A novel high electrode count spike recording array using an 81,920 pixel transimpedance amplifier-based imaging chip.

Microelectrode recording arrays of 60-100 electrodes are commonly used to record neuronal biopotentials, and these have aided our understanding of brain function, development and pathology. However, higher density microelectrode recording arrays of larger area are needed to study neuronal function over broader brain regions such as in cerebral cortex or hippocampal slices. Here, we present a novel design of a high electrode count picocurrent imaging array (PIA), based on an 81,920 pixel Indigo ISC9809 readout integrated circuit camera chip. While originally developed for interfacing to infrared photodetector arrays, we have adapted the chip for neuron recording by bonding it to microwire glass resulting in an array with an inter-electrode pixel spacing of 30 µm. In a high density electrode array, the ability to selectively record neural regions at high speed and with good signal to noise ratio are both functionally important. A critical feature of our PIA is that each pixel contains a dedicated low noise transimpedance amplifier (∼0.32 pA rms) which allows recording high signal to noise ratio biocurrents comparable to single electrode voltage amplifier recordings. Using selective sampling of 256 pixel subarray regions, we recorded the extracellular biocurrents of rabbit retinal ganglion cell spikes at sampling rates up to 7.2 kHz. Full array local electroretinogram currents could also be recorded at frame rates up to 100 Hz. A PIA with a full complement of 4 readout circuits would span 1cm and could acquire simultaneous data from selected regions of 1024 electrodes at sampling rates up to 9.3 kHz.

Spatiotemporal aspects of pulsed electrical stimuli on the responses of rabbit retinal ganglion cells.

Implanted intraocular microelectrode arrays are being used to provide sight to individuals who are blind due to photoreceptor degeneration. It is envisioned that this retinal prosthesis will create the illusion of motion by stimulating focal areas of the retina in a sequential fashion through neighboring electrodes, much like the rapid succession of still images in movies and computer animation gives rise to apparent motion. Using a high-density microelectrode array, we examined the extracellularly recorded responses of rabbit retinal ganglion cells to a bar-shaped electrode array that was stepped at 50 microm increments at different rates across the retina and compared these responses to the responses generated to a similarly shaped light stimulus that was stepped across the retina. When the retina was stimulated at 1 step/s, retinal ganglion cells gave robust bursts of action potentials to both the electrode array and the light stimulus. The responses to the 'moving' electrode array decreased progressively with increasing stepping frequency. At 16 steps/s (highest frequency tested), the number of spikes per sweep and the number of bursts per sweep were reduced 75% and 67% respectively. In contrast, when the retina was stimulated at 16 steps/s with the 'moving' light stimulus, the number of spikes per sweep and the number of bursts per sweep were reduced only 43% and 25% respectively. These findings suggest that simple translation of object motion to sequential stimulation through neighboring electrodes may not be the best way to convey the perception of object motion in a patient with a retinal prosthesis.

Impedance-based retinal contact imaging as an aid for the placement of high resolution epiretinal prostheses.

An important factor in effective stimulation of the retina is close contact with the retina. The design of the electrode surface and the placement of the electrode against the retina both affect the degree of contact with the retina. We have addressed the design factor by creating a curved surface 3200-electrode array. The placement factor we have addressed by use of an impedance sensitive feedback from the array. The feedback is in the form of an image showing contact with the retina, where greater pixel intensity indicates greater impedance and thus closer contact with the retina. In this paper, we present qualitative and quantitative assessments of the relationship between impedance and the device output as well as an in vivo demonstration of contact imaging. In addition, we evaluated the three-dimensional profile of the stimulation voltage distribution to assess the importance of close retinal contact for high resolution stimulation.

Electrical stimulation of isolated retina with microwire glass electrodes.

The development of high-resolution retinal prostheses fabricated from silicon wafers presents an interesting problem: how to electrically bridge the space between the flat silicon wafer and the curved retinal surface. One potential "bridge" is a microwire glass electrode. In this paper we present our results in evaluating microwire glass electrodes. We stimulated isolated rabbit retina (n = 5) with a 0.0256 cm(2) microwire electrode. The current and pulse duration were varied from 498 to 1660 microA and 0.1 to 3 ms, respectively. We found that short pulses produced more spikes per coulomb and longer pulses produced more spikes per milliamp. The optimal pulse duration range of 0.7-1 ms was identified as a compromise between the advantages of short and long pulses. Stimulation of isolated rabbit retina with microwire glass results in consistent neuronal spike formation at safe charge density, 20.7 +/- 4.3 microC/cm(2). We also examined the response of retinas (n = 6) to stimulation with a smaller microwire electrode, 0.0002 cm(2). We found that less current was required (15 microA versus 756 microA) for a 1 ms pulse, but at the expense of greater charge density (75 microC/cm(2) versus 29.5 microC/cm(2)). Nonetheless, a 128-fold reduction in area resulted in only a 2.7-fold increase in charge density required for a 1 ms pulse duration. The results presented here indicate that microwire glass can be used as a neural stimulating electrode to bridge the gap between flat microelectronic stimulator chips and curved neuronal tissue.

Retinal prosthesis for the blind.

Most of current concepts for a visual prosthesis are based on neuronal electrical stimulation at different locations along the visual pathways within the central nervous system. The different designs of visual prostheses are named according to their locations (i.e., cortical, optic nerve, subretinal, and epiretinal). Visual loss caused by outer retinal degeneration in diseases such as retinitis pigmentosa or age-related macular degeneration can be reversed by electrical stimulation of the retina or the optic nerve (retinal or optic nerve prostheses, respectively). On the other hand, visual loss caused by inner or whole thickness retinal diseases, eye loss, optic nerve diseases (tumors, ischemia, inflammatory processes etc.), or diseases of the central nervous system (not including diseases of the primary and secondary visual cortices) can be reversed by a cortical visual prosthesis. The intent of this article is to provide an overview of current and future concepts of retinal and optic nerve prostheses. This article will begin with general considerations that are related to all or most of visual prostheses and then concentrate on the retinal and optic nerve designs. The authors believe that the field has grown beyond the scope of a single article so cortical prostheses will be described only because of their direct effect on the concept and technical development of the other prostheses, and this will be done in a more general and historic perspective.