Prediction and shaping of visual cortex activity for retinal prostheses

Abstract

Retinal prostheses are a promising treatment for blindness caused by photoreceptor degeneration. Electrodes implanted in the retina deliver electrical stimuli in the form of current pulses that activate surviving neurons to restore a sense of vision. Clinical trials for such devices have shown that the visual percepts evoked are informative, and can improve the day-to-day life of recipients. However, the spatial resolution of retinal prostheses is a limiting factor, with those who have the highest reported acuity measures still classified as legally blind. Simultaneous stimulation of multiple electrodes is a possible strategy to improve device resolution without increasing the number of physical electrodes. However, electrode interactions that occur during simultaneous stimulation are not well understood. This thesis investigates the characteristics of cortical responses to simultaneous stimulation of multiple electrodes.

We formulated a quantitative model to characterise the responses of visual cortex neurons to multi-electrode stimulation of the retina to understand how simultaneous stimulation can improve resolution. Activity was recorded in the visual cortex of normally sighted, anaesthetised cats in response to temporally sparse, spatially white stimulation with 21 or 42 electrodes in the suprachoroidal space of the retina. These data were used to constrain the parameters of a linear-nonlinear model using a spike-triggered covariance technique. The recovered model accurately predicted cortical responses to arbitrary patterns of stimulation, and demonstrated that interactions between electrodes are predominantly linear. The linear filters of the model, which can be considered as weighting matrices for the effect of the stimulating electrodes on each cortical site, showed that cortical responses were topographically organised.

Photoreceptor degeneration results in a number of changes in the surviving cells of the retina that can negatively impact stimulation strategies. Therefore, in the second study, we investigated the effect of multi-electrode stimulation on the degenerate retina. Characteristics of cortical responses to simultaneous stimulation of multiple electrodes were evaluated in unilaterally, chronically blind anaesthetised cats, bilaterally implanted with suprachoroidal retinal prostheses. Significant differences were found between responses to stimulation of the normally sighted and blind eyes, which may help to explain the varied perceptual observations in clinical trials with simultaneous stimulation.

The success of the linear-nonlinear model in predicting responses to arbitrary patterns of stimulation indicated that it may provide a basis for optimising stimulation strategies to shape cortical activity. Therefore, we investigated the possibility of inverting the model to generate stimuli aimed at reliably altering the spatial characteristics of cortical responses. An in vivo preparation with a normally sighted, anaesthetised cat showed that the response characteristics derived by the model could be exploited to steer current and evoke predictable cortical activity.

Overall, these results demonstrate that cortical responses to simultaneous stimulation of both the normal and degenerate retina are repeatable, and can be predicted by a simple linear-nonlinear model. Furthermore, the interactions between electrodes are predominantly linear, and can be harnessed to shape cortical activity through inversion of the model. The method shows promise for improving the efficacy of retinal prostheses and patient outcomes.