Rio J. Vetter

Flexible polyimide-based intracortical electrode arrays with bioactive capability

The promise of advanced neuroprosthetic systems to significantly improve the quality of life for a segment of the deaf, blind, or paralyzed population hinges on the development of an efficacious, and safe, multichannel neural interface for the central nervous system. The candidate implantable device that is to provide such an interface must exceed a host of exacting design parameters. The authors present a thin-film, polyimide-based, multichannel intracortical Bio-MEMS interface manufactured with standard planar photo-lithographic CMOS-compatible techniques on 4-in silicon wafers. The use of polyimide provides a mechanically flexible substrate which can be manipulated into unique three-dimensional designs. Polyimide also provides an ideal surface for the selective attachment of various important bioactive species onto the device in order to encourage favorable long-term reactions at the tissue-electrode interface. Structures have an integrated polyimide cable providing efficient contact points for a high-density connector. This report details in vivo and in vitro device characterization of the biological, electrical and mechanical properties of these arrays. Results suggest that these arrays could be a candidate device for long-term neural implants.

Chronic neural recording using silicon-substrate microelectrode arrays implanted in cerebral cortex

An important aspect of the development of cortical prostheses is the enhancement of suitable implantable microelectrode arrays for chronic neural recording. The objective of this study was to investigate the recording performance of silicon-substrate micromachined probes in terms of reliability and signal quality. These probes were found to consistently and reliably provide high-quality spike recordings over extended periods of time lasting up to 127 days. In a consecutive series of ten rodents involving 14 implanted probes, 13/14 (93%) of the devices remained functional throughout the assessment period. More than 90% of the probe sites consistently recorded spike activity with signal-to-noise ratios sufficient for amplitudes and waveform-based discrimination. Histological analysis of the tissue surrounding the probes generally indicated the development of a stable interface sufficient for sustained electrical contact. The results of this study demonstrate that these planar silicon probes are suitable for long-term recording in the cerebral cortex and provide an effective platform technology foundation for microscale intracortical neural interfaces for use in humans.

Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex

This study investigated the use of planar, silicon-substrate microelectrodes for chronic unit recording in the cerebral cortex. The 16-channel microelectrodes consisted of four penetrating shanks with four recording sites on each shank. The chronic electrode assembly included an integrated silicon ribbon cable and percutaneous connector. In a consecutive series of six rats, 5/6 (83%) of the implanted microelectrodes recorded neuronal spike activity for more than six weeks, with four of the implants (66%) remaining functional for more than 28 weeks. In each animal, more than 80% of the electrode sites recorded spike activity over sequential recording sessions during the postoperative time period. These results provide a performance baseline to support further electrode system development for intracortical neural implant systems for medical applications.

Spatial steering of deep brain stimulation volumes using a novel lead design

OBJECTIVE To investigate steering the volume of activated tissue (VTA) with deep brain stimulation (DBS) using a novel high spatial-resolution lead design. METHODS We examined the effect of asymmetric current-injection across the DBS-array on the VTA. These predictions were then evaluated acutely in a non-human primate implanted with the DBS-array, using motor side-effect thresholds as the metric for estimating VTA asymmetries. RESULTS Simulations show the DBS-array, with electrodes arranged together in a cylindrical configuration, can generate field distributions equivalent to commercial DBS leads, and these field distributions can be modulated using field-steering methods. Stimulation with implanted DBS-arrays showed directionally-selective muscle activation, presumably through spread of stimulation fields into portions of the corticospinal tract lying in the internal capsule. CONCLUSIONS Our computational and experimental studies demonstrate that the DBS-array is capable of spatially selective stimulation. Displacing VTAs away from the leads axis can be achieved using a single simple and intuitive control parameter. SIGNIFICANCE Optimal DBS likely requires non-uniform VTAs that may differentially affect a nucleus or fiber pathway. The DBS-array allows positioning VTAs with sub-millimeter precision, which is especially relevant for those patients with DBS leads placed in sub-optimal locations. This may present clinicians with an additional degree of freedom to optimize the DBS therapy.

3-D silicon probe array with hybrid polymer interconnect for chronic cortical recording

The desire to perform chronic recordings from many channels in cortex is high among both neuroscientists and neural prosthesis researchers. The Michigan probe with integrated silicon ribbon cable has been used successfully for obtaining chronic cortical recordings in rodents. As these silicon devices are applied in larger animals and potentially in humans, however, a more mechanically robust, scalable system is required. Here we present a device that takes advantage of several existing, well-characterized technologies and methods and combines them to form a hybrid cortical assembly. The components of the assembly include thin-film multichannel silicon probes and polyimide cables that are electrically and mechanically coupled using thermocompression ball bonding. The resulting probe/cable assembly is low profile (<500 microns) and can be combined with other assemblies to form a 3-D array. Sixteen channel 2-D arrays have been implanted into rat motor cortex and have recorded chronic unit activity.

Development of a Microscale Implantable Neural Interface (MINI) Probe System

Cortical recording devices hold promise for providing augmented control of neuroprostheses and brain-computer interfaces in patients with severe loss of motor function due to injury or disease. This paper reports on the preliminary in vitro and in vivo results of our microscale implantable neural interface (MINI) probe system. The MINI is designed to use proven components and materials with a modular structure to facilitate ongoing improvements as new technologies become available. This device takes advantage of existing, well-characterized Michigan probe technologies and combines them to form a multichannel, multiprobe cortical assembly. To date, rat, rabbit, and non-human primate models have been implanted to test surgical techniques and in vivo functionality of the MINI. Results demonstrate the ability to form a contained hydrostatic environment surrounding the implanted probes for extended periods and the ability of this device to record electrophysiological signals with high SNRs. This is the first step in the realization of a cortically-controlled neuroprosthesis designed for human applications

Multifunctional Flexible Parylene-Based Intracortical Microelectrodes

Delivering drugs directly to the brain tissue opens new approaches to disease treatment and improving neural interfaces. Several approaches using neural prostheses have been made to deliver drugs directly with bypassing the blood-brain barrier (BBB). In this paper, we propose a new polymer-based flexible microelectrode with drug delivery capability. The probe was fabricated and tested for electrical and fluidic functionality in early stage design. In vivo chronic recording experiments succeeded in demonstrating the in vivo reliability of the probe. Successful in vivo experiments confirm the suitability of the probes as implantable chronic recording devices with robust fluid delivery function

Advanced neural implants using thin-film polymers

BioMEMS devices can be designed to provide viable neural interfaces for long-term, high-density, two-way communication with selected areas of cerebral cortex. Prototype thin-film polymer implantable microelectrode arrays were developed to extend the microelectrode design space in several ways, including enhanced flexibility, engineered surfaces and coatings, and new types of microchannels. Prototype MEMS silicon microdevices were developed as microsurgical tools for reliably inserting the flexible polymer electrodes into the cerebral cortex. Hybrid polymer microdevices were also developed for neural recording and stimulation combined with micro-drug delivery.

The use of ALGEL/spl reg/ as an artificial dura for chronic cortical implant neuroprosthetics

Surgical techniques are a critical contributor to the level of success achieved with chronically implanted cortical neuroprosthetic devices. Many different factors contribute to the amount of irritation the tissue is exposed to from the implanted device. Factors include mechanical irritations, infectious pathogens, dural regrowth, etc. In this paper we describe a novel application of the hydrogel polymer, ALGEL/spl reg/ (Neural Intervention Technologies, Ann Arbor, MI), in conjunction with an implanted Michigan probe (CNCT, University of Michigan). This polymer contains many inherent properties that are beneficial to this type of procedure. Properties include: 1) ease of application, 2) biocompatibility, 3) exemplary mechanical properties, and 4) translucent clarity. We believe that ALGEL has been a large contributor to the high level of success achieved with our chronic electrode implantations.

A Novel Lead Design for Modulation and Sensing of Deep Brain Structures

Goal: Develop and characterize the functionality of a novel thin-film probe technology with a higher density of electrode contacts than are currently available with commercial deep brain stimulation (DBS) lead technology. Such technology has potential to enhance the spatial precision of DBS and enable a more robust approach to sensing local field potential activity in the context of adaptive DBS strategies. Methods: Thin-film planar arrays were microfabricated and then assembled on a cylindrical carrier to achieve a lead with 3-D conformation. Using an integrated and removable stylet, the arrays were chronically implanted in the subthalamic nucleus and globus pallidus in two parkinsonian nonhuman primates. Results: This study provides the first in vivo data from chronically implanted DBS arrays for translational nonhuman primate studies. Stimulation through the arrays induced a decrease in parkinsonian rigidity, and directing current around the lead showed an orientation dependence for eliciting motor capsule side effects. The array recordings also showed that oscillatory activity in the basal ganglia is heterogeneous at a smaller scale than detected by the current DBS lead technology. Conclusion: These 3-D DBS arrays provide an enabling tool for future studies that seek to monitor and modulate deep brain activity through chronically implanted leads. Significance: DBS lead technology with a higher density of electrode contacts has potential to enable sculpting DBS current flow and sensing biomarkers of disease and therapy.