Improving the SNR of EEG generated by deep sources with weighted multielectrode leads

We have developed a multielectrode lead technique to improve the signal-to-noise ratio (SNR) of scalp-recorded electroencephalography (EEG) signals generated deep in the brain. The basis of the method lies in optimization of the measurement sensitivity distribution of the multielectrode lead. We claim that two factors improve the SNR in a multielectrode lead: (1) the sensitivity distribution of a multielectrode lead is more specific in measuring signals generated deep in the brain and (2) spatial averaging of noise occurs when several electrodes are applied in the synthesis of a multielectrode lead. We showed theoretically that within a three-layer spherical head model the sensitivity distributions of multielectrode leads are more specific for deep sources than those of traditional bipolar leads. We also estimated with simulations and with preliminary measurements the total improvement in SNR achieved by both the more specific lead field and spatial averaging. Results obtained with simulations and with experimental measurements show an apparent improvement in SNR obtained with multielectrode leads. This encourages for future development of the method.     

Neuronal Networks on Multielectrode Arrays as High Sensitive Biosensors of the Functional State of Nerve Cells

The dynamics of changes of spontaneous neuronal activity in primary hippocampal cell cultures developing on a multielectrode array (MEA) was studied using a multielectrode system. The intensification of bioelectrical activity, which depended on the duration of cultivation and stabilized by the second week in vitro, has been revealed. An increase in the concentration of glutamate (up to 2 μM) by addition into the incubation medium during the stabilization period resulted in a rapid and significant reorganization of the neuronal network activity pattern. On the other hand, inhibition and subsequent gradual recovery of the neuronal network activity immediately after the neurotransmitter addition at higher concentrations (50 or 100 μM) have been observed. At the same time, on some electrodes in the presence of high doses of glutamate (100 μM), a complete or partially irreversible suppression of the activity has been recorded. A significant reduction in spontaneous activity of the neuronal network, which was not accompanied by neuronal death, also occurred when copper ions (Cu²⁺) at a concentration of 10 μM were added into the incubation medium for 48 h. The obtained data demonstrate high biosensor sensitivity of the neuronal network cultured on the multielectrode array, which makes it possible to use it as an effective test system for studies of biologically active compounds.     

Employing ICA and SOM for spike sorting of multielectrode recordings from CNS

For classification of action potential shapes in multineuron recordings, we present a spike sorting system employing independent component analysis (ICA) and an unsupervised artificial neural network (Kohonen's self-organizing map, SOM). We focus on how ICA in the first stage of the spike sorting system can be used to address specific problems arising in recordings using multielectrode arrays in the CNS. Using real data recorded from the pontine nuclei in rats and simulated data, we evaluate the performance of several ICA algorithms to remove cross-talk between electrodes using data from continuous recording (or simulation). When using cut-out data, the standard format of extracellular spike recordings, new problems emerge and robust algorithms are needed. We demonstrate that several ICA algorithms show a good performance on cut-out data from multielectrode array recordings (simulated and real data). In tetrode recordings the same neuron is purposely recorded by several electrodes simultaneously and we show, how independent component analysis can be used in this case to identify redundant information and hence to compress relevant information, improving subsequent clustering of a SOM.     

Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants

Multielectrodes have been used with great success to simultaneously record the activity of neuronal populations in awake, behaving animals. In particular, there is great promise in the use of this technique to allow the control of neuroprosthetic devices by human patients. However, it is crucial to fully characterize the tissue response to the chronic implants in animal models ahead of the initiation of human clinical trials. Here we evaluated the effects of unilateral multielectrode implants on the motor cortex of rats weekly recorded for 1-6 months using several histological methods to assess metabolic markers, inflammatory response, immediate-early gene (IEG) expression, cytoskeletal integrity and apoptotic profiles. We also investigated the correlations between each of these features and firing rates, to estimate the impact of post-implant time on neuronal recordings. Overall, limited neuronal loss and glial activation were observed on the implanted sites. Reactivity to enzymatic metabolic markers and IEG expression were not significantly different between implanted and non-implanted hemispheres. Multielectrode recordings remained viable for up to 6 months after implantation, and firing rates correlated well to the histochemical and immunohistochemical markers. Altogether, our results indicate that chronic tungsten multielectrode implants do not substantially alter the histological and functional integrity of target sites in the cerebral cortex.     

Chronic pain as expression of neural substrates. Issues from the neuronal dynamics and mutual relations

The Thalamo-Cortical somatosensory loop shows important synaptic re-organization in cases of chronic pain. Animal models exhibit severe functional distortions, potentially related to the anatomic rearrangements. Connectivity and information theoretic measurement represent important tools to quantify the functional disarrays. We performed electrophysiological experiments with multisite, multielectrode simultaneous recordings in the Thalamus and in the Somatosensory Cortex. The recurrent anomalies in the analytic estimates induce to hypothesize a potential neurodynamical explanation of the sensory context.     

Borna disease virus infection impairs synaptic plasticity

The mechanisms whereby Borna disease virus (BDV) can impair neuronal function and lead to neurobehavioral disease are not well understood. To analyze the electrophysiological properties of neurons infected with BDV, we used cultures of neurons grown on multielectrode arrays, allowing a real-time monitoring of the electrical activity across the network shaped by synaptic transmission. Although infection did not affect spontaneous neuronal activity, it selectively blocked activity-dependent enhancement of neuronal network activity, one form of synaptic plasticity thought to be important for learning and memory. These findings highlight the original mechanism of the neuronal dysfunction caused by noncytolytic infection with BDV.     

Long-term Relationships between Cholinergic Tone, Synchronous Bursting and Synaptic Remodeling

Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.     

Direction selectivity in the retina is established independent of visual experience and cholinergic retinal waves

Direction selectivity in the retina requires the asymmetric wiring of inhibitory inputs onto four subtypes of On-Off direction-selective ganglion cells (DSGCs), each preferring motion in one of four cardinal directions. The primary model for the development of direction selectivity is that patterned activity plays an instructive role. Here, we use a unique, large-scale multielectrode array to demonstrate that DSGCs are present at eye opening, in mice that have been reared in darkness and in mice that lack cholinergic retinal waves. These data suggest that direction selectivity in the retina is established largely independent of patterned activity and is therefore likely to emerge as a result of complex molecular interactions.     

视觉编码的快速学习

活动依赖的神经可塑性在视觉皮层信息处理过程中起着很重要的作用。该文将讲述几个关于视觉刺激引起皮层反应发生快速变化的研究工作。在体膜片钳的实验结果表明,将视觉刺激与能够诱发孽个视皮层神经元发放动作电位的电刺激相偶联可以改变神经元的感受野特性。单电极和多电极胞外记录的实验结果显示,反复地给予自然图形电影刺激,不仅能增加视皮层神经元反应的可靠性,而且能造成之后的自发活动中存在“记忆的痕迹”。最后,用电压敏感染料成像的方法对群体细胞活动进行考察,结果提示视觉活动之后的皮层回放可能是由皮层波介导的。     

Low dose isoflurane exerts opposing effects on neuronal network excitability in neocortex and hippocampus

The anesthetic excitement phase occurring during induction of anesthesia with volatile anesthetics is a well-known phenomenon in clinical practice. However, the physiological mechanisms underlying anesthetic-induced excitation are still unclear. Here we provide evidence from in vitro experiments performed on rat brain slices that the general anesthetic isoflurane at a concentration of about 0.1 mM can enhance neuronal network excitability in the hippocampus, while simultaneously reducing it in the neocortex. In contrast, isoflurane tissue concentrations above 0.3 mM expectedly caused a pronounced reduction in both brain regions. Neuronal network excitability was assessed by combining simultaneous multisite stimulation via a multielectrode array with recording intrinsic optical signals as a measure of neuronal population activity.     

Retinal coding of visual scenes -- repetitive and redundant too?

Visual information reaches the brain by way of a fine cable, the optic nerve. The million or so axons in the optic nerve represent an information bottleneck in the visual pathway-where the fewest number of neurons convey the visual scene. It has long been thought that to make the most of the optic nerve's limited capacity the retina may encode visual information in an optimally efficient manner. In this issue of Neuron, Puchalla et al. report a test of this hypothesis using multielectrode recordings from retinal ganglion cells stimulated with movies of natural scenes. The authors find substantial redundancy in the retinal code and estimate that there is an approximately 10-fold overrepresentation of visual information.     

A lightweight microdrive for single-unit recording in freely moving rats and pigeons

A design for an inexpensive and reliable subminiature microdrive for recording single neurons in the freely moving animal is presented. The Scribe microdrive is small and lightweight and has been used successfully to record in freely moving rats and pigeons. It would also be suitable for recording in mice. The device is simple and inexpensive yet allows for stable and precise manipulation of the recording electrodes. As a result it supports stable recordings conducted over long periods. Because the Scribe microdrive is a small-diameter device it is also suitable for multisite, multielectrode applications. Here we discuss the construction of the device and comment on its use in recording from freely moving rats and pigeons.     

A case of successful radiofrequency catheter ablation for atrial tachycardia originating from the inferior vena cava using high-resolution mapping

A 60-year-old man presented with sustained supraventricular tachycardia. Atrial tachycardia (AT), with the earliest atrial activation (EAA) occurring at the ostium of the coronary sinus, was reproducibly induced.Three-dimensional electroanatomical mapping (3DEAM) using a 3.5-mm distal electrode tip linear catheter (Thermocool) and radiofrequency energy (RF) was performed at the fractionated atrial electrogram site. It preceded at 30 ms to the EAA but did not terminate AT. Further 3DEAM using a multielectrode mapping catheter (Pentaray) demonstrated a centrifugal propagation pattern at the boundary zone between the right atrium and inferior vena cava. RF application here terminated AT, which then became non-inducible.     

A biosensor for detecting changes in cognitive processing based on nonlinear systems analysis.

A new type of biosensor, based on hippocampal slices cultured on multielectrode arrays, and using nonlinear systems analysis for the detection and classification of agents interfering with cognitive function is described. A new method for calculating first and second order kernel was applied for impulse input-spike output datasets and results are presented to show the reliability of the estimations of this parameter. We further decomposed second order kernels as a sum of nine exponentially decaying Laguerre base functions. The data indicate that the method also reliably estimates these nine parameters. Thus, the state of the system can now be described with a set of ten parameters (first order kernel plus nine coefficients of Laguerre base functions) that can be used for detection and classification purposes.     

Long-lived plasmoids as initiators of combustion of gas mixtures

A slipping surface discharge excited along a multielectrode metal-dielectric system in a chemically active (combustible) CH₄-O₂ mixture has been studied experimentally. Results obtained with the help of high-speed hotography, shadowgraphy, optical spectroscopy, and piezoelectric measurements are presented. It is hown that the slipping surface discharge is a source of high-temperature, thermally equilibrium metal plasmoids hose lifetime is much longer than the plasma recombination time (long-lived plasmoids). The experimental investigation of the evolution of plasmoids introduced into a combustible gaseous medium allows one to conclude that the medium significantly increases the lifetime of plasmoids and that plasmoids, in turn, play an important role in the initiation of gas-mixture combustion.     

Relationship between Growth and Electric Oscillations in Bean Roots

Extracellular and intracellular electric potentials in bean roots are known to show electric oscillations along the longitudinal axis with a period of several minutes. The relationship between growth and the electric oscillations was studied using roots of adzuki (Phaseolus chrysanthos). We measured surface electric potentials with a multielectrode apparatus while simultaneously measuring elongation using a CCD camera and monitor. Roots having an electric oscillation grew faster than roots with no oscillation. Furthermore, elongation rate was higher in roots with higher oscillation frequency. Oscillation frequency had a strong dependence on temperature; i.e. Q₁₀ was estimated at 1.7. These results suggest a correlation between electric oscillation and elongation.     

Retinal ganglion cells do not extend axons by default: promotion by neurotrophic signaling and electrical activity

We investigate the signaling mechanisms that induce retinal ganglion cell (RGC) axon elongation by asking whether surviving neurons extend axons by default. We show that bcl-2 overexpression is sufficient to keep purified RGCs alive in the absence of any glial or trophic support. The bcl-2-expressing RGCs do not extend axons or dendrites unless signaled to do so by single peptide trophic factors. Axon growth stimulated by peptide trophic factors is remarkably slow but is profoundly potentiated by physiological levels of electrical activity spontaneously generated within embryonic explants or mimicked on a multielectrode silicon chip. These findings demonstrate that these surviving neurons do not constitutively extend axons and provide insight into the signals that may be necessary to promote CNS regeneration.     

Perisomatic feedback inhibition underlies cholinergically induced fast network oscillations in the rat hippocampus in vitro

Gamma frequency network oscillations are assumed to be important in cognitive processes, including hippocampal memory operations, but the precise functions of these oscillations remain unknown. Here, we examine the cellular and network mechanisms underlying carbachol-induced fast network oscillations in the hippocampus in vitro, which closely resemble hippocampal gamma oscillations in the behaving rat. Using a combination of planar multielectrode array recordings, imaging with voltage-sensitive dyes, and recordings from single hippocampal neurons within the CA3 gamma generator, active current sinks and sources were localized to the stratum pyramidale. These proximal currents were driven by phase-locked rhythmic inhibitory inputs to pyramidal cells from identified perisomatic-targeting interneurons. AMPA receptor-mediated recurrent excitation was necessary for the synchronization of interneuronal discharge, which strongly supports a synaptic feedback model for the generation of hippocampal gamma oscillations.     

EEG source identification: frequency analysis during sleep

This article deals with a new approach in sleep characterization that combines EEG source localisation methods with standard frequency analysis of multielectrode EEGs. First, we describe the theoretical methodology and the benefits that we get from a three-dimensional image (LORETA) of the cerebral activity related to a frequency band. Then, this new application is used as signal-processing technique on sleep EEG recordings obtained from young male adults using four frequency bands (delta 0.5-3.5 Hz, theta 4.0-7.5 Hz, alpha 8.0-12.5 Hz and beta 13.0-32.0 Hz) in different sleep stages. Finally, we show that the obtained results are highly consistent with other physiological assessments (standard EEG mapping, functional magnetic resonance imaging, etc.), but give us more realistic additional information on the generators of electromagnetic cerebral activity.