Electrical stimulation of different retinal components and the effect of asymmetric pulses

Raz-Prag, Dorit; Beit-Yaakov, Giora; Hanein, Yael

doi:10.1016/j.jneumeth.2017.07.028

Cited by 11 publications

(12 citation statements)

References 34 publications

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“…The latency of a direct response becomes larger when detected on electrodes that are further away from the stimulating electrode. Indeed, measured propagation direction (red and blue regression lines in Figure a) and speed of 0.33 ± 0.045 m s −1 (calculated from the latency of the response between two adjacent electrodes, 500 µm apart), correspond well with fiber layer alignment (Figure c) and known action potential propagation speed in the chick retina . The photocapacitive pixels elicit the same direct response as current‐injected MEA electrodes ( n = 4 retinas), verifying that the devices are photocapacitively evoking direct retinal responses.…”

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confidence: 65%

“…In the chick retina, direct responses are easily recognized as they propagate in both directions along the nerve fibers (retrograde and anterograde). We have previously shown that these responses result from direct activation of ganglion cells, they can be suppressed by the presence of voltage‐gated sodium channels blocker, tetrodotoxin, but not in the presence of synaptic transmission blockers . The latency of a direct response becomes larger when detected on electrodes that are further away from the stimulating electrode.…”

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confidence: 99%

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Direct Electrical Neurostimulation with Organic Pigment Photocapacitors

et al. 2018

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An efficient nanoscale semiconducting optoelectronic system is reported, which is optimized for neuronal stimulation: the organic electrolytic photocapacitor. The devices comprise a thin (80 nm) trilayer of metal and p-n semiconducting organic nanocrystals. When illuminated in physiological solution, these metal-semiconductor devices charge up, transducing light pulses into localized displacement currents that are strong enough to electrically stimulate neurons with safe light intensities. The devices are freestanding, requiring no wiring or external bias, and are stable in physiological conditions. The semiconductor layers are made using ubiquitous and nontoxic commercial pigments via simple and scalable deposition techniques. It is described how, in physiological media, photovoltage and charging behavior depend on device geometry. To test cell viability and capability of neural stimulation, photostimulation of primary neurons cultured for three weeks on photocapacitor films is shown. Finally, the efficacy of the device is demonstrated by achieving direct optoelectronic stimulation of light-insensitive retinas, proving the potential of this device platform for retinal implant technologies and for stimulation of electrogenic tissues in general. These results substantiate the conclusion that these devices are the first non-Si optoelectronic platform capable of sufficiently large photovoltages and displacement currents to enable true capacitive stimulation of excitable cells.

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confidence: 99%

Direct Electrical Neurostimulation with Organic Pigment Photocapacitors

et al. 2018

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“…In particular, 192 trials (8 levels of pulse frequency and 24 levels of pulse amplitude at each frequency) of biphasic pulse trains were delivered to each RGC. This process is time-consuming and potentially unattainable when a large stimulation parameter space (e.g., up to the frequency of 25 kHz) is to be evaluated, or if other pulse waveform shapes are to be considered (Hadjinicolaou et al, 2015 ; Raz-Prag et al, 2017 ). In addition, responses to HFS may be variable across functionally-distinct RGC types (Cai et al, 2011 , 2013 ; Twyford et al, 2014 ) and a comprehensive description of electrically-evoked RGC responses is yet to be compiled, due to their large diversity in both intrinsic and morphological properties (O'Brien et al, 2002 ; Margolis and Detwiler, 2007 ; Wong et al, 2012 ).…”

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confidence: 99%

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

et al. 2018

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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.

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“…Unconventional waveform designs have also been explored to improve selective stimulation of specific neuronal populations inside retinal cell networks [19][20][21][22][23][24]. Sinusoidal waveforms have been suggested to preferentially activate photoreceptors, bipolar cells, or ganglion cell populations [19,20].…”

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confidence: 99%

“…Sinusoidal waveforms have been suggested to preferentially activate photoreceptors, bipolar cells, or ganglion cell populations [19,20]. Furthermore, asymmetric biphasic waveforms have been found to provide control over direct versus indirect activation of retinal cells [21]. Other studies have suggested that the duration of stimulation can be utilised to selectively activate between retinal ganglion cells, bipolar cells, and amacrine cells [22], modulate the selectivity for ON versus OFF responses [23] and produce precise temporal patterns of ganglion cell firing [24].…”

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Stimulus waveform design for decreasing charge and increasing stimulation selectivity in retinal prostheses

Kosta

Loizos

Lazzi

2020

Healthcare Technology Letters

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Retinal degenerative diseases, such as retinitis pigmentosa, begin with damage to the photoreceptor layer of the retina. In the absence of presynaptic input from photoreceptors, networks of electrically coupled AII amacrine and cone bipolar cells have been observed to exhibit oscillatory behaviour and result in spontaneous firing of ganglion cells. This ganglion cell activity could interfere with external stimuli provided by retinal prosthetic devices and potentially degrade their performance. In this work, the authors computationally investigate stimulus waveform designs, which can improve the performance of retinal prostheses by suppressing undesired spontaneous firing of ganglion cells and generating precise temporal spiking patterns. They utilise a multi-scale computational model for electrical stimulation of degenerated retina based on the admittance method and NEURON simulation environments. They present a class of asymmetric biphasic pulses that can generate precise ganglion cell firing patterns with up to 55% lower current requirements compared to traditional symmetric biphasic pulses. This lower current results in activation of only proximal ganglion cells, provides more focused stimulation and lowers the risk of tissue damage.

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Electrical stimulation of different retinal components and the effect of asymmetric pulses

Cited by 11 publications

References 34 publications

Direct Electrical Neurostimulation with Organic Pigment Photocapacitors

Direct Electrical Neurostimulation with Organic Pigment Photocapacitors

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

Stimulus waveform design for decreasing charge and increasing stimulation selectivity in retinal prostheses

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