Browsing by Subject "electrophysiology"
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Item Open Access A modular simulation system for the bidomain equationsPormann, JCardiac arrhythmias and fibrillation are potentially life threatening diseases that can result from the improper conduction of electrical impulses in the heart. Experimental study of such cardiac abnormalities are dangerous at best, often requiring the subject to be placed in fibrillation for some time before attempting a large ``rescue'' shock. Thus, most all studies are done in animals and not humans. Furthermore, there is some indication that heart size may have considerable implications for fibrillation and other conduction abnormalities. Thus animal models for defibrillation studies must be chosen with great care. As an alternative, researchers are now using computer simulation to study the factors that generate and sustain arrhythmias, hoping to obtain at least preliminary data to guide fewer, more targeted experimental studies. Computer simulations of the Bidomain Equations have become very complex as they have been applied to many problems in cardiac electrophysiology. More complex membrane dynamics, irregular grids, and 3-D data sets are all being investigated. Software engineering principles will need to be applied to manage this continuing growth in complexity. We propose a modular framework for development of a Simulation System whereby a researcher may mix and match program elements to generate a simulator tailored to their particular problem. The modular approach will simplify the generation and maintenance of the different program elements and it will enable the end-researcher to determine the proper mix of complexity versus speed for their particular problem of interest. The contrary approach, one monolithic program which can run all simulations of all complexities, is simply unrealistic. It would impose too great a burden on maintenance and upgradability, and it would be difficult to provide good performance for a wide range of applications. The modular approach also allows for the incremental inclusion of various complexities in the bidomain model. From a simple 2-D homogeneous, isotropic regular grid, monodomain simulation, we can progress, step by step, to a bidomain simulation with a fully implicit time-integration scheme on irregular, 3-D grids with arbitrary anisotropy and inhomogeneity, with a non-trivial membrane model. Simulations with such a wealth of complexity have not been performed to date. As microprocessors have become cheaper and more powerful, parallel computing has become more widespread. Machines with hundreds of high-performance CPUs connected by fast networks are commonplace and are now capable of surpassing traditional vector-based supercomputers in terms of overall performance. The Simulation System presented here incorporates data-parallelism to allow large scale Bidomain problems to be run on these newest parallel supercomputers. The large amount of distributed memory in such machines can be harnessed to allow extremely large scale simulations to be run. The large number of CPUs provide a tremendous amount of computational power which can be used to run such simulations more quickly. Finally, the results presented here show that a modular Simulation System is feasible for a wide range of pplications, and that it can obtain very good performance over this range of applications. The parallel speed-up seen was very good, regularly achieving a factor of 13 speed-up on 16 processors. The results presented here also show that we can simulate bidomain problems using an implicit time-integrator with an irregular, anisotropic and inhomogeneous, grid and a non-trivial membrane model. We are able to run such simulations on parallel computers, thereby harnessing a tremendous amount of memory and computational resources. Such simulations have not been run to date.Item Open Access An Intracortical Implantable Brain-Computer Interface for Telemetric Real-Time Recording and Manipulation of Neuronal Circuits for Closed-Loop Intervention.(Frontiers in human neuroscience, 2021-01) Zaer, Hamed; Deshmukh, Ashlesha; Orlowski, Dariusz; Fan, Wei; Prouvot, Pierre-Hugues; Glud, Andreas Nørgaard; Jensen, Morten Bjørn; Worm, Esben Schjødt; Lukacova, Slávka; Mikkelsen, Trine Werenberg; Fitting, Lise Moberg; Adler, John R; Schneider, M Bret; Jensen, Martin Snejbjerg; Fu, Quanhai; Go, Vinson; Morizio, James; Sørensen, Jens Christian Hedemann; Stroh, AlbrechtRecording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity brain-computer interfaces (BCIs) should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. The animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions.Item Open Access Regulatory switch at the cytoplasmic interface controls TRPV channel gating.(eLife, 2019-05-09) Zubcevic, Lejla; Borschel, William F; Hsu, Allen L; Borgnia, Mario J; Lee, Seok-YongTemperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, and are involved in various physiological processes. ThermoTRPV channels possess a large cytoplasmic ring consisting of N-terminal ankyrin repeat domains (ARD) and C-terminal domains (CTD). The cytoplasmic inter-protomer interface is unique and consists of a CTD coiled around a β-sheet which makes contacts with the neighboring ARD. Despite much existing evidence that the cytoplasmic ring is important for thermoTRPV function, the mechanism by which this unique structure is involved in thermoTRPV gating has not been clear. Here, we present cryo-EM and electrophysiological studies which demonstrate that TRPV3 gating involves large rearrangements at the cytoplasmic inter-protomer interface and that this motion triggers coupling between cytoplasmic and transmembrane domains, priming the channel for opening. Furthermore, our studies unveil the role of this interface in the distinct biophysical and physiological properties of individual thermoTRPV subtypes.