Universal Processor Architecture for Biomedical Implants: The SiMS Project

HEALTHCARE in the 21st century is changing rapidly. In advanced countries, in particular, healthcare is moving from a public to a more personalized nature. However, the costs of healthcare worldwide are increasing every year. Better use of technology can and should be used to get control of these costs. At the same time, implants have clearly benefitted from the astounding technology-miniaturization trends of late, boasting smaller sizes, lower power consumption and increased performance of the transistor devices. However, such advances do not come for free. Adverse effects in current implant designs are being witnessed, such as increasing power consumption, absence of design for reliability and highly application-specific nature. Operating under the assumption that implants will constitute an important means towards improved, personal healthcare and, in view of the aforementioned design phenomena, we believe that a new paradigm in implant design is required. This dissertation establishes the concept of Smart implantable Medical Systems (SiMS). SiMS is a systematic approach – a framework – for providing biomedical researchers and, hopefully, industry with a toolbox of ready-to-use, highly reliable implant sub-systems and models in order to construct optimal implants for various medical applications. The SiMS framework has to guarantee essential attributes, such as high dependability, modular design, ultra-low power consumption and miniature size. Having defined the SiMS framework, this dissertation is, then, concerned with exploring the optimal microarchitectural details of a crucial SiMS component: the SiMS processor. Contrary to the current state of the art, this processor aspires to be a new universal, low-power and low-cost processor and capable of efficiently serving a wide range of diverse implant applications.Computer Science and EngineeringElectrical Engineering, Mathematics and Computer Scienc

EDEN: A High-Performance, General-Purpose, NeuroML-Based Neural Simulator

Modern neuroscience employs in silico experimentation on ever-increasing and more detailed neural networks. The high modeling detail goes hand in hand with the need for high model reproducibility, reusability and transparency. Besides, the size of the models and the long timescales under study mandate the use of a simulation system with high computational performance, so as to provide an acceptable time to result. In this work, we present EDEN (Extensible Dynamics Engine for Networks), a new general-purpose, NeuroML-based neural simulator that achieves both high model flexibility and high computational performance, through an innovative model-analysis and code-generation technique. The simulator runs NeuroML-v2 models directly, eliminating the need for users to learn yet another simulator-specific, model-specification language. EDEN's functional correctness and computational performance were assessed through NeuroML models available on the NeuroML-DB and Open Source Brain model repositories. In qualitative experiments, the results produced by EDEN were verified against the established NEURON simulator, for a wide range of models. At the same time, computational-performance benchmarks reveal that EDEN runs from one to nearly two orders-of-magnitude faster than NEURON on a typical desktop computer, and does so without additional effort from the user. Finally, and without added user effort, EDEN has been built from scratch to scale seamlessly over multiple CPUs and across computer clusters, when available.Computer EngineeringBio-Electronic

Improving the Security of the IEEE 802.15.6 Standard for Medical BANs

A Medical Body Area Network (MBAN) is an ensemble of collaborating, potentially heterogeneous, medical devices located inside, on the surface of or around the human body with the objective of tackling one or multiple medical conditions of the MBAN host. These devices-which are a special category of Wireless Body Area Networks (WBANs)–collect, process and transfer medical data outside of the network, while in some cases they also administer medical treatment autonomously. Since communication is so pivotal to their operation, the newfangled IEEE 802.15.6 standard is aimed at the communication aspects of WBANs. It places a set of physical and communication constraints while it also includes association/disassociation protocols and security services that WBAN applications need to comply with. However, the security specifications put forward by the standard can be easily shown to be insufficient when considering realistic MBAN use cases and need further enhancements. The present work addresses these shortcomings by, first, providing a structured analysis of the IEEE 802.15.6 security features and, afterwards, proposing comprehensive and tangible recommendations on improving the standard’s security.Computer EngineeringQuantum & Computer EngineeringBio-Electronic

NeuroDots: From Single-Target to Brain-Network Modulation: Why and What Is Needed?

Objectives: Current techniques in brain stimulation are still largely based on a phrenologic approach that a single brain target can treat a brain disorder. Nevertheless, meta-analyses of brain implants indicate an overall success rate of 50% improvement in 50% of patients, irrespective of the brain-related disorder. Thus, there is still a large margin for improvement. The goal of this manuscript is to 1) develop a general theoretical framework of brain functioning that is amenable to surgical neuromodulation, and 2) describe the engineering requirements of the next generation of implantable brain stimulators that follow from this theoretic model. Materials and Methods: A neuroscience and engineering literature review was performed to develop a universal theoretical model of brain functioning and dysfunctioning amenable to surgical neuromodulation. Results: Even though a single target can modulate an entire network, research in network science reveals that many brain disorders are the consequence of maladaptive interactions among multiple networks rather than a single network. Consequently, targeting the main connector hubs of those multiple interacting networks involved in a brain disorder is theoretically more beneficial. We, thus, envision next-generation network implants that will rely on distributed, multisite neuromodulation targeting correlated and anticorrelated interacting brain networks, juxtaposing alternative implant configurations, and finally providing solid recommendations for the realization of such implants. In doing so, this study pinpoints the potential shortcomings of other similar efforts in the field, which somehow fall short of the requirements. Conclusion: The concept of network stimulation holds great promise as a universal approach for treating neurologic and psychiatric disorders.Quantum & Computer EngineeringComputer EngineeringSignal Processing SystemsBio-Electronic

Securing Implantable Medical Devices Using Ultrasound Waves

Modern Implantable Medical Devices (IMDs) are vulnerable to security attacks because of their wireless connectivity to the outside world. One of the main security challenges is establishing trust between the IMD and an external reader/programmer in order to facilitate secure communication. Numerous device-pairing schemes have been proposed to address this specific challenge. However, they alone cannot protect against a battery-depletion attack in which the adversary is able to keep the IMD occupied with continuous authentication requests until the battery empties. As a result, energy harvesting has been employed as an ancillary mechanism for implementing Zero-Power Defense (ZPD) functionality in order to protect against such a low-cost attack. In this paper, we propose SecureEcho, a device-pairing scheme based on MHz-range ultrasound that establishes trust between the IMD and an external reader. In addition, SecureEcho achieves ZPD without requiring any energy harvesting, which significantly reduces the design complexity. We also provide a proof-of-concept implementation and a first ever security evaluation of the ultrasound channel, which proves that it is infeasible for the attacker to eavesdrop or insert messages even from a range of a few millimeters.Quantum & Computer EngineeringComputer EngineeringElectronicsBio-Electronic

FlexHH: A Flexible Hardware Library for Hodgkin-Huxley-Based Neural Simulations

The Hodgkin-Huxley (HH) neuron is one of the most biophysically-meaningful models used in computational neuroscience today. Ironically, the model's high experimental value is offset by its disproportional computational complexity. To such an extent that neuroscientists have either resorted to simpler models, losing precious neuron detail, or to using high-performance computing systems, to gain acceleration, for complex models. However, multicore/multinode CPU-based systems have proven too slow while FPGA-based ones have proven too time-consuming to (re)deploy to. Clearly, a solution that bridges user friendliness and high speedups is necessary. This paper presents flexHH, a flexible FPGA library implementing five popular, highly parameterizable variants of the HH neuron model. flexHH is the first crucial step towards making FPGA-based simulations of compute-intensive neural models available to neuroscientists without the debilitating penalty of re-engineering and re-synthesis. Through flexHH, the user can instantiate custom models and immediately take advantage of the acceleration without the mediation of an engineer, which has proven to be a major inhibitor to full adoption of FPGAs in neuroscience labs. In terms of performance, flexHH achieves speedups between 8 × - 20 × compared to sequential-C implementations, while only a small drop in real-time capabilities is observed when compared to hardcoded FPGA-based versions of the models tested. Computer EngineeringNumerical AnalysisBio-Electronic

Severity-based Hierarchical ECG Classification using Neural Networks

Timely detection of cardiac arrhythmia characterized by abnormal heartbeats can help in the early diagnosis and treatment of cardiovascular diseases. Wearable healthcare devices typically use neural networks to provide the most convenient way of continuously monitoring heart activity for arrhythmia detection. However, it is challenging to achieve high accuracy and energy efficiency in these smart wearable healthcare devices. In this work, we provide architecture-level solutions to deploy neural networks for cardiac arrhythmia classification. We have created a hierarchical structure after analyzing various neural network topologies where only required network components are activated to improve energy efficiency while maintaining high accuracy. In our proposed architecture, we introduce a severity-based classification approach to directly help the users of the wearable healthcare device as well as the medical professionals. Additionally, we have employed computation-in-memory based hardware to improve energy efficiency and area consumption by leveraging in-situ data processing and scalability of emerging memory technologies such as resistive random access memory (RRAM). Simulation experiments conducted using the MIT-BIH arrhythmia dataset show that the proposed architecture provides high accuracy while consuming average energy of 0.11 $\mu$J per heartbeat classification and 0.11 mm2 area, thereby achieving 25× improvement in average energy consumption and 12× improvement in area compared to the state-of-the-art.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Computer EngineeringQuantum & Computer Engineerin

WhiskEras: A New Algorithm for Accurate Whisker Tracking

Rodents engage in active touch using their facial whiskers: they explore their environment by making rapid back-and-forth movements. The fast nature of whisker movements, during which whiskers often cross each other, makes it notoriously difficult to track individual whiskers of the intact whisker field. We present here a novel algorithm, WhiskEras, for tracking of whisker movements in high-speed videos of untrimmed mice, without requiring labeled data. WhiskEras consists of a pipeline of image-processing steps: first, the points that form the whisker centerlines are detected with sub-pixel accuracy. Then, these points are clustered in order to distinguish individual whiskers. Subsequently, the whiskers are parameterized so that a single whisker can be described by four parameters. The last step consists of tracking individual whiskers over time. We describe that WhiskEras performs better than other whisker-tracking algorithms on several metrics. On our four video segments, WhiskEras detected more whiskers per frame than the Biotact Whisker Tracking Tool. The signal-to-noise ratio of the output of WhiskEras was higher than that of Janelia Whisk. As a result, the correlation between reflexive whisker movements and cerebellar Purkinje cell activity appeared to be stronger than previously found using other tracking algorithms. We conclude that WhiskEras facilitates the study of sensorimotor integration by markedly improving the accuracy of whisker tracking in untrimmed mice.Computer EngineeringBio-Electronic

High Frequency Functional Ultrasound in Mice

Functional ultrasound (fUS) is a relatively new imaging modality to study the brain with a high spatiotemporal resolution and a wide field-of-view. In fUS detailed images of cerebral blood flow and volume are used to derive functional information, as changes in local flow and/or volume may reflect neuronal activation through neurovascular coupling. Most fUS studies so far have been performed in rats. Translating fUS to mice, which is a favorable animal model for neuroscience, pleads for a higher spatial resolution than what has been reported so far. As a consequence the temporal sampling of the blood flow should also be increased in order to adequately capture the wide range in blood velocities, as the Doppler shifts are inversely proportional to the spatial resolution. Here we present our first detailed images of the mouse brain vasculature at high spatiotemporal resolution. In addition we show some early experimental work on tracking brain activity upon local electrical stimulation.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Circuits and System

Purkinje Cell Activity Resonation Generates Rhythmic Behaviors at the Preferred Frequency of 8 Hz

Neural activity exhibits oscillations, bursts, and resonance, enhancing responsiveness at preferential frequencies. For example, theta-frequency bursting and resonance in granule cells facilitate synaptic transmission and plasticity mechanisms at the input stage of the cerebellar cortex. However, whether theta-frequency bursting of Purkinje cells is involved in generating rhythmic behavior has remained neglected. We recorded and optogenetically modulated the simple and complex spike activity of Purkinje cells while monitoring whisker movements with a high-speed camera of awake, head-fixed mice. During spontaneous whisking, both simple spike activity and whisker movement exhibit peaks within the theta band. Eliciting either simple or complex spikes at frequencies ranging from 0.5 to 28 Hz, we found that 8 Hz is the preferred frequency around which the largest movement is induced. Interestingly, oscillatory whisker movements at 8 Hz were also generated when simple spike bursting was induced at 2 and 4 Hz, but never via climbing fiber stimulation. These results indicate that 8 Hz is the resonant frequency at which the cerebellar-whisker circuitry produces rhythmic whisking.Computer EngineeringBio-Electronic