Modelling and Analysis of Electrical Potentials Recorded in Microelectrode Arrays (MEAs)

Abstract

Microelectrode arrays (MEAs), substrate-integrated planar arrays of up to thousands of closely spaced metal electrode contacts, have long been used to record neuronal activity in in vitro brain slices with high spatial and temporal resolution. However, the analysis of the MEA potentials has generally been mainly qualitative. Here we use a biophysical forward-modelling formalism based on the finite element method (FEM) to establish quantitatively accurate links between neural activity in the slice and potentials recorded in the MEA set-up. Then we develop a simpler approach based on the method of images (MoI) from electrostatics, which allows for computation of MEA potentials by simple formulas similar to what is used for homogeneous volume conductors. As we find MoI to give accurate results in most situations of practical interest, including anisotropic slices covered with highly conductive saline and MEA-electrode contacts of sizable physical extensions, a Python software package (ViMEAPy) has been developed to facilitate forward-modelling of MEA potentials generated by biophysically detailed multicompartmental neurons. We apply our scheme to investigate the influence of the MEA set-up on single-neuron spikes as well as on potentials generated by a cortical network comprising more than 3000 model neurons. The generated MEA potentials are substantially affected by both the saline bath covering the brain slice and a (putative) inadvertent saline layer at the interface between the MEA chip and the brain slice. We further explore methods for estimation of current-source density (CSD) from MEA potentials, and find the results to be much less sensitive to the experimental set-up.

Impedance Spectrum in Cortical Tissue: Implications for Propagation of LFP Signals on the Microscopic Level

“…Note that for σ T = σ S , this reduces to give twice the size of the potential predicted from the homogeneous point source Equation 1. This is as expected for a source positioned in a semi-infinite half-space above a semi-infinite nonconducting medium (Jackson, 1998; Ness et al, 2015). The expression contains an infinite sum, but in practice the sum converges fast when terms are added.…”

“…The present MEA setup does not correspond to an infinite homogeneous volume conductor, but by using the method of images, Equation 1 can be extended to also be applicable for in vitro slice MEA measurements, where one has a three-layered medium (nonconducting MEA plate, brain tissue slice, and ACSF bath; Ness et al, 2015; Fig. 1 A ).…”

“…1 A ). With a single current point source, I ( t ), positioned at ( x' , y' , z' ) in the middle slab of a three-layered medium (i.e., a lower, nonconducting glass electrode plate, an electrically homogeneous brain tissue slice with vertical extension from z = 0 to z = h , and an infinitely thick ACSF layer covering the brain slice), the extracellular potential at the electrode–slice boundary ( z = 0) is given by Ness et al (2015) as follows:${\varphi }_{MEA}(x,y,0,t)=2{\varphi }_h(x,y,0,t)+2{\displaystyle {\sum }_{n=1}^{\infty }{\left(\frac{{\sigma }_T-{\sigma }_S}{{\sigma }_T+{\sigma }_S}\right)}^n\left({\varphi }_{h}false(x,y,2nh,t)+{\varphi }_{h}false(x,y,-2nh,tfalse)\right)}\mathrm{.}$ …”

Extracellular Potential Recording of Patterned Rat Olfactory Bulb Neuronal Network Using Planar Microelectrode Arrays

“…By varying the cell-electrode coupling and other biophysical parameters, they got signals of different durations, intensities and shapes. Spike shape was also influenced by both of cell geometry and cell size [17].…”

Visualization of electrical field of electrode using voltage-controlled fluorescence release

“…To model the electrical potentials recorded in microelectrode arrays, Ness et al . established a biophysical forward model based on the FEM to link the neural activity in the brain tissue slice and the potentials recorded by microelectrode arrays [16]. Howell et al, studied the influences of electrode geometry, and the electrode–tissue interface on models of electric fields produced by DBS [6].…”