A benchtop system to assess cortical neural interface micromechanics.

A benchtop brain tissue-microelectrode insertion model system was developed to aid in improving the design of cortical neural interfaces. The model partially mimics the in vivo environment via the use of human cadaver brain specimens (nspecimen = 6), or agar gel exposed to physiologically relevant mechanical oscillations. 150 lpm diameter stainless-steel microelectrode wires (TS = 600 MPa) implanted 3.0 cm within fixed human primary auditory cortex (ntrial > 10) experienced 133 +/- 8 and 64 +/- 4 mN of peak and steady axial forces. When subjected to a 3 Hz, 3-mm vertical oscillation, dynamic force amplitudes (ntrial > 10) of 148 +/- 10 mN were measured. The model system allows the study and comparison of static and dynamic forces and their mechanical influences on proposed implanted microelectrode structures.

Encoding of self-paced, repetitive forelimb movements in rat primary motor cortex.

Multi-unit, intra-cortical recordings from the primary motor cortex have been shown to provide information about functional movement of the body, and thus, have been used as command signals for control of an external robotic arm in rat and monkey. However, study of the M1 responses has shown that movement encoding may be dependent on both the functional and behavioral context of the intended motion. The main objective of the present work was to determine if self-paced, repetitive forelimb movements are effectively encoded in multiple-unit recordings from the primary motor cortex (M1) in freely moving, non-constrained rats. Four rats were chronically implanted with 7-channel, 50 microm tungsten micro-wire arrays. Standard psychophysical techniques were first used to train the rats to depress a response paddle in return for a food reward. We computed peri-event time histograms and found both statistically significant excitatory (24/49) and inhibitory (9/49) pre-paddle activity up to 200 ms before a paddle hit. On average, responses from 161+/-37 individual paddle hits were necessary in order to detect statistically significant (> 95%), excitatory pre-paddle action. Thus, while it is possible to detect self-paced, forelimb movements in multi-unit recordings of M1, the high number of repetitions required would limit the efficacy of a real-time cortical neuroprosthesis.

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. We 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.

Examination of the spatial and temporal distribution of sensory cortical activity using a 100-electrode array.

This paper introduces improved techniques for multichannel extracellular electrophysiological recordings of neurons distributed across a single layer of topographically mapped cortex. We describe the electrode array, the surgical implant techniques, and the procedures for data collection and analysis. Neural events are acquired through an array of 25 or 100 microelectrodes with a 400-microm inter-electrode spacing. One advantage of the new methodology is that implantation is achieved through transdural penetration, thereby reducing the disruption of the cortical tissue. The overall cortical territory sampled by the 25-electrode array is 1.6 x 1.6 mm (2.56 mm2) and by the 100-electrode array 3.6 x 3.6 mm (12.96 mm2). Using a recording system with 100 channels available, neural activity is simultaneously acquired on all electrodes, amplified, digitized, and stored on computer. In our data, average peak-to-peak signal/noise ratio was 11.5 and off-line waveform analysis typically allowed the separation of at least one well-discriminated single-unit per channel. The reported technique permits analysis of cortical function with high temporal and spatial resolution. We use the technique to create an 'image' of neural activity distributed across the whisker representation of rat somatosensory (barrel) cortex.

A neural interface for a cortical vision prosthesis.

The development of a cortically based vision prosthesis has been hampered by a lack of basic experiments on phosphene psychophysics. This basic research has been hampered by the lack of a means to safely stimulate large numbers of cortical neurons. Recently, a number of laboratories have developed arrays of silicon microelectrodes that could enable such basic studies on phosphene psychophysics. This paper describes one such array, the Utah electrode array, and summarizes neurosurgical, physiological and histological experiments that suggest that such an array could be implanted safely in visual cortex. We also summarize a series of chronic behavioral experiments that show that modest levels of electrical currents passed into cortex via this array can evoke sensory percepts. Pending the successful outcome of biocompatibility studies using such arrays, high count arrays of penetrating microelectrodes similar to this design could provide a useful tool for studies of the psychophysics of phosphene perception in human volunteers. Such studies could provide a proof-of-concept for cortically based artificial vision.

Chronic intracortical microstimulation (ICMS) of cat sensory cortex using the Utah Intracortical Electrode Array.

In an effort to assess the safety and efficacy of focal intracortical microstimulation (ICMS) of cerebral cortex with an array of penetrating electrodes as might be applied to a neuroprosthetic device to aid the deaf or blind, we have chronically implanted three trained cats in primary auditory cortex with the 100-electrode Utah Intracortical Electrode Array (UIEA). Eleven of the 100 electrodes were hard-wired to a percutaneous connector for chronic access. Prior to implant, cats were trained to "lever-press" in response to pure tone auditory stimulation. After implant, this behavior was transferred to "lever-presses" in response to current injections via single electrodes of the implanted arrays. Psychometric function curves relating injected charge level to the probability of response were obtained for stimulation of 22 separate electrodes in the three implanted cats. The average threshold charge/phase required for electrical stimulus detection in each cat was, 8.5, 8.6, and 11.6 nC/phase respectively, with a maximum charge/phase of 26 nC/phase and a minimum of 1.5 nC/phase thresholds were tracked for varying time intervals, and seven electrodes from two cats were tracked for up to 100 days. Electrodes were stimulated for no more than a few minutes each day. Neural recordings taken from the same electrodes before and after multiple electrical stimulation sessions were very similar in signal/noise ratio and in the number of recordable units, suggesting that the range of electrical stimulation levels used did not damage neurons in the vicinity of the electrodes. Although a few early implants failed, we conclude that ICMS of cerebral cortex to evoke a behavioral response can be achieved with the penetrating UIEA. Further experiments in support of a sensory cortical prosthesis based on ICMS are warranted.

Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.

The Utah Intracortical Electrode Array (UIEA) is an array of 100 penetrating silicon microelectrodes designed to focally electrically stimulate or record neurons residing in a single layer up to 1.5 mm beneath the surface of the cerebral cortex. Apart from its use as a unique tool to study parallel processing in the central nervous system, this array could form the platform for a cortical neuroprosthetic system. Although the UIEA has been used extensively in acute neural recording and stimulation experiments, its long-term performance in a chronic application has yet to be demonstrated. As an initial investigation into the feasibility of long-term cortical recording with an array of microelectrodes, we have hard-wired a subset of 11 electrodes of the UIEA to a percutaneous connector. This chronic UIEA assembly was then implanted into the cerebral cortices of ten cats for durations ranging from 2 to 13 months; over which time, both random and stimulus-evoked single and multiple unit action potentials were periodically recorded. On average, after a 6-month implant period, 60% of implanted arrays could still record some type of activity. Post-sacrifice dissections revealed a fibrous encapsulation of the UIEA. Although most implanted cortex was histologically normal, evidence of a chronic astroglial response was seen in a few cases. The results of the reported experiments indicate that the UIEA can be successfully used for limited times in a chronic recording application.

Optimizing recording capabilities of the Utah Intracortical Electrode Array.

The Utah Intracortical Electrode Array is a unique silicon-based monolithic structure designed for use as a multichannel interface to the central nervous system. In this paper, we describe a series of acute experiments designed to determine the neural recording capabilities of this electrode array and the dependence of the signal-to-noise ratio (SNR) of the recordings on the electrode surface area (length of metallized tip). We found that both separable unit and multiunit cluster responses could be recorded. Additionally, high SNR recordings could be achieved for some electrodes (with electrode tip lengths of 30-220 microns), while recordings with signals substantially greater than the noise could be made from most of the electrodes provided that the proper electrode surface area was used. The demonstrated recording capabilities of the Utah Intracortical Electrode Array and its unique three-dimensional structure should form the basis for innovative physiological investigations into the functional organization of the cortex as well as for long term neuroprosthesis development.

A method for pneumatically inserting an array of penetrating electrodes into cortical tissue.

The goal of this research was to find a practical means by which an array of 100 needle-shaped electrodes could be implanted into the cerebral cortex with minimal brain tissue trauma. It was found that insertion of these structures into cortical tissues could only be performed using high insertion speeds. A pneumatically actuated impact insertion system has been developed that is capable of inserting an electrode array into feline brain tissue at speeds from about 1 to 11 m/s. We found that a minimum array insertion speed of 8.3 m/s was necessary for a complete, safe insertion of all 100 electrodes in the array to a depth of 1.5 mm into feline cortex. The performance of the impact insertion system is discussed in terms of a simplified representation of cortical tissue.