Sabrina Jade Meikle

A new electrical stimulation focused computational model of the visual cortex had been created to aid in the development of cortical visual prosthesis. The model consists of 10,666 biophysical neurons representing 0.13mm ³ of a layer 2/3 of the primary visual cortex and was calibrated to match the baseline activity of rat brain recordings. A novel model of electrical stimulation was developed to allow for selective activation of specific neuron types, and matched the single cell stimulation response generated by known stimulation models. The electrode was tuned to match recorded population level change in activity across distances and currents recorded in the rat’s brain. The model is now ready to explore electrical stimulation effects on the visual cortex for examination of neuron specific stimulation to assist in the development of cortical visual prosthesis.

Objective. Development of cortical visual prostheses requires optimization of evoked responses to electrical stimulation to reduce charge requirements and improve safety, efficiency, and efficacy. One promising approach is timing stimulation to the local field potential (LFP), where action potentials have been found to occur preferentially at specific phases. To assess the relationship between electrical stimulation and the phase of the LFP, we recorded action potentials from primary (V1) and secondary (V2) visual cortex in marmosets while delivering single-pulse electrical microstimulation at different phases of the LFP. Approach. A 64-channel 4 shank probe was inserted into V1 and V2. Microstimulation (single biphasic pulse, 10 µA and 200 µs per phase) was applied to selected channels in V1, and action potentials recorded simultaneously in V1 and V2. Microstimulation pulses were jittered in time to randomize the phase of the LFP at the time of stimulation. Results. We found frequency-specific phase modulation in a subset of units, where microstimulation in V1 evokes a higher firing rate in both V1 and V2 when delivered at specific phases of the LFP. We characterize phase modulation in terms of the preferred phase and frequency of V1 stimulation for responses in both V1 and V2, and effect size as a function of phase estimation accuracy. Significance. Phase modulation could reduce charge requirements for neural activation, reducing the volume of activated tissue and improving the safety, efficacy, and specificity of cortical visual prostheses. Phase modulation could allow cortical visual prostheses to stimulate using more simultaneous electrodes, with improved neural specificity, and, potentially, targeting downstream cortical activation.

Cortical visual prostheses are designed to treat blindness by restoring visual perceptions through artificial electrical stimulation of the primary visual cortex (V1). Intracortical microelectrodes produce the smallest visual percepts and thus higher resolution vision - like a higher density of pixels on a monitor. However, intracortical microelectrodes must maintain a minimum spacing to preserve tissue integrity. One solution to increase the density of percepts is to implant and stimulate multiple visual areas, such as V1 and V2, although the properties of microstimulation in V2 remain largely unexplored. We provide a direct comparison of V1 and V2 microstimulation in two common marmoset monkeys. We find similarities in response trends between V1 and V2 but differences in threshold, neural activity duration, and spread of activity at the threshold current. This has implications for using multi-area stimulation to increase the resolution of cortical visual prostheses.

: Objective. Blindness affects approximately 40 million people worldwide and has inspired the development of cortical visual prostheses for restoring sight. Cortical visual prostheses electrically stimulate neurons of the visual cortex to artificially evoke visual percepts. Of the 6 layers of the visual cortex, layer 4 contains neurons that are likely to evoke a visual percept. Intracortical prostheses therefore aim to target layer 4; however, this can be difficult due to cortical curvature, inter-subject cortical variability, blindness-induced anatomical changes in cortex, and electrode placement variations. We investigated the feasibility of using current steering to stimulate specific cortical layers between electrodes in the laminar column. Approach. We explored whether the multiunit neural activity peak can be manipulated between two simultaneously stimulating electrodes in different layers of the cortical column. A 64-channel, 4-shank electrode array was implanted into the visual cortex of Sprague–Dawley rats (n = 7) orthogonal to the cortical surface. A remote return electrode was positioned over the frontal cortex in the same hemisphere. Charge was supplied to two stimulating electrodes along a single shank. Differing ratios of charge (100:0, 75:25, 50:50) and separation distances (300–500 μm) were tested. Results. Current steering across the cortical layers did not result in a consistent shift of the neural activity peak. Both single-electrode and dual-electrode stimulation induced activity throughout the cortical column. This contrasts observations that current steering evoked a controllable peak of neural activity between electrodes implanted at similar cortical depths. However, dual-electrode stimulation across the layers did reduce the stimulation threshold at each site compared to single-electrode stimulation. Significance. Multi-electrode stimulation is not suitable for targeted activation of layers using current steering. However, it can be used to reduce activation thresholds at adjacent electrodes within a given cortical layer. This may be applied to reduce the stimulation side effects of neural prostheses, such as seizures.

Objective. Intracortical visual prostheses are being developed to restore sight in people who are blind. The resolution of artificial vision is dictated by the location, proximity and number of electrodes implanted in the brain. However, increasing electrode count and proximity is traded off against tissue damage. Hence, new stimulation methods are needed that can improve the resolution of artificial vision without increasing the number of electrodes. We investigated whether a technique known as current steering can improve the resolution of artificial vision provided by intracortical prostheses without increasing the number of physical electrodes in the brain. Approach. We explored how the locus of neuronal activation could be steered when low amplitude microstimulation was applied simultaneously to two intracortical electrodes. A 64-channel, four-shank electrode array was implanted into the visual cortex of rats ( n = 7). The distribution of charge ranged from single-electrode stimulation (100%:0%) to an equal distribution between the two electrodes (50%:50%), thereby steering the current between the physical electrodes. The stimulating electrode separation varied between 300 and 500 μ m. The peak of the evoked activity was defined as the ‘virtual electrode’ location. Main results. Current steering systematically shifted the virtual electrode on average between the stimulating electrodes as the distribution of charge was moved from one stimulating electrode to another. This effect was unclear in single trials due to the limited sampling of neurons. A model that scales the cortical response to each physical electrode when stimulated in isolation predicts the evoked virtual electrode response. Virtual electrodes were found to elicit a neural response as effectively and predictably as physical electrodes within cortical tissue on average. Significance. Current steering could be used to increase the resolution of intracortical electrode arrays without altering the number of physical electrodes which will reduce neural tissue damage, power consumption and potential heat dispersion issues.

Neural implants have the potential to restore visual capabilities in blind individuals by electrically stimulating the neurons of the visual system. This stimulation can produce visual percepts known as phosphenes. The ideal location of electrical stimulation for achieving vision restoration is widely debated and dependent on the physiological properties of the targeted tissue. Here, the neurophysiology of several potential target structures within the visual system will be explored regarding their benefits and downfalls in producing phosphenes. These regions will include the lateral geniculate nucleus, primary visual cortex, visual area 2, visual area 3, visual area 4 and the middle temporal area. Based on the existing engineering limitations of neural prostheses, we anticipate that electrical stimulation of any singular brain region will be incapable of achieving high-resolution naturalistic perception including color, texture, shape and motion. As improvements in visual acuity facilitate improvements in quality of life, emulating naturalistic vision should be one of the ultimate goals of visual prostheses. To achieve this goal, we propose that multiple brain areas will need to be targeted in unison enabling different aspects of vision to be recreated.