Biomedical Engineering - Research Publications
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ItemFaster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in the Nlgn3R451C Mouse Model of Autism(MDPI, 2024-01)Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here, we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show a 30.9% faster gastrointestinal transit (p = 0.0004) in vivo and have 6% longer small intestines (p = 0.04) compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter (proximal jejunum: 10.6% decrease, p = 0.02; mid: 9.8%, p = 0.04; distal: 11.5%, p = 0.009) and neurally regulated dysmotility as well as shorter durations of contractile complexes (mid: 25.6% reduction in duration, p = 0.009; distal: 30.5%, p = 0.004) in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABAA antagonist, gabazine, compared to 40.6% in wild-type mice (p = 0.007). The inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum (WT p = 0.0006, Nlgn3R451C p = 0.002), but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.
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ItemMulti-frequency steady-state visual evoked potential dataset(NATURE PORTFOLIO, 2024-01-04)The Steady-State Visual Evoked Potential (SSVEP) is a widely used modality in Brain-Computer Interfaces (BCIs). Existing research has demonstrated the capabilities of SSVEP that use single frequencies for each target in various applications with relatively small numbers of commands required in the BCI. Multi-frequency SSVEP has been developed to extend the capability of single-frequency SSVEP to tasks that involve large numbers of commands. However, the development on multi-frequency SSVEP methodologies is falling behind compared to the number of studies with single-frequency SSVEP. This dataset was constructed to promote research in multi-frequency SSVEP by making SSVEP signals collected with different frequency stimulation settings publicly available. In this dataset, SSVEPs were collected from 35 participants using single-, dual-, and tri-frequency stimulation and with three different multi-frequency stimulation variants.
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ItemNo Preview AvailableThomson-Einstein's Tea Leaf Paradox Revisited: Aggregation in Rings(MDPI, 2023-11)A distinct particle focusing spot occurs in the center of a rotating fluid, presenting an apparent paradox given the presence of particle inertia. It is recognized, however, that the presence of a secondary flow with a radial component drives this particle aggregation. In this study, we expand on the examination of this "Thomson-Einstein's tea leaf paradox" phenomenon, where we use a combined experimental and computational approach to investigate particle aggregation dynamics. We show that not only the rotational velocity, but also the vessel shape, have a significant influence on a particle's equilibrium position. We accordingly demonstrate the formation of a single focusing spot in a vessel center, as has been conclusively demonstrated elsewhere, but also the repeatable formation of stable ring-shaped particle arrangements.
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ItemNo Preview AvailableOptimizing coupling layer and superstrate thickness in attachable acoustofluidic devices.(Elsevier BV, 2024-02)Superstrate-based acoustofluidic devices, where the fluidic elements are reversibly coupled to a transducer rather than bonded to it, offer advantages for cost, interchangeability and preventing contamination between samples. A variety of coupling materials can be used to transmit acoustic energies into attachable superstrates, though the dimensions and material composition of the system elements are not typically optimized. This work analyzes these coupling layers for bulk wavefront transmission, including water, ultrasound gel and polydimethylsiloxane (PDMS), as well as the material makeup and thickness of the superstrate component, which is commonly comprised of glass, quartz or silicon. Our results highlight the importance of coupling layer and superstrate dimensions, identifying frequencies and component thicknesses that maximize transmission efficiency. Our results indicate that superstrate thicknesses 0.55 times the acoustic wavelength result in maximal acoustic coupling. While various coupling layers and superstrate materials are capable of similar acoustic energy transmission, the inherent dimensional stability of the PDMS coupling layers, somewhat less common in superstrate work compared to liquid-based agents, presents advantages for practically maximizing acoustic efficiency.
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ItemNo Preview AvailableThe contribution of the ligamentum teres to the hip fluid seal: A biomechanics study.(Elsevier BV, 2024-02)BACKGROUND: The suction seal of the hip plays an important role in maintaining hip stability; however, the function of the ligamentum teres in maintaining this seal remains poorly understood. This study aimed to evaluate the effectiveness of the hip suction seal in ligamentum teres deficient hips for joint positions occurring during gait. METHODS: Six fresh-frozen human cadaveric hips were dissected and mounted to an Instron materials test system. Each specimen was analyzed for average peak distraction force, stiffness, and total energy during hip displacement. Testing was performed in the native intact ligamentum teres state and the deficient ligamentum teres state. Specimens were examined in 20° of flexion, neutral, and 10° of extension. FINDINGS: In the neutral position, the ligamentum teres deficient state displayed a significant decrease in peak distraction force (mean difference: 33.2 N, p < 0.001), average stiffness (mean difference: 63.7 N/mm, p = 0.016), and total energy (mean difference: 82.3 mJ, p = 0.022) compared to the intact controls. In extension, the deficient state exhibited a significant decrease in peak distraction force (mean difference: 42.8 N, p < 0.001) and total energy (mean difference: 72.9 mJ, p = 0.007). In flexion, the deficient state displayed a significant decrease in peak distraction force relative to contols (mean difference: 7.1 N, p = 0.003). INTERPRETATION: The ligamentum teres plays a significant role in maintaining the suction seal of the hip, with its effect being most prominent when the hip is in neural alignment or in extension. The findings suggest that ligamentum teres deficiency may be a relevant treatment target in the clinical setting.
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ItemNo Preview AvailableComputational Fluid Dynamics of Stent-Mounted Neural Interfaces in an Idealized Cerebral Venous Sinus.(IEEE, 2023-07)Hemodynamic changes in stented blood vessels play a critical role in stent-associated complications. The majority of work on the hemodynamics of stented blood vessels has focused on coronary arteries but not cerebral venous sinuses. With the emergence of endovascular electrophysiology, there is a growing interest in stenting cerebral blood vessels. We investigated the hemodynamic impact of a stent-mounted neural interface inside the cerebral venous sinus. The stent was virtually implanted into an idealized superior sagittal sinus (SSS) model. Local venous blood flow was simulated. Results showed that blood flow was altered by the stent, generating recirculation and low wall shear stress (WSS) around the device. However, the effect of the electrodes on blood flow was not prominent due to their small size. This is an early exploration of the hemodynamics of a stent-mounted neural interface. Future work will shed light on the key factors that influence blood flow and stenting outcomes.Clinical Relevance-The study investigates blood flow through a stent-based electrode array inside the cerebral venous sinus. The hemodynamic impact of the stent can provide insight into neointimal growth and thrombus formation.
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ItemNo Preview AvailablePredictive Shared Control of Robotic Arms Using Simulated Brain-Computer Interface Inputs(IEEE, 2023)Low decoding accuracy makes brain-computer interface (BCI) control of a robotic arm difficult. Shared control (SC) can overcome limitations of a BCI by leveraging external sensor data and generating commands to assist the user. Our study explored whether reaching targets with a robot end-effector was easier using SC rather than direct control (DC). We simulated a motor imagery BCI using a joystick with noise introduced to explicitly control interface accuracy to be 65% or 79%. Compared to DC, our prediction-based implementation of SC led to a significant reduction in the trajectory length of successful reaches for 4 (3) out of 5 targets using the 65% (79%) accurate interface, with failure rates being equivalent to DC for 2 (1) out of 5 targets. Therefore, this implementation of SC is likely to improve reaching efficiency but at the cost of more failures. Additionally, the NASA Task Load Index results suggest SC reduced user workload.Clinical relevance-Shared control can minimise the impact of BCI decoder errors on robot motion, making robotic arm control using noninvasive BCIs more viable.
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ItemNo Preview AvailableEstablishing the Calibration Curve of a Compressive Ophthalmodynamometry Device(IEEE, 2023)The relationship between externally applied force and intraocular pressure was determined using an ex-vivo porcine eye model (N=9). Eyes were indented through the sclera with a convex ophthalmodynamometry head (ODM). Intraocular pressure and ophthalmodynamometric force were simultaneously recorded to establish a calibration curve of this indenter head. A calibration coefficient of 0.140 ± 0.009 mmHg/mN was established and was shown to be highly linear (r = 0.998 ± 0.002). Repeat application of ODM resulted in a 0.010 ± 0.002 mmHg/mN increase to the calibration coefficient.Clinical Relevance- ODM has been highlighted as a potential method of non-invasively estimating intracranial pressure. This study provides relevant data for the practical performance of ODM with similar compressive devices.
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ItemNo Preview AvailableTiming is Everything: Stochastic Optogenetic Stimulation Reduces Adaptation in Retinal Ganglion Cells.(IEEE, 2023-07)Optogenetics gives us unprecedented power to investigate brain connectivity. The ability to activate neural circuits with single cell resolution and its ease of application has provided a wealth of knowledge in brain function. More recently, optogenetics has shown tremendous utility in prosthetics applications, including vision restoration for patients with retinitis pigmentosa. One of the disadvantages of optogenetics, however, is its poor temporal bandwidth, i.e. the cell's inability to fire at a rate that matches the optical stimulation rate at high frequencies (>30 Hz). This research proposes a new strategy to overcome the temporal limits of optogenetic stimulation. Using whole-cell current clamp recordings in mouse retinal ganglion cells expressing channelrhodopsin-2 (H134R variant), we observed that randomizing inter-pulse intervals can significantly increase a retinal ganglion cell's temporal response to high frequency stimulation.Clinical Relevance- A significant disadvantage of optogenetic stimulation is its poor temporal dynamics which prohibit its widespread use in retinal prosthetics. We have shown that randomizing the interval between stimulation pulses reduces adaptation in retinal ganglion cells. This stimulation strategy may contribute to new levels of functional restoration in therapeutics which incorporate optogenetics.
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ItemNo Preview AvailableEffect of alpha range activity on SSVEP decoding in brain-computer interfaces(IEEE, 2023)Brain-computer interfaces (BCIs) facilitate direct communication between the brain and external devices. For BCI technology to be commercialized for wide scale applications, BCIs should be accurate, efficient, and exhibit consistency in performance for a wide variety of users. A core challenge is the physiological and anatomical differences amongst people, which causes a high variability amongst participants in BCI studies. Hence, it becomes necessary to analyze the mechanisms causing this variability and address them by improving the decoding algorithms. In this paper, a publicly available steady-state visual evoked potential (SSVEP) dataset is analyzed to study the effect of SSVEP flicker on the endogenous alpha power and the subsequent overall effect on the classification accuracy of the participants. It was observed that the participants with classification accuracy below 95% showed increased alpha power in their brain activities. Incorrect prediction in the decoding algorithm was observed a maximum number of times when the predicted frequency was in the range 9-12 Hz. We conclude that frequencies between 9-12 Hz may result in below par performance in some participants when canonical correlation analysis is used for classification.Clinical relevance-If alpha-band frequencies are used for SSVEP stimulation, alpha power interference in EEG may alter BCI accuracy for some users.