Abstract
The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 μA) and frequencies (2–6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40–90 μA) across all tested frequencies (1–6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation.
Highlights
Retinal neuroprostheses or bionic eyes, aim to restore functional visual percepts to those suffering from retinal degenerative diseases (Rizzo and Wyatt, 1997; Palanker et al, 2005; Weiland et al, 2005)
To test the hypothesis that high frequency stimulation (HFS) neuromodulation is able to preferentially excite ON and OFF retinal ganglion cells (RGCs) pathways, we evaluated the performance of a range of electrical stimulation amplitudes (10–240 μA) and frequencies (1–6.25 kHz) on RGC responses using murine retinal preparations
Preferential RGC Activation Can Be Achieved by Modulating Stimulation Amplitude and Frequency in Vitro In Figure 2, we explored the ability of epiretinal HFS to preferentially activate ON (N = 11) and OFF (N = 12) RGC populations obtained in 12 mice
Summary
Retinal neuroprostheses or bionic eyes, aim to restore functional visual percepts to those suffering from retinal degenerative diseases (Rizzo and Wyatt, 1997; Palanker et al, 2005; Weiland et al, 2005) With such devices, it is desirable to elicit visual percepts by activating retinal neuron populations in a controlled spatiotemporal pattern. Human vision is primarily mediated by two major retinal ganglion cell (RGC) classes—the ON and OFF cells, which respond to an increase and decrease in light intensity, respectively If these RGCs can be selectively or preferentially activated in a desired temporospatial sequence, more physiologically-realistic patterns of neural activity could be elicited by a neural prosthesis. While the underlying cause(s) are topics of ongoing research, we reasoned that by obeying more physiological coding scheme of the visual system, through preferential stimulation of neuronal types, visual information can be conveyed and interpreted more accurately by the brain, thereby improving the quality of the evoked percepts
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