The Future of Intracranial EEG Recording in Epilepsy: a Technological Issue?

Intracranial EEG information used for epilepsy surgery has been provided from large widely spaced electrodes over a narrow bandwidth. However, over the last decades, research on animal and more recently on human, promoted by increased interest in developing high-density microelectrode arrays (MEA), has opened new windows for the comprehension of seizure origin and propagation at a submillimeter scale. From an electrophysiological perspective MEA demonstrate to be able to record local field potentials recordings and possibly single units in the mouse cortex. The limitations on the number of channels that can be recorded simultaneously may limit the number of microelectrodes that can be considered and consequently the extent of brain coverage. Thanks to improving microfabrication techniques, several prototypes of MEA are under development and investigation. They will certainly play an important role in the improvement of the understanding of the complicated and evolving concept of epileptogenesis and provide the development of new strategies regarding neurosurgical therapeutic issues

Controlled release nanoparticle-embedded coatings reduce the tissue reaction to neuroprostheses

Controlled release coatings were developed for neuroprostheses with the aim of combating the tissue reaction following implantation in the brain. The coatings consist of poly(propylene sulfide) drug-eluting nanoparticles embedded in a poly(ethylene oxide) matrix. The nanoparticles are loaded with dexamethasone, an anti-inflammatory drug known to have an effect on the cells activated during the damage caused by implantation. The nanoparticles are not affected by the coating process and the drug remains bioactive after it is released. The coating was applied to microfabricated cortical neuroprostheses consisting of platinum and polyimide. Coated drug-eluting devices were implanted in the cortex of rats. After implantation the matrix dissolves, exposing the electrode surfaces, while the nanoparticles remain in the vicinity of the tissue–implant interface. Using electrical impedance spectroscopy and comparative histology, a long-term decrease in the tissue response in comparison to control devices was observed. These coatings can therefore be used to increase the reliability and long-term efficacy of neuroprostheses

The tissue reaction to neuroprostheses

Neuroprostheses were developed for a variety of applications using unique microfabrication methods. A technology platform that enables novel microelectrode array designs and microfluidic channels is described. Experiments demonstrating the in vivo utility and unique capabilities of these neuroprostheses were performed. Despite their demonstrated effectiveness, the long term use of microscale neuroprosthetic devices is compromised by the post-implantation tissue reaction which forms around the device. This tissue reaction consists of glial cells on the same size scale as microelectrodes and microfluidic channels. In order to quantify the tissue reaction a new analytical method using Electrical Impedance Spectroscopy was developed called Peak Resistance Frequency analysis. A lumped parameter model describing the microelectrode-tissue interface was elaborated which identified and isolated the electrical characteristics of the different interface components. The model accurately predicted how the post-implantation tissue reaction increases the electrical impedance of the interface as demonstrated by in vivo experiments. The major goal of this work was to determine whether the tissue reaction to an implanted neuroprosthesis could be reduced using a controlled drug release mechanism and to measure the effect quantitatively. It was hypothesized that highly localized delivery for several days of an anti-inflammatory drug around the implant would disrupt the tissue reaction, thereby decreasing the electrical impedance of the microelectrode-tissue interface. Controlled release drug coatings were designed to deliver dexamethasone-loaded nanoparticles in the immediate region surrounding the implant. Drug-eluting and control probes were evaluated in the rat cortex. The electrical resistance of the encapsulation tissue was isolated and its progression as a function of post-implantation time was compared using Peak Resistance Frequency analysis and immunohistochemistry. These in vivo experiments demonstrated a decreased tissue reaction for drug-eluting probes and the effect was sustained chronically, therefore proving the hypothesis. These techniques offer a solution to the problem of tissue reaction around microscale neuroprostheses and an improvement in neural stimulation and recording capability

Implantable neurological probe for performing physiological measurement of patient, has microelectrode element that is arranged along the protrusion extended away from surface of supportive backing layer

Described herein are microelectrode array devices, and methods of fabrication and use of the same, to provide highly localized and efficient electrical stimulation of a neurological target. The device includes multiple microelectrode elements arranged along an supportive backing layer. The microelectrode elements are dimensioned and shaped so as to target individual neurons, groups of neurons, and neural tissue as may be located in an animal nervous system, such as along a region of a cortex of a human brain. Beneficially, the neurological probe can be used to facilitate location of the neurological target and remain implanted for long-term monitoring and/or stimulation

Implantable probe for stimulating neurological target e.g. neurons and subthalamic nucleus, has several microelectrode elements arranged at distal end of elongated probe shaft, and electrical contact arranged proximally along shaft

Described herein are microelectrode array devices, and methods of fabrication and use of the same, to provide highly localized and efficient electrical stimulation of a neurological target. The device includes multiple microelectrode elements arranged along an elongated probe shaft. The microelectrode elements are dimensioned and shaped so as to target individual neurons, groups of neurons, and neural tissue as may be located in an animal nervous system, such as deep within a human brain. Beneficially, the neurological probe can be used to facilitate location of the neurological target and remain implanted for long-term monitoring and/or stimulation

Stimulating apparatus for stimulating neurological target of live animal has stimulation source in communication with at least one micro-electrode to stimulate neurological target at respective preferred frequency

A preferred frequency is identified, being usable to stimulate a neurological target within a mammalian body using at least one microelectrode positioned at or near the target. To establish efficient and effective stimulation, an impedance analyzer is provided for measuring electrical impedance values indicative of a microelectrode-tissue interface across a range of different frequencies. A preferred one of the measured electrical impedance values is identified as being closest to a pure resistance. The neurological target can then be stimulated at or near the frequency associated with the preferred impedance value (peak resistance frequency), thereby promoting desirable traits, such as optimum charge transfer, minimum signal distortion, increased stimulation efficiency, and prevention of microelectrode corrosion. The peak resistance frequency can be used to determine an preferred pulse shape. A target can be identified by microelectrode measurements of neuronal activity and/or impedance magnitude at peak resistance frequency

Microfabricated Cortical Neuroprostheses

The use of neural implants for stimulation and recording show excellent promise in restoring certain functions to the central nervous system; and neuroprostheses remains one of the most important tools of neuroscientists for the elucidation of the brain's function. Ailments such as Parkinson's disease, obesity, blindness, and epilepsy are being studied from this angle. Development of better electrodes for recording and stimulation is therefore critical to ensure continuing progress in this field. This book addresses one of the main clinical complications with the use of electrodes, namely the reaction of the neurological tissue in the immediate vicinity of an implanted device. The authors describe new techniques for assessing this phenomenon, as well as new microfabrication techniques to impede the inflammatory response of the brain. Inflammation can adversely effect these devices, limiting their lifetime and reducing their effectiveness. The measurement protocols and improved fabrication protocols described within these pages will become standard tools in the future of neuroprostheses

Directional Local Field Potentials in the Subthalamic Nucleus During Deep Brain Implantation of Parkinson’s Disease Patients

Segmented deep brain stimulation leads feature directional electrodes that allow for a finer spatial control of electrical stimulation compared to traditional ring-shaped electrodes. These segmented leads have demonstrated enlarged therapeutic windows and have thus the potential to improve the treatment of Parkinson's disease patients. Moreover, they provide a unique opportunity to record directional local field potentials. Here, we investigated whether directional local field potentials can help identify the best stimulation direction to assist device programming. Four Parkinson's disease patients underwent routine implantation of the subthalamic nucleus. Firstly, local field potentials were recorded in three directions for two conditions: In one condition, the patient was at rest; in the other condition, the patient's arm was moved. Secondly, current thresholds for therapeutic and side effects were identified intraoperatively for directional stimulation. Therapeutic windows were calculated from these two thresholds. Thirdly, the spectral power of the total beta band (13-35 Hz) and its sub-bands low, high, and peak beta were analyzed post hoc. Fourthly, the spectral power was used by different algorithms to predict the ranking of directions. The spectral power profiles were patient-specific, and spectral peaks were found both in the low beta band (13-20 Hz) and in the high beta band (20.5-35 Hz). The direction with the highest spectral power in the total beta band was most indicative of the 1st best direction when defined by therapeutic window. Based on the total beta band, the resting condition and the moving condition were similarly predictive about the direction ranking and classified 83.3% of directions correctly. However, different algorithms were needed to predict the ranking defined by therapeutic window or therapeutic current threshold. Directional local field potentials may help predict the best stimulation direction. Further studies with larger sample sizes are needed to better distinguish the informative value of different conditions and the beta sub-bands. Keywords: Parkinson’s disease; deep brain stimulation; local field potentials; segmented leads; subthalamic nucleus

Integration of 2D and 3D Thin Film Glassy Carbon Electrode Arrays for Electrochemical Dopamine Sensing in Flexible Neuroelectronic Implants

Here we present the development and characterization of a flexible implantable neural probe with glassy carbon electrode arrays. The use of carbon electrodes allows for these devices to be used as chemical sensors, in addition to their typical use as electrical sensors and stimulators. The devices are fabricated out of polyimide, platinum, titanium, and carbon with standard microfabrication techniques on carrier wafers. The devices are released from the substrate through either chemical or electrochemical dissolution of the underlying substrate material. The glassy carbon electrode arrays are produced through the pyrolysis of SU-8 pillars at 900 °C as the first process step, as this temperature is incompatible with the other device materials. The process demonstrated here is generally applicable, allowing for the integration of various high temperature materials into flexible devices

in vivo Electrical Impedance Spectroscopy of Tissue Reaction to Microelectrode Arrays

The goal of this experiment was to determine the electrical properties of the tissue reaction to implanted microelectrode arrays. We describe a new method of analyzing electrical impedance spectroscopy data to determine the complex impedance of the tissue reaction as a function of postimplantation time. A model is used to extract electrical model parameters of the electrode-tissue interface, and is used to isolate the impedance of the tissue immediately surrounding the microelectrode. The microelectrode arrays consist of microfabricated polyimide probes, incorporating four 50-mum- diameter platinum microelectrodes. The devices were implanted in the primary motor cortex of adult rats, and measurements were performed for 12 weeks. Histology was performed on implants at three time points in one month. Results demonstrate that the tissue reaction causes a rapid increase in bioimpedance over the first 20 days, and then stabilizes. This result is supported by histological data