Digital neural circuits : from ions to networks

PhD ThesisThe biological neural computational mechanism is always fascinating to human beings since it shows several state-of-the-art characteristics: strong fault tolerance, high power efficiency and self-learning capability. These behaviours lead the developing trend of designing the next-generation digital computation platform. Thus investigating and understanding how the neurons talk with each other is the key to replicating these calculation features. In this work I emphasize using tailor-designed digital circuits for exactly implementing bio-realistic neural network behaviours, which can be considered a novel approach to cognitive neural computation. The first advance is that biological real-time computing performances allow the presented circuits to be readily adapted for real-time closed-loop in vitro or in vivo experiments, and the second one is a transistor-based circuit that can be directly translated into an impalpable chip for high-level neurologic disorder rehabilitations. In terms of the methodology, first I focus on designing a heterogeneous or multiple-layer-based architecture for reproducing the finest neuron activities both in voltage-and calcium-dependent ion channels. In particular, a digital optoelectronic neuron is developed as a case study. Second, I focus on designing a network-on-chip architecture for implementing a very large-scale neural network (e.g. more than 100,000) with human cognitive functions (e.g. timing control mechanism). Finally, I present a reliable hybrid bio-silicon closed-loop system for central pattern generator prosthetics, which can be considered as a framework for digital neural circuit-based neuro-prosthesis implications. At the end, I present the general digital neural circuit design principles and the long-term social impacts of the presented work

A Neural Signal Processor for Low-Latency Spike Inference

This thesis describes the development of a system that can assign identities to a population of single-units, in multi-electrode recordings, at single-spike resolution with low-latency. The system has two parts. The first is a Field-Programmable Gate Array (FPGA)-based Neural Signal Processor (NSP) that receives raw input and generates labelled spikes as output, a process referred to as real-time spike inference. The second is a piece of software (Spiketag) that runs on a PC, communicates with the NSP, and generates a spike-sorted model to guide the real-time spike inference. The NSP provides clocks and control signals to five 32-channel INTAN RHD2132 chips to manage the acquisition of 160 channels of raw neural data. In parallel, the NSP further filters, detects and extracts extracellular spike waveforms from the raw neural data recorded by tetrodes or silicon probes and assigns single-unit identity to each detected spike. A set of Python application programming interfaces (APIs) was developed in Spiketag to enable the communication between the NSP and the PC. These APIs allow the NSP to obtain a model from the PC, which holds parameters such as reference channels, spike detection thresholds, spike feature transformation matrix and vector quantized clusters generated by spike sorting a short recording session. Using the spike-sorted model, the NSP performs data acquisition and real-time spike inference simultaneously. Algorithmic modules were implemented in the FPGA and pipelined to compute during 40 ms acquisition intervals. At the output end of the FPGA NSP, the real-time assigned single-unit identity (spike-id) is packaged with the timestamp, the electrode group, and the spike features as a spike-id packet. Spike-id packets are asynchronously transmitted through a low-latency Peripheral Component Interconnect Express (PCIe) interface to the PC, producing the real-time spike trains. The real-time spike trains can be used for further processing, such as real-time decoding. Several types of ground-truth data, including intracellular/extracellular paired recordings, synthesized tetrode extracellular waveforms with ground-truth spike timing and high-channel-count silicon probe recordings with ground-truth animal positions during navigation were used to validate the low-latency (1 ms) and high-accuracy (as high as state-of-the-art offline sorting and decoding algorithms) of the NSP’s real-time spike inference and the NSP-based real-time population decoding performance

Closed-loop approaches for innovative neuroprostheses

The goal of this thesis is to study new ways to interact with the nervous system in case of damage or pathology. In particular, I focused my effort towards the development of innovative, closed-loop stimulation protocols in various scenarios: in vitro, ex vivo, in vivo

Mixed signal VLSI circuit implementation of the cortical microcircuit models

This thesis proposes a novel set of generic and compact biologically plausible VLSI (Very Large Scale Integration) neural circuits, suitable for implementing a parallel VLSI network that closely resembles the function of a small-scale neocortical network. The proposed circuits include a cortical neuron, two different long-term plastic synapses and four different short-term plastic synapses. These circuits operate in accelerated-time, where the time scale of neural responses is approximately three to four orders of magnitude faster than the biological-time scale of the neuronal activities, providing higher computational throughput in computing neural dynamics. Further, a novel biological-time cortical neuron circuit with similar dynamics as of the accelerated-time neuron is proposed to demonstrate the feasibility of migrating accelerated-time circuits into biological-time circuits. The fabricated accelerated-time VLSI neuron circuit is capable of replicating distinct firing patterns such as regular spiking, fast spiking, chattering and intrinsic bursting, by tuning two external voltages. It reproduces biologically plausible action potentials. This neuron circuit is compact and enables implementation of many neurons in a single silicon chip. The circuit consumes extremely low energy per spike (8pJ). Incorporating this neuron circuit in a neural network facilitates diverse non-linear neuron responses, which is an important aspect in neural processing. Two of the proposed long term plastic synapse circuits include spike-time dependent plasticity (STDP) synapse, and dopamine modulated STDP synapse. The short-term plastic synapses include excitatory depressing, inhibitory facilitating, inhibitory depressing, and excitatory facilitating synapses. Many neural parameters of short- and long- term synapses can be modified independently using externally controlled tuning voltages to obtain distinct synaptic properties. Having diverse synaptic dynamics in a network facilitates richer network behaviours such as learning, memory, stability and dynamic gain control, inherent in a biological neural network. To prove the concept in VLSI, different combinations of these accelerated-time neural circuits are fabricated in three integrated circuits (ICs) using a standard 0.35 µm CMOS technology. Using first two ICs, functions of cortical neuron and STDP synapses have been experimentally verified. The third IC, the Cortical Neural Layer (CNL) Chip is designed and fabricated to facilitate cortical network emulations. This IC implements neural circuits with a similar composition to the cortical layer of the neocortex. The CNL chip comprises 120 cortical neurons and 7 560 synapses. Many of these CNL chips can be combined together to form a six-layered VLSI neocortical network to validate the network dynamics and to perform neural processing of small-scale cortical networks. The proposed neuromorphic systems can be used as a simulation acceleration platform to explore the processing principles of biological brains and also move towards realising low power, real-time intelligent computing devices and control systems.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mixed signal VLSI circuit implementation of the cortical microcircuit models

This thesis proposes a novel set of generic and compact biologically plausible VLSI (Very Large Scale Integration) neural circuits, suitable for implementing a parallel VLSI network that closely resembles the function of a small-scale neocortical network. The proposed circuits include a cortical neuron, two different long-term plastic synapses and four different short-term plastic synapses. These circuits operate in accelerated-time, where the time scale of neural responses is approximately three to four orders of magnitude faster than the biological-time scale of the neuronal activities, providing higher computational throughput in computing neural dynamics. Further, a novel biological-time cortical neuron circuit with similar dynamics as of the accelerated-time neuron is proposed to demonstrate the feasibility of migrating accelerated-time circuits into biological-time circuits. The fabricated accelerated-time VLSI neuron circuit is capable of replicating distinct firing patterns such as regular spiking, fast spiking, chattering and intrinsic bursting, by tuning two external voltages. It reproduces biologically plausible action potentials. This neuron circuit is compact and enables implementation of many neurons in a single silicon chip. The circuit consumes extremely low energy per spike (8pJ). Incorporating this neuron circuit in a neural network facilitates diverse non-linear neuron responses, which is an important aspect in neural processing. Two of the proposed long term plastic synapse circuits include spike-time dependent plasticity (STDP) synapse, and dopamine modulated STDP synapse. The short-term plastic synapses include excitatory depressing, inhibitory facilitating, inhibitory depressing, and excitatory facilitating synapses. Many neural parameters of short- and long- term synapses can be modified independently using externally controlled tuning voltages to obtain distinct synaptic properties. Having diverse synaptic dynamics in a network facilitates richer network behaviours such as learning, memory, stability and dynamic gain control, inherent in a biological neural network. To prove the concept in VLSI, different combinations of these accelerated-time neural circuits are fabricated in three integrated circuits (ICs) using a standard 0.35 µm CMOS technology. Using first two ICs, functions of cortical neuron and STDP synapses have been experimentally verified. The third IC, the Cortical Neural Layer (CNL) Chip is designed and fabricated to facilitate cortical network emulations. This IC implements neural circuits with a similar composition to the cortical layer of the neocortex. The CNL chip comprises 120 cortical neurons and 7 560 synapses. Many of these CNL chips can be combined together to form a six-layered VLSI neocortical network to validate the network dynamics and to perform neural processing of small-scale cortical networks. The proposed neuromorphic systems can be used as a simulation acceleration platform to explore the processing principles of biological brains and also move towards realising low power, real-time intelligent computing devices and control systems.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

In Vitro Studies of Neuronal Networks and Synaptic Plasticity in Invertebrates and in Mammals Using Multielectrode Arrays

Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments

Study of neural circuits using multielectrode arrays in movement disorders

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Rodríguez Allué, Manuel JoséNeurodegenerative movement-related disorders are characterized by a progressive degeneration and loss of neurons, which lead to motor control impairment. Although the precise mechanisms underlying these conditions are still unknown, an increasing number of studies point towards the analysis of neural networks and functional connectivity to unravel novel insights. The main objective of this work is to understand cellular mechanisms related to dysregulated motor control symptoms in movement disorders, such as Chorea-Acanthocytosis (ChAc), by employing multielectrode arrays to analyze the electrical activity of neuronal networks in mouse models. We found no notable differences in cell viability between neurons with and without VPS13A knockdown, that is the only gene known to be implicated in the disease, suggesting that the absence of VPS13A in neurons may be partially compensated by other proteins. The MEA setup used to capture the electrical activity from neuron primary cultures is described in detail, pointing out its specific characteristics. At last, we present the alternative backup approach implemented to overcome the challenges faced during the research process and to explore the advanced algorithms for signal processing and analysis. In this report, we present a thorough account of the conception and implementation of our research, outlining the multiple limitations that have been encountered all along the course of the project. We provide a detailed analysis on the project’s economical and technical feasibility, as well as a comprehensive overview of the ethical and legal aspects considered during the execution