- NSF-PAR ID:
- 10492240
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Journal of Neural Engineering
- Volume:
- 21
- Issue:
- 1
- ISSN:
- 1741-2560
- Format(s):
- Medium: X Size: Article No. 016030
- Size(s):
- ["Article No. 016030"]
- Sponsoring Org:
- National Science Foundation
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Abstract Objective . Retinal prostheses aim to restore sight by electrically stimulating the surviving retinal neurons. In clinical trials of the current retinal implants, prosthetic visual acuity does not exceed 20/550. However, to provide meaningful restoration of central vision in patients blinded by age-related macular degeneration (AMD), prosthetic acuity should be at least 20/200, necessitating a pixel pitch of about 50µ m or lower. With such small pixels, stimulation thresholds are high due to limited penetration of electric field into tissue. Here, we address this challenge with our latest photovoltaic arrays and evaluate their performancein vivo .Approach . We fabricated photovoltaic arrays with 55 and 40µ m pixels (a) in flat geometry, and (b) with active electrodes on 10µ m tall pillars. The arrays were implanted subretinally into rats with degenerate retina. Stimulation thresholds and grating acuity were evaluated using measurements of the visually evoked potentials (VEP).Main results . With 55µ m pixels, we measured grating acuity of 48 ± 11µ m, which matches the linear pixel pitch of the hexagonal array. This geometrically corresponds to a visual acuity of 20/192 in a human eye, matching the threshold of legal blindness in the US (20/200). With pillar electrodes, the irradiance threshold was nearly halved, and duration threshold reduced by more than three-fold, compared to flat pixels. With 40µ m pixels, VEP was too low for reliable measurements of the grating acuity, even with pillar electrodes.Significance . While being helpful for treating a complete loss of sight, current prosthetic technologies are insufficient for addressing the leading cause of untreatable visual impairment—AMD. Subretinal photovoltaic arrays may provide sufficient visual acuity for restoration of central vision in patients blinded by AMD. -
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Abstract Objective . Patients with photovoltaic subretinal implant PRIMA demonstrated letter acuity ∼0.1 logMAR worse than sampling limit for 100μ m pixels (1.3 logMAR) and performed slower than healthy subjects tested with equivalently pixelated images. To explore the underlying differences between natural and prosthetic vision, we compare the fidelity of retinal response to visual and subretinal electrical stimulation through single-cell modeling and ensemble decoding.Approach . Responses of retinal ganglion cells (RGCs) to optical or electrical white noise stimulation in healthy and degenerate rat retinas were recorded via multi-electrode array. Each RGC was fit with linear–nonlinear and convolutional neural network models. To characterize RGC noise, we compared statistics of spike-triggered averages (STAs) in RGCs responding to electrical or visual stimulation of healthy and degenerate retinas. At the population level, we constructed a linear decoder to determine the accuracy of the ensemble of RGCs onN -way discrimination tasks.Main results . Although computational models can match natural visual responses well (correlation ∼0.6), they fit significantly worse to spike timings elicited by electrical stimulation of the healthy retina (correlation ∼0.15). In the degenerate retina, response to electrical stimulation is equally bad. The signal-to-noise ratio of electrical STAs in degenerate retinas matched that of the natural responses when 78 ± 6.5% of the spikes were replaced with random timing. However, the noise in RGC responses contributed minimally to errors in ensemble decoding. The determining factor in accuracy of decoding was the number of responding cells. To compensate for fewer responding cells under electrical stimulation than in natural vision, more presentations of the same stimulus are required to deliver sufficient information for image decoding.Significance . Slower-than-natural pattern identification by patients with the PRIMA implant may be explained by the lower number of electrically activated cells than in natural vision, which is compensated by a larger number of the stimulus presentations. -
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Abstract Objective. Our laboratory has proposed chemical stimulation of retinal neurons using exogenous glutamate as a biomimetic strategy for treating vision loss caused by photoreceptor (PR) degenerative diseases. Although our previousin-vitro studies using pneumatic actuation indicate that chemical retinal stimulation is achievable, an actuation technology that is amenable to microfabrication, as needed for anin-vivo implantable device, has yet to be realized. In this study, we sought to evaluate electroosmotic flow (EOF) as a mechanism for delivering small quantities of glutamate to the retina. EOF has great potential for miniaturization.Approach. An EOF device to dispense small quantities of glutamate was constructed and its ability to drive retinal output tested in anin-vitro preparation of PR degenerate rat retina.Main results. We built and tested an EOF microfluidic system, with 3D printed and off-the-shelf components, capable of injecting small volumes of glutamate in a pulsatile fashion when a low voltage control signal was applied. With this device, we produced excitatory and inhibitory spike rate responses in PR degenerate rat retinae. Glutamate evoked spike rate responses were also observed to be voltage-dependent and localized to the site of injection.Significance. The EOF device performed similarly to a previously tested conventional pneumatic microinjector as a means of chemically stimulating the retina while eliminating the moving plunger of the pneumatic microinjector that would be difficult to miniaturize and parallelize. Although not implantable, the prototype device presented here as a proof of concept indicates that a retinal prosthetic based on EOF-driven chemical stimulation is a viable and worthwhile goal. EOF should have similar advantages for controlled dispensing of charged neurochemicals at any neural interface. -
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Abstract Objective. The objective of this study was to investigate the effects of micromagnetic stimuli strength and frequency from theMag neticPen (MagPen) on the rat right sciatic nerve. The nerve’s response was measured by recording muscle activity and movement of the right hind limb.Approach. The MagPen was custom-built to be stably held over the sciatic nerve. Rat leg muscle twitches were captured on video, and movements were extracted using image processing algorithms. EMG recordings were also used to measure muscle activity.Main results. The MagPen prototype, when driven by an alternating current, generates a time-varying magnetic field, which, according to Faraday’s law of electromagnetic induction, induces an electric field for neuromodulation. The orientation-dependent spatial contour maps of the induced electric field from the MagPen prototype have been numerically simulated. Furthermore, in thisin vivo work onµ MS, a dose-response relationship has been reported by experimentally studying how varying the amplitude (Range: 25 mV p-pthrough 6V p-p) and frequency (range: 100 Hz through 5 kHz) of the MagPen stimuli alters hind limb movement. The primary highlight of this dose-response relationship (repeated overn rats, wheren = 7) is that for aµ MS stimuli of higher frequency, significantly smaller amplitudes can trigger hind limb muscle twitch. This frequency-dependent activation can be justified by Faraday’s Law, which states that the magnitude of the induced electric field is directly proportional to the frequency.Significance. This work reports thatµ MS can successfully activate the sciatic nerve in a dose-dependent manner. The impact of this dose-response curve addresses the controversy in this research community about whether the stimulation from theseμ coils arise from a thermal effect or micromagnetic stimulation. MagPen probes do not have a direct electrochemical interface with tissue and therefore do not experience electrode degradation, biofouling, and irreversible redox reactions like traditional direct contact electrodes. Magnetic fields from theμ coils create more precise activation than electrodes because they apply more focused and localized stimulation. Finally, unique features ofµ MS, such as the orientation dependence, directionality, and spatial specificity, have been discussed. -
Abstract Objective. To understand neural circuit dynamics, it is critical to manipulate and record many individual neurons. Traditional recording methods, such as glass microelectrodes, can only control a small number of neurons. More recently, devices with high electrode density have been developed, but few of them can be used for intracellular recording or stimulation in intact nervous systems. Carbon fiber electrodes (CFEs) are 8 µ m-diameter electrodes that can be assembled into dense arrays (pitches ⩾ 80 µ m). They have good signal-to-noise ratios (SNRs) and provide stable extracellular recordings both acutely and chronically in neural tissue in vivo (e.g. rat motor cortex). The small fiber size suggests that arrays could be used for intracellular stimulation. Approach. We tested CFEs for intracellular stimulation using the large identified and electrically compact neurons of the marine mollusk Aplysia californica . Neuron cell bodies in Aplysia range from 30 µ m to over 250 µ m. We compared the efficacy of CFEs to glass microelectrodes by impaling the same neuron’s cell body with both electrodes and connecting them to a DC coupled amplifier. Main results. We observed that intracellular waveforms were essentially identical, but the amplitude and SNR in the CFE were lower than in the glass microelectrode. CFE arrays could record from 3 to 8 neurons simultaneously for many hours, and many of these recordings were intracellular, as shown by simultaneous glass microelectrode recordings. CFEs coated with platinum-iridium could stimulate and had stable impedances over many hours. CFEs not within neurons could record local extracellular activity. Despite the lower SNR, the CFEs could record synaptic potentials. CFEs were less sensitive to mechanical perturbations than glass microelectrodes. Significance. The ability to do stable multi-channel recording while stimulating and recording intracellularly make CFEs a powerful new technology for studying neural circuit dynamics.more » « less
