Helmut Kröger

Modeling Extracellular Field Potentials and the Frequency-Filtering Properties of Extracellular Space

Extracellular local field potentials are usually modeled as arising from a set of current sources embedded in a homogeneous extracellular medium. Although this formalism can successfully model several properties of extracellular local field potentials, it does not account for their frequency-dependent attenuation with distance, a property essential to correctly model extracellular spikes. Here we derive expressions for the extracellular potential that include this frequency-dependent attenuation. We first show that, if the extracellular conductivity is nonhomogeneous, there is induction of nonhomogeneous charge densities that may result in a low-pass filter. We next derive a simplified model consisting of a punctual (or spherical) current source with spherically symmetric conductivity/permittivity gradients around the source. We analyze the effect of different radial profiles of conductivity and permittivity on the frequency-filtering behavior of this model. We show that this simple model generally displays low-pass filtering behavior, in which fast electrical events (such as Na(+)-mediated action potentials) attenuate very steeply with distance, whereas slower (K(+)-mediated) events propagate over larger distances in extracellular space, in qualitative agreement with experimental observations. This simple model can be used to obtain frequency-dependent extracellular field potentials without taking into account explicitly the complex folding of extracellular space.

Does the 1/f frequency-scaling of brain signals reflect self-organized critical states ?

Many complex systems display self-organized critical states characterized by 1/f frequency scaling of power spectra. Global variables such as the electroencephalogram, scale as 1/f, which could be the sign of self-organized critical states in neuronal activity. By analyzing simultaneous recordings of global and neuronal activities, we confirm the 1/f scaling of global variables for selected frequency bands, but show that neuronal activity is not consistent with critical states. We propose a model of 1/f scaling which does not rely on critical states, and which is testable experimentally.

Model of low-pass filtering of local field potentials in brain tissue.

Local field potentials (LFPs) are routinely measured experimentally in brain tissue, and exhibit strong low-pass frequency filtering properties, with high frequencies (such as action potentials) being visible only at very short distances (approximately 10 microm) from the recording electrode. Understanding this filtering is crucial to relate LFP signals with neuronal activity, but not much is known about the exact mechanisms underlying this low-pass filtering. In this paper, we investigate a possible biophysical mechanism for the low-pass filtering properties of LFPs. We investigate the propagation of electric fields and its frequency dependence close to the current source, i.e., at length scales in the order of average interneuronal distances. We take into account the presence of a high density of cellular membranes around current sources, such as glial cells. By considering them as passive cells, we show that under the influence of the electric source field, they respond by polarization. Because of the finite velocity of ionic charge movements, this polarization will not be instantaneous. Consequently, the induced electric field will be frequency-dependent, and much reduced for high frequencies. Our model establishes that this situation is analogous to an equivalent RC circuit, or better yet a system of coupled RC circuits. We present a number of numerical simulations of an induced electric field for biologically realistic values of parameters, and show the frequency filtering effect as well as the attenuation of extracellular potentials with distance. We suggest that induced electric fields in passive cells surrounding neurons are the physical origin of frequency filtering properties of LFPs. Experimentally testable predictions are provided allowing us to verify the validity of this model.

Efficacy of Synaptic Inhibition Depends on Multiple, Dynamically Interacting Mechanisms Implicated in Chloride Homeostasis

Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABAA receptors (GABAARs). The impact of changes in steady state Cl− gradient is relatively straightforward to understand, but how dynamic interplay between Cl− influx, diffusion, extrusion and interaction with other ion species affects synaptic signaling remains uncertain. Here we used electrodiffusion modeling to investigate the nonlinear interactions between these processes. Results demonstrate that diffusion is crucial for redistributing intracellular Cl− load on a fast time scale, whereas Cl−extrusion controls steady state levels. Interaction between diffusion and extrusion can result in a somato-dendritic Cl− gradient even when KCC2 is distributed uniformly across the cell. Reducing KCC2 activity led to decreased efficacy of GABAAR-mediated inhibition, but increasing GABAAR input failed to fully compensate for this form of disinhibition because of activity-dependent accumulation of Cl−. Furthermore, if spiking persisted despite the presence of GABAAR input, Cl− accumulation became accelerated because of the large Cl− driving force that occurs during spikes. The resulting positive feedback loop caused catastrophic failure of inhibition. Simulations also revealed other feedback loops, such as competition between Cl− and pH regulation. Several model predictions were tested and confirmed by [Cl−]i imaging experiments. Our study has thus uncovered how Cl− regulation depends on a multiplicity of dynamically interacting mechanisms. Furthermore, the model revealed that enhancing KCC2 activity beyond normal levels did not negatively impact firing frequency or cause overt extracellular K− accumulation, demonstrating that enhancing KCC2 activity is a valid strategy for therapeutic intervention.

Fastest learning in small-world neural networks

We investigate supervised learning in neural networks. We consider a multi-layered feed-forward network with back propagation. We find that the network of small-world connectivity reduces the learning error and learning time when compared to the networks of regular or random connectivity. Our study has potential applications in the domain of data-mining, image processing, speech recognition, and pattern recognition.

Fractal geometry in quantum mechanics, field theory and spin systems

Abstract The goal of this article is to review the role of fractal geometry in quantum physics. There are two aspects: (a) The geometry of underlying space (space–time in relativistic systems) is fractal and one studies the dynamics of the quantum system. Example: percolation. (b) The underlying space–time is regular, and fractal geometry which shows up in particular observables is generated by the dynamics of the quantum system. Example: Brownian motion (imaginary time quantum mechanics), zig-zag paths of propagation in quantum mechanics (Feynmans path integral). Historically, the first example of fractal geometry in quantum mechanics was invoked by Feynman and Hibbs describing the self-similarity (fractal behavior) of paths occurring in the path integral. We discuss the geometry of such paths. We present analytical as well as numerical results, yielding Hausdorff dimension dH=2. Velocity-dependent interactions (propagation in a solid, Brueckners theory of nuclear matter) allow for dH

Modeling Thalamocortical Cell: Impact of Ca2+ Channel Distribution and Cell Geometry on Firing Pattern

The influence of calcium channel distribution and geometry of the thalamocortical cell upon its tonic firing and the low threshold spike (LTS) generation was studied in a 3-compartment model, which represents soma, proximal and distal dendrites as well as in multi-compartment model using the morphology of a real reconstructed neuron. Using an uniform distribution of Ca2+ channels, we determined the minimal number of low threshold voltage-activated calcium channels and their permeability required for the onset of LTS in response to a hyperpolarizing current pulse. In the 3-compartment model, we found that the channel distribution influences the firing pattern only in the range of 3% below the threshold value of total T-channel density. In the multi-compartmental model, the LTS could be generated by only 64% of unequally distributed T-channels compared to the minimal number of equally distributed T-channels. For a given channel density and injected current, the tonic firing frequency was found to be inversely proportional to the size of the cell. However, when the Ca2+ channel density was elevated in soma or proximal dendrites, then the amplitude of LTS response and burst spike frequencies were determined by the ratio of total to threshold number of T-channels in the cell for a specific geometry.

MONTE CARLO HAMILTONIAN

Abstract We construct an effective Hamiltonian via Monte Carlo from a given action. This Hamiltonian describes physics in the low energy regime. We test it by computing spectrum, wave functions and thermodynamical observables (average energy and specific heat) for the free system and the harmonic oscillator. The method is shown to work also for other local potentials.

Quantum Instantons and Quantum Chaos

We suggest a closed form expression for the path integral of quantum transition amplitudes to construct a quantum action. Based on this we propose rigorous definitions of both, quantum instantons and quantum chaos. As an example we compute the quantum instanton of the double well potential.

Quantum chaos at finite temperature

Abstract We use the quantum action to study quantum chaos at finite temperature. We present a numerical study of a classically chaotic 2-D Hamiltonian system — harmonic oscillators with anharmonic coupling. We construct the quantum action non-perturbatively and find temperature-dependent quantum corrections in the action parameters. We compare Poincare sections of the quantum action at finite temperature with those of the classical action.