Objective. This study focused on characterising the response of four major functionally-different retinal ganglion cells (RGCs) to a high frequency stimulus (HFS) paradigm. Approach. We used in vitro patch clamp experiments to assess the viability of evoking a differential response between different RGC types—OFF-Sustained, OFF-Transient, ON-Sustained and ON-Transient—under a wide range of HFS and stimulation amplitude combinations. Main results . Of the four types, we found that the OFF-Sustained, OFF-Transient and ON-Transient RGCs could be differentially activated at various frequency and amplitude combinations, in particular, OFF-Sustained cells can be differentially targeted between 20–100 µ A at all frequencies, OFF-Transient cells between 150–240 µ A at 1 kHz and ON-Transient between 180–240 µ A and 4–6 kHz. We further found that this differential activation held true when the stimulus duration was reduced from 300 ms to 50 ms. Finally, we found that the cell spiking response was not primarily dependent on total charge contained in the pulse train or current amplitude alone, but a combination of amplitude and frequency. Significance. These results indicate that HFS may be a promising method to target functionally-distinct neural pathways in the retina in an effort to improve the vision quality with retinal prostheses.

This paper explores the extent to which a solid-state transmitter can be miniaturized, while still using RF for wireless information transfer and working with power densities and operating voltages comparable to what could be harvested from a living system. A 3.1 nJ/bit pulsed millimeter-wave transmitter, 300 μm by 300 μm by 250 μm in size, designed in 32-nm SOI CMOS, operates on an electric potential of 130 mV and 3.1 nW of dc power. Far-field data transmission at 33 GHz is achieved by supply-switching an LC-oscillator with a duty cycle of 10 ^-6 . The time interval between pulses carries information on the amount of power harvested by the radio, supporting a data rate of ~ 1 bps. The inductor of the oscillator also acts as an electrically small (λ/30) on-chip antenna, which, combined with millimeter-wave operation, enables the extremely small form factor.

Multiplexing is an important strategy in multichannel acquisition systems. The per-channel antialiasing filters needed in the traditional multiplexing architecture limit its scalability for applications requiring high channel density, high channel count, and low noise. A particularly challenging example is multielectrode arrays for recording from neural systems. We show that conventional approaches must tradeoff recording density and noise performance, at a scale far from the ideal goal of one-to-one mapping between neurons and sensors. We present a multiplexing architecture without per-channel antialiasing filters. The sparsely sampled data are recovered through a compressed sensing strategy, involving statistical reconstruction and removal of the undersampled thermal noise. In doing so, we replace large analog components with digital signal processing blocks, which are much more amenable to scaled CMOS implementation. The resulting statistically reconstructed multiplexing architecture recovers input signals at significantly improved signal-to-noise ratios when compared to conventional multiplexing with antialiasing filters at the same per-channel area. We implement the new architecture in a 65 536-channel neural recording system and show that it is able to recover signals with performance comparable to conventional high-performance, single-channel systems, despite a more than four-orders-of-magnitude increase in channel density.

Objective . Retinal prostheses seek to create artificial vision by stimulating surviving retinal neurons of patients with profound vision impairment. Notwithstanding tremendous research efforts, the performance of all implants tested to date has remained rudimentary, incapable of overcoming the threshold for legal blindness. To maximize the perceptual efficacy of retinal prostheses, a device must be capable of controlling retinal neurons with greater spatiotemporal precision. Most studies of retinal stimulation were derived from either non-primate species or the peripheral primate retina. We investigated if artificial stimulation could leverage the high spatial resolution afforded by the neural substrates at the primate fovea and surrounding regions to achieve improved percept qualities. Approach. We began by developing a new computational model capable of generating anatomically accurate retinal ganglion cell (RGC) populations within the human central retina. Next, multiple RGC populations across the central retina were stimulated in-silico to compare clinical and recently proposed neurostimulation configurations based on their ability to improve perceptual efficacy and reduce activation thresholds. Main results. Our model uniquely upholds eccentricity-dependent characteristics such as RGC density and dendritic field diameter, whilst incorporating anatomically accurate features such as axon projection and three-dimensional (3D) RGC layering, features often forgone in favor of reduced computational complexity. Following epiretinal stimulation, the RGCs in our model produced response patterns in shapes akin to the complex and non-trivial percepts reported in clinical trials. Our results also demonstrated that even within the neuron-dense central retina, epiretinal stimulation using a multi-return hexapolar electrode arrangement could reliably achieve spatially focused RGC activation and could achieve single-cell excitation in 56% of all tested locations. Significance . This study establishes an anatomically accurate 3D model of RGC populations within the human central retina and demonstrates the potential for an epiretinal hexapolar configuration to achieve consistent, spatially confined retinal responses, even within the unique and neuron-dense foveal region. Our results and model promote the prospect and optimization of higher spatial resolution in future epiretinal implants.

Electrical stimulation is an important tool in neuroscience research and clinically. In the retina, extensive work has revealed how the retinal ganglion cells respond to extracellular electrical stimulation. But little is known about the responses of other neuronal types, and more generally, how the network responds to stimulation. We conducted a survey of electrically evoked responses, over a range of pulse amplitudes and pulse widths, for 21 cell types spanning the inner two layers of the rabbit retina. It revealed: (i) the evoked responses of some neurons were charge insensitive; (ii) pulse-width sensitivity varied between cell types, allowing preferential recruitment of cell types; and (iii) 10–20 Hz damped oscillations across retinal layers. These oscillations were generated by reciprocal excitatory / inhibitory synapses, at locations as early as the cone-horizontal-cell synapses. These results illustrate at cellular resolution how a network responds to extracellular stimulation, and could inform the development of bioelectronic implants for treating blindness.

Objective. A transverse intrafascicular multichannel electrode (TIME) may offer advantages over more conventional cuff electrodes including higher spatial selectivity and reduced stimulation charge requirements. However, the performance of TIME, especially in the context of non-conventional stimulation waveforms, remains relatively unexplored. As part of our overarching goal of investigating stimulation efficacy of TIME, we developed a computational toolkit that automates the creation and usage of in silico nerve models with TIME setup, which solves nerve responses using cable equations and computes extracellular potentials using finite element method. Approach. We began by implementing a flexible and scalable Python/MATLAB-based toolkit for automatically creating models of nerve stimulation in the hybrid NEURON/COMSOL ecosystems. We then developed a sciatic nerve model containing 14 fascicles with 1,170 myelinated (A-type, 30%) and unmyelinated (C-type, 70%) fibers to study fiber responses over a variety of TIME arrangements (monopolar and hexapolar) and stimulation waveforms (kilohertz stimulation and cathodic ramp modulation). Main results. Our toolkit obviates the conventional need to re-create the same nerve in two disparate modeling environments and automates bi-directional transfer of results. Our population-based simulations suggested that kilohertz stimuli provide selective activation of targeted C fibers near the stimulating electrodes but also tended to activate non-targeted A fibers further away. However, C fiber selectivity can be enhanced by hexapolar TIME arrangements that confined the spatial extent of electrical stimuli. Improved upon prior findings, we devised a high-frequency waveform that incorporates cathodic DC ramp to completely remove undesirable onset responses. Conclusion. Our toolkit allows agile, iterative design cycles involving the nerve and TIME, while minimizing the potential operator errors during complex simulation. The nerve model created by our toolkit allowed us to study and optimize the design of next-generation intrafascicular implants for improved spatial and fiber-type selectivity.