Jan R. Buitenweg

Anodal vs cathodal stimulation of motor cortex: A modeling study

OBJECTIVEnTo explore the effects of electrical stimulation performed by an anode, a cathode or a bipole positioned over the motor cortex for chronic pain management.nnnMETHODSnA realistic 3D volume conductor model of the human precentral gyrus (motor cortex) was used to calculate the stimulus-induced electrical field. The subsequent response of neural elements in the precentral gyrus and in the anterior wall and lip of the central sulcus was simulated using compartmental neuron models including the axon, soma and dendritic trunk.nnnRESULTSnWhile neural elements perpendicular to the electrode surface are preferentially excited by anodal stimulation, cathodal stimulation excites those with a direction component parallel to its surface. When stimulating bipolarly, the excitation of neural elements parallel to the bipole axis is additionally facilitated. The polarity of the contact over the precentral gyrus determines the predominant response. Inclusion of the soma-dendritic model generally reduces the excitation threshold as compared to simple axon model.nnnCONCLUSIONSnElectrode polarity and electrode position over the precentral gyrus and central sulcus have a large and distinct influence on the response of cortical neural elements to stimuli.nnnSIGNIFICANCEnModeling studies like this can help to identify the effects of electrical stimulation on cortical neural tissue, elucidate mechanisms of action and ultimately to optimize the therapy.

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 culture.

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.

Measurement of sealing resistance of cell-electrode interfaces in neuronal cultures using impedance spectroscopy.

Sealing resistance is highly significant with respect to the electrical neuronelectrode contact because it decreases the stimulation threshold of neurons cultured on a planar micro-electrode array. A method is proposed for measurement of the sealing resistance using impedance spectroscopy. The effect of the sealing resistance on the total impedance spectrum of a cell-electrode interface is modelled for complete coverage of the electrode by the cell. Sensitivity analysis demonstrates that the impedance spectrum is determined by four parameters: two electrode parameters, the sealing resistance and the shunt capacitance between the lead of the electrode and the culture medium. Experimental verification of the model is performed by simultaneous measurement of the impedance spectrum and electrode coverage. A good and unique fit between the simulated and measured impedance spectra was obtained by varying the two electrode parameters and the sealing resistance.

The role of intra-operative motor evoked potentials in the optimization of chronic cortical stimulation for the treatment of neuropathic pain

OBJECTIVEnTo explore the significance of intra-operative motor evoked potentials (MEPs) obtained by monopolar and bipolar stimulation in determining the location of the electrode(s) giving most pain relief in chronic motor cortex stimulation (MCS).nnnMETHODSnEight patients with chronic refractory neuropathic pain were implanted epidurally with two parallel leads of four electrodes each and placed normal to the central sulcus (CS). We measured the peak-peak amplitude (V(p-p)) of the MEPs recorded intra-operatively at the contralateral hand with the same stimulus delivered by each single electrode used as an anode or a cathode. Those electrodes giving the largest MEPs in monopolar stimulation were also tested in bipolar stimulation with an adjacent electrode located on the same or the other lead. It was analyzed whether a relation was present between the electrode providing the largest V(p-p) in the monopolar condition and the bipolar combination selected for chronic stimulation.nnnRESULTSnIn monopolar stimulation the median amplitude of MEPs evoked with an anode was 59% larger than with a cathode. The mean amplitude of the bipolarly evoked MEPs was only 21% and 37%, respectively, of the corresponding monopoles when the anode and cathode were separated by 6mm and by more than 8mm. A significant pain relief was obtained in 5 out of 8 patients post-operatively. In all these patients, one of the cathodes used in chronic stimulation was one of the anodes producing the largest MEP intra-operatively. Conversely, in the 3 patients who did not benefit from MCS, one of the cathodes used in chronic stimulation was one of the cathodes producing the largest MEPs intra-operatively.nnnCONCLUSIONSnMonopolar stimulation should be applied in intra-operative neurophysiological testing because, contrary to bipolar stimulation, the corresponding MEPs are unambiguously related to a single stimulating electrode and their amplitude is not affected by the anode-cathode distance. The anode providing the largest MEPs intra-operatively should be selected as the cathode in chronic stimulation. However, implantable pulse generators allowing monopolar (cathodal and anodal) stimulation for MCS should become available to compare the respective analgesic efficacy of monopolar and bipolar chronic cortical stimulation.nnnSIGNIFICANCEnIntra-operative MEP recordings can predict which electrode should be used as the cathode to obtain the best analgesic effect with chronic MCS.

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.

Intermittent Stimulation Delays Adaptation to Electrocutaneous Sensory Feedback

Electrotactile displays deliver information to the user by means of electrocutaneous stimulation. If such displays are used in prostheses, the functionality depends on long term stability of this information channel. The perceived sensation, however, decays within 15 min due to central adaptation if the stimulation is applied continuously and at constant strength. In this study, the effects of stimulus amplitude and intermittent stimulation on adaptation were investigated in ten healthy subjects. The perceived sensation was recorded during 15 min of constant stimulation using a visual analog scale (VAS). The sensation level with time thus measured were parameterized by the initial sensation level, the time constant of decay and the end sensation level after fitting of an exponential function through the VAS data. The time constant increased significantly when applying a high stimulation level (at 80% of the range between sensation and pain thresholds) if compared with lower levels of stimulation (20% and 50%) during continuous stimulation. Intermittent stimulation at this high stimulation level significantly increased end sensation level.

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.

Extracellular detection of active membrane currents in the neuron–electrode interface

Although measurement of sealing resistance is an important tool in the assessment of the electrical contacts between cultured cells and substrate embedded microelectrodes, it does not offer information about the type of cell, i.e. neuron or non-neuronal cell. Also, rules for translation of a measured sealing resistance into parameters for successful stimulation, i.e. eliciting an action potential, are not available yet. Therefore, a method is proposed for the detection of active membrane currents, elicited by extracellular current stimulation. The method is based on the prediction of the linear part of the response to an applied stimulus current pulse using an impedance model of the neuron-electrode contact. Active membrane currents are detected in the nonlinear response, which is obtained by subtraction of the predicted linear response from the measured response. The required impedance model parameters are extracted from impedance spectroscopy or directly from the measured responses.

Finite element modeling of the neuron-electrode interface

The electrical contact between an embedded microelectrode and a cultured neuron depends on the geometry of the neuron-electrode interface. The contact is improved when the electrode is covered, or sealed, completely by the neuron. In this article, the finite element method is proposed as a tool for modeling the electrical properties of the neuron-electrode interface. This method permits numerical solutions of volume conductor problems for a variety of geometries, without prior restriction of the current paths. Simulations are focused on the influence of the geometry on the transfer of an extracellularly applied stimulus current to the neuron and on the sealing resistance. A comparison is also made between finite element modeling and lumped circuit modeling. In conclusion, finite element analysis is a valuable tool for studying and optimizing the neuron-electrode contact.