Biomedical Engineering - Research Publications

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    Conversion of Upper-Limb Inertial Measurement Unit Data to Joint Angles: A Systematic Review.
    Fang, Z ; Woodford, S ; Senanayake, D ; Ackland, D (MDPI AG, 2023-07-19)
    Inertial measurement units (IMUs) have become the mainstay in human motion evaluation outside of the laboratory; however, quantification of 3-dimensional upper limb motion using IMUs remains challenging. The objective of this systematic review is twofold. Firstly, to evaluate computational methods used to convert IMU data to joint angles in the upper limb, including for the scapulothoracic, humerothoracic, glenohumeral, and elbow joints; and secondly, to quantify the accuracy of these approaches when compared to optoelectronic motion analysis. Fifty-two studies were included. Maximum joint motion measurement accuracy from IMUs was achieved using Euler angle decomposition and Kalman-based filters. This resulted in differences between IMU and optoelectronic motion analysis of 4° across all degrees of freedom of humerothoracic movement. Higher accuracy has been achieved at the elbow joint with functional joint axis calibration tasks and the use of kinematic constraints on gyroscope data, resulting in RMS errors between IMU and optoelectronic motion for flexion-extension as low as 2°. For the glenohumeral joint, 3D joint motion has been described with RMS errors of 6° and higher. In contrast, scapulothoracic joint motion tracking yielded RMS errors in excess of 10° in the protraction-retraction and anterior-posterior tilt direction. The findings of this study demonstrate high-quality 3D humerothoracic and elbow joint motion measurement capability using IMUs and underscore the challenges of skin motion artifacts in scapulothoracic and glenohumeral joint motion analysis. Future studies ought to implement functional joint axis calibrations, and IMU-based scapula locators to address skin motion artifacts at the scapula, and explore the use of artificial neural networks and data-driven approaches to directly convert IMU data to joint angles.
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    GutMap: A New Interface for Analysing Regional Motility Patterns in ex vivo Mouse Gastrointestinal Preparations.
    Abo-Shaban, T ; Lee, CYQ ; Hosie, S ; Balasuriya, GK ; Mohsenipour, M ; Johnston, LA ; Hill-Yardin, EL (Bio-Protocol, LLC, 2023-10-05)
    Different regions of the gastrointestinal tract have specific functions and thus distinct motility patterns. Motility is primarily regulated by the enteric nervous system (ENS), an intrinsic network of neurons located within the gut wall. Under physiological conditions, the ENS is influenced by the central nervous system (CNS). However, by using ex vivo organ bath experiments, ENS regulation of gut motility can also be studied in the absence of CNS influences. The current technique enables the characterisation of small intestinal, caecal, and colonic motility patterns using an ex vivo organ bath and video imaging protocol. This approach is combined with the novel edge detection script GutMap, available in MATLAB, that functions across Windows and Mac platforms. Dissected intestinal segments are cannulated in an organ bath containing physiological saline with a camera mounted overhead. Video recordings of gut contractions are then converted to spatiotemporal heatmaps and analysed using the GutMap software interface. Using data analysed from the heatmaps, parameters of contractile patterns (including contraction propagation frequency and velocity as well as gut diameter) at baseline and in the presence of drugs/treatments/genetic mutations can be compared. Here, we studied motility patterns of female mice at baseline and in the presence of a nitric oxide synthase inhibitor (Nω-Nitro-L-arginine; NOLA) (nitric oxide being the main inhibitory neurotransmitter of gut motility) to showcase the application of GutMap. This technique is suitable for application to a broad range of animal models of clinical disorders to understand underlying biological pathways contributing to gastrointestinal dysfunction. Key features • Enhanced video imaging analysis of gut contractility in rodents using a novel software interface. • New edge detection algorithm to accurately contour curvatures of the gastrointestinal tract. • Allows for output of high-resolution spatiotemporal heatmaps across Windows and Mac platforms. • Edge detection and analysis method makes motility measurements accessible in different gut regions including the caecum and stomach.
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    Spike-timing dependent plasticity partially compensates for neural delays in a multi-layered network of motion-sensitive neurons.
    Sexton, CM ; Burkitt, AN ; Hogendoorn, H ; Perrinet, LU (Public Library of Science (PLoS), 2023-09)
    The ability of the brain to represent the external world in real-time is impacted by the fact that neural processing takes time. Because neural delays accumulate as information progresses through the visual system, representations encoded at each hierarchical level are based upon input that is progressively outdated with respect to the external world. This 'representational lag' is particularly relevant to the task of localizing a moving object-because the object's location changes with time, neural representations of its location potentially lag behind its true location. Converging evidence suggests that the brain has evolved mechanisms that allow it to compensate for its inherent delays by extrapolating the position of moving objects along their trajectory. We have previously shown how spike-timing dependent plasticity (STDP) can achieve motion extrapolation in a two-layer, feedforward network of velocity-tuned neurons, by shifting the receptive fields of second layer neurons in the opposite direction to a moving stimulus. The current study extends this work by implementing two important changes to the network to bring it more into line with biology: we expanded the network to multiple layers to reflect the depth of the visual hierarchy, and we implemented more realistic synaptic time-courses. We investigate the accumulation of STDP-driven receptive field shifts across several layers, observing a velocity-dependent reduction in representational lag. These results highlight the role of STDP, operating purely along the feedforward pathway, as a developmental strategy for delay compensation.
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    A debate on the neuronal origin of focal seizures
    Wenzel, M ; Huberfeld, G ; Grayden, DB ; de Curtis, M ; Trevelyan, AJ (WILEY, 2023-05-15)
    A critical question regarding how focal seizures start is whether we can identify particular cell classes that drive the pathological process. This was the topic for debate at the recent International Conference for Technology and Analysis of Seizures (ICTALS) meeting (July 2022, Bern, CH) that we summarize here. The debate has been fueled in recent times by the introduction of powerful new ways to manipulate subpopulations of cells in relative isolation, mostly using optogenetics. The motivation for resolving the debate is to identify novel targets for therapeutic interventions through a deeper understanding of the etiology of seizures.
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    Effect of sparsity on network stability in random neural networks obeying Dale's law
    Harris, ID ; Meffin, H ; Burkitt, AN ; Peterson, ADH (American Physical Society (APS), 2023-10-01)
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    Evaluation of Optimal Stimuli for SSVEP-Based Augmented Reality Brain-Computer Interfaces
    Zehra, SR ; Mu, J ; Syiem, BV ; Burkitt, AN ; Grayden, DB (IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2023)
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    Continuous synthesis of artificial speech sounds from human cortical surface recordings during silent speech production
    Meng, K ; Goodarzy, F ; Kim, E ; Park, YJ ; Kim, JS ; Cook, MJ ; Chung, CK ; Grayden, DB (IOP Publishing Ltd, 2023-08-01)
    Objective. Brain-computer interfaces can restore various forms of communication in paralyzed patients who have lost their ability to articulate intelligible speech. This study aimed to demonstrate the feasibility of closed-loop synthesis of artificial speech sounds from human cortical surface recordings during silent speech production.Approach. Ten participants with intractable epilepsy were temporarily implanted with intracranial electrode arrays over cortical surfaces. A decoding model that predicted audible outputs directly from patient-specific neural feature inputs was trained during overt word reading and immediately tested with overt, mimed and imagined word reading. Predicted outputs were later assessed objectively against corresponding voice recordings and subjectively through human perceptual judgments.Main results. Artificial speech sounds were successfully synthesized during overt and mimed utterances by two participants with some coverage of the precentral gyrus. About a third of these sounds were correctly identified by naïve listeners in two-alternative forced-choice tasks. A similar outcome could not be achieved during imagined utterances by any of the participants. However, neural feature contribution analyses suggested the presence of exploitable activation patterns during imagined speech in the postcentral gyrus and the superior temporal gyrus. In future work, a more comprehensive coverage of cortical surfaces, including posterior parts of the middle frontal gyrus and the inferior frontal gyrus, could improve synthesis performance during imagined speech.Significance.As the field of speech neuroprostheses is rapidly moving toward clinical trials, this study addressed important considerations about task instructions and brain coverage when conducting research on silent speech with non-target participants.
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    Chronic intracranial EEG recordings and interictal spike rate reveal multiscale temporal modulations in seizure states
    Schroeder, GM ; Karoly, PJ ; Maturana, M ; Panagiotopoulou, M ; Taylor, PN ; Cook, MJ ; Wang, Y (OXFORD UNIV PRESS, 2023-08-31)
    Many biological processes are modulated by rhythms on circadian and multidien timescales. In focal epilepsy, various seizure features, such as spread and duration, can change from one seizure to the next within the same patient. However, the specific timescales of this variability, as well as the specific seizure characteristics that change over time, are unclear. Here, in a cross-sectional observational study, we analysed within-patient seizure variability in 10 patients with chronic intracranial EEG recordings (185-767 days of recording time, 57-452 analysed seizures/patient). We characterized the seizure evolutions as sequences of a finite number of patient-specific functional seizure network states. We then compared seizure network state occurrence and duration to (1) time since implantation and (2) patient-specific circadian and multidien cycles in interictal spike rate. In most patients, the occurrence or duration of at least one seizure network state was associated with the time since implantation. Some patients had one or more seizure network states that were associated with phases of circadian and/or multidien spike rate cycles. A given seizure network state's occurrence and duration were usually not associated with the same timescale. Our results suggest that different time-varying factors modulate within-patient seizure evolutions over multiple timescales, with separate processes modulating a seizure network state's occurrence and duration. These findings imply that the development of time-adaptive treatments in epilepsy must account for several separate properties of epileptic seizures and similar principles likely apply to other neurological conditions.
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    A tissue-engineered neural interface with photothermal functionality.
    Nascimento, ATD ; Mendes, AX ; Begeng, JM ; Duchi, S ; Stoddart, PR ; Quigley, AF ; Kapsa, RMI ; Ibbotson, MR ; Silva, SM ; Moulton, SE (Royal Society of Chemistry (RSC), 2023-07-25)
    Neural interfaces are well-established as a tool to understand the behaviour of the nervous system via recording and stimulation of living neurons, as well as serving as neural prostheses. Conventional neural interfaces based on metals and carbon-based materials are generally optimised for high conductivity; however, a mechanical mismatch between the interface and the neural environment can significantly reduce long-term neuromodulation efficacy by causing an inflammatory response. This paper presents a soft composite material made of gelatin methacryloyl (GelMA) containing graphene oxide (GO) conjugated with gold nanorods (AuNRs). The soft hydrogel presents stiffness within the neural environment range of modulus below 5 kPa, while the AuNRs, when exposed to light in the near infrared range, provide a photothermal response that can be used to improve the spatial and temporal precision of neuromodulation. These favourable properties can be maintained at safer optical power levels when combined with electrical stimulation. In this paper we provide mechanical and biological characterization of the optical activity of the GO-AuNR composite hydrogel. The optical functionality of the material has been evaluated via photothermal stimulation of explanted rat retinal tissue. The outcomes achieved with this study encourage further investigation into optical and electrical costimulation parameters for a range of biomedical applications.
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    The impact of electrical stimulation protocols on neuronal cell survival and proliferation using cell-laden GelMA/graphene oxide hydrogels
    Mendes, AX ; do Nascimento, AT ; Duchi, S ; Quigley, AF ; Aguilar, LCM ; Dekiwadia, C ; Kapsa, RMI ; Silva, SM ; Moulton, SE (ROYAL SOC CHEMISTRY, 2022-12-19)
    The development of electroactive cell-laden hydrogels (bioscaffolds) has gained interest in neural tissue engineering research due to their inherent electrical properties that can induce the regulation of cell behaviour. Hydrogels combined with electrically conducting materials can respond to external applied electric fields, where these stimuli can promote electro-responsive cell growth and proliferation. A successful neural interface for electrical stimulation should present the desired stable electrical properties, such as high conductivity, low impedance, increased charge storage capacity and similar mechanical properties related to a target neural tissue. We report how different electrical stimulation protocols can impact neuronal cells' survival and proliferation when using cell-laden GelMA/GO hydrogels. The rat pheochromocytoma cell line, PC12s encapsulated into hydrogels showed an increased proliferation behaviour with increasing current amplitudes applied. Furthermore, the presence of GO in GelMA hydrogels enhanced the metabolic activity and DNA content of PC12s compared with GelMA alone. Similarly, hydrogels provided survival of encapsulated cells at higher current amplitudes when compared to cells seeded onto ITO flat surfaces, which expressed significant cell death at a current amplitude of 2.50 mA. Our findings provide new rational choices for electroactive hydrogels and electrical stimulation with broad potential applications in neural tissue engineering research.