No Arabic abstract
Previous papers have developed a statistical mechanics of neocortical interactions (SMNI) fit to short-term memory and EEG data. Adaptive Simulated Annealing (ASA) has been developed to perform fits to such nonlinear stochastic systems. An N-dimensional path-integral algorithm for quantum systems, qPATHINT, has been developed from classical PATHINT. Both fold short-time propagators (distributions or wave functions) over long times. Previous papers applied qPATHINT to two systems, in neocortical interactions and financial options. textbf{Objective}: In this paper the quantum path-integral for Calcium ions is used to derive a closed-form analytic solution at arbitrary time that is used to calculate interactions with classical-physics SMNI interactions among scales. Using fits of this SMNI model to EEG data, including these effects, will help determine if this is a reasonable approach. textbf{Method}: Methods of mathematical-physics for optimization and for path integrals in classical and quantum spaces are used for this project. Studies using supercomputer resources tested various dimensions for their scaling limits. In this paper the quantum path-integral is used to derive a closed-form analytic solution at arbitrary time that is used to calculate interactions with classical-physics SMNI interactions among scales. textbf{Results}: The mathematical-physics and computer parts of the study are successful, in that there is modest improvement of cost/objective functions used to fit EEG data using these models. textbf{Conclusion}: This project points to directions for more detailed calculations using more EEG data and qPATHINT at each time slice to propagate quantum calcium waves, synchronized with PATHINT propagation of classical SMNI.
The random transitions of ion channels between conducting and non-conducting states generate a source of internal fluctuations in a neuron, known as channel noise. The standard method for modeling fluctuations in the states of ion channels uses continuous-time Markov chains nonlinearly coupled to a differential equation for voltage. Beginning with the work of Fox and Lu, there have been attempts to generate simpler models that use stochastic differential equation (SDEs) to approximate the stochastic spiking activity produced by Markov chain models. Recent numerical investigations, however, have raised doubts that SDE models can preserve the stochastic dynamics of Markov chain models. We analyze three SDE models that have been proposed as approximations to the Markov chain model: one that describes the states of the ion channels and two that describe the states of the ion channel subunits. We show that the former channel-based approach can capture the distribution of channel noise and its effect on spiking in a Hodgkin-Huxley neuron model to a degree not previously demonstrated, but the latter two subunit-based approaches cannot. Our analysis provides intuitive and mathematical explanations for why this is the case: the temporal correlation in the channel noise is determined by the combinatorics of bundling subunits into channels, and the subunit-based approaches do not correctly account for this structure. Our study therefore confirms and elucidates the findings of previous numerical investigations of subunit-based SDE models. Moreover, it presents the first evidence that Markov chain models of the nonlinear, stochastic dynamics of neural membranes can be accurately approximated by SDEs. This finding opens a door to future modeling work using SDE techniques to further illuminate the effects of ion channel fluctuations on electrically active cells.
Spike time response curves (STRCs) are used to study the influence of synaptic stimuli on the firing times of a neuron oscillator without the assumption of weak coupling. They allow us to approximate the dynamics of synchronous state in networks of neurons through a discrete map. Linearization about the fixed point of the discrete map can then be used to predict the stability of patterns of synchrony in the network. General theory for taking into account the contribution from higher order STRC terms, in the approximation of the discrete map for coupled neuronal oscillators in synchrony is still lacking. Here we present a general framework to account for higher order STRC corrections in the approximation of discrete map to determine the domain of 1:1 phase locking state in the network of two interacting neurons. We begin by demonstrating that the effect of synaptic stimuli through a shunting synapse to a neuron firing in the gamma frequency band (20-80 Hz) last for three consecutive firing cycles. We then show that the discrete map derived by taking into account the higher order STRC contributions is successfully able predict the domain of synchronous 1:1 phase locked state in a network of two heterogeneous interneurons coupled through a shunting synapse.
Recent calculations further supports the premise that large-scale synchronous firings of neurons may affect molecular processes. The context is scalp electroencephalography (EEG) during short-term memory (STM) tasks. The mechanism considered is $mathbf{Pi} = mathbf{p} + q mathbf{A}$ (SI units) coupling, where $mathbf{p}$ is the momenta of free $mathrm{Ca}^{2+}$ waves $q$ the charge of $mathrm{Ca}^{2+}$ in units of the electron charge, and $mathbf{A}$ the magnetic vector potential of current $mathbf{I}$ from neuronal minicolumnar firings considered as wires, giving rise to EEG. Data has processed using multiple graphs to identify sections of data to which spline-Laplacian transformations are applied, to fit the statistical mechanics of neocortical interactions (SMNI) model to EEG data, sensitive to synaptic interactions subject to modification by $mathrm{Ca}^{2+}$ waves.
Many cells use calcium signalling to carry information from the extracellular side of the plasma membrane to targets in their interior. Since virtually all cells employ a network of biochemical reactions for Ca2+ signalling, much effort has been devoted to understand the functional role of Ca2+ responses and to decipher how their complex dynamics is regulated by the biochemical network of Ca2+-related signal transduction pathways. Experimental observations show that Ca2+ signals in response to external stimuli encode information via frequency modulation or alternatively via amplitude modulation. Although minimal models can capture separately both types of dynamics, they fail to exhibit different and more advanced encoding modes. By arguments of bifurcation theory, we propose instead that under some biophysical conditions more complex modes of information encoding can also be manifested by minimal models. We consider the minimal model of Li and Rinzel and show that information encoding can occur by amplitude modulation (AM) of Ca2+ oscillations, by frequency modulation (FM) or by both modes (AFM). Our work is motivated by calcium signalling in astrocytes, the predominant type of cortical glial cells that is nowadays recognized to play a crucial role in the regulation of neuronal activity and information processing of the brain. We explain that our results can be crucial for a better understanding of synaptic information transfer. Furthermore, our results might also be important for better insight on other examples of physiological processes regulated by Ca2+ signalling.
Seizure activity is a ubiquitous and pernicious pathophysiology that, in principle, should yield to mathematical treatments of (neuronal) ensemble dynamics - and therefore interventions on stochastic chaos. A seizure can be characterised as a deviation of neural activity from a stable dynamical regime, i.e. one in which signals fluctuate only within a limited range. In silico treatments of neural activity are an important tool for understanding how the brain can achieve stability, as well as how pathology can lead to seizures and potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the (neuronal) state equation used in Dynamic Causal Modelling generalises to a Fokker-Planck formalism when propagation of neuronal activity along structural connections is considered. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity (i.e., connectivity that disperses neuronal fluctuations). We show, for neural systems prone to epileptic seizures, that such a reduction can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror epileptic activity in the areas adjoining an affected brain region - thus fighting seizures with seizures. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network. Our hope is that this technique can form the basis for real-time monitoring and intervention devices that are capable of suppressing or even preventing seizures in a non-invasive manner.