals using a novel Adaptive-Multiple-Reference Least-Means-Squares filter (AMR-LMS). In practice, the filter successfully removes electrical interference and muscle noise generated during movement which contaminates EEG, allowing subjects to maintain maximum mobility throughout signal acquisition and during the use of a Brain Computer Interface

Computational Intelligence in Electromyography Analysis

Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG may be used clinically for the diagnosis of neuromuscular problems and for assessing biomechanical and motor control deficits and other functional disorders. Furthermore, it can be used as a control signal for interfacing with orthotic and/or prosthetic devices or other rehabilitation assists. This book presents an updated overview of signal processing applications and recent developments in EMG from a number of diverse aspects and various applications in clinical and experimental research. It will provide readers with a detailed introduction to EMG signal processing techniques and applications, while presenting several new results and explanation of existing algorithms. This book is organized into 18 chapters, covering the current theoretical and practical approaches of EMG research