Yan T. Wong

Focal activation of the feline retina via a suprachoroidal electrode array

This paper presents the results of the first investigations into the use of bipolar electrical stimulation of the retina with a suprachoroidal vision prosthesis, and the effects of different electrode configurations on localization of responses on the primary visual cortex. Cats were implanted with electrodes in the suprachoroidal space, and electrically evoked potentials were recorded on the visual cortex. Responses were elicited to bipolar and monopolar stimuli, with each stimulating electrode coupled with either six-return electrodes, two-return electrodes, or a single-return electrode. The average charge threshold to elicit a response with bipolar stimulation and six-return electrodes was 76.47+/-8.76 nC. Bipolar stimulation using six-return electrodes evoked responses half the magnitude of those elicited with a single or two-return electrodes. Monopolar stimulation evoked a greater magnitude, and area of cortical activation than bipolar stimulation. This study showed that suprachoroidal, bipolar stimulation can elicit localized activity in the primary visual cortex, with the extent of localization and magnitude of response dependent on the electrode configuration.

Retinal Neurostimulator for a Multifocal Vision Prosthesis

A neurostimulator application-specific integrated circuit (ASIC) with scalable circuitry that can stimulate 14 channels, has been developed for an epi-retinal vision prosthesis. This ASIC was designed to allow seven identical units to be connected to control up to 98 channels, with the ability to stimulate 14 electrodes simultaneously. The neurostimulator forms part of a vision prosthesis, designed to restore vision to patients who have lost their sight due to retinal diseases such as retinitis pigmentosa and macular degeneration. For charge balance, the neurostimulator was designed to stimulate with current sources and sinks operating together, and with the ability to drive a hexagonal mosaic of electrodes to reduce the electrical crosstalk that occurs when multiple bipolar stimulation sites are active simultaneously. A hexagonal mosaic of electrodes surrounds each stimulation site and has been shown to effectively isolate each site, increasing the ability to inject localized independent charge into multiple regions simultaneously.

Optimizing the Decoding of Movement Goals from Local Field Potentials in Macaque Cortex

The successful development of motor neuroprosthetic devices hinges on the ability to accurately and reliably decode signals from the brain. Motor neuroprostheses are widely investigated in behaving non-human primates, but technical constraints have limited progress in optimizing performance. In particular, the organization of movement-related neuronal activity across cortical layers remains poorly understood due, in part, to the widespread use of fixed-geometry multielectrode arrays. In this study, we use chronically implanted multielectrode arrays with individually movable electrodes to examine how the encoding of movement goals depends on cortical depth. In a series of recordings spanning several months, we varied the depth of each electrode in the prearcuate gyrus of frontal cortex in two monkeys as they performed memory-guided eye movements. We decode eye movement goals from local field potentials (LFPs) and multiunit spiking activity recorded across a range of depths up to 3 mm from the cortical surface. We show that both LFP and multiunit signals yield the highest decoding performance at superficial sites, within 0.5 mm of the cortical surface, while performance degrades substantially at sites deeper than 1 mm. We also analyze performance by varying bandpass filtering characteristics and simulating changes in microelectrode array channel count and density. The results indicate that the performance of LFP-based neuroprostheses strongly depends on recording configuration and that recording depth is a critical parameter limiting system performance.

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

A CMOS retinal neurostimulator capable of focussed, simultaneous stimulation

Restoring vision to the blind by way of medical device technology has been an objective of several research teams for a number of years. It is known that spots of light-phosphenes-can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this our understanding of prosthetic vision remains rudimentary. We have designed and manufactured an integrated circuit neurostimulator with substantial versatility, able to provide focussed, simultaneous stimulation using current sources and sinks, steering the current to the intended site of stimulation. The ASIC utilizes high-voltage CMOS transistors in key circuits, to manage voltage compliance issues (due to an unknown or changing electrode/tissue interface impedance) given the relatively high stimulation thresholds necessary to elicit physiological excitation of retinal neurons. In addition, a unique multiplexing system comprised of electrodes arranged in a hexagonal mosaic is used, wherein each electrode can be addressed to be a stimulating electrode and all adjacent electrodes serve as the return path. This allows for simultaneous stimulation to be delivered while appropriately managing cross-talk between the stimulating electrodes. Test results indicate highly linear current sources and sinks (differential nonlinearity error of 0.13 least significant bits -2.6 microA), with the ASIC clearly able to provide focussed stimulation using electrodes immersed in a saline solution.

A retinal neuroprosthesis design based on simultaneous current injection

We present an epiretinal neuroprosthesis design based on a hexagonally-latticed 98 electrode array and the capacity to multiplex up to 14 simultaneous current sources. The digital and analogue electronics required to perform this function and how this would be incorporated into an application specific integrated circuit (ASIC) are described. Simulation data and data from saline bath testing of a platinum/silicone electrode array (and associated driving electronics) are presented. Simulations were performed using a 2D computational model solved using a custom collocation method. The guarding affect of the hexagonal array is investigated and shown in simple simulations to be an approach worthy of further investigation.

Efficacy of supra-choroidal, bipolar, electrical stimulation in a vision prosthesis

The key to successful, clinical application of therapeutic neurostimulators lies primarily with the safety and efficacy of their electrode-tissue interfaces. The authors posit that for electrical stimulation of the visual system, supra-choroidal electrode placement provides a safe, stable and readily-accessible site for implantation and the provision of electrical stimulation. The present paper explores the efficacy of supra-choroidal electrical stimulation of retinal neurons. Based upon recordings made with surface electrodes placed on the primary visual cortex, areas of activation in the cortex were shown to change when different areas on the supra-choroidal space were stimulated. Finally, the threshold to elicit a response from neurons in the visual cortex, was found to be 77.55 ± 29.85 nC.

The Design and Testing of an Epi-Retinal Vision Prosthesis Neurostimulator Capable of Concurrent Parallel Stimulation

An application specific integrated circuit (ASIC) neurostimulator capable of stimulating multiple electrodes in unison has been designed and tested. The ASIC utilizes multiple matched current sinks and sources to provide localized stimulation and is designed to drive electrodes organized in a hexagonal mosaic. This organization allows each stimulating electrode to be surrounded by up to six return electrodes, effectively isolating each stimulation site. The ASIC was manufactured using a high-voltage complementary metal-oxide-semiconductor process, which allows up to 20 V to be applied across the circuitry. This provides the greatest versatility for testing with electrodes and tissues of varying impedances in-situ and allows the device to be used in other neurostimulation applications such as functional electrical stimulation. The design has been thoroughly tested and meets all the design specifications

Competition for visual selection in the oculomotor system

During behavior, the oculomotor system is tasked with selecting objects from an ever-changing visual field and guiding eye movements to these locations. The attentional priority given to visual targets during selection can be strongly influenced by external stimulus properties or internal goals based on previous experience. Although these exogenous and endogenous drivers of selection are known to operate across partially overlapping timescales, the form of their interaction over time remains poorly understood. Using a novel choice task that simultaneously manipulates stimulus- and goal-driven attention, we demonstrate that exogenous and endogenous attentional biases change linearly as a function of time after stimulus onset and have an additive influence on the visual selection process in rhesus macaques (Macaca mulatta). We present a family of computational models that quantify this interaction over time and detail the history dependence of both processes. The computational models reveal the existence of a critical 140–180 ms attentional “switching” time, when stimulus- and goal-driven processes simultaneously favor competing visual targets. These results suggest that the brain uses a linear sum of attentional biases to guide visual selection.

Microelectronic Retinal Prosthesis: II. Use of High-Voltage CMOS in Retinal Neurostimulators

For part 1, see ibid., p. Z004336-9 (2006). This paper presents the design, implementation, and simulated and measured results of a complementary metal-oxide-semiconductor neurostimulator implemented in a 0.35 mum high-voltage process. To allow for a high stimulation voltage, and hence the greatest versatility of the neurostimulator in situ, a high-voltage CMOS process was used. The neurostimulator utilized current sources and sinks to simultaneously deliver and recover charge. It has the ability to deliver stimulus in three output current ranges using a current sink only, current source only, or both a current source and sink combined to provide focused stimulation. The worst case integral non-linearity and differential non-linearity errors were 0.2 LSB and 0.1 LSB respectively, and the current source and sink turn-on times were under 500 ns, providing fast switching time in response to stimuli instructions. The total die area was under 13 mm2, well within the area constraints of our implantable vision prosthesis device