Gaze-contingent processing improves mobility, scene recognition and visual search in simulated head-steered prosthetic vision.

Objective.The enabling technology of visual prosthetics for the blind is making rapid progress. However, there are still uncertainties regarding the functional outcomes, which can depend on many design choices in the development. In visual prostheses with a head-mounted camera, a particularly challenging question is how to deal with the gaze-locked visual percept associated with spatial updating conflicts in the brain. The current study investigates a recently proposed compensation strategy based on gaze-contingent image processing with eye-tracking. Gaze-contingent processing is expected to reinforce natural-like visual scanning and reestablished spatial updating based on eye movements. The beneficial effects remain to be investigated for daily life activities in complex visual environments.Approach.The current study evaluates the benefits of gaze-contingent processing versus gaze-locked and gaze-ignored simulations in the context of mobility, scene recognition and visual search, using a virtual reality simulated prosthetic vision paradigm with sighted subjects.Main results.Compared to gaze-locked vision, gaze-contingent processing was consistently found to improve the speed in all experimental tasks, as well as the subjective quality of vision. Similar or further improvements were found in a control condition that ignores gaze-dependent effects, a simulation that is unattainable in the clinical reality.Significance.Our results suggest that gaze-locked vision and spatial updating conflicts can be debilitating for complex visually-guided activities of daily living such as mobility and orientation. Therefore, for prospective users of head-steered prostheses with an unimpaired oculomotor system, the inclusion of a compensatory eye-tracking system is strongly endorsed.

Optogenetic activation of visual thalamus generates artificial visual percepts.

The lateral geniculate nucleus (LGN), a retinotopic relay center where visual inputs from the retina are processed and relayed to the visual cortex, has been proposed as a potential target for artificial vision. At present, it is unknown whether optogenetic LGN stimulation is sufficient to elicit behaviorally relevant percepts, and the properties of LGN neural responses relevant for artificial vision have not been thoroughly characterized. Here, we demonstrate that tree shrews pretrained on a visual detection task can detect optogenetic LGN activation using an AAV2-CamKIIα-ChR2 construct and readily generalize from visual to optogenetic detection. Simultaneous recordings of LGN spiking activity and primary visual cortex (V1) local field potentials (LFPs) during optogenetic LGN stimulation show that LGN neurons reliably follow optogenetic stimulation at frequencies up to 60 Hz and uncovered a striking phase locking between the V1 LFP and the evoked spiking activity in LGN. These phase relationships were maintained over a broad range of LGN stimulation frequencies, up to 80 Hz, with spike field coherence values favoring higher frequencies, indicating the ability to relay temporally precise information to V1 using light activation of the LGN. Finally, V1 LFP responses showed sensitivity values to LGN optogenetic activation that were similar to the animal's behavioral performance. Taken together, our findings confirm the LGN as a potential target for visual prosthetics in a highly visual mammal closely related to primates.

Optogenetic Retinal Gene Therapy with the Light Gated GPCR Vertebrate Rhodopsin.

In retinal disease, despite the loss of light sensitivity as photoreceptors die, many retinal interneurons survive in a physiologically and metabolically functional state for long periods. This provides an opportunity for treatment by genetically adding a light sensitive function to these cells. Optogenetic therapies are in development, but, to date, they have suffered from low light sensitivity and narrow dynamic response range of microbial opsins. Expression of light-sensitive G protein coupled receptors (GPCRs), such as vertebrate rhodopsin , can increase sensitivity by signal amplification , as shown by several groups. Here, we describe the methods to (1) express light gated GPCRs in retinal neurons, (2) record light responses in retinal explants in vitro, (3) record cortical light responses in vivo, and (4) test visually guided behavior in treated mice.

Eye Movement Compensation and Spatial Updating in Visual Prosthetics: Mechanisms, Limitations and Future Directions.

Despite appearing automatic and effortless, perceiving the visual world is a highly complex process that depends on intact visual and oculomotor function. Understanding the mechanisms underlying spatial updating (i.e., gaze contingency) represents an important, yet unresolved issue in the fields of visual perception and cognitive neuroscience. Many questions regarding the processes involved in updating visual information as a function of the movements of the eyes are still open for research. Beyond its importance for basic research, gaze contingency represents a challenge for visual prosthetics as well. While most artificial vision studies acknowledge its importance in providing accurate visual percepts to the blind implanted patients, the majority of the current devices do not compensate for gaze position. To-date, artificial percepts to the blind population have been provided either by intraocular light-sensing circuitry or by using external cameras. While the former commonly accounts for gaze shifts, the latter requires the use of eye-tracking or similar technology in order to deliver percepts based on gaze position. Inspired by the need to overcome the hurdle of gaze contingency in artificial vision, we aim to provide a thorough overview of the research addressing the neural underpinnings of eye compensation, as well as its relevance in visual prosthetics. The present review outlines what is currently known about the mechanisms underlying spatial updating and reviews the attempts of current visual prosthetic devices to overcome the hurdle of gaze contingency. We discuss the limitations of the current devices and highlight the need to use eye-tracking methodology in order to introduce gaze-contingent information to visual prosthetics.

Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells.

Most inherited forms of blindness are caused by mutations that lead to photoreceptor cell death but spare second- and third-order retinal neurons. Expression of the light-gated excitatory mammalian ion channel light-gated ionotropic glutamate receptor (LiGluR) in retinal ganglion cells (RGCs) of the retina degeneration (rd1) mouse model of blindness was previously shown to restore some visual functions when stimulated by UV light. Here, we report restored retinal function in visible light in rodent and canine models of blindness through the use of a second-generation photoswitch for LiGluR, maleimide-azobenzene-glutamate 0 with peak efficiency at 460 nm (MAG0(460)). In the blind rd1 mouse, multielectrode array recordings of retinal explants revealed robust and uniform light-evoked firing when LiGluR-MAG0(460) was targeted to RGCs and robust but diverse activity patterns in RGCs when LiGluR-MAG0(460) was targeted to ON-bipolar cells (ON-BCs). LiGluR-MAG0(460) in either RGCs or ON-BCs of the rd1 mouse reinstated innate light-avoidance behavior and enabled mice to distinguish between different temporal patterns of light in an associative learning task. In the rod-cone dystrophy dog model of blindness, LiGluR-MAG0(460) in RGCs restored robust light responses to retinal explants and intravitreal delivery of LiGluR and MAG0(460) was well tolerated in vivo. The results in both large and small animal models of photoreceptor degeneration provide a path to clinical translation.