The pathological phenomena of seizures and spreading depression have long been considered separate physiological events in the brain. By incorporating conservation of particles and charge, and ...accounting for the energy required to restore ionic gradients, we extend the classic Hodgkin-Huxley formalism to uncover a unification of neuronal membrane dynamics. By examining the dynamics as a function of potassium and oxygen, we now account for a wide range of neuronal activities, from spikes to seizures, spreading depression (whether high potassium or hypoxia induced), mixed seizure and spreading depression states, and the terminal anoxic "wave of death." Such a unified framework demonstrates that all of these dynamics lie along a continuum of the repertoire of the neuron membrane. Our results demonstrate that unified frameworks for neuronal dynamics are feasible, can be achieved using existing biological structures and universal physical conservation principles, and may be of substantial importance in enabling our understanding of brain activity and in the control of pathological states.
Towards model-based control of Parkinson's disease Schiff, Steven J.
Philosophical transactions - Royal Society. Mathematical, Physical and engineering sciences/Philosophical transactions - Royal Society. Mathematical, physical and engineering sciences,
05/2010, Letnik:
368, Številka:
1918
Journal Article
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Modern model-based control theory has led to transformative improvements in our ability to track the nonlinear dynamics of systems that we observe, and to engineer control systems of unprecedented ...efficacy. In parallel with these developments, our ability to build computational models to embody our expanding knowledge of the biophysics of neurons and their networks is maturing at a rapid rate. In the treatment of human dynamical disease, our employment of deep brain stimulators for the treatment of Parkinsons disease is gaining increasing acceptance. Thus, the confluence of these three developmentscontrol theory, computational neuroscience and deep brain stimulationoffers a unique opportunity to create novel approaches to the treatment of this disease. This paper explores the relevant state of the art of science, medicine and engineering, and proposes a strategy for model-based control of Parkinsons disease. We present a set of preliminary calculations employing basal ganglia computational models, structured within an unscented Kalman filter for tracking observations and prescribing control. Based upon these findings, we will offer suggestions for future research and development.
High resolution Magnetic Resonance (MR) images are desired for accurate diagnostics. In practice, image resolution is restricted by factors like hardware and processing constraints. Recently, deep ...learning methods have been shown to produce compelling state-of-the-art results for image enhancement/super-resolution. Paying particular attention to desired hi-resolution MR image structure, we propose a new regularized network that exploits image priors, namely a low-rank structure and a sharpness prior to enhance deep MR image super-resolution (SR). Our contributions are then incorporating these priors in an analytically tractable fashion as well as towards a novel prior guided network architecture that accomplishes the super-resolution task. This is particularly challenging for the low rank prior since the rank is not a differentiable function of the image matrix (and hence the network parameters), an issue we address by pursuing differentiable approximations of the rank. Sharpness is emphasized by the variance of the Laplacian which we show can be implemented by a fixed feedback layer at the output of the network. As a key extension, we modify the fixed feedback (Laplacian) layer by learning a new set of training data driven filters that are optimized for enhanced sharpness. Experiments performed on publicly available MR brain image databases and comparisons against existing state-of-the-art methods show that the proposed prior guided network offers significant practical gains in terms of improved SNR/image quality measures. Because our priors are on output images, the proposed method is versatile and can be combined with a wide variety of existing network architectures to further enhance their performance.
Epilepsy has been historically seen as a functional brain disorder associated with excessive synchronization of large neuronal populations leading to a hypersynchronous state. Recent evidence showed ...that epileptiform phenomena, particularly seizures, result from complex interactions between neuronal networks characterized by heterogeneity of neuronal firing and dynamical evolution of synchronization. Desynchronization is often observed preceding seizures or during their early stages; in contrast, high levels of synchronization observed towards the end of seizures may facilitate termination. In this review we discuss cellular and network mechanisms responsible for such complex changes in synchronization. Recent work has identified cell‐type‐specific inhibitory and excitatory interactions, the dichotomy between neuronal firing and the non‐local measurement of local field potentials distant to that firing, and the reflection of the neuronal dark matter problem in non‐firing neurons active in seizures. These recent advances have challenged long‐established views and are leading to a more rigorous and realistic understanding of the pathophysiology of epilepsy.
Neonatal sepsis (NS) kills 750,000 infants every year. Effectively treating NS requires timely diagnosis and antimicrobial therapy matched to the causative pathogens, but most blood cultures for ...suspected NS do not recover a causative pathogen. We refer to these suspected but unidentified pathogens as microbial dark matter. Given these low culture recovery rates, many non-culture-based technologies are being explored to diagnose NS, including PCR, 16S amplicon sequencing, and whole metagenomic sequencing. However, few of these newer technologies are scalable or sustainable globally. To reduce worldwide deaths from NS, one possibility may be performing population-wide pathogen discovery. Because pathogen transmission patterns can vary across space and time, computational models can be built to predict the pathogens responsible for NS by region and season. This approach could help to optimally treat patients, decreasing deaths from NS and increasing antimicrobial stewardship until effective diagnostics that are scalable become available globally.
How powerful new methods in nonlinear control engineering can be applied to neuroscience, from fundamental model formulation to advanced medical applications.
Observability and controllability are essential concepts to the design of predictive observer models and feedback controllers of networked systems. For example, noncontrollable mathematical models of ...real systems have subspaces that influence model behavior, but cannot be controlled by an input. Such subspaces can be difficult to determine in complex nonlinear networks. Since almost all of the present theory was developed for linear networks without symmetries, here we present a numerical and group representational framework, to quantify the observability and controllability of nonlinear networks with explicit symmetries that shows the connection between symmetries and nonlinear measures of observability and controllability. We numerically observe and theoretically predict that not all symmetries have the same effect on network observation and control. Our analysis shows that the presence of symmetry in a network may decrease observability and controllability, although networks containing only rotational symmetries remain controllable and observable. These results alter our view of the nature of observability and controllability in complex networks, change our understanding of structural controllability, and affect the design of mathematical models to observe and control such networks.
Observability of a dynamical system requires an understanding of its state-the collective values of its variables. However, existing techniques are too limited to measure all but a small fraction of ...the physical variables and parameters of neuronal networks. We constructed models of the biophysical properties of neuronal membrane, synaptic, and microenvironment dynamics, and incorporated them into a model-based predictor-controller framework from modern control theory. We demonstrate that it is now possible to meaningfully estimate the dynamics of small neuronal networks using as few as a single measured variable. Specifically, we assimilate noisy membrane potential measurements from individual hippocampal neurons to reconstruct the dynamics of networks of these cells, their extracellular microenvironment, and the activities of different neuronal types during seizures. We use reconstruction to account for unmeasured parts of the neuronal system, relating micro-domain metabolic processes to cellular excitability, and validate the reconstruction of cellular dynamical interactions against actual measurements. Data assimilation, the fusing of measurement with computational models, has significant potential to improve the way we observe and understand brain dynamics.
Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little of how cell volume affects neuronal dynamics. We here performed the first detailed ...study of the effects of cell volume on neuronal dynamics. By incorporating cell swelling together with dynamic ion concentrations and oxygen supply into Hodgkin-Huxley type spiking dynamics, we demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. Our use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial K buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia. We argue that the dynamics of seizures, spreading depression, and anoxic depolarization lie along a continuum of the repertoire of the neuron membrane that can be understood only when the dynamic ion concentrations, oxygen homeostasis,and cell swelling in response to osmotic pressure are taken into consideration. Our results demonstrate the feasibility of a unified framework for a wide range of neuronal behaviors that may be of substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states.
Rainfall is an important variable to be able to monitor and forecast across Africa, due to its impact on agriculture, food security, climate‐related diseases and public health. Numerical weather ...models (NWMs) are an important component of this work, due to their complete spatial coverage, high resolution and ability to forecast into the future. In this study, the spatio‐temporal skill of short‐term forecasts of rainfall across Africa from 2016 through 2018 is evaluated. Specifically, the European Centre for Medium‐Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction‐Global Forecast System (NCEP‐GFS) forecast models are verified by Rainfall Estimates 2.0 (RFE2) and African Rainfall Climatology Version 2 (ARC2), which are fused products of satellite and in situ observations and are commonly used in analysis of African rainfall. Model rainfall forecasts show good consistency with the satellite rainfall observations in spatial distribution over Africa on the seasonal timescale. Evaluation metrics of daily and weekly forecasts show high spatial and seasonal variations over the African continent, including a strong link to the location of the inter‐tropical convergence zone (ITCZ) and topographically enhanced precipitation. The rainfall forecasts at 1 week aggregation time are improved against daily forecasts.
This manuscript evaluates the performance of numerical weather model rainfall forecasts against satellite rainfall estimates over Africa using several metrics. For example, root mean square errors, RMSEs (mm day−1), vary spatially across the African continent and vary by season, prediction model (panels a, b versus c, d) and whether the rainfall amounts are aggregated daily (a, c) or weekly (b, d).
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