Measurements of electric potentials from neural activity have played a key role in neuroscience for almost a century, and simulations of neural activity is an important tool for understanding such measurements. Volume conductor (VC) theory is used to compute extracellular electric potentials such as extracellular spikes, MUA, LFP, ECoG and EEG surrounding neurons, and also inversely, to reconstruct neuronal current source distributions from recorded potentials through current source density methods. In this book chapter, we show how VC theory can be derived from a detailed electrodiffusive theory for ion concentration dynamics in the extracellular medium, and show what assumptions that must be introduced to get the VC theory on the simplified form that is commonly used by neuroscientists. Furthermore, we provide examples of how the theory is applied to compute spikes, LFP signals and EEG signals generated by neurons and neuronal populations.
Neurons generate magnetic fields which can be recorded with macroscopic techniques such as magneto-encephalography. The theory that accounts for the genesis of neuronal magnetic fields involves dendritic cable structures in homogeneous resistive extracellular media. Here, we generalize this model by considering dendritic cables in extracellular media with arbitrarily complex electric properties. This method is based on a multi-scale mean-field theory where the neuron is considered in interaction with a "mean" extracellular medium (characterized by a specific impedance). We first show that, as …
Simulation of extracellular fields is one of the substantial methods used in the area of computational neuroscience. Its most common usage is validation of experimental methods as EEG and extracellular spike recordings or modeling of physiological phenomena which can not be easily determined empirically. Continuous experimental work has been re-raising the importance of polarization effects between neuronal structures to neuronal communication. As this effects relies on very small potential changes, better modeling methods are necessary to quantify the weak electrical fields in the microscopic…
One step in the conventional analysis of extracellularly recorded neuronal data is spike sorting, which separates electrical signal into action potentials from different neurons. Because spike sorting involves human judgment, it can be subjective and time intensive, particularly for large sets of neurons. Here we propose a simple, automated way to construct alternative representations of neuronal activity, called spectral representation (SR). In this approach, neuronal spikes are mapped to a discrete space of spike- waveform features and time. Spectral representation enables us to find single-…
Neuronal and glial cells release diverse proteoglycans and glycoproteins, which aggregate in the extracellular space and form the extracellular matrix (ECM) that may in turn regulate major cellular functions. Brain cells also release extracellular proteases that may degrade the ECM, and both synthesis and degradation of ECM are activity-dependent. In this study we introduce a mathematical model describing population dynamics of neurons interacting with ECM molecules over extended timescales. It is demonstrated that depending on the prevalent biophysical mechanism of ECM-neuronal interactions, …
Numerous measurements in the brain of the impedance between two extracellular electrodes have shown that it is approximately resistive in the range of biological interest, $<10\,$kHz, and has a value close to that expected from the conductivity of physiological saline and the extracellular volume fraction in brain tissue. Recent work from the group of Claude Bédard and Alain Destexhe has claimed that the impedance of the extracellular space is some three orders of magnitude greater than these values and also displays a $1/\sqrt{f}$ frequency dependence (above a low-frequency corner frequency).…
Neuronal models based on the Hodgkin-Huxley equation form a fundamental framework in the field of computational neuroscience. While the neuronal state is often modeled deterministically, experimental recordings show stochastic fluctuations, presumably driven by molecular noise from the underlying microphysical conditions. In turn, the firing of individual neurons gives rise to an electric field n extracellular space, also thought to affect the firing pattern of nearby neurons. We develop a multiscale model which combines a stochastic ion channel gating process taking place on the neuronal memb…
The electrical properties of extracellular space around neurons are important to understand the genesis of extracellular potentials, as well as for localizing neuronal activity from extracellular recordings. However, the exact nature of these extracellular properties is still uncertain. We introduce a method to measure the impedance of the tissue, and which preserves the intact cell-medium interface, using whole-cell patch-clamp recordings in vivo and in vitro. We find that neural tissue has marked non-ohmic and frequency-filtering properties, which are not consistent with a resistive (ohmic) …
We demonstrate that human electrophysiological recordings of the local field potential (LFP) from intracranial electrodes, acquired from a variety of cerebral regions, show a ubiquitous $1/f^2$ scaling within the power spectrum. We develop a quantitative model that treats the generation of these fields in an analogous way to that of electronic shot noise, and use this model to specifically address the cause of this $1/f^2$ Brownian noise. The model gives way to two analytically tractable solutions, both displaying Brownian noise: 1) uncorrelated cells that display sharp initial activity, whose…
Newcastle University（纽卡斯尔大学）；Okinawa Institute of Science and Technology（冲绳科学技术大学院大学）；University of York（约克大学）
Local field potentials (LFPs) sampled with extracellular electrodes are frequently used as a measure of population neuronal activity. However, relating such measurements to underlying neuronal behaviour and connectivity is non-trivial. To help study this link, we developed the Virtual Electrode Recording Tool for EXtracellular potentials (VERTEX). We first identified a reduced neuron model that retained the spatial and frequency filtering characteristics of extracellular potentials from neocortical neurons. We then developed VERTEX as an easy-to-use Matlab tool for simulating LFPs from large p…
Extracellular recordings with multi-electrode arrays is one of the basic tools of contemporary neuroscience. These recordings are mostly used to monitor the activities, understood as sequences of emitted action potentials, of many individual neurons. But the raw data produced by extracellular recordings are most commonly a mixture of activities from several neurons. In order to get the activities of the individual contributing neurons, a pre-processing step called spike sorting is required. We present here a pure Python implementation of a well tested spike sorting procedure. The latter was de…
We describe a new, computationally simple method for analyzing the dynamics of neuronal spike trains driven by external stimuli. The goal of our method is to test the predictions of simple spike-generating models against extracellularly recorded neuronal responses. Through a new statistic called the power ratio, we distinguish between two broad classes of responses: (1) responses that can be completely characterized by a variable firing rate, (for example, modulated Poisson and gamma spike trains); and (2) responses for which firing rate variations alone are not sufficient to characterize resp…
This article provides a theoretical basis for relating macroscopic electrical signals recorded from biological tissue, such as electroencephalogram (EEG) and local field potential (LFP), to the electrophysiological processes at the cellular level in a manner consistent with Maxwell's equations. Concepts of the apparent extracellular current density and the apparent extracellular space with apparent permittivity and conductivity are introduced from the conservation of current and Gauss's theorem. A general equation for the current source density (CSD) analysis is derived for biological tissue w…
Information processing in the brain is conducted by a concerted action of multiple neural populations. Gaining insights in the organization and dynamics of such populations can best be studied with broadband intracranial recordings of so-called extracellular field potential, reflecting neuronal spiking as well as mesoscopic activities, such as waves, oscillations, intrinsic large deflections, and multiunit spiking activity. Such signals are critical for our understanding of how neuronal ensembles encode sensory information and how such information is integrated in the large networks underlying…
Based upon the membrane currents generated by an action potential in a biologically realistic model of a pyramidal, hippocampal cell within rat CA1, we perform a moment expansion of the extracellular field potential. We decompose the potential into both inverse and classical moments and show that this method is a rapid and efficient way to calculate the extracellular field both near and far from the cell body. The action potential gives rise to a large quadrupole moment that contributes to the extracellular field up to distances of almost 1 cm. This method will serve as a starting point in con…
Information Technologies Institute, Centre for Research and Technology – Hellas (CERTH)（希腊研究与技术中心信息技术研究所）；Aristotle University of Thessaloniki（塞萨洛尼基亚里士多德大学）
Extracellular recordings are severely contaminated by a considerable amount of noise sources, rendering the denoising process an extremely challenging task that should be tackled for efficient spike sorting. To this end, we propose an end-to-end deep learning approach to the problem, utilizing a Fully Convolutional Denoising Autoencoder, which learns to produce a clean neuronal activity signal from a noisy multichannel input. The experimental results on simulated data show that our proposed method can improve significantly the quality of noise-corrupted neural signals, outperforming widely-use…
In computational neuroscience, it is common to use the simplifying assumption that diffusive currents are negligible compared to Ohmic currents. However, endured periods of intense neural signaling may cause local ion concentration changes in the millimolar range. Theoretical studies have identified scenarios where steep concentration gradients give rise to diffusive currents that are of comparable magnitude with Ohmic currents, and where the simplifying assumption that diffusion can be neglected does not hold. We here propose a novel formalism for computing (1) the ion concentration dynamics …
The mammalian hippocampus plays a principal role in producing a cognitive map of space---an internalized representation of the animal's environment. The neuronal mechanisms producing this map depend primarily on the temporal structure of the hippocampal neurons' spiking activity, which is modulated by the oscillatory extracellular electrical field potential. In this paper, we discuss the integrative effect of the gamma rhythm, one of the principal components of these oscillations, on the ability of the place cell ensembles to encode a spatial map. Using methods of algebraic topology and statis…
The ongoing activity of neurons generates a spatially- and time-varying field of extracellular voltage ($V_e$). This $V_e$ field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates $V_e$ and how this $V_e$ feeds back and influences membrane potential ($V_m$). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate $V_e$ with millivolt-scale amplitude and this $V_e$ perturbs the $V_m$ of "n…
Understanding neuronal communication is fundamental in neuroscience but there are few methodologies offering detailed analysis for well-controlled conditions. By interfacing microElectrode arrays with microFluidics (μEF devices), it is possible to compartmentalize neuronal cultures with a specified alignment of axons and microelectrodes. This setup allows extracellular recordings of spike propagation with high signal-to-noise ratio over the course of several weeks. Addressing these μEF systems we developed an advanced, yet easy-to-use, open-source computational tool, μSpikeHunter, which provid…
In studies of the brain and the nervous system, extracellular signals - as measured by local field potentials (LFPs) or electroencephalography (EEG) - are of capital importance, as they allow to simultaneously obtain data from multiple neurons. The exact biophysical basis of these signals is, however, still not fully understood. Most models for the extracellular potential today are based on volume conductor theory, which assumes that the extracellular fluid is electroneutral and that the only contributions to the electric field are given by membrane currents, which can be imposed as boundary c…
The extracellular space has an ambiguous role in neuroscience. It is present in every physiologically relevant system and often used as a measurement site in experimental recordings, but it has received subordinate attention compared to the intracellular domain. In computational modeling, it is often regarded as a passive, homogeneous resistive medium with a constant conductivity, which greatly simplifies the computation of extracellular potentials. However, recent studies have shown that local ionic diffusion and capacitive effects of electrically active membranes can have a substantial impac…
In this paper we present an efficient model of the neuronal potentials recorded by a deep brain stimulation microelectrode (DBS MER) in the subthalamic nucleus. It is shown that a computationally efficient filtered point process consisting of 10,000 neurons, including extracellular filtering closely matches recordings from 13 Parkinson's disease patients. The recordings were compared using their voltage amplitude distributions, power spectral density estimates and phase synchrony. It was found that interspike interval times modeled using a Weibull distribution with a shape parameter of 0.8, sl…
The investigation of the neuronal environment allows us to better understand the activity of a cerebral region as a whole. The recent experimental evidences of the presence of transporters for glutamate and GABA in both neuronal and astrocyte compartments raise the question of the functional importance of the astrocytes in the regulation of the neuronal activity. We propose a new computational model at the mesoscopic scale embedding the recent knowledge on the physiology of neuron and astrocyte coupled activities. The neural compartment is a neural mass model with double excitatory feedback, a…
Intracellular access with high spatiotemporal resolution can enhance our understanding of how neurons or cardiomyocytes regulate and orchestrate network activity, and how this activity can be affected with pharmacology or other interventional modalities. Nanoscale devices often employ electroporation to transiently permeate the cell membrane and record intracellular potentials, which tend to decrease rapidly to extracellular potential amplitudes with time. Here, we report innovative scalable, vertical, ultra-sharp nanowire arrays that are individually addressable to enable long-term, native re…
NMDA receptors (NMDA-R) typically contribute to excitatory synaptic transmission in the central nervous system. While calcium influx through NMDA-R plays a critical role in synaptic plasticity, experimental evidence indicates that NMDAR-mediated calcium influx also modifies neuronal excitability through the activation of calcium-activated potassium channels. This mechanism has not yet been studied theoretically. Our theoretical model provides a simple description of neuronal electrical activity that takes into account the tonic activity of extrasynaptic NMDA receptors and a cytosolic calcium c…
Small-World Networks (SWNs) represent a fundamental model for the comprehension of many complex man-made and biological networks. In the central nervous system, SWN models have been shown to fit well both anatomical and functional maps at the macroscopic level. However the functional microscopic level, where the nodes of a network are composed of single neurons, is still poorly understood. At this level, although recent evidences suggest that functional connectivity maps exhibit small-world organization, it is not known whether and how these maps, distributed in multiple brain regions, change …
In this work, we propose to catch the complexity of the membrane potential's dynamic of a motoneuron between its spikes, taking into account the spikes from other neurons around. Our approach relies on two types of data: extracellular recordings of multiple spikes trains and intracellular recordings of the membrane potential of a central neuron. Our main contribution is to provide a unified framework and a complete pipeline to analyze neuronal activity from data extraction to statistical inference. The first step of the procedure is to select a subnetwork of neurons impacting the central neuro…
Neuron is the most important building block in our brain, and information processing in individual neuron involves the transformation of input synaptic spike trains into an appropriate output spike train. Hardware implementation of neuron by individual ionic/electronic coupled device is of great importance for enhancing our understanding of the brain and solving sensory processing and complex recognition tasks. Here, we provide a proof-of-principle artificial neuron with multiple presynaptic inputs and one modulatory terminal based on a proton-coupled oxide-based electric-double-layer transist…
Neural stimulation represents a powerful technique for neural disorder treatment. This paper deals with optimization of coil design parameters to be used during stimulation for modulation of neuronal firing to achieve pain relief. Pain mechanism is briefly introduced and a hierarchical stimulation model from coil stimulation to neuronal firing is proposed. Electromagnetic field distribution for circular, figure of 8 and Magnetic resonance coupling figure of 8 coils are analyzed with respect to the variation of stimulation parameters such as distance between coils, stimulation frequency, number…
School of Electrical Engineering and Computer Science（电气工程与计算机科学学院）；The Pennsylvania State University（宾夕法尼亚州立大学）
Developing electrophysiological recordings of brain neuronal activity and their analysis provide a basis for exploring the structure of brain function and nervous system investigation. The recorded signals are typically a combination of spikes and noise. High amounts of background noise and possibility of electric signaling recording from several neurons adjacent to the recording site have led scientists to develop neuronal signal processing tools such as spike sorting to facilitate brain data analysis. Spike sorting plays a pivotal role in understanding the electrophysiological activity of ne…
Spikes in the membrane electrical potentials of neurons play a major role in the functioning of nervous systems of animals. Obtaining the spikes from different neurons has been a challenging problem for decades. Several schemes have been proposed for spike sorting to isolate the spikes of individual neurons from electrical recordings in extracellular media. However, there is much scope for improvement in the accuracies obtained using the prevailing methods of spike sorting. To determine more effective spike sorting strategies using well known methods, we compared different types of signal feat…
We present a microscopic approach for the coupling of cortical activity, as resulting from proper dipole currents of pyramidal neurons, to the electromagnetic field in extracellular fluid in presence of diffusion and Ohmic conduction. Starting from a full-fledged three-compartment model of a single pyramidal neuron, including shunting and dendritic propagation, we derive an observation model for dendritic dipole currents in extracellular space and thereby for the dendritic field potential that contributes to the local field potential of a neural population. Under reasonable simplifications, we…
Neuronal avalanches are a novel mode of activity in neuronal networks, experimentally found in vitro and in vivo, and exhibit a robust critical behaviour: These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems. We present a recent model inspired in self-organized criticality, which consists of an electrical network with threshold firing, refractory period and activity-dependent synaptic plasticity. The model reproduces the critical behaviour of the distribution of avalanche size…
In this viewpoint article, we discuss the electric properties of the medium around neurons, which are important to correctly interpret extracellular potentials or electric field effects in neural tissue. We focus on how these electric properties shape the frequency scaling of brain signals at different scales, such as intracellular recordings, the local field potential (LFP), the electroencephalogram (EEG) or the magnetoencephalogram (MEG). These signals display frequency-scaling properties which are not consistent with resistive media. The medium appears to exert a frequency filtering scaling…
Neuronal electricality founded in murburn-thermodynamic principles: 1. Background and basic theoretical formulation
Amrita School of Artificial Intelligence, Coimbatore, Amrita Vishwa Vidyapeetham（阿穆里塔人工智能学院，科因巴托尔，阿穆里塔维迪亚佩特汉大学）；Satyamjayatu: The Science & Ethics Foundation（真理即胜利：科学与伦理基金会）；Department of Biomedical Engineering, Wayne State University（韦恩州立大学生物医学工程系）
We propose a novel discrete model of central pattern generators (CPG), neuronal ensembles generating rhythmic activity. The model emphasizes the role of nonsynaptic interactions and the diversity of electrical properties in nervous systems. Neurons in the model release different neurotransmitters into the shared extracellular space (ECS) so each neuron with the appropriate set of receptors can receive signals from other neurons. We consider neurons, differing in their electrical activity, represented as finite-state machines functioning in discrete time steps. Discrete modeling is aimed to pro…
We present a microscopic approach for the coupling of cortical activity, as resulting from proper dipole currents of pyramidal neurons, to the electromagnetic field in extracellular fluid in presence of diffusion and Ohmic conduction. As a result, neural activity becomes represented by a continuous neural field equation, while an observation model for electric field potentials is obtained from the interaction of cortical dipole currents with charge density in non-resistive extracellular space as described by the Nernst-Planck equation.
This paper deals with the EEG/MEG neuroimaging problem: given measurements of scalp electric potential differences (EEG: electroencephalogram) and extracranial magnetic fields (MEG: magnetoencephalogram), find the 3D distribution of the generating electric neuronal activity. This problem has no unique solution. Only particular solutions with "good" localization properties are of interest, since neuroimaging is concerned with the localization of brain function. In this paper, a general family of linear imaging methods with exact, zero error localization to point-test sources is presented. One p…
Neuroprosthesis, as one type of precision medicine device, is aiming for manipulating neuronal signals of the brain in a closed-loop fashion, together with receiving stimulus from the environment and controlling some part of our brain/body. In terms of vision, incoming information can be processed by the brain in millisecond interval. The retina computes visual scenes and then sends its output as neuronal spikes to the cortex for further computation. Therefore, the neuronal signal of interest for retinal neuroprosthesis is spike. Closed-loop computation in neuroprosthesis includes two stages: …
A good understanding of how neurons use electrical pulses (i.e, spikes) to encode the signal information remains elusive. Analyzing spike sequences generated by individual neurons and by two coupled neurons (using the stochastic FitzHugh-Nagumo model), recent theoretical studies have found that the relative timing of the spikes can encode the signal information. Using a symbolic method to analyze the spike sequence, preferred and infrequent spike patterns were detected, whose probabilities vary with both, the amplitude and the frequency of the signal. To investigate if this encoding mechanism …
We present a biophysical approach for the coupling of neural network activity as resulting from proper dipole currents of cortical pyramidal neurons to the electric field in extracellular fluid. Starting from a reduced threecompartment model of a single pyramidal neuron, we derive an observation model for dendritic dipole currents in extracellular space and thereby for the dendritic field potential that contributes to the local field potential of a neural population. This work aligns and satisfies the widespread dipole assumption that is motivated by the "open-field" configuration of the dendr…
A recurrent loop consisting of a single neuron is considered which is influenced by a chemical excitatory delayed synaptic feedback. We show the response of the system is dependent to the duration of the activity of the synapse which is determined by the deactivation time constant of the synapse. We show that loops with slow synapses, those which the effect of the synaptic activation remains for time constants comparable to the period of firing, show more predictable results where the effect of the fast synapses is tightly dependent on the loop delay time. The results are compared to those of …
Many experiments have evidenced that electrical and chemical synapses -- hybrid synapses -- coexist in most organisms and brain structures. The role of electrical and chemical synapse connection in diversity of neural activity generation has been investigated separately in networks of varying complexities. Nevertheless, theoretical understanding of hybrid synapses in diverse dynamical states of neural networks for self-organization and robustness still has not been fully studied. Here, we present a model of neural network built with hybrid synapses to investigate the emergence of global and co…
Power spectra of awake resting state EEG recordings in humans typically have an Alpha peak at around 10 Hz riding a decreasing background "Xi process". Normal and pathological variations may have more than one peak or none. The single channel Xi-Alpha model (Pascual-Marqui et al 1988, https://doi.org/10.3109/00207458808985730) separated these two processes, providing a low-dimensional parametric description of EEG spectra. Currently lacking is a generative whole cortex model for activity spectra and intracortical functional connectivity. Here we introduce the "cortical Xi-Alpha model". The cro…
We propose a neural network model of multi-neuron interacting system that simulates neurons to interact each other through the surroundings of neuronal cell bodies. We physically model the neuronal cell surroundings, include the dendrites, the axons and the synapses as well as the surrounding glial cells, as a collection of all kinds of oscillating modes arisen from the electric circuital environment of neuronal action potentials. By analyzing the dynamics of this neural model through the master equation approach of open quantum systems, we investigate the collective behavior of neurons. After…
Alzheimer's disease (AD) is a common form of dementia observed in the elderly due to neurodegenerative disorder and dysfunction. This arises from alterations in synaptic functioning of neurons leading to cognitive impairment and memory loss. Recent experimental studies indicate that the amyloid beta (A beta) protein, in its dimer and oligomer forms, affects the synaptic activity of neurons in the early stages of AD. However, the precise mechanism underlying A beta induced synaptic depression is still not clearly understood. In this paper, we introduce an electrical model that provides a possib…
