Spencer C. Chen

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.

Performance of conducting polymer electrodes for stimulating neuroprosthetics

OBJECTIVE Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. APPROACH PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. MAIN RESULTS It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. SIGNIFICANCE These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

Visual acuity measurement of prosthetic vision: a virtual-reality simulation study

A virtual-reality simulation tested prosthetic visual acuity for both rectangular and hexagonal phosphene grids. Thirteen normally sighted, untrained subjects were required to identify the Landolt C optotype over ten sessions. Overall performance, performance by filter setting (image analysis), and performance by size and orientation of the Landolt C optotype are reported. The results indicated that the hexagonal grid had a slight (4.1%) but statistically significant (p < 0.0001) performance advantage over the rectangular grid for correct identification of the testing symbol. It was also observed that both the phosphene grids had distinct performance profiles relating to their respective spatial orientation. Over the course of the ten sessions, learning afforded subjects an averaged improved performance of 10%.

Responses of Retinal Ganglion Cells to Extracellular Electrical Stimulation, from Single Cell to Population: Model-Based Analysis

Retinal ganglion cells (RGCs), which survive in large numbers following neurodegenerative diseases, could be stimulated with extracellular electric pulses to elicit artificial percepts. How do the RGCs respond to electrical stimulation at the sub-cellular level under different stimulus configurations, and how does this influence the whole-cell response? At the population level, why have experiments yielded conflicting evidence regarding the extent of passing axon activation? We addressed these questions through simulations of morphologically and biophysically detailed computational RGC models on high performance computing clusters. We conducted the analyses on both large-field RGCs and small-field midget RGCs. The latter neurons are unique to primates. We found that at the single cell level the electric potential gradient in conjunction with neuronal element excitability, rather than the electrode center location per se, determined the response threshold and latency. In addition, stimulus positioning strongly influenced the location of RGC response initiation and subsequent activity propagation through the cellular structure. These findings were robust with respect to inhomogeneous tissue resistivity perpendicular to the electrode plane. At the population level, RGC cellular structures gave rise to low threshold hotspots, which limited axonal and multi-cell activation with threshold stimuli. Finally, due to variations in neuronal element excitability over space, following supra-threshold stimulation some locations favored localized activation of multiple cells, while others favored axonal activation of cells over extended space.

Integration and segregation of multiple motion signals by neurons in area MT of primate.

We used multielectrode arrays to measure the response of populations of neurons in primate middle temporal area to the transparent motion of two superimposed dot fields moving in different directions. The shape of the population response was well predicted by the sum of the responses to the constituent fields. However, the population response profile for transparent dot fields was similar to that for coherent plaid motion and hence an unreliable cue to transparency. We then used single-unit recording to characterize component and pattern cells from their response to drifting plaids. Unlike for plaids, component cells responded to the average direction of superimposed dot fields, whereas pattern cells could signal the constituent motions. This observation provides support for a strong prediction of the Simoncelli and Heeger (1998) model of motion analysis in area middle temporal, and suggests that pattern cells have a special status in the processing of superimposed dot fields.

Current Steering in Retinal Stimulation via a Quasimonopolar Stimulation Paradigm

PURPOSE Research to restore some degree of vision to patients suffering from retinal degeneration is becoming increasingly more promising. Several groups have chosen electrical stimulation of the remaining network of a degenerate retina as a means to generate discrete light percepts (phosphenes). Approaches vary significantly, with the greatest difference being the location of the stimulating electrode itself. METHODS Suprachoroidal positioning offers excellent mechanical stability and surgical simplicity; however, at the cost of activation thresholds and focused stimulation due to the distance from the electrodes to the target neurons. Past studies proposed a hexapolar electrode configuration to focus the cortical activation and minimize cross-talk between electrodes during concurrent stimulation. The high impedance nature of the choroid and pigment epithelium, however, cause current to shunt between the stimulating and return electrodes, resulting in even higher activation thresholds. In our study, we analyzed the effect of stimulating the feline retina using a quasimonopolar stimulation by simultaneously stimulating a hexapolar and distant monopolar return configurations. RESULTS Results of in vivo studies showed that quasimonopolar stimulation can be used to maintain the activation containment properties of hexapolar stimulation, while lowering the activation threshold to values almost equivalent to those of monopolar stimulation. CONCLUSIONS The optimal stimulus was found to be composed of a subthreshold monopolar stimulus combined with a suprathreshold hexapolar stimulation. This resulted in a decrease of activation threshold of 60% with respect to hexapolar alone, but with no discernible deleterious effect on the charge containment of a pure hexapolar stimulation.

Local and Global Correlations between Neurons in the Middle Temporal Area of Primate Visual Cortex

In humans and other primates, the analysis of visual motion includes populations of neurons in the middle-temporal (MT) area of visual cortex. Motion analysis will be constrained by the structure of neural correlations in these populations. Here, we use multi-electrode arrays to measure correlations in anesthetized marmoset, a New World monkey where area MT lies exposed on the cortical surface. We measured correlations in the spike count between pairs of neurons and within populations of neurons, for moving dot fields and moving gratings. Correlations were weaker in area MT than in area V1. The magnitude of correlations in area MT diminished with distance between receptive fields, and difference in preferred direction. Correlations during presentation of moving gratings were stronger than those during presentation of moving dot fields, extended further across cortex, and were less dependent on the functional properties of neurons. Analysis of the timescales of correlation suggests presence of 2 mechanisms. A local mechanism, associated with near-synchronous spiking activity, is strongest in nearby neurons with similar direction preference and is independent of visual stimulus. A global mechanism, operating over larger spatial scales and longer timescales, is independent of direction preference and is modulated by the type of visual stimulus presented.

A quantitative analysis of head movement behaviour during visual acuity assessment under prosthetic vision simulation

In most current vision prosthesis designs, head movement is the sole director of visual gaze and scanning due to the head-mounted nature of the camera. Study of this unnatural behaviour may provide insight into improved prosthesis designs and rehabilitation procedures. In this paper, we conducted a psychophysical study to investigate the characteristics of head movements of normally sighted subjects undergoing a visual acuity task in simulated prosthetic vision (SPV). In 12 naïve, untrained subjects, we recorded spontaneous changes in the amount of head movements during SPV sessions compared to control (normal vision) sessions. The observed behaviour continued to be refined until five or six sessions of practice. Increased head movement velocity was shown to be correlated to improved visual acuity performance, up to 0.3 logMAR, an equivalent of detecting details at half the physical size compared to complete deprivation of head movements. We postulate that visual scanning can as much as double the spatial frequency information in prosthetic vision. Increased head movement velocity observed when subjects were attempting smaller test items and for low-pass filtering schemes with higher cut-off frequencies may be further evidence that higher frequency content may be available through visual scanning, unconsciously driving subjects to increase head movement velocity.

Learning prosthetic vision: a virtual-reality study

Acceptance of prosthetic vision will be heavily dependent on the ability of recipients to form useful information from such vision. Training strategies to accelerate learning and maximize visual comprehension would need to be designed in the light of the factors affecting human learning under prosthetic vision. Some of these potential factors were examined in a visual acuity study using the Landolt C optotype under virtual-reality simulation of prosthetic vision. Fifteen normally sighted subjects were tested for 10-20 sessions. Potential learning factors were tested at p<0.05 with regression models. Learning was most evident across-sessions, though 17% of sessions did express significant within-session trends. Learning was highly concentrated toward a critical range of optotype sizes, and subjects were less capable in identifying the closed optotype (a Landolt C with no gap, forming a closed annulus). Training for implant recipients should target these critical sizes and the closed optotype to extend the limit of visual comprehension. Although there was no evidence that image processing affected overall learning, subjects showed varying personal preferences.

Biological–Machine Systems Integration: Engineering the Neural Interface

The state of the art of biological-machine systems integration (BMSI) with an emphasis on neural interfacing is reported. The goal of BMSI from a medical viewpoint is to effectively replace or facilitate activation of, or recording from, neural elements in a part of the nervous system. BMSI will be firstly examined from a generic level whereby the current technologies for noninvasive and invasive neural recording and neural stimulation will be detailed. A case study in the area of visual neuroprosthesis will be presented to elucidate the current and future issues facing BMSI. This will include a discussion on biocompatibility, design of stimulating electrodes, the implanted microelectronic neurostimulator, and parallelization of stimulus encoding and delivery.