Imperial College London

Professor Timothy Constandinou

Faculty of EngineeringDepartment of Electrical and Electronic Engineering

Professor of Bioelectronics
 
 
 
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Contact

 

+44 (0)20 7594 0790t.constandinou Website

 
 
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Assistant

 

Miss Izabela Wojcicka-Grzesiak +44 (0)20 7594 0701

 
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Location

 

B407Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

255 results found

Savolainen O, Zhang Z, Feng P, Constandinou Tet al., 2022, Hardware-efficient compression of neural multi-unit activity, IEEE Access, ISSN: 2169-3536

Journal article

Zaaimi B, Turnbull M, Hazra A, Wang Y, Gandara C, McLeod F, McDermott EE, Escobedo-Cousin E, Idil AS, Bailey RG, Tardio S, Patel A, Ponon N, Gausden J, Walsh D, Hutchings F, Kaiser M, Cunningham MO, Clowry GJ, LeBeau FEN, Constandinou TG, Baker SN, Donaldson N, Degenaar P, O'Neill A, Trevelyan AJ, Jackson Aet al., 2022, Closed-loop optogenetic control of the dynamics of neural activity in non-human primates, NATURE BIOMEDICAL ENGINEERING, ISSN: 2157-846X

Journal article

Lauteslager T, Tommer M, Lande TS, Constandinou TGet al., 2022, Dynamic Microwave Imaging of the Cardiovascular System Using Ultra-Wideband Radar-on-Chip Devices, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 69, Pages: 2935-2946, ISSN: 0018-9294

Journal article

Rapeaux A, Syed O, Cuttaz E, Chapman C, Green R, Constandinou Tet al., 2022, Preparation of rat sciatic nerve for ex vivo neurophysiology, Jove-Journal of Visualized Experiments, Vol: 185, Pages: 1-14, ISSN: 1940-087X

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.

Journal article

Zhang Z, Constandinou TG, 2022, Selecting an effective amplitude threshold for neural spike detection., Annu Int Conf IEEE Eng Med Biol Soc, Vol: 2022, Pages: 2328-2331

This paper assesses and challenges whether commonly used methods for defining amplitude thresholds for spike detection are optimal. This is achieved through empirical testing of single amplitude thresholds across multiple recordings of varying SNR levels. Our results suggest that the most widely used noise-statistics-driven threshold can suffer from parameter deviation in different noise levels. The spike-noise-driven threshold can be an ideal approach to set the threshold for spike detection, which suffers less from the parameter deviation and is robust to sub-optimal settings.

Journal article

Teversham J, Wong SS, Hsieh B, Rapeaux A, Troiani F, Savolainen O, Zhang Z, Maslik M, Constandinou TGet al., 2022, Development of an Ultra Low-Cost SSVEP-based BCI Device for Real-Time On-Device Decoding., Annu Int Conf IEEE Eng Med Biol Soc, Vol: 2022, Pages: 208-213

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.

Journal article

Oprea A, Zhang Z, Constandinou TG, 2022, Hardware evaluation of spike detection algorithms towards wireless brain machine interfaces

<jats:title>Abstract</jats:title><jats:p>The current trend for implantable Brain Machine Interfaces (BMIs) is to increase the channel count, towards next generation devices that improve on information transfer rate. This however increases the raw data bandwidth for wired or wireless systems that ultimately impacts the power budget (and thermal dissipation). On-implant feature extraction and/or compression are therefore becoming essential to reduce the data rate, however the processing power is of concern. One common feature extraction technique for intracortical BMIs is spike detection. In this work, we have empirically compared the performance, resource utilization, and power consumption of three hardware efficient spike emphasizers, Non-linear Energy Operator (NEO), Amplitude Slope Operator (ASO) and Energy of Derivative (ED), and two common statistical thresholding mechanisms (using mean or median). We also propose a novel median approximation to address the issue of the median operator not being hardware-efficient to implement. These have all been implemented and evaluated on reconfigurable hardware (FPGA) to estimate their hardware efficiency in an ultimate ASIC design. Our results suggest that ED with average thresholding provides the most hardware efficient (low power/resource) choice, while using median has the advantage of improved detection accuracy and higher robustness on threshold multiplier settings. This work is significant because it is the first to implement and compare the hardware and algorithm trade-offs that have to be made before translating the algorithms into hardware instances to design wireless implantable BMIs.</jats:p>

Journal article

Rapeaux A, Constandinou T, 2022, HFAC dose repetition and accumulation leads to progressively longer block carryover effect in rat sciatic nerve, Frontiers in Neuroscience, Vol: 16, ISSN: 1662-453X

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

Journal article

Zamora M, Toth R, Morgante F, Ottaway J, Gillbe T, Martin S, Lamb G, Noone T, Benjaber M, Nairac Z, Sehgal D, Constandinou TG, Herron J, Aziz TZ, Gillbe I, Green AL, Pereira EAC, Denison Tet al., 2022, DyNeuMo Mk-1: Design and pilot validation of an investigational motion-adaptive neurostimulator with integrated chronotherapy, EXPERIMENTAL NEUROLOGY, Vol: 351, ISSN: 0014-4886

Journal article

Savolainen OW, Zhang Z, Feng P, Constandinou TGet al., 2022, Hardware-Efficient Compression of Neural Multi-Unit Activity

<jats:title>Abstract</jats:title><jats:p>Brain-machine interfaces (BMI) are tools for treating neurological disorders and motor-impairments. It is essential that the next generation of intracortical BMIs is wireless so as to remove percutaneous connections, i.e. wires, and the associated mechanical and infection risks. This is required for the effective translation of BMIs into clinical applications and is one of the remaining bottlenecks. However, due to cortical tissue thermal dissipation safety limits, the on-implant power consumption must be strictly limited. Therefore, both the neural signal processing and wireless communication power should be minimal, while the implants should provide signals that offer high behavioural decoding performance (BDP). The Multi-Unit Activity (MUA) signal is the most common signal in modern BMIs. However, with an ever-increasing channel count, the raw data bandwidth is becoming prohibitively high due to the associated communication power exceeding the safety limits. Data compression is therefore required. To meet this need, this work developed hardware-efficient static Huffman compression schemes for MUA data. Our final system reduced the bandwidth to 27 bps/channel, compared to the standard MUA rate of 1 kbps/channel. This compression is over an order of magnitude more than has been achieved before, while using only 0.96 uW/channel processing power and 246 logic cells. Our results were verified on 3 datasets and less than 1% loss in BDP was observed. As such, with the use of effective data compression, an order more of MUA channels can be fitted on-implant, enabling the next generation of high-performance wireless intracortical BMIs.</jats:p>

Journal article

Ahmadi N, Adiono T, Purwarianti A, Constandinou T, Bouganis Cet al., 2022, Improved spike-based brain-machine interface using bayesian adaptive kernel smoother and deep learning, IEEE Access, Vol: 10, Pages: 29341-29356, ISSN: 2169-3536

Multiunit activity (MUA) has been proposed to mitigate the robustness issue faced by single-unit activity (SUA)-based brain-machine interfaces (BMIs). Most MUA-based BMIs still employ a binning method for estimating firing rates and linear decoder for decoding behavioural parameters. The limitations of binning and linear decoder lead to suboptimal performance of MUA-based BMIs. To address this issue, we propose a method which consists of Bayesian adaptive kernel smoother (BAKS) as the firing rate estimation algorithm and deep learning, particularly quasi-recurrent neural network (QRNN), as the decoding algorithm. We evaluated the proposed method for reconstructing (offline) hand kinematics from intracortical neural data chronically recorded from the primary motor cortex of two non-human primates. Extensive empirical results across recording sessions and subjects showed that the proposed method consistently outperforms other combinations of firing rate estimation algorithm and decoding algorithm. Overall results suggest the effectiveness of the proposed method for improving the decoding performance of MUA-based BMIs.

Journal article

Zhang Z, Savolainen OW, Constandinou TG, 2022, Algorithm and hardware considerations for real-time neural signal on-implant processing, JOURNAL OF NEURAL ENGINEERING, Vol: 19, ISSN: 1741-2560

Journal article

Teversham J, Wong SS, Hsieh B, Rapeaux A, Troiani F, Savolainen O, Zhang Z, Maslik M, Constandinou TGet al., 2022, Development of an Ultra Low-Cost SSVEP-based BCI Device for Real-Time On-Device Decoding

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

Journal article

Zhang Z, Constandinou TG, 2022, Selecting an effective amplitude threshold for neural spike detection

<jats:title>Abstract</jats:title><jats:p>This paper assesses and challenges whether commonly used methods for defining amplitude thresholds for spike detection are optimal. This is achieved through empirical testing of single amplitude thresholds across multiple recordings of varying SNR levels. Our results suggest that the most widely used noise-statistics-driven threshold can suffer from parameter deviation in different noise levels. The spike-noise-driven threshold can be an ideal approach to set the threshold for spike detection, which suffers less from the parameter deviation and is robust to sub-optimal settings.</jats:p>

Journal article

Di Patrizio Stanchieri G, De Marcellis A, Battisti G, Faccio M, Palange E, Constandinou TGet al., 2022, A Multilevel Synchronized Optical Pulsed Modulation for High Efficiency Biotelemetry, IEEE Transactions on Biomedical Circuits and Systems, ISSN: 1932-4545

The paper describes the design, implementation, and characterization of a novel multilevel synchronized pulse position modulation paradigm for high efficiency optical biotelemetry links. The entire optoelectronic architecture has been designed with the aim to improve the efficiency of the data transmission and decrease the overall power consumption that are key factors for the fabrication of implantable and wearable medical devices. By employing specially designed digital architectures, the proposed modulation technique automatically transmits more than one bit per symbol together with the reference clock signal enabling the decoding process of the received coded data. In the present case, the paper demonstrates the capability of the modulation technique to transmit symbols composed by 3 and 4 bits. This has been achieved by developing a prototype of an optical biotelemetry system implemented on an FPGA board that, making use of 500 ps laser pulses, operates under the following two working conditions: (i) 40 MHz clock signal corresponding to a baud rate of 40 Mega symbol per second for symbols composed by 3 bits; (ii) 30 MHz clock signal corresponding to a baud rate of 30 Mega symbol per second for symbols composed by 4 bits. Thus, for both these two configurations the transmission data rate is 120 Mbps and the measured BER was lower than 10&#x2013;10. Finally, the power consumption was found to be 1.95 and 1.8 mW and the resulting energy efficiencies were 16.25 and 15 pJ&#x002F;bit for transmitted symbols composed by 3 and 4 bits&#x002F;symbol, respectively.

Journal article

Antoniadis D, Mifsud A, Feng P, Constandinou TGet al., 2022, An Open-Source RRAM Compiler, 2022 20TH IEEE INTERREGIONAL NEWCAS CONFERENCE (NEWCAS), Pages: 465-469

Journal article

Rapeaux AB, Constandinou TG, 2021, Implantable brain machine interfaces: first-in-human studies, technology challenges and trends, CURRENT OPINION IN BIOTECHNOLOGY, Vol: 72, Pages: 102-111, ISSN: 0958-1669

Journal article

Maheshwari S, Stathopoulos S, Wang J, Serb A, Pan Y, Mifsud A, Leene LB, Shen J, Papavassiliou C, Constandinou TG, Prodromakis Tet al., 2021, Design flow for hybrid CMOS/memristor systems--Part I: modeling and verification steps, IEEE Transactions on Circuits and Systems I: Regular Papers, Vol: 68, Pages: 4862-4875, ISSN: 1549-8328

Memristive technology has experienced explosive growth in the last decade, with multiple device structures being developed for a wide range of applications. However, transitioning the technology from the lab into the marketplace requires the development of an accessible and user-friendly design flow, supported by an industry-grade toolchain. In this work, we demonstrate the behaviour of our in-house fabricated custom memristor model and its integration into the Cadence Electronic Design Automation (EDA) tools for verification. Various input stimuli were given to record the memristive device characteristics both at the device level as well as the schematic level for verification of the memristor model. This design flow from device to industrial level EDA tools is the first step before the model can be used and integrated with Complementary Metal-Oxide Semiconductor (CMOS) in applications for hybrid memristor/CMOS system design.

Journal article

Maheshwari S, Stathopoulos S, Wang J, Serb A, Pan Y, Mifsud A, Leene LB, Shen J, Papavassiliou C, Constandinou TG, Prodromakis Tet al., 2021, Design flow for hybrid CMOS/memristor systems--Part II: circuit schematics and layout, IEEE Transactions on Circuits and Systems I: Regular Papers, Vol: 68, Pages: 4876-4888, ISSN: 1549-8328

\normalsize The capability of in-memory computation, reconfigurability, low power operation as well as multistate operation of the memristive device deems them a suitable candidate for designing electronic circuits with a broad range of applications. Besides, the integrability of memristor with CMOS enables it to use in logic circuits too. In this work, we demonstrate with examples the design flow for memristor-based electronics, after the custom memristor model already being integrated and validated into our chosen Computer-Aided Design (CAD) tool to performing layout-versus-schematic and post-layout checks including the memristive device. We envisage that this step-by-step guide to introducing memristor into the standard integrated circuit design flow will be a useful reference document for both device developers who wish to benchmark their technologies and circuit designers who wish to experiment with memristive-enhanced systems.

Journal article

Harding EC, Ba W, Zahir R, Yu X, Yustos R, Hsieh B, Lignos L, Vyssotski AL, Merkle FT, Constandinou TG, Franks NP, Wisden Wet al., 2021, Nitric oxide synthase neurons in the preoptic hypothalamus are NREM and REM sleep-active and lower body temperature, Frontiers in Neuroscience, Vol: 15, ISSN: 1662-453X

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.

Journal article

Ahmadi N, Constandinou T, Bouganis C, 2021, Inferring entire spiking activity from local field potentials, Scientific Reports, Vol: 11, Pages: 1-13, ISSN: 2045-2322

Extracellular recordings are typically analysed by separating them into two distinct signals: local field potentials (LFPs) andspikes. Previous studies have shown that spikes, in the form of single-unit activity (SUA) or multiunit activity (MUA), can beinferred solely from LFPs with moderately good accuracy. SUA and MUA are typically extracted via threshold-based techniquewhich may not be reliable when the recordings exhibit a low signal-to-noise ratio (SNR). Another type of spiking activity, referredto as entire spiking activity (ESA), can be extracted by a threshold-less, fast, and automated technique and has led to betterperformance in several tasks. However, its relationship with the LFPs has not been investigated. In this study, we aim toaddress this issue by inferring ESA from LFPs intracortically recorded from the motor cortex area of three monkeys performingdifferent tasks. Results from long-term recording sessions and across subjects revealed that ESA can be inferred from LFPswith good accuracy. On average, the inference performance of ESA was consistently and significantly higher than those of SUAand MUA. In addition, local motor potential (LMP) was found to be the most predictive feature. The overall results indicate thatLFPs contain substantial information about spiking activity, particularly ESA. This could be useful for understanding LFP-spikerelationship and for the development of LFP-based BMIs.

Journal article

Antoniadis DD, Feng P, Mifsud A, Constandinou TGet al., 2021, Open-source memory compiler for automatic RRAM generation and verification, 2021 IEEE International Midwest Symposium on Circuits and Systems (MWSCAS), Publisher: IEEE, Pages: 97-100

The lack of open-source memory compilers in academia typically causes significant delays in research and design implementations. This paper presents an open-source memory compiler that is directly integrated within the Cadence Virtuoso environment using physical verification tools provided by Mentor Graphics (Calibre). It facilitates the entire memory generation process from netlist generation to layout implementation, and physical implementation verification. To the best of our knowledge, this is the first open-source memory compiler that has been developed specifically to automate Resistive Random Access Memory (RRAM) generation. RRAM holds the promise of achieving high speed, high density and non-volatility. A novel RRAM architecture, additionally is proposed, and a number of generated RRAM arrays are evaluated to identify their worst case control line parasitics and worst case settling time across the memristors of their cells. The total capacitance of lines SEL, N and P is 5.83 fF/cell, 3.31 fF/cell and 2.48 fF/cell respectively, while the total calculated resistance for SEL is 1.28 Ω/cell and 0.14 Ω/cell for both N and P lines.

Conference paper

Firfilionis D, Hutchings F, Tamadoni R, Walsh D, Turnbull M, Escobedo-Cousin E, Bailey RG, Gausden J, Patel A, Haci D, Liu Y, LeBeau FEN, Trevelyan A, Constandinou TG, O'Neill A, Kaiser M, Degenaar P, Jackson Aet al., 2021, A closed-loop optogenetic platform, Frontiers in Neuroscience, Vol: 15, Pages: 1-10, ISSN: 1662-453X

Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity. We are developing an open-source system to provide a platform for closed-loop optogenetic neuromodulation, incorporating custom integrated circuitry for recording and stimulation, real-time closed-loop algorithms running on a microcontroller and experimental control via a PC interface. We include commercial components to validate performance, with the ultimate aim of translating this approach to humans. In the meantime our system is flexible and expandable for use in a variety of preclinical neuroscientific applications. The platform consists of a Controlling Abnormal Network Dynamics using Optogenetics (CANDO) Control System (CS) that interfaces with up to four CANDO headstages responsible for electrical recording and optical stimulation through custom CANDO LED optrodes. Control of the hardware, inbuilt algorithms and data acquisition is enabled via the CANDO GUI (Graphical User Interface). Here we describe the design and implementation of this system, and demonstrate how it can be used to modulate neuronal oscillations in vitro and in vivo.

Journal article

Constandinou TG, Tang KT, Wang G, 2021, Editorial special section on selected papers from ISICAS 2020, IEEE Transactions on Biomedical Circuits and Systems, Vol: 15, Pages: 646-646, ISSN: 1932-4545

Journal article

Szostak KM, Keshavarz M, Constandinou T, 2021, Hermetic chip-scale packaging using Au:Sn eutectic bonding for implantable devices, Journal of Micromechanics and Microengineering, Vol: 31, Pages: 1-13, ISSN: 0960-1317

Advancements in miniaturisation and new capabilities of implantable devices impose a need for the development of compact, hermetic, and CMOS-compatible micro packaging methods. Gold-tin-based eutectic bonding presents the potential for achieving low-footprint seals with low permeability to moisture at process temperatures below 350 compfnC. This work describes a method for the deposition of Au:Sn eutectic alloy frames by sequential electroplating from commercially available solutions. Frames were bonded on the chip-level in the process of eutectic bonding. Bond quality was characterised through shear force measurements, scanning electron microscopy, visual inspection, and immersion tests. Characterisation of seals geometry, solder thickness, and bonding process parameters was evaluated, along with toxicity assessment of bonding layers to the human fibroblast cells. With a successful bond yield of over 70% and no cytotoxic effect, Au:Sn eutectic bonding appears as a suitable method for the protection of integrated circuitry in implantable applications.

Journal article

Chen Z, Bannon A, Rapeaux A, Constandinou TGet al., 2021, Towards robust, unobtrusive sensing of respiration using UWB impulse Radar for the care of people living with dementia, 10th International IEEE-EMBS Conference on Neural Engineering (NER), Publisher: IEEE, Pages: 866-871, ISSN: 1948-3546

The unobtrusive monitoring of vital signals and behaviour can be used to gather intelligence to support the care of people living with dementia. This can provide insights into the person's wellbeing and the neurogenerative process, as well as enable them to continue to live safely at home, thereby improving their quality of life. Within this context, this study investigated the deployability of non-contact respiration rate (RR) measurement based on an Ultra-Wideband (UWB) radar System-on-Chip (SoC). An algorithm was developed to simultaneously and continuously extract the respiration signal, together with the confidence level of the respiration signal and the target position, without needing any prior calibration. The radar-measured RR results were compared to the RR results obtained from a ground truth measure based on the breathing sound, and the error rates were within 8% with a mean value of 2.5%. The target localisation results match to the radar-to-chest distances with a mean error rate of 5.8%. The tested measurement range was up to 5m. The results suggest that the algorithm could perform sufficiently well in non-contact stationary respiration rate detection.

Conference paper

Harding EC, Ba W, Zahir R, Yu X, Yustos R, Hsieh B, Lignos L, Vyssotski AL, Constandinou T, Franks NP, Wisden Wet al., 2021, Nitric oxide synthase neurons in the preoptic hypothalamus are sleep-active and contribute to regulating NREM and REM sleep and lowering body temperature, Publisher: Cold Spring Harbor Laboratory

When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM active. This is the first instance of a predominantly NREM-active population in the PO area, or to our knowledge, elsewhere in the brain. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 hours, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer. In particular, mice were warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.

Working paper

Savolainen OW, Constandinou TG, 2021, Investigating the effects of macaque primary motor cortex multi-unit activity binning period on behavioural decoding performance, 10th International IEEE-EMBS Conference on Neural Engineering (NER), Publisher: IEEE, Pages: 436-439, ISSN: 1948-3546

This paper investigates the relationship between Multi-Unit Activity (MUA) Binning Period (BP) and Brain-Computer Interface (BCI) decoding performance using Long-Short Term Memory decoders. The motivation is to determine whether lossy compression of MUA via increasing BP has any adverse consequences for BCI Behavioral Decoding Performance (BDP). The Neural data originates from intracortical recordings from Macaque Primary Motor cortex. The BDP is measured by the Pearson correlation r between the observed and predicted velocity of the subject's X- Y hand coordinates in reaching tasks. The results suggest a statistically significant but slight linear relationship between increasing MUA BP and decreasing BDP. For example, when using a 100 ms moving average window, increasing the BP by 10 ms on average reduces the BDP r by approximately 0.85%. This relationship may be due to the reduced number of training examples, or due to the loss of Behavioral information because of reduced MUA temporal resolution.

Conference paper

Zhang Z, Constandinou TG, 2021, A robust and automated algorithm that uses single-channel spike sorting to label multi-channel Neuropixels data, 10th International IEEE-EMBS Conference on Neural Engineering (NER), Publisher: IEEE, Pages: 783-787, ISSN: 1948-3546

This paper describes preliminary work towards an automated algorithm for labelling Neuropixel data that exploits the fact that adjacent recording sites are spatially oversampled. This is achieved by combining classical single channel spike sorting with spatial spike grouping, resulting in an improvement in both accuracy and robustness. This is additionally complemented by an automated method for channel selection that determines which channels contain high quality data. The algorithm has been applied to a freely accessible dataset, produced by Cortex Lab, UCL. This has been evaluated to have a accuracy of over 77% compared to a manually curated ground truth.

Conference paper

Zhang Z, Constandinou T, 2021, Adaptive spike detection and hardware optimization towards autonomous, high-channel-count BMIs, Journal of Neuroscience Methods, Vol: 354, ISSN: 0165-0270

BackgroundThe progress in microtechnology has enabled an exponential trend in the number of neurons that can be simultaneously recorded. The data bandwidth requirement is however increasing with channel count. The vast majority of experimental work involving electrophysiology stores the raw data and then processes this offline; to detect the underlying spike events. Emerging applications however require new methods for local, real-time processing.New MethodsWe have developed an adaptive, low complexity spike detection algorithm that combines three novel components for: (1) removing the local field potentials; (2) enhancing the signal-to-noise ratio; and (3) computing an adaptive threshold. The proposed algorithm has been optimised for hardware implementation (i.e. minimising computations, translating to a fixed-point implementation), and demonstrated on low-power embedded targets.Main resultsThe algorithm has been validated on both synthetic datasets and real recordings yielding a detection sensitivity of up to 90%. The initial hardware implementation using an off-the-shelf embedded platform demonstrated a memory requirement of less than 0.1 kb ROM and 3 kb program flash, consuming an average power of 130 μW.Comparison with Existing MethodsThe method presented has the advantages over other approaches, that it allows spike events to be robustly detected in real-time from neural activity in a completely autonomous way, without the need for any calibration, and can be implemented with low hardware resources.ConclusionThe proposed method can detect spikes effectively and adaptively. It alleviates the need for re-calibration, which is critical towards achieving a viable BMI, and more so with future ‘high bandwidth’ systems’ targeting 1000s of channels.

Journal article

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