Remote Gait Analysis Using Ultra-Wideband Radar Technology Based on Joint Range-Doppler-Time Representation.

OBJECTIVE: In recent years, radar technology has been extensively utilized in contactless human behavior monitoring systems. The unique capabilities of ultra-wideband (UWB) radars compared to conventional radar technologies, due to time-of-flight measurements, present new untapped opportunities for in-depth monitoring of human movement during overground locomotion. This study aims to investigate the deployability of UWB radars in accurately capturing the gait patterns of healthy individuals with no known walking impairments. METHODS: A novel algorithm was developed that can extract ten clinical spatiotemporal gait features using the Doppler information captured from three monostatic UWB radar sensors during a 6-meter walking task. Key gait events are detected from lower-extremity movements based on the joint range-Doppler-time representation of recorded radar data. The estimated gait parameters were validated against a gold-standard optical motion tracking system using 12 healthy volunteers. RESULTS: On average, nine gait parameters can be consistently estimated with 90-98% accuracy, while capturing 94.5% of participants' gait variability and 90.8% of inter-limb symmetry. Correlation and Bland-Altman analysis revealed a strong correlation between radar-based parameters and the ground-truth values, with average discrepancies consistently close to 0. CONCLUSION: Results prove that radar sensing can provide accurate biomarkers to supplement clinical human gait assessment, with quality similar to gold standard assessment. SIGNIFICANCE: Radars can potentially allow a transition from expensive and cumbersome lab-based gait analysis tools toward a completely unobtrusive and affordable solution for in-home deployment, enabling continuous long-term monitoring of individuals for research and healthcare applications.

Functional Electrochemistry: On-Nerve Assessment of Electrode Materials for Electrochemistry and Functional Neurostimulation.

Emerging therapies in bioelectronic medicine highlight the need for deeper understanding of electrode material performance in the context of tissue stimulation. Electrochemical properties are characterized on the benchtop, facilitating standardization across experiments. On-nerve electrochemistry differs from benchtop characterization and the relationship between electrochemical performance and nerve activation thresholds are not commonly established. This relationship is important in understanding differences between electrical stimulation requirements and electrode performance. We report functional electrochemistry as a follow-up to benchtop testing, describing a novel experimental approach for evaluating on-nerve electrochemical performance in the context of nerve activation. An ex-vivo rat sciatic nerve preparation was developed to quantify activation thresholds of fiber subtypes and electrode material charge injection limits for platinum iridium, iridium oxide, titanium nitride and PEDOT. Finally, we address experimental complexities arising in these studies, and demonstrate statistical solutions that support rigorous material performance comparisons for decision making in neural interface development.

Multicohort cross-sectional study of cognitive and behavioural digital biomarkers in neurodegeneration: the Living Lab Study protocol.

INTRODUCTION AND AIMS: Digital biomarkers can provide a cost-effective, objective and robust measure for neurological disease progression, changes in care needs and the effect of interventions. Motor function, physiology and behaviour can provide informative measures of neurological conditions and neurodegenerative decline. New digital technologies present an opportunity to provide remote, high-frequency monitoring of patients from within their homes. The purpose of the living lab study is to develop novel digital biomarkers of functional impairment in those living with neurodegenerative disease (NDD) and neurological conditions. METHODS AND ANALYSIS: The Living Lab study is a cross-sectional observational study of cognition and behaviour in people living with NDDs and other, non-degenerative neurological conditions. Patients (n≥25 for each patient group) with dementia, Parkinson's disease, amyotrophic lateral sclerosis, mild cognitive impairment, traumatic brain injury and stroke along with controls (n≥60) will be pragmatically recruited. Patients will carry out activities of daily living and functional assessments within the Living Lab. The Living Lab is an apartment-laboratory containing a functional kitchen, bathroom, bed and living area to provide a controlled environment to develop novel digital biomarkers. The Living Lab provides an important intermediary stage between the conventional laboratory and the home. Multiple passive environmental sensors, internet-enabled medical devices, wearables and electroencephalography (EEG) will be used to characterise functional impairments of NDDs and non-NDD conditions. We will also relate these digital technology measures to clinical and cognitive outcomes. ETHICS AND DISSEMINATION: Ethical approvals have been granted by the Imperial College Research Ethics Committee (reference number: 21IC6992). Results from the study will be disseminated at conferences and within peer-reviewed journals.

Development of an Ultra Low-Cost SSVEP-based BCI Device for Real-Time On-Device Decoding.

This study details the development of a novel, approx. £20 electroencephalogram (EEG)-based brain-computer interface (BCI) intended to offer a financially and operationally accessible device that can be deployed on a mass scale to facilitate education and public engagement in the domain of EEG sensing and neurotechnologies. Real-time decoding of steady-state visual evoked potentials (SSVEPs) is achieved using variations of the widely-used canonical correlation analysis (CCA) algorithm: multi-set CCA and generalised CCA. All BCI functionality is executed on board an inexpensive ESP32 microcontroller. SSVEP decoding accuracy of 95.56 ± 3.74% with an ITR of 102 bits/min was achieved with modest calibration.

Preparation of Rat Sciatic Nerve for Ex Vivo Neurophysiology.

Ex vivo preparations enable the study of many neurophysiological processes in isolation from the rest of the body while preserving local tissue structure. This work describes the preparation of rat sciatic nerves for ex vivo neurophysiology, including buffer preparation, animal procedures, equipment setup and neurophysiological recording. This work provides an overview of the different types of experiments possible with this method. The outlined method aims to provide 6 h of stimulation and recording on extracted peripheral nerve tissue in tightly controlled conditions for optimal consistency in results. Results obtained using this method are A-fibre compound action potentials (CAP) with peak-to-peak amplitudes in the millivolt range over the entire duration of the experiment. CAP amplitudes and shapes are consistent and reliable, making them useful to test and compare new electrodes to existing models, or the effects of interventions on the tissue, such as the use of chemicals, surgical alterations, or neuromodulatory stimulation techniques. Both conventional commercially available cuff electrodes with platinum-iridium contacts and custom-made conductive elastomer electrodes were tested and gave similar results in terms of nerve stimulus strength-duration response.

HFAC Dose Repetition and Accumulation Leads to Progressively Longer Block Carryover Effect in Rat Sciatic Nerve.

This paper describes high-frequency nerve block experiments carried out on rat sciatic nerves to measure the speed of recovery of A fibres from block carryover. Block carryover is the process by which nerve excitability remains suppressed temporarily after High Frequency Alternative (HFAC) block is turned off following its application. In this series of experiments 5 rat sciatic nerves were extracted and prepared for ex-vivo stimulation and recording in a specially designed perfusion chamber. For each nerve repeated HFAC block and concurrent stimulation trials were carried out to observe block carryover after signal shutoff. The nerve was allowed to recover fully between each trial. Time to recovery from block was measured by monitoring for when relative nerve activity returned to within 90% of baseline levels measured at the start of each trial. HFAC block carryover duration was found to be dependent on accumulated dose by statistical test for two different HFAC durations. The carryover property of HFAC block on A fibres could enable selective stimulation of autonomic nerve fibres such as C fibres for the duration of carryover. Block carryover is particularly relevant to potential chronic clinical applications of block as it reduces power requirements for stimulation to provide the blocking effect. This work characterizes this process toward the creation of a model describing its behavior.

Translating node of Ranvier currents to extraneural electrical fields: a flexible FEM modeling approach.

Simulations of electroneurogram recording could help find the optimal set of electrodes and algorithms for selective neural recording. However, no flexible methods are established for selective neural recording as for neural stimulation. This paper proposes a method to couple a compartmental and a FEM nerve model, implemented in NEURON and COMSOL, respectively, to translate Node of Ranvier currents into extraneural electric fields. The study simulate ex-vivo experimental conditions, and the method allows flexibility in electrode geometries and nerve topologies. This model has been made available in a public repository4. So far, the model behavior complies with available experimental results and expectations from literature. There is good agreement in terms of signal amplitude and waveform, and computational times are acceptable, leaving room for flexible simulation studies complementary to animal tests.

Tiresias: A low-cost networked UWB radar system for in-home monitoring of dementia patients.

This paper describes Tiresias, a low-cost, unobtrusive networked radar system designed to monitor vulnerable patients in domestic environments and provide high quality behavioural and health data. Dementia is a disease that affects millions worldwide and progressively degrades an individual's ability to care for themselves. Eventually most people living with dementia will need to reside in assisted living facilities as they become unable to care for themselves. Understanding the effects dementia has on ability to self-care and extending the length of time people living with dementia can remain living independently are key goals of dementia research and care. The networked radar system proposed in this paper is designed to provide high quality behavioural and health data from domestic environments. This is achieved using multiple radar sensors networked together with their data outputs integrated and processed to produce high confidence measures of position and movement. It is hoped the data produced by this system will both provide insights into how dementia progresses, and also help monitor vulnerable individuals in their own homes, allowing them to remain independent longer than would otherwise be possible.

Implantable brain machine interfaces: first-in-human studies, technology challenges and trends.

Implantable brain machine interfaces (BMIs) are now on a trajectory to go mainstream, wherein what was once considered last resort will progressively become elective at earlier stages in disease treatment. First-in-human successes have demonstrated the ability to decode highly dexterous motor skills such as handwriting, and speech from human cortical activity. These have been used for cursor and prosthesis control, direct-to-text communication and speech synthesis. Along with these breakthrough studies, technology advancements have enabled the observation of more channels of neural activity through new concepts for centralised/distributed implant architectures. This is complemented by research in flexible substrates, packaging, surgical workflows and data processing. New regulatory guidance and funding has galvanised the field. This culmination of resource, efforts and capability is now attracting significant investment for BMI commercialisation. This paper reviews recent developments and describes the paradigm shift in BMI development that is leading to new innovations, insights and BMI translation.

SenseBack - An Implantable System for Bidirectional Neural Interfacing.

Chronic in-vivo neurophysiology experiments require highly miniaturized, remotely powered multi-channel neural interfaces which are currently lacking in power or flexibility post implantation. To resolve this problem we present the SenseBack system, a post-implantation reprogrammable wireless 32-channel bidirectional neural interfacing device that can enable chronic peripheral electrophysiology experiments in freely behaving small animals. The large number of channels for a peripheral neural interface, coupled with fully implantable hardware and complete software flexibility enable complex in-vivo studies where the system can adapt to evolving study needs as they arise. In complementary \textit{ex-vivo} and \textit{in-vivo} preparations, we demonstrate that this system can record neural signals and perform high-voltage, bipolar stimulation on any channel. In addition, we demonstrate transcutaneous power delivery and Bluetooth 5 data communication with a PC. The SenseBack system is capable of stimulation on any channel with 20 V of compliance and up to 315 A of current, and highly configurable recording with per-channel adjustable gain and filtering with 8 sets of 10-bit ADCs to sample data at 20 kHz for each channel. To our knowledge this is the first such implantable research platform offering this level of performance and flexibility post-implantation (including complete reprogramming even after encapsulation) for small animal electrophysiology. Here we present initial acute trials, demonstrations and progress towards a system that we expect to enable a wide range of electrophysiology experiments in freely behaving animals.

An HFAC block-capable and module-extendable 4-channel stimulator for acute neurophysiology.

OBJECTIVE: This paper describes the design, testing and use of a novel multichannel block-capable stimulator for acute neurophysiology experiments to study highly selective neural interfacing techniques. This paper demonstrates the stimulator's ability to excite and inhibit nerve activity in the rat sciatic nerve model concurrently using monophasic and biphasic nerve stimulation as well as high-frequency alternating current (HFAC). APPROACH: The proposed stimulator uses a Howland Current Pump circuit as the main analogue stimulator element. 4 current output channels with a common return path were implemented on printed circuit board using Commercial Off-The-Shelf components. Programmable operation is carried out by an ARM Cortex-M4 Microcontroller on the Freescale freedom development platform (K64F). MAIN RESULTS: This stimulator design achieves ± 10 mA of output current with ± 15 V of compliance and less than 6 µA of resolution using a quad-channel 12-bit external DAC, for four independently driven channels. This allows the stimulator to carry out both excitatory and inhibitory (HFAC block) stimulation. DC Output impedance is above 1 M Ω. Overall cost for materials i.e. PCB boards and electronic components is less than USD 450 or GBP 350 and device size is approximately 9 cm × 6 cm × 5 cm. SIGNIFICANCE: Experimental neurophysiology often requires significant investment in bulky equipment for specific stimulation requirements, especially when using HFAC block. Different stimulators have limited means of communicating with each other, making protocols more complicated. This device provides an effective solution for multi-channel stimulation and block of nerves, enabling studies on selective neural interfacing in acute scenarios with an affordable, portable and space-saving design for the laboratory. The stimulator can be further upgraded with additional modules to extend functionality while maintaining straightforward programming and integration of functions with one controller. Additionally, all source files including all code and PCB design files are freely available to the community to use and further develop.

The Crucial Role of Nerve Depolarisation in High Frequency Conduction Block in Mammalian Nerves: Simulation Study.

Neurostimulations which use High Frequency Alternating Current (HFAC) block show great promise for neuromodulatory therapies. Treatments have been developed for various health conditions including obesity and obesity related health risks, and now even stomach cancer treatments are being considered. However the mechanism of the block is still not completely clear, as well as how various neural and electrode parameters affect it. In order to study conduction block during HF stimulation in mammalian axons, we describe a detailed computational model and perform comprehensive simulations. We establish relationships between the blocking frequency and amplitude versus fibre diameter and the distance between the electrode and fibre. We found that only a certain level of depolarisation will universally create a block irrespective of the fibre size, and it is in the range 24-30mV depending on the stimulus frequency. Our study crucially improves our knowledge about this important technique which is rapidly emerging as a commercially available therapy.

Preliminary Study of Time to Recovery of Rat Sciatic Nerve from High Frequency Alternating Current Nerve Block.

High-Frequency alternating current nerve block has great potential for neuromodulation-based therapies. However, no precise measurements have been made of the time needed for nerves to recover from block once the signal has been turned off. This study aims to characterise time to recovery of the rat sciatic nerve after 30 seconds of block at varying amplitudes and frequencies. Experiments were carried out invivo to quantify recovery times and recovery completeness within 0.7 s from the end of block. The sciatic nerve was blocked with an alternating square wave signal of amplitude and frequency ranging from 2 to 9mA and 10 to 50 kHz respectively. To determine the recovery dynamics the nerve was stimulated at 100 Hz after cessation of the blocking stimulus. Electromyogram signals were measured from the gastrocnemius medialis and tibialis anterior muscles during trials as indicators of nerve function. This allowed for nerve recovery to be measured with a resolution of 10 ms. This resolution is much greater than previous measurements of nerve recovery in the literature. Times for the nerve to recover to a steady state of activity ranged from 20 to 430 milliseconds and final relative recovery activity at 0.7 seconds spanned 0.2 to 1 approximately. Higher blocking signal amplitudes increased recovery time and decreased recovery completeness. These results suggest that blocking signal properties affect nerve recovery dynamics, which could help improve neuromodulation therapies and allow more precise comparison of results across studies using different blocking signal parameters.

A 64-Channel Versatile Neural Recording SoC With Activity-Dependent Data Throughput.

Modern microtechnology is enabling the channel count of neural recording integrated circuits to scale exponentially. However, the raw data bandwidth of these systems is increasing proportionately, presenting major challenges in terms of power consumption and data transmission (especially for wireless systems). This paper presents a system that exploits the sparse nature of neural signals to address these challenges and provides a reconfigurable low-bandwidth event-driven output. Specifically, we present a novel 64-channel low-noise (2.1 V), low-power (23  W per analogue channel) neural recording system-on-chip (SoC). This features individually configurable channels, 10-bit analogue-to-digital conversion, digital filtering, spike detection, and an event-driven output. Each channel's gain, bandwidth, and sampling rate settings can be independently configured to extract local field potentials at a low data-rate and/or action potentials (APs) at a higher data rate. The sampled data are streamed through an SRAM buffer that supports additional on-chip processing such as digital filtering and spike detection. Real-time spike detection can achieve 2 orders of magnitude data reduction, by using a dual polarity simple threshold to enable an event driven output for neural spikes (16-sample window). The SoC additionally features a latency-encoded asynchronous output that is critical if used as part of a closed-loop system. This has been specifically developed to complement a separate on-node spike sorting coprocessor to provide a real-time (low latency) output. The system has been implemented in a commercially available 0.35-m CMOS technology occupying a silicon area of 19.1 mm (0.3 mm gross per channel), demonstrating a low-power and efficient architecture that could be further optimized by aggressive technology and supply voltage scaling.

Fiber size-selective stimulation using action potential filtering for a peripheral nerve interface: A simulation study.

Functional electrical stimulation is a powerful tool for restoration of function after nerve injury. However selectivity of stimulation remains an issue. This paper presents an alternative stimulation technique to obtain fiber size-selective stimulation of nerves using FDA-approved electrode implants. The technique was simulated for the ventral roots of Xenopus Laevis, motivated by an application in bladder control. The technique relies on applying a high frequency alternating current to filter out action potentials in larger fibers, resulting in selective stimulation of the smaller fibers. Results predict that the technique can distinguish fibers with only a 2 µm difference in diameter (for nerves not exceeding 2mm in diameter). The study investigates the behaviour of electrically blocked nerves in detail. Model imperfections and simplifications yielded some artefacts in the results, as well as unexpected nerve behaviour which is tentatively explained.