1. |
- Koivumäki, Jussi T., et al.
(author)
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Computational cardiac physiology for new modelers : Origins, foundations, and future
- 2022
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In: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 236:2
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Research review (peer-reviewed)abstract
- Mathematical models of the cardiovascular system have come a long way since they were first introduced in the early 19th century. Driven by a rapid development of experimental techniques, numerical methods, and computer hardware, detailed models that describe physical scales from the molecular level up to organs and organ systems have been derived and used for physiological research. Mathematical and computational models can be seen as condensed and quantitative formulations of extensive physiological knowledge and are used for formulating and testing hypotheses, interpreting and directing experimental research, and have contributed substantially to our understanding of cardiovascular physiology. However, in spite of the strengths of mathematics to precisely describe complex relationships and the obvious need for the mathematical and computational models to be informed by experimental data, there still exist considerable barriers between experimental and computational physiological research. In this review, we present a historical overview of the development of mathematical and computational models in cardiovascular physiology, including the current state of the art. We further argue why a tighter integration is needed between experimental and computational scientists in physiology, and point out important obstacles and challenges that must be overcome in order to fully realize the synergy of experimental and computational physiological research.
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2. |
- Hagen, Espen, et al.
(author)
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Hybrid Scheme for Modeling Local Field Potentials from Point-Neuron Networks
- 2016
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In: Cerebral Cortex. - : OXFORD UNIV PRESS INC. - 1047-3211 .- 1460-2199. ; 26:12, s. 4461-4496
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Journal article (peer-reviewed)abstract
- With rapidly advancing multi-electrode recording technology, the local field potential (LFP) has again become a popular measure of neuronal activity in both research and clinical applications. Proper understanding of the LFP requires detailed mathematical modeling incorporating the anatomical and electrophysiological features of neurons near the recording electrode, as well as synaptic inputs from the entire network. Here we propose a hybrid modeling scheme combining efficient point-neuron network models with biophysical principles underlying LFP generation by real neurons. The LFP predictions rely on populations of network-equivalent multicompartment neuron models with layer-specific synaptic connectivity, can be used with an arbitrary number of point-neuron network populations, and allows for a full separation of simulated network dynamics and LFPs. We apply the scheme to a full-scale cortical network model for a similar to 1 mm(2) patch of primary visual cortex, predict laminar LFPs for different network states, assess the relative LFP contribution from different laminar populations, and investigate effects of input correlations and neuron density on the LFP. The generic nature of the hybrid scheme and its public implementation in hybridLFPy form the basis for LFP predictions from other and larger point-neuron network models, as well as extensions of the current application with additional biological detail.
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3. |
- Leski, Szymon, et al.
(author)
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Frequency Dependence of Signal Power and Spatial Reach of the Local Field Potential
- 2013
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In: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 9:7, s. e1003137-
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Journal article (peer-reviewed)abstract
- Despite its century-old use, the interpretation of local field potentials (LFPs), the low-frequency part of electrical signals recorded in the brain, is still debated. In cortex the LFP appears to mainly stem from transmembrane neuronal currents following synaptic input, and obvious questions regarding the 'locality' of the LFP are: What is the size of the signal-generating region, i.e., the spatial reach, around a recording contact? How far does the LFP signal extend outside a synaptically activated neuronal population? And how do the answers depend on the temporal frequency of the LFP signal? Experimental inquiries have given conflicting results, and we here pursue a modeling approach based on a well-established biophysical forward-modeling scheme incorporating detailed reconstructed neuronal morphologies in precise calculations of population LFPs including thousands of neurons. The two key factors determining the frequency dependence of LFP are the spatial decay of the single-neuron LFP contribution and the conversion of synaptic input correlations into correlations between single-neuron LFP contributions. Both factors are seen to give low-pass filtering of the LFP signal power. For uncorrelated input only the first factor is relevant, and here a modest reduction (<50%) in the spatial reach is observed for higher frequencies (>100 Hz) compared to the near-DC (similar to 0Hz) value of about 200 mu m. Much larger frequency-dependent effects are seen when populations of pyramidal neurons receive correlated and spatially asymmetric inputs: the low-frequency (similar to 0Hz) LFP power can here be an order of magnitude or more larger than at 60 Hz. Moreover, the low-frequency LFP components have larger spatial reach and extend further outside the active population than high-frequency components. Further, the spatial LFP profiles for such populations typically span the full vertical extent of the dendrites of neurons in the population. Our numerical findings are backed up by an intuitive simplified model for the generation of population LFP.
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4. |
- Lindén, Henrik, et al.
(author)
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Modeling the spatial reach of the LFP
- 2011
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In: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 72:5, s. 859-872
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Journal article (peer-reviewed)abstract
- The local field potential (LFP) reflects activity of many neurons in the vicinity of the recording electrode and is therefore useful for studying local network dynamics. Much of the nature of the LFP is, however, still unknown. There are, for instance, contradicting reports on the spatial extent of the region generating the LFP. Here, we use a detailed biophysical modeling approach to investigate the size of the contributing region by simulating the LFP from a large number of neurons around the electrode. We find that the size of the generating region depends on the neuron morphology, the synapse distribution, and the correlation in synaptic activity. For uncorrelated activity, the LFP represents cells in a small region (within a radius of a few hundred micrometers). If the LFP contributions from different cells are correlated, the size of the generating region is determined by the spatial extent of the correlated activity.
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5. |
- Pettersen, Klas H., et al.
(author)
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Power Laws from Linear Neuronal Cable Theory : Power Spectral Densities of the Soma Potential, Soma Membrane Current and Single-Neuron Contribution to the EEG
- 2014
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In: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 10:11, s. e1003928-
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Journal article (peer-reviewed)abstract
- Power laws, that is, power spectral densities (PSDs) exhibiting 1/f(alpha) behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic highfrequency 1/f(alpha) power laws with power-law exponents analytically identified as alpha(I)(infinity) =1/2 for the soma membrane current, alpha(p)(infinity) = 3/2 for the current-dipole moment, and alpha(V)(infinity) = 2 for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink (1/f) noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how 1/f(alpha) power laws with a wide range of values for the power-law exponent a may arise from a simple, linear partial differential equation.
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