Biomedical Engineering - Research Publications

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    Tissue Programmed Hydrogels Functionalized with GDNF Improve Human Neural Grafts in Parkinson's Disease (Adv. Funct. Mater. 47/2021)
    Hunt, CPJ ; Penna, V ; Gantner, CW ; Moriarty, N ; Wang, Y ; Franks, S ; Ermine, CM ; de Luzy, IR ; Pavan, C ; Long, BM ; Williams, RJ ; Thompson, LH ; Nisbet, DR ; Parish, CL (Wiley, 2021-11)
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    Predictive Visual Motion Extrapolation Emerges Spontaneously and without Supervision at Each Layer of a Hierarchical Neural Network with Spike-Timing-Dependent Plasticity
    Burkitt, AN ; Hogendoorn, H (SOC NEUROSCIENCE, 2021-05-19)
    The fact that the transmission and processing of visual information in the brain takes time presents a problem for the accurate real-time localization of a moving object. One way this problem might be solved is extrapolation: using an object's past trajectory to predict its location in the present moment. Here, we investigate how a simulated in silico layered neural network might implement such extrapolation mechanisms, and how the necessary neural circuits might develop. We allowed an unsupervised hierarchical network of velocity-tuned neurons to learn its connectivity through spike-timing-dependent plasticity (STDP). We show that the temporal contingencies between the different neural populations that are activated by an object as it moves causes the receptive fields of higher-level neurons to shift in the direction opposite to their preferred direction of motion. The result is that neural populations spontaneously start to represent moving objects as being further along their trajectory than where they were physically detected. Because of the inherent delays of neural transmission, this effectively compensates for (part of) those delays by bringing the represented position of a moving object closer to its instantaneous position in the world. Finally, we show that this model accurately predicts the pattern of perceptual mislocalization that arises when human observers are required to localize a moving object relative to a flashed static object (the flash-lag effect; FLE).SIGNIFICANCE STATEMENT Our ability to track and respond to rapidly changing visual stimuli, such as a fast-moving tennis ball, indicates that the brain is capable of extrapolating the trajectory of a moving object to predict its current position, despite the delays that result from neural transmission. Here, we show how the neural circuits underlying this ability can be learned through spike-timing-dependent synaptic plasticity and that these circuits emerge spontaneously and without supervision. This demonstrates how the neural transmission delays can, in part, be compensated to implement the extrapolation mechanisms required to predict where a moving object is at the present moment.
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    Source data from a systematic review and meta-analysis of EEG and MEG studies investigating functional connectivity in idiopathic generalized epilepsy
    Dharan, AL ; Bowden, SC ; Lai, A ; Peterson, ADH ; Cheung, MW-L ; Woldman, W ; D'Souza, WJ (ELSEVIER, 2021-12)
    This article describes source data from a systematic review and meta-analysis of electroencephalography (EEG) and magnetoencephalography (MEG) studies investigating functional connectivity in idiopathic generalized epilepsy. Data selection, analysis and reporting was performed according to PRISMA guidelines. Eligible studies for review were identified from human case-control, and cohort studies. Twenty-two studies were included in the review. Extracted descriptive data included sample characteristics, acquisition of EEG or MEG recordings and network construction. Reported differences between IGE and control groups in functional connectivity or network metrics were extracted as the main outcome measure. Qualitative group differences in functional connectivity were synthesized through narrative review. Meta-analysis was performed for group-level, quantitative estimates of common network metrics clustering coefficient, path length, mean degree and nodal strength. Six studies were included in the meta-analysis. Risk of bias was assessed across all studies. Raw and synthesized data for included studies are reported, alongside effect size and heterogeneity statistics from meta-analyses. Network neurosciences is a rapidly expanding area of research, with significant potential for clinical applications in epilepsy. This data article provides novel, statistical estimates of brain network differences from patients with IGE relative to healthy controls, across the existing literature. Increasing data accessibility supports study replication and improves study comparability for future reviews, enabling a better understanding of network characteristics in IGE.
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    Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease
    Siddiqi, SH ; Schaper, FLWVJ ; Horn, A ; Hsu, J ; Padmanabhan, JL ; Brodtmann, A ; Cash, RFH ; Corbetta, M ; Choi, KS ; Dougherty, DD ; Egorova, N ; Fitzgerald, PB ; George, MS ; Gozzi, SA ; Irmen, F ; Kuhn, AA ; Johnson, KA ; Naidech, AM ; Pascual-Leone, A ; Phan, TG ; Rouhl, RPW ; Taylor, SF ; Voss, JL ; Zalesky, A ; Grafman, JH ; Mayberg, HS ; Fox, MD (NATURE PORTFOLIO, 2021-12)
    Damage to specific brain circuits can cause specific neuropsychiatric symptoms. Therapeutic stimulation to these same circuits may modulate these symptoms. To determine whether these circuits converge, we studied depression severity after brain lesions (n = 461, five datasets), transcranial magnetic stimulation (n = 151, four datasets) and deep brain stimulation (n = 101, five datasets). Lesions and stimulation sites most associated with depression severity were connected to a similar brain circuit across all 14 datasets (P < 0.001). Circuits derived from lesions, deep brain stimulation and transcranial magnetic stimulation were similar (P < 0.0005), as were circuits derived from patients with major depression versus other diagnoses (P < 0.001). Connectivity to this circuit predicted out-of-sample antidepressant efficacy of transcranial magnetic stimulation and deep brain stimulation sites (P < 0.0001). In an independent analysis, 29 lesions and 95 stimulation sites converged on a distinct circuit for motor symptoms of Parkinson's disease (P < 0.05). We conclude that lesions, transcranial magnetic stimulation and DBS converge on common brain circuitry that may represent improved neurostimulation targets for depression and other disorders.
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    Brainhack: Developing a culture of open, inclusive, community-driven neuroscience
    Gau, R ; Noble, S ; Heuer, K ; Bottenhorn, KL ; Bilgin, IP ; Yang, Y-F ; Huntenburg, JM ; Bayer, JMM ; Bethlehem, RAI ; Rhoads, SA ; Vogelbacher, C ; Borghesani, V ; Levitis, E ; Wang, H-T ; Van den Bossche, S ; Kobeleva, X ; Legarreta, JH ; Guay, S ; Atay, SM ; Varoquaux, GP ; Huijser, DC ; Sandstrom, MS ; Herholz, P ; Nastase, SA ; Badhwar, A ; Dumas, G ; Schwab, S ; Moia, S ; Dayan, M ; Bassil, Y ; Brooks, PP ; Mancini, M ; Shine, JM ; O'Connor, D ; Xie, X ; Poggiali, D ; Friedrich, P ; Heinsfeld, AS ; Riedl, L ; Toro, R ; Caballero-Gaudes, C ; Eklund, A ; Garner, KG ; Nolan, CR ; Demeter, DV ; Barrios, FA ; Merchant, JS ; McDevitt, EA ; Oostenveld, R ; Craddock, RC ; Rokem, A ; Doyle, A ; Ghosh, SS ; Nikolaidis, A ; Stanley, OW ; Urunuela, E (CELL PRESS, 2021-06-02)
    Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
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    Low-Profile Electromagnetic Field Sensors in the Measurement and Modelling of Three-Dimensional Jaw Kinematics and Occlusal Loading
    Woodford, SC ; Robinson, DL ; Edelmann, C ; Mehl, A ; Roehrle, O ; Vee Sin Lee, P ; Ackland, DC (SPRINGER, 2021-06)
    Dynamic occlusal loading during mastication is clinically relevant in the design and functional assessment of dental restorations and removable dentures, and in evaluating temporomandibular joint dysfunction. The aim of this study was to develop a modelling framework to evaluate subject-specific dynamic occlusal loading during chewing and biting over the entire dental arch. Measurements of jaw motion were performed on one healthy male adult using low-profile electromagnetic field sensors attached to the teeth, and occlusal anatomy quantified using an intra-oral scanner. During testing, the subject chewed and maximally compressed a piece of rubber between both second molars, first molars, premolars and their central incisors. The occlusal anatomy, rubber geometry and experimentally measured rubber material properties were combined in a finite element model. The measured mandibular motion was used to kinematically drive model simulations of chewing and biting of the rubber sample. Three-dimensional dynamic bite forces and contact pressures across the occlusal surfaces were then calculated. Both chewing and biting on the first molars produced the highest bite forces across the dental arch, and a large amount of anterior shear force was produced at the incisors and the second molars. During chewing, the initial tooth-rubber contact evolved from the buccal sides of the molars to the lingual sides at full mouth closure. Low-profile electromagnetic field sensors were shown to provide a clinically relevant measure of jaw kinematics with sufficient accuracy to drive finite element models of occlusal loading during chewing and biting. The modelling framework presented provides a basis for calculation of physiological, dynamic occlusal loading across the dental arch.
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    The Potential of Calcium Phosphate Nanoparticles as Adjuvants and Vaccine Delivery Vehicles
    Sun, Z ; Li, W ; Lenzo, JC ; Holden, JA ; McCullough, MJ ; O'Connor, AJ ; O'Brien-Simpson, NM (FRONTIERS MEDIA SA, 2021-12-22)
    Vaccination is one of the most efficacious and cost-effective ways to protect people from infectious diseases and potentially cancer. The shift in vaccine design from disrupted whole pathogens to subunit antigens has brought attention on to vaccine delivery materials. For the last two decades, nanotechnology-based vaccines have attracted considerable attention as delivery vehicles and adjuvants to enhance immunogenicity, exemplified with the current COVID vaccines. The nanoparticle vaccines display unique features in protecting antigens from degradation, controlled antigen release and longer persisting immune response. Due to their size, shape and surface charge, they can be outstanding adjuvants to achieve various immunological effects. With the safety and biodegradable benefit of calcium phosphate nanoparticles (CaP NPs), they are an efficient carrier for vaccine design and adjuvants. Several research groups have studied CaP NPs in the field of vaccination with great advances. Although there are several reports on the overview of CaP NPs, they are limited to the application in biomedicine, drug delivery, bone regeneration and the methodologies of CaP NPs synthesis. Hence, we summarised the basic properties of CaP NPs and the recent vaccine development of CaP NPs in this review.
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    Microbial Transglutaminase Improves ex vivo Adhesion of Gelatin Methacryloyl Hydrogels to Human Cartilage
    Trengove, A ; Duchi, S ; Onofrillo, C ; O'Connell, CD ; Di Bella, C ; O'Connor, AJ (FRONTIERS MEDIA SA, 2021-11-18)
    Current surgical techniques to treat articular cartilage defects fail to produce a satisfactory long-term repair of the tissue. Regenerative approaches show promise in their ability to generate hyaline cartilage using biomaterials in combination with stem cells. However, the difficulty of seamlessly integrating the newly generated cartilage with the surrounding tissue remains a likely cause of long-term failure. To begin to address this integration issue, our strategy exploits a biological enzyme (microbial transglutaminase) to effect bioadhesion of a gelatin methacryloyl implant to host tissue. Mechanical characterization of the bioadhesive material shows that enzymatic crosslinking is compatible with photocrosslinking, allowing for a dual-crosslinked system with improved mechanical properties, and a slower degradation rate. Biocompatibility is illustrated with a 3D study of the metabolic activity of encapsulated human adipose derived stem cells. Furthermore, enzymatic crosslinking induced by transglutaminase is not prevented by the presence of cells, as measured by the bulk modulus of the material. Adhesion to human cartilage is demonstrated ex vivo with a significant increase in adhesive strength (5.82 ± 1.4 kPa as compared to 2.87 ± 0.9 kPa, p < 0.01) due to the addition of transglutaminase. For the first time, we have characterized a bioadhesive material composed of microbial transglutaminase and GelMA that can encapsulate cells, be photo crosslinked, and bond to host cartilage, taking a step toward the integration of regenerative implants.
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    Concurrent TMS/fMRI validates MDD target network engagement
    Tik, M ; Woletz, M ; Schuler, A-L ; Vasileiadi, M ; Cash, R ; Zalesky, A ; Lamm, C ; Windischberger, C (Elsevier BV, 2021-11)
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    Non-Invasive Measurement of Intracranial Pressure Through Application of Venous Ophthalmodynamometry.
    Lo, L ; Zhao, D ; Ayton, L ; Grayden, D ; Bui, B ; Morokoff, A ; John, S (IEEE, 2021-11)
    Non-invasive intracranial pressure (ICP) monitoring is possible using venous ophthalmodynamometry to observe a pulsation in retinal blood vessels when intraocular pressure (IOP) exceeds ICP. Here, we identify features in the eye - optic disc and retinal blood vessel locations - and identify pulsation in large retinal blood vessels. The relationship between force and the magnitude of pulsation is used to estimate ICP when force is applied to the eye to gradually increase IOP over time. This approach yields 77% accuracy in automatically observing vessel pulsation.Clinical Relevance - Non-invasive ICP monitoring is desirable to improve patient outcome by reducing potential trauma and complications associated with invasive assessment with intracranial sensors or lumbar puncture.