Justin C. Williams

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.

Cortical Firing and Sleep Homeostasis

The need to sleep grows with the duration of wakefulness and dissipates with time spent asleep, a process called sleep homeostasis. What are the consequences of staying awake on brain cells, and why is sleep needed? Surprisingly, we do not know whether the firing of cortical neurons is affected by how long an animal has been awake or asleep. Here, we found that after sustained wakefulness cortical neurons fire at higher frequencies in all behavioral states. During early NREM sleep after sustained wakefulness, periods of population activity (ON) are short, frequent, and associated with synchronous firing, while periods of neuronal silence are long and frequent. After sustained sleep, firing rates and synchrony decrease, while the duration of ON periods increases. Changes in firing patterns in NREM sleep correlate with changes in slow-wave activity, a marker of sleep homeostasis. Thus, the systematic increase of firing during wakefulness is counterbalanced by staying asleep.

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.

Long-term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex

This paper describes a detailed protocol for obtaining chronic, multi-site unit recordings in cerebral cortex of awake animals for periods of three months or more. The protocol includes details for making relatively simple and inexpensive implantable multichannel electrodes that consist of arrays of separate microwires. The results reported in this paper suggest that a viable implant will have discriminable unit activity on about 80% of the electrodes, resulting in, on average, the simultaneous unit recording of upwards of 60 units during a daily recording session. The active electrodes during one recording session tend to remain active in subsequent recording sessions for several weeks. Using the methods described here, implants have been constructed which incorporate several different electrode materials, coatings, sizes, and electrode separation within a single array. These microwire electrode arrays provide the basic technology for obtaining unit recordings for several months. This provides a model system for studying biocompatibility of neural implants, which is a critical component for the development of neural implants that have an indefinite working span.

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.

Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants

A series of animal experiments was conducted to characterize changes in the complex impedance of chronically implanted electrodes in neural tissue. Consistent trends in impedance changes were observed across all animals, characterized as a general increase in the measured impedance magnitude at 1 kHz. Impedance changes reach a peak approximately 7 days post-implant. Reactive responses around individual electrodes were described using immuno- and histo-chemistry and confocal microscopy. These observations were compared to measured impedance changes. Several features of impedance changes were able to differentiate between confined and extensive histological reactions. In general, impedance magnitude at 1 kHz was significantly increased in extensive reactions, starting about 4 days post-implant. Electrodes with extensive reactions also displayed impedance spectra with a characteristic change at high frequencies. This change was manifested in the formation of a semi-circular arc in the Nyquist space, suggestive of increased cellular density in close proximity to the electrode site. These results suggest that changes in impedance spectra are directly influenced by cellular distributions around implanted electrodes over time and that impedance measurements may provide an online assessment of cellular reactions to implanted devices.

Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications

Neural micro-electrode arrays that are transparent over a broad wavelength spectrum from ultraviolet to infrared could allow for simultaneous electrophysiology and optical imaging, as well as optogenetic modulation of the underlying brain tissue. The long-term biocompatibility and reliability of neural micro-electrodes also require their mechanical flexibility and compliance with soft tissues. Here we present a graphene-based, carbon-layered electrode array (CLEAR) device, which can be implanted on the brain surface in rodents for high-resolution neurophysiological recording. We characterize optical transparency of the device at >90% transmission over the ultraviolet to infrared spectrum and demonstrate its utility through optical interface experiments that use this broad spectrum transparency. These include optogenetic activation of focal cortical areas directly beneath electrodes, in vivo imaging of the cortical vasculature via fluorescence microscopy and 3D optical coherence tomography. This study demonstrates an array of interfacing abilities of the CLEAR device and its utility for neural applications.

ECoG factors underlying multimodal control of a brain-computer interface

Most current brain-computer interface (BCI) systems for humans use electroencephalographic activity recorded from the scalp, and may be limited in many ways. Electrocorticography (ECoG) is believed to be a minimally-invasive alternative to electroencephalogram (EEG) for BCI systems, yielding superior signal characteristics that could allow rapid user training and faster communication rates. In addition, our preliminary results suggest that brain regions other than the sensorimotor cortex, such as auditory cortex, may be trained to control a BCI system using similar methods as those used to train motor regions of the brain. This could prove to be vital for users who have neurological disease, head trauma, or other conditions precluding the use of sensorimotor cortex for BCI control.

Counterpart Models in Facility Location Science and Reserve Selection Science

Five classes of zero–one programming models for discrete facility location problems are compared to counterpart models for the selection of conservation reserves. The basic problem of siting facilities to cover demand for services is analogous to the problem of selecting reserves to support species diversity. The classes of models include the set covering and maximal covering models, as well as models for backup and redundant coverage. Issues of reliability and uncertainty are addressed by chance constrained covering models and maximal expected covering models. Exact and heuristic solution approaches are discussed. Multi-objective and economic issues are considered.

Using mathematical optimization models to design nature reserves

Designing an optimal nature reserve for the protection of biological diversity has been a long-standing challenge in conservation biology. A fundamental question has always been, which areas of land should be set aside. During the past two decades, quantitative methods from the field of operations research have been applied to the problem of selecting reserve sites. Here, we trace the development of decision models for systematic reserve design, from the iterative methods developed in the 1980s to the sophisticated spatial models being formulated today. Collaborations among ecologists, conservation biologists, and operations researchers have been key to the progress made thus far. We expect that mathematical reserve design models will become more widely used, in response to a growing need to identify effective alternatives for complex conservation problems worldwide.