Neuromorphic-Based Neuroprostheses for Brain Rewiring: State-of-the-Art and Perspectives in Neuroengineering.

Neuroprostheses are neuroengineering devices that have an interface with the nervous system and supplement or substitute functionality in people with disabilities. In the collective imagination, neuroprostheses are mostly used to restore sensory or motor capabilities, but in recent years, new devices directly acting at the brain level have been proposed. In order to design the next-generation of neuroprosthetic devices for brain repair, we foresee the increasing exploitation of closed-loop systems enabled with neuromorphic elements due to their intrinsic energy efficiency, their capability to perform real-time data processing, and of mimicking neurobiological computation for an improved synergy between the technological and biological counterparts. In this manuscript, after providing definitions of key concepts, we reviewed the first exploitation of a real-time hardware neuromorphic prosthesis to restore the bidirectional communication between two neuronal populations in vitro. Starting from that 'case-study', we provide perspectives on the technological improvements for real-time interfacing and processing of neural signals and their potential usage for novel in vitro and in vivo experimental designs. The development of innovative neuroprosthetics for translational purposes is also presented and discussed. In our understanding, the pursuit of neuromorphic-based closed-loop neuroprostheses may spur the development of novel powerful technologies, such as 'brain-prostheses', capable of rewiring and/or substituting the injured nervous system

On the development of slime mould morphological, intracellular and heterotic computing devices

The use of live biological substrates in the fabrication of unconventional computing (UC) devices is steadily transcending the barriers between science fiction and reality, but efforts in this direction are impeded by ethical considerations, the field’s restrictively broad multidisciplinarity and our incomplete knowledge of fundamental biological processes. As such, very few functional prototypes of biological UC devices have been produced to date. This thesis aims to demonstrate the computational polymorphism and polyfunctionality of a chosen biological substrate — slime mould Physarum polycephalum, an arguably ‘simple’ single-celled organism — and how these properties can be harnessed to create laboratory experimental prototypes of functionally-useful biological UC prototypes. Computing devices utilising live slime mould as their key constituent element can be developed into a) heterotic, or hybrid devices, which are based on electrical recognition of slime mould behaviour via machine-organism interfaces, b) whole-organism-scale morphological processors, whose output is the organism’s morphological adaptation to environmental stimuli (input) and c) intracellular processors wherein data are represented by energetic signalling events mediated by the cytoskeleton, a nano-scale protein network. It is demonstrated that each category of device is capable of implementing logic and furthermore, specific applications for each class may be engineered, such as image processing applications for morphological processors and biosensors in the case of heterotic devices. The results presented are supported by a range of computer modelling experiments using cellular automata and multi-agent modelling. We conclude that P. polycephalum is a polymorphic UC substrate insofar as it can process multimodal sensory input and polyfunctional in its demonstrable ability to undertake a variety of computing problems. Furthermore, our results are highly applicable to the study of other living UC substrates and will inform future work in UC, biosensing, and biomedicine

Scalable event-driven modelling architectures for neuromimetic hardware

Neural networks present a fundamentally different model of computation from the conventional sequential digital model. Dedicated hardware may thus be more suitable for executing them. Given that there is no clear consensus on the model of computation in the brain, model flexibility is at least as important a characteristic of neural hardware as is performance acceleration. The SpiNNaker chip is an example of the emerging 'neuromimetic' architecture, a universal platform that specialises the hardware for neural networks but allows flexibility in model choice. It integrates four key attributes: native parallelism, event-driven processing, incoherent memory and incremental reconfiguration, in a system combining an array of general-purpose processors with a configurable asynchronous interconnect. Making such a device usable in practice requires an environment for instantiating neural models on the chip that allows the user to focus on model characteristics rather than on hardware details. The central part of this system is a library of predesigned, 'drop-in' event-driven neural components that specify their specific implementation on SpiNNaker. Three exemplar models: two spiking networks and a multilayer perceptron network, illustrate techniques that provide a basis for the library and demonstrate a reference methodology that can be extended to support third-party library components not only on SpiNNaker but on any configurable neuromimetic platform. Experiments demonstrate the capability of the library model to implement efficient on-chip neural networks, but also reveal important hardware limitations, particularly with respect to communications, that require careful design. The ultimate goal is the creation of a library-based development system that allows neural modellers to work in the high-level environment of their choice, using an automated tool chain to create the appropriate SpiNNaker instantiation. Such a system would enable the use of the hardware to explore abstractions of biological neurodynamics that underpin a functional model of neural computation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Digital CMOS ISFET architectures and algorithmic methods for point-of-care diagnostics

Over the past decade, the surge of infectious diseases outbreaks across the globe is redefining how healthcare is provided and delivered to patients, with a clear trend towards distributed diagnosis at the Point-of-Care (PoC). In this context, Ion-Sensitive Field Effect Transistors (ISFETs) fabricated on standard CMOS technology have emerged as a promising solution to achieve a precise, deliverable and inexpensive platform that could be deployed worldwide to provide a rapid diagnosis of infectious diseases. This thesis presents advancements for the future of ISFET-based PoC diagnostic platforms, proposing and implementing a set of hardware and software methodologies to overcome its main challenges and enhance its sensing capabilities. The first part of this thesis focuses on novel hardware architectures that enable direct integration with computational capabilities while providing pixel programmability and adaptability required to overcome pressing challenges on ISFET-based PoC platforms. This section explores oscillator-based ISFET architectures, a set of sensing front-ends that encodes the chemical information on the duty cycle of a PWM signal. Two initial architectures are proposed and fabricated in AMS 0.35um, confirming multiple degrees of programmability and potential for multi-sensing. One of these architectures is optimised to create a dual-sensing pixel capable of sensing both temperature and chemical information on the same spatial point while modulating this information simultaneously on a single waveform. This dual-sensing capability, verified in silico using TSMC 0.18um process, is vital for DNA-based diagnosis where protocols such as LAMP or PCR require precise thermal control. The COVID-19 pandemic highlighted the need for a deliverable diagnosis that perform nucleic acid amplification tests at the PoC, requiring minimal footprint by integrating sensing and computational capabilities. In response to this challenge, a paradigm shift is proposed, advocating for integrating all elements of the portable diagnostic platform under a single piece of silicon, realising a ``Diagnosis-on-a-Chip". This approach is enabled by a novel Digital ISFET Pixel that integrates both ADC and memory with sensing elements on each pixel, enhancing its parallelism. Furthermore, this architecture removes the need for external instrumentation or memories and facilitates its integration with computational capabilities on-chip, such as the proposed ARM Cortex M3 system. These computational capabilities need to be complemented with software methods that enable sensing enhancement and new applications using ISFET arrays. The second part of this thesis is devoted to these methods. Leveraging the programmability capabilities available on oscillator-based architectures, various digital signal processing algorithms are implemented to overcome the most urgent ISFET non-idealities, such as trapped charge, drift and chemical noise. These methods enable fast trapped charge cancellation and enhanced dynamic range through real-time drift compensation, achieving over 36 hours of continuous monitoring without pixel saturation. Furthermore, the recent development of data-driven models and software methods open a wide range of opportunities for ISFET sensing and beyond. In the last section of this thesis, two examples of these opportunities are explored: the optimisation of image compression algorithms on chemical images generated by an ultra-high frame-rate ISFET array; and a proposed paradigm shift on surface Electromyography (sEMG) signals, moving from data-harvesting to information-focused sensing. These examples represent an initial step forward on a journey towards a new generation of miniaturised, precise and efficient sensors for PoC diagnostics.Open Acces

Enabling rapid iterative model design within the laboratory environment

This thesis presents a proof of concept study for the better integration of the electrophysiological and modelling aspects of neuroscience. Members of these two sub-disciplines collaborate regularly, but due to differing resource requirements, and largely incompatible spheres of knowledge, cooperation is often impeded by miscommunication and delays. To reduce the model design time, and provide a platform for more efficient experimental analysis, a rapid iterative model design method is proposed. The main achievement of this work is the development of a rapid model evaluation method based on parameter estimation, utilising a combination of evolutionary algorithms (EAs) and graphics processing unit (GPU) hardware acceleration. This method is the primary force behind the better integration of modelling and laboratorybased electrophysiology, as it provides a generic model evaluation method that does not require prior knowledge of model structure, or expertise in modelling, mathematics, or computer science. If combined with a suitable intuitive and user targeted graphical user interface, the ideas presented in this thesis could be developed into a suite of tools that would enable new forms of experimentation to be performed. The latter part of this thesis investigates the use of excitability-based models as the basis of an iterative design method. They were found to be computationally and structurally simple, easily extensible, and able to reproduce a wide range of neural behaviours whilst still faithfully representing underlying cellular mechanisms. A case study was performed to assess the iterative design process, through the implementation of an excitability-based model. The model was extended iteratively, using the rapid model evaluation method, to represent a vasopressin releasing neuron. Not only was the model implemented successfully, but it was able to suggest the existence of other more subtle cell mechanisms, in addition to highlighting potential failings in previous implementations of the class of neuron

Computational strategies for a system-level understanding of metabolism

Cell metabolism is the biochemical machinery that provides energy and building blocks to sustain life. Understanding its fine regulation is of pivotal relevance in several fields, from metabolic engineering applications to the treatment of metabolic disorders and cancer. Sophisticated computational approaches are needed to unravel the complexity of metabolism. To this aim, a plethora of methods have been developed, yet it is generally hard to identify which computational strategy is most suited for the investigation of a specific aspect of metabolism. This review provides an up-to-date description of the computational methods available for the analysis of metabolic pathways, discussing their main advantages and drawbacks. In particular, attention is devoted to the identification of the appropriate scale and level of accuracy in the reconstruction of metabolic networks, and to the inference of model structure and parameters, especially when dealing with a shortage of experimental measurements. The choice of the proper computational methods to derive in silico data is then addressed, including topological analyses, constraint-based modeling and simulation of the system dynamics. A description of some computational approaches to gain new biological knowledge or to formulate hypotheses is finally provided

Dynamically reconfigurable bio-inspired hardware

During the last several years, reconfigurable computing devices have experienced an impressive development in their resource availability, speed, and configurability. Currently, commercial FPGAs offer the possibility of self-reconfiguring by partially modifying their configuration bitstream, providing high architectural flexibility, while guaranteeing high performance. These configurability features have received special interest from computer architects: one can find several reconfigurable coprocessor architectures for cryptographic algorithms, image processing, automotive applications, and different general purpose functions. On the other hand we have bio-inspired hardware, a large research field taking inspiration from living beings in order to design hardware systems, which includes diverse topics: evolvable hardware, neural hardware, cellular automata, and fuzzy hardware, among others. Living beings are well known for their high adaptability to environmental changes, featuring very flexible adaptations at several levels. Bio-inspired hardware systems require such flexibility to be provided by the hardware platform on which the system is implemented. In general, bio-inspired hardware has been implemented on both custom and commercial hardware platforms. These custom platforms are specifically designed for supporting bio-inspired hardware systems, typically featuring special cellular architectures and enhanced reconfigurability capabilities; an example is their partial and dynamic reconfigurability. These aspects are very well appreciated for providing the performance and the high architectural flexibility required by bio-inspired systems. However, the availability and the very high costs of such custom devices make them only accessible to a very few research groups. Even though some commercial FPGAs provide enhanced reconfigurability features such as partial and dynamic reconfiguration, their utilization is still in its early stages and they are not well supported by FPGA vendors, thus making their use difficult to include in existing bio-inspired systems. In this thesis, I present a set of architectures, techniques, and methodologies for benefiting from the configurability advantages of current commercial FPGAs in the design of bio-inspired hardware systems. Among the presented architectures there are neural networks, spiking neuron models, fuzzy systems, cellular automata and random boolean networks. For these architectures, I propose several adaptation techniques for parametric and topological adaptation, such as hebbian learning, evolutionary and co-evolutionary algorithms, and particle swarm optimization. Finally, as case study I consider the implementation of bio-inspired hardware systems in two platforms: YaMoR (Yet another Modular Robot) and ROPES (Reconfigurable Object for Pervasive Systems); the development of both platforms having been co-supervised in the framework of this thesis

Exploring the potential of brain-inspired computing

The gap between brains and computers regarding both their cognitive capability and power efficiency is remarkably huge. Brains process information massively in parallel and its constituents are intrinsically self-organizing, while in digital computers the execution of instructions is deterministic and rather serial. The recent progress in the development of dedicated hardware systems implementing physical models of neurons and synapses enables to efficiently emulate spiking neural networks. In this work, we verify the design and explore the potential for brain-inspired computing of such an analog neuromorphic system, called Spikey. We demonstrate the versatility of this highly configurable substrate by the implementation of a rich repertoire of network models, including models for signal propagation and enhancement, general purpose classifiers, cortical models and decorrelating feedback systems. Network emulations on Spikey are highly accelerated and consume less than 1 nJ per synaptic transmission. The Spikey system, hence, outperforms modern desktop computers in terms of fast and efficient network simulations closing the gap to brains. During this thesis the stability, performance and user-friendliness of the Spikey system was improved integrating it into the neuroscientific tool chain and making it available for the community. The implementation of networks suitable to solve everyday tasks, like object or speech recognition, qualifies this technology to be an alternative to conventional computers. Considering the compactness, computational capability and power efficiency, neuromorphic systems may qualify as a valuable complement to classical computation