Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called “Neural Matrix,” that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.

Objective. The clinical use of microsignals recorded over broad cortical regions is largely limited by the chronic reliability of the implanted interfaces. Approach. We evaluated the chronic reliability of novel 61-channel micro-electrocorticographic (μECoG) arrays in rats chronically implanted for over one year and using accelerated aging. Devices were encapsulated with polyimide (PI) or liquid crystal polymer (LCP), and fabricated using commercial manufacturing processes. In vitro failure modes and predicted lifetimes were determined from accelerated soak testing. Successful designs were implanted epidurally over the rodent auditory cortex. Trends in baseline signal level, evoked responses and decoding performance were reported for over one year of implantation. Main results. Devices fabricated with LCP consistently had longer in vitro lifetimes than PI encapsulation. Our accelerated aging results predicted device integrity beyond 3.4 years. Five implanted arrays showed stable performance over the entire implantation period (247–435 days). Our regression analysis showed that impedance predicted signal quality and information content only in the first 31 days of recordings and had little predictive value in the chronic phase (> 31 days). In the chronic phase, site impedances slightly decreased yet decoding performance became statistically uncorrelated with impedance. We also employed an improved statistical model of spatial variation to measure sensitivity to locally varying fields, which is typically concealed in standard signal power calculations. Significance. These findings show that μECoG arrays can reliably perform in chronic applications in vivo for over one year, which facilitates the development of a high-density, clinically viable interface.

Objective Micro-electrocorticography (μECoG) offers a minimally invasive neural interface with high spatial resolution over large areas of cortex. However, electrode arrays with many contacts that are individually wired to external recording systems are cumbersome and make recordings in freely-behaving rodents challenging. We report a novel high-density 60-electrode system for μECoG recording in freely-moving rats. Approach Multiplexed headstages overcome the problem of wiring complexity by combining signals from many electrodes to a smaller number of connections We have developed a low-cost, multiplexed recording system with 60 contacts at 406 μm spacing. We characterized the quality of the electrode signals using multiple metrics that tracked spatial variation, evoked-response detectability, and decoding value. Performance of the system was validated both in anesthetized animals and freely-moving awake animals. Main results We recorded μECoG signals over the primary auditory cortex, measuring responses to acoustic stimuli across all channels. Single-trial responses had high signal-to-noise ratios (up to 25 dB under anesthesia), and were used to rapidly measure network topography within ~10 seconds by constructing all single-channel receptive fields in parallel. We characterized evoked potential amplitudes and spatial correlations across the array in the anesthetized and awake animals. Recording quality in awake animals was stable for at least 30 days. Finally, we used these responses to accurately decode auditory stimuli on single trials. Significance This study introduces (1) a μECoG recording system based on practical hardware design and (2) a rigorous analytical method for characterizing the signal characteristics of μECoG electrode arrays. This methodology can be applied to evaluate the fidelity and lifetime of any μECoG electrode array. Our μECoG-based recording system is accessible and will be useful for studies of perception and decision-making in rodents, particularly over the entire time course of behavioral training and learning.

. A simulation study of the combined thermoelectric extracellular stimulation of the sciatic nerve of the Xenopus laevis: the localized transient heat block. IEEE Transactions on Biomedical Engineering, 59(6), pp. 1758 -1769 . doi: 10.1109 /TBME.2012 This is the accepted version of the paper.This version of the publication may differ from the final published version. 1  Abstract-This paper presents the response of the Xenopus laevis nerve fibers to combinations of electrical (cuff electrodes) and optical (infrared laser, low power sub-5mW) stimulation. Assuming that the main effect of the laser irradiation on the nerve tissue is the localized temperature increase, this paper analyzes and gives new insights into the function of the combined thermoelectric stimulation on both excitation and blocking of the nerve action potentials (AP). The calculations involve a finite-element model (COMSOL) to represent the electrical properties of the nerve and cuff. Electric field distribution along the nerve was computed for the given stimulation current profile and imported into a NEURON model, which was built to simulate the electrical behavior of myelinated nerve fiber under extracellular stimulation. The main result of this study of combined thermoelectric stimulation showed that local temperature increase, for the given electric field, can create a transient block of both the generation and propagation of the APs. Some preliminary experimental data in support of this conclusion are also shown. Permanent

Objective. Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans. Here we describe the development, validation, and dissemination of flexible, high-resolution, thin-film (TF) electrodes for recording neural activity in animals and humans. Approach. We leveraged standard flexible printed-circuit manufacturing processes to build high-resolution TF electrode arrays. We used biocompatible materials to form the substrate (liquid crystal polymer; LCP), metals (Au, PtIr, and Pd), molding (medical-grade silicone), and 3D-printed housing (nylon). We designed a custom, miniaturized, digitizing headstage to reduce the number of cables required to connect to the acquisition system and reduce the distance between the electrodes and the amplifiers. A custom mechanical system enabled the electrodes and headstages to be pre-assembled prior to sterilization, minimizing the setup time required in the operating room. PtIr electrode coatings lowered impedance and enabled stimulation. High-volume, commercial manufacturing enables cost-effective production of LCP-TF electrodes in large quantities. Main Results. Our LCP-TF arrays achieve 25× higher electrode density, 20× higher channel count, and 11× reduced stiffness than conventional clinical electrodes. We validated our LCP-TF electrodes in multiple human intraoperative recording sessions and have disseminated this technology to >10 research groups. Using these arrays, we have observed high-frequency neural activity with sub-millimeter resolution. Significance. Our LCP-TF electrodes will advance human neuroscience research and improve clinical care by enabling broad access to transformative, high-resolution electrode arrays.

Micro-electrocorticographic (μECοG) electrode arrays provide a minimally invasive, high-resolution neural interface with broad cortical coverage. Previously, we fabricated μECoG arrays at a lower cost than commercially available devices using low-cost industrial processes [1], [2]. Here, we report the in vitro electrical performance of five μECoG designs undergoing an accelerated aging protocol. The impedance and yield of the μECoG arrays were tracked over time. The equivalent lifetime at 37°C depended on the manufacturer and material stack-up, and ranged between 30 and greater than 760 days (ongoing). The main failure modes of these devices were delamination at the site of the electrode contact and broken traces due to metal dissolution. Based on these in vitro results, we offer several recommendations for μECoG designs suitable for chronic implantation.

While mammography remains the gold standard for breast cancer screening, additional adjunctive tools for early detection of breast cancer are needed especially for young women, women with dense breast tissue and those at increased risk due to genetic factors. These patient populations, along with those populations for whom mammography is not readily available, require alternative technologies capable of effectively detecting breast cancer. One such adjunctive modality for breast cancer detection is Electrical Impedance Tomography (EIT). It is a non-invasive technique that measures tissue conductivity by injecting a small current through a surface electrode while measuring electrode voltage(s). The surface measurements are then used to reconstruct a conductivity mapping of the tissue. The difference in conductivities between healthy tissue and that of carcinoma enable EIT to detect cancer. Electrical Impedance Tomography does not subject the patient to ionizing radiation, and offers significant potential for detecting very small tumors in early stages of development at a low cost. While prior systems have demonstrated success using EIT for breast cancer detection, the resolution of the reconstructed image was limited by the spatial resolution of the sensing electrode array. Here, we report the use of higher density (3mm spacing) flexible micro-electrode arrays to obtain tissue impedance maps. Accurate EIT reconstruction is highly dependent on the spatial resolution and fidelity of the surface measurements. High-density, flexible arrays that conform to the breast surface can offer great potential in reconstructing higher resolution conductivity maps than have been previously achieved.

Micro-Electrocorticography (µECoG) offers a minimally invasive, high resolution interface with large areas of cortex. A wide variety of µECoG designs have been developed and customized [1]-[4], including active, multiplexed arrays [5] and arrays on dissolving substrates for increased conformal contact [6]. However, designing and fabricating customized µECoG arrays requires access to microfabrication facilities, which many neuroscience labs do not have. Microfabrication is also typically labor intensive and expensive. Commercial µECoG arrays with 64 electrodes and coarser dimensions cost approximately $1000, limiting their suitability for chronic implantation in large numbers of animals. Here we present a high density (406 µm spacing), flexible (~30 µm thin), 61-contact µECoG electrode array fabricated using a low-cost, commercial manufacturing process. The array costs just $26 when ordered in quantities of 100, with the cost per electrode increasing slightly when lower quantities are ordered. Fine pitch wires minimize the size of the interconnections, enabling chronic implantation in rodents. In-house post-processing of the fabricated µECoG arrays added optional electrode coatings, such as platinum black, to reduce the electrode impedance. Our electrode design and manufacturing process dramatically improves the accessibility and reduces the cost of highvolume, high-resolution neuroscience.