Biomedical Engineering - Research Publications
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ItemGait compensatory mechanisms in unilateral transfemoral amputees(Elsevier, 2020-03)Individuals with unilateral transfemoral amputation depend on compensatory muscle and joint function to generate motion of the lower limbs, which can produce gait asymmetry; however, the functional role of the intact and residual limb muscles of transfemoral amputees in generating progression, support, and mediolateral balance of the body during walking is not well understood. The aim of this study was to quantify the contributions of the intact and the residual limb's contralateral muscles to body center of mass (COM) acceleration during walking in transfemoral amputees. Three-dimensional subject-specific musculoskeletal models of 6 transfemoral amputees fitted with a socket-type prosthesis were developed and used to quantify muscle forces and muscle contributions to the fore-aft, vertical, and mediolateral body COM acceleration using a pseudo-inverse ground reaction force decomposition method during over-ground walking. Anterior pelvic tilt and hip range of motion in the sagittal and frontal planes of the intact limb was significantly larger than those in the residual limb (p<0.05). The mean contributions of the intact limb hip muscles to body COM support, forward propulsion and mediolateral balance were significantly greater than those in the residual limb (p<0.05). Gluteus maximus contributed more to propulsion and support, while gluteus medius contributed more to balance than other muscles in the intact limb than the residual limb. The findings demonstrate the role of the intact limb hip musculature in compensating for reduced or absent muscles and joint function in the residual limb of transfemoral amputees during walking. The results may be useful in developing rehabilitation programs and design of prostheses to improve gait symmetry and mitigate post-operative musculoskeletal pathology.
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ItemIndividual muscle contributions to hip joint-contact forces during walking in unilateral transfemoral amputees with osseointegrated prostheses(Taylor & Francis, 2020-07-21)Direct skeletal attachment of prostheses in transfemoral amputees circumvents skin-interface complications associated with conventional sockets; however, joint pain and musculoskeletal disease is known to occur postoperatively. This study quantified hip contact forces and the roles of individual muscles in producing hip contact forces during walking in transfemoral amputees with osseointegrated prostheses. Musculoskeletal models were developed for four transfemoral amputees. Gluteus maximus and gluteus medius were the major contributors to the hip contact forces, and the intact limb hip muscles demonstrated greater contributions to hip contact forces than those of the residual limb. The findings may be useful for mitigating walking asymmetry.
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ItemNo Preview AvailableSource data from a systematic review and meta-analysis of EEG and MEG studies investigating functional connectivity in idiopathic generalized epilepsy(ELSEVIER, 2021-12-06)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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ItemNo Preview AvailableBrain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease(NATURE PORTFOLIO, 2021-07-08)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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ItemNo Preview AvailableBrainhack: Developing a culture of open, inclusive, community-driven neuroscience(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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ItemNo Preview AvailableLow-Profile Electromagnetic Field Sensors in the Measurement and Modelling of Three-Dimensional Jaw Kinematics and Occlusal Loading(SPRINGER, 2021-01-06)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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ItemThe Potential of Calcium Phosphate Nanoparticles as Adjuvants and Vaccine Delivery Vehicles(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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ItemMulti-timepoint pattern analysis: Influence of personality and behavior on decoding context-dependent brain connectivity dynamics(WILEY, 2021-12-03)Behavioral traits are rarely considered in task-evoked functional magnetic resonance imaging (MRI) studies, yet these traits can affect how an individual engages with the task, and thus lead to heterogeneity in task-evoked brain responses. We aimed to investigate whether interindividual variation in behavior associates with the accuracy of predicting task-evoked changes in the dynamics of functional brain connectivity measured with functional MRI. We developed a novel method called multi-timepoint pattern analysis (MTPA), in which binary logistic regression classifiers were trained to distinguish rest from each of 7 tasks (i.e., social cognition, working memory, language, relational, motor, gambling, emotion) based on functional connectivity dynamics measured in 1,000 healthy adults. We found that connectivity dynamics for multiple pairs of large-scale networks enabled individual classification between task and rest with accuracies exceeding 70%, with the most discriminatory connections relatively unique to each task. Crucially, interindividual variation in classification accuracy significantly associated with several behavioral, cognition and task performance measures. Classification between task and rest was generally more accurate for individuals with higher intelligence and task performance. Additionally, for some of the tasks, classification accuracy improved with lower perceived stress, lower aggression, higher alertness, and greater endurance. We conclude that heterogeneous dynamic adaptations of functional brain networks to changing cognitive demands can be reliably captured as linearly separable patterns by MTPA. Future studies should account for interindividual variation in behavior when investigating context-dependent dynamic functional connectivity.
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ItemPhase-Amplitude Markers of Synchrony and Noise: A Resting-State and TMS-EEG Study of Schizophrenia.(Oxford University Press (OUP), 2020)The electroencephalogram (EEG) of schizophrenia patients is known to exhibit a reduction of signal-to-noise ratio and of phase locking, as well as a facilitation of excitability, in response to a variety of external stimuli. Here, we demonstrate these effects in transcranial magnetic stimulation (TMS)-evoked potentials and in the resting-state EEG. To ensure veracity, we used 3 weekly sessions and analyzed both resting-state and TMS-EEG data. For the TMS responses, our analysis verifies known results. For the resting state, we introduce the methodology of mean-normalized variation to the EEG analysis (quartile-based coefficient of variation), which allows for a comparison of narrow-band EEG amplitude fluctuations to narrow-band Gaussian noise. This reveals that amplitude fluctuations in the delta, alpha, and beta bands of healthy controls are different from those in schizophrenia patients, on time scales of tens of seconds. We conclude that the EEG-measured cortical activity patterns of schizophrenia patients are more similar to noise, both in alpha- and beta-resting state and in TMS responses. Our results suggest that the ability of neuronal populations to form stable, locally, and temporally correlated activity is reduced in schizophrenia, a conclusion, that is, in accord with previous experiments on TMS-EEG and on resting-state EEG.
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ItemMicrobial Transglutaminase Improves ex vivo Adhesion of Gelatin Methacryloyl Hydrogels to Human Cartilage.(Frontiers Media SA, 2021)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.