Geometry-based finite-element modeling of the electrical contact between a cultured neuron and a microelectrode

The electrical contact between a substrate embedded microelectrode and a cultured neuron depends on the geometry of the neuron-electrode interface. Interpretation and improvement of these contacts requires proper modeling of all coupling mechanisms. In literature, it is common practice to model the neuron-electrode contact using lumped circuits in which large simplifications are made in the representation of the interface geometry. In this paper, the finite-element method is used to model the neuron-electrode interface, which permits numerical solutions for a variety of interface geometries. The simulation results offer detailed spatial and temporal information about the combined electrical behavior of extracellular volume, electrode-electrolyte interface and neuronal membrane

Extracellular stimulation window explained by a geometry-based model of the neuron-electrode contact

Extracellular stimulation of single cultured neurons which are completely sealing a microelectrode is usually performed using anodic or biphasic currents of at least 200 nA. However, recently obtained experimental data demonstrate the possibility to stimulate a neuron using cathodic current pulses with less amplitude. Also, a stimulation window is observed. These findings can be explained by a finite-element model which permits geometry-based electrical representation of the neuron-electrode interface and can be used to explore the required conditions for extracellular stimulation in detail. Modulation of the voltage sensitive channels in the sealing part of the membrane appears to be the key to successful cathodic stimulation. Furthermore, the upper limit of the stimulation window can be explained as a normal consequence of the neuronal membrane electrophysiology

Modeled channel distributions explain extracellular recordings from cultured neurons sealed to microelectrodes

Amplitudes and shapes of extracellular recordings from single neurons cultured on a substrate embedded microelectrode depend not only on the volume conducting properties of the neuron-electrode interface, but might also depend on the distribution of voltage-sensitive channels over the neuronal membrane. In this paper, finite-element modeling is used to quantify the effect of these channel distributions on the neuron-electrode contact. Slight accumulation or depletion of voltage-sensitive channels in the sealing membrane of the neuron results in various shapes and amplitudes of simulated extracellular recordings. However, estimation of channel-specific accumulation factors from extracellular recordings can be obstructed by co-occuring ion currents and defect sealing. Experimental data from cultured neuron-electrode interfaces suggest depletion of sodium channels and accumulation of potassium channels

Neuroelectronic interfacing with cultured multielectrode arrays toward a cultured probe

Efficient and selective electrical stimulation and recording of neural activity in peripheral, spinal, or central pathways requires multielectrode arrays at micrometer scale. ¿Cultured probe¿ devices are being developed, i.e., cell-cultured planar multielectrode arrays (MEAs). They may enhance efficiency and selectivity because neural cells have been grown over and around each electrode site as electrode-specific local networks. If, after implantation, collateral sprouts branch from a motor fiber (ventral horn area) and if they can be guided and contacted to each ¿host¿ network, a very selective and efficient interface will result. Four basic aspects of the design and development of a cultured probe, coated with rat cortical or dorsal root ganglion neurons, are described. First, the importance of optimization of the cell-electrode contact is presented. It turns out that impedance spectroscopy, and detailed modeling of the electrode-cell interface, is a very helpful technique, which shows whether a cell is covering an electrode and how strong the sealing is. Second, the dielectrophoretic trapping method directs cells efficiently to desired spots on the substrate, and cells remain viable after the treatment. The number of cells trapped is dependent on the electric field parameters and the occurrence of a secondary force, a fluid flow (as a result of field-induced heating). It was found that the viability of trapped cortical cells was not influenced by the electric field. Third, cells must adhere to the surface of the substrate and form networks, which are locally confined, to one electrode site. For that, chemical modification of the substrate and electrode areas with various coatings, such as polyethyleneimine (PEI) and fluorocarbon monolayers promotes or inhibits adhesion of cells. Finally, it is shown how PEI patterning, by a stamping technique, successfully guides outgrowth of collaterals from a neonatal rat lumbar spinal cord explant, after six days in cultur

Extracellular electrical signals in a neuron-surface junction: model of heterogeneous membrane conductivity

Signals recorded from neurons with extracellular planar sensors have a wide range of waveforms and amplitudes. This variety is a result of different physical conditions affecting the ion currents through a cellular membrane. The transmembrane currents are often considered by macroscopic membrane models as essentially a homogeneous process. However, this assumption is doubtful, since ions move through ion channels, which are scattered within the membrane. Accounting for this fact, the present work proposes a theoretical model of heterogeneous membrane conductivity. The model is based on the hypothesis that both potential and charge are distributed inhomogeneously on the membrane surface, concentrated near channel pores, as the direct consequence of the inhomogeneous transmembrane current. A system of continuity equations having non-stationary and quasi-stationary forms expresses this fact mathematically. The present work performs mathematical analysis of the proposed equations, following by the synthesis of the equivalent electric element of a heterogeneous membrane current. This element is further used to construct a model of the cell-surface electric junction in a form of the equivalent electrical circuit. After that a study of how the heterogeneous membrane conductivity affects parameters of the extracellular electrical signal is performed. As the result it was found that variation of the passive characteristics of the cell-surface junction, conductivity of the cleft and the cleft height, could lead to different shapes of the extracellular signals

Doctor of Philosophy

dissertationIntracortical microelectrode arrays create a direct interface between the brain and external devices. This “brain-machine interface” has found clinical application by allowing patients with tetraplegia to control computer cursors and robotic limbs. Unfortunately, use of intracortical microelectrode array technology is currently limited by its inconsistent ability to record neural signals over time. It is widely believed that the foreign body response (FBR) contributes to recording inconsistency. Most characterizations of the FBR to intracortical microelectrodes have been in the rat using devices with simple architecture, while the only device currently used in humans, the Utah Electrode Array (UEA), is much larger and more complex. In this work, we characterized the FBR to the UEA and found that, unlike with simpler devices, implantation of a UEA results in extensive vascular injury and loss of cortical tissue. We also sought to determine which features of the FBR correlated with recording inconsistency and found that biomarkers of astrogliosis, blood-brain barrier leakage, and tissue loss were associated with decreased recording performance. Next, since a significant portion of potential brain-machine interface recipients are aged, we applied similar methods in an aged cohort of rats in order to understand the effect of aging on the FBR and recording performance. We found that, surprisingly, recording performance was superior in the aged cohort. Astrogliosis was again associated with decreased recording performance in the aged cohort. Finally, we continued our development and validation of a finite element model of cytokine diffusion to assist in designing next-generation devices with a reduced FBR. Taken as a whole, this work provides meaningful insights into the mechanisms of inconsistent recording performance and discusses several promising avenues for overcoming them

Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex.

Bioresorbable silicon electronics technology offers unprecedented opportunities to deploy advanced implantable monitoring systems that eliminate risks, cost and discomfort associated with surgical extraction. Applications include postoperative monitoring and transient physiologic recording after percutaneous or minimally invasive placement of vascular, cardiac, orthopaedic, neural or other devices. We present an embodiment of these materials in both passive and actively addressed arrays of bioresorbable silicon electrodes with multiplexing capabilities, which record in vivo electrophysiological signals from the cortical surface and the subgaleal space. The devices detect normal physiologic and epileptiform activity, both in acute and chronic recordings. Comparative studies show sensor performance comparable to standard clinical systems and reduced tissue reactivity relative to conventional clinical electrocorticography (ECoG) electrodes. This technology offers general applicability in neural interfaces, with additional potential utility in treatment of disorders where transient monitoring and modulation of physiologic function, implant integrity and tissue recovery or regeneration are required

In silico study on in vitro experiments to determine the electric membrane properties of a realistic cochlear model for electric field simulations on cochlear implants

To further develop and optimise the design of cochlear implants, a numerical model with precise material properties and authentic geometry is required. Since simulation results strongly depend on the accuracy of the estimates of the electrical properties of cochlear membranes, it is important to have a reliable in vivo method for measuring electrical impedance changes in the cochlear compartments. This work is a preliminary attempt to model, simulate and analyse the behaviour of a novel in-vitro experimental system for conducting plausible in-vivo measurements on mammalian cochlea membranes.Zur Weiterentwicklung und Optimierung des Designs von Cochlea-Implantaten ist ein detailliertes numerisches Modell der Cochlea erforderlich. Da die Simulationsergebnisse stark von den elektrischen Eigenschaften der Cochlea-Membranen abhängen, ist es wichtig, ein zuverlässiges In-vivo-Verfahren zur Messung des elektrischen Impedanzverlaufs zu haben. Diese Arbeit ist eine vorbereitende Studie, das Verhalten eines neuartigen In-vitro-Versuchssystems zur Durchführung plausibler In-vivo-Messungen an Cochlea-Membranen von Säugetieren zu modellieren, zu simulieren und zu analysieren