Avoidance of axonal stimulation with sinusoidal epiretinal stimulation
Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here we investigate focal and axonal activation of Retinal Ganglion Cells (R...
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| Published in: | Journal of neural engineering Vol. 21; no. 2 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
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IOP Publishing
01.04.2024
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| ISSN: | 1741-2560, 1741-2552, 1741-2552 |
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| Abstract | Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here we investigate focal and axonal activation of Retinal Ganglion Cells (RGCs) for different sinusoidal stimulation frequencies. Our results can be exploited to define a selective stimulation strategy to avoid axonal activation in retina implants.
RGC responses to epiretinal sinusoidal stimulation at frequencies between 40 and 100 Hz were tested in ex-vivo photoreceptor degenerated (rd10) retina explants. Experiments were conducted using a high-density CMOS-based Micro Electrode Array, which allows to locate RGC cell bodies and axons with high spatial resolution while performing simultaneous recording and stimulation.
We report current and charge density threshold for focal and distal axon activation for sinusoidal stimulation at 40, 60, 80 and 100 Hz, in the order of 0.5 µA. We identify selective stimulation for 40 and 60 Hz up to 0.23 and 0.28 µA (173 and 148 nC/mm
), showing how the selective stimulation window increases when reducing the stimulation frequency. With the use of synaptic blockers, we demonstrate the underlying direct activation mechanism of the ganglion cells. Finally, with the use of high resolution electrical imaging and axon tracking, we investigated the extent of the activation in axonal bundles.
. 40 and 60 Hz sinusoidal electrical stimulation can be applied to achieve focal activation of RGCs in epiretinal configuration. The presented results can be implemented as a stimulation strategy to avoid axonal stimulation solving one of the major limitations of artificial vision and retina implants. The results could be extended to other fields of neuroprosthetics to achieve selective focal electrical stimulation. |
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| AbstractList | Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here we investigate focal and axonal activation of Retinal Ganglion Cells (RGCs) for different sinusoidal stimulation frequencies. Our results can be exploited to define a selective stimulation strategy to avoid axonal activation in retina implants.
RGC responses to epiretinal sinusoidal stimulation at frequencies between 40 and 100 Hz were tested in ex-vivo photoreceptor degenerated (rd10) retina explants. Experiments were conducted using a high-density CMOS-based Micro Electrode Array, which allows to locate RGC cell bodies and axons with high spatial resolution while performing simultaneous recording and stimulation.
We report current and charge density threshold for focal and distal axon activation for sinusoidal stimulation at 40, 60, 80 and 100 Hz, in the order of 0.5 µA. We identify selective stimulation for 40 and 60 Hz up to 0.23 and 0.28 µA (173 and 148 nC/mm
), showing how the selective stimulation window increases when reducing the stimulation frequency. With the use of synaptic blockers, we demonstrate the underlying direct activation mechanism of the ganglion cells. Finally, with the use of high resolution electrical imaging and axon tracking, we investigated the extent of the activation in axonal bundles.
. 40 and 60 Hz sinusoidal electrical stimulation can be applied to achieve focal activation of RGCs in epiretinal configuration. The presented results can be implemented as a stimulation strategy to avoid axonal stimulation solving one of the major limitations of artificial vision and retina implants. The results could be extended to other fields of neuroprosthetics to achieve selective focal electrical stimulation. Objective.Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here, we investigate focal and axonal activation of retinal ganglion cells (RGCs) in epiretinal configuration for different sinusoidal stimulation frequencies.Approach.RGC responses to epiretinal sinusoidal stimulation at frequencies between 40 and 100 Hz were tested inex-vivophotoreceptor degenerated (rd10) isolated retinae. Experiments were conducted using a high-density CMOS-based microelectrode array, which allows to localize RGC cell bodies and axons at high spatial resolution.Main results.We report current and charge density thresholds for focal and distal axon activation at stimulation frequencies of 40, 60, 80, and 100 Hz for an electrode size with an effective area of 0.01 mm2. Activation of distal axons is avoided up to a stimulation amplitude of 0.23µA (corresponding to 17.3µC cm-2) at 40 Hz and up to a stimulation amplitude of 0.28µA (14.8µC cm-2) at 60 Hz. The threshold ratio between focal and axonal activation increases from 1.1 for 100 Hz up to 1.6 for 60 Hz, while at 40 Hz stimulation frequency, almost no axonal responses were detected in the tested intensity range. With the use of synaptic blockers, we demonstrate the underlying direct activation mechanism of the ganglion cells. Finally, using high-resolution electrical imaging and label-free electrophysiological axon tracking, we demonstrate the extent of activation in axon bundles.Significance.Our results can be exploited to define a spatially selective stimulation strategy avoiding axonal activation in future retinal implants, thereby solving one of the major limitations of artificial vision. The results may be extended to other fields of neuroprosthetics to achieve selective focal electrical stimulation.Objective.Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal implants, this is hindered by the undesired activation of distal axons. Here, we investigate focal and axonal activation of retinal ganglion cells (RGCs) in epiretinal configuration for different sinusoidal stimulation frequencies.Approach.RGC responses to epiretinal sinusoidal stimulation at frequencies between 40 and 100 Hz were tested inex-vivophotoreceptor degenerated (rd10) isolated retinae. Experiments were conducted using a high-density CMOS-based microelectrode array, which allows to localize RGC cell bodies and axons at high spatial resolution.Main results.We report current and charge density thresholds for focal and distal axon activation at stimulation frequencies of 40, 60, 80, and 100 Hz for an electrode size with an effective area of 0.01 mm2. Activation of distal axons is avoided up to a stimulation amplitude of 0.23µA (corresponding to 17.3µC cm-2) at 40 Hz and up to a stimulation amplitude of 0.28µA (14.8µC cm-2) at 60 Hz. The threshold ratio between focal and axonal activation increases from 1.1 for 100 Hz up to 1.6 for 60 Hz, while at 40 Hz stimulation frequency, almost no axonal responses were detected in the tested intensity range. With the use of synaptic blockers, we demonstrate the underlying direct activation mechanism of the ganglion cells. Finally, using high-resolution electrical imaging and label-free electrophysiological axon tracking, we demonstrate the extent of activation in axon bundles.Significance.Our results can be exploited to define a spatially selective stimulation strategy avoiding axonal activation in future retinal implants, thereby solving one of the major limitations of artificial vision. The results may be extended to other fields of neuroprosthetics to achieve selective focal electrical stimulation. |
| Author | Bui, Mai Thu Werginz, Paul Cojocaru, Andreea-Elena Zeck, Günther Corna, Andrea |
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| Snippet | Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In epiretinal... Objective.Neuromodulation, particularly electrical stimulation, necessitates high spatial resolution to achieve artificial vision with high acuity. In... |
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| Title | Avoidance of axonal stimulation with sinusoidal epiretinal stimulation |
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