Mechanisms underlying activation of retinal bipolar cells through targeted electrical stimulation: a computational study

Objective. Retinal implants have been developed to electrically stimulate healthy retinal neurons in the progressively degenerated retina. Several stimulation approaches have been proposed to improve the visual percept induced in patients with retinal prostheses. We introduce a computational model capable of simulating the effects of electrical stimulation on retinal neurons. Leveraging this computational platform, we delve into the underlying mechanisms influencing the sensitivity of retinal neurons’ response to various stimulus waveforms. Approach. We implemented a model of spiking bipolar cells (BCs) in the magnocellular pathway of the primate retina, diffuse BC subtypes (DB4), and utilized our multiscale Admittance Method (AM)-NEURON computational platform to characterize the response of BCs to epiretinal electrical stimulation with monophasic, symmetric, and asymmetric biphasic pulses. Main Results. Our investigations yielded four notable results: (i) The latency of BCs increases as stimulation pulse duration lengthens; conversely, this latency decreases as the current amplitude increases. (ii) Stimulation with a long anodic-first symmetric biphasic pulse (duration > 8 ms) results in a significant decrease in spiking threshold compared to stimulation with similar cathodic-first pulses (from 98.2 µA to 57.5 µA). (iii) The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel was a prominent contributor to the reduced threshold of BCs in response to long anodic-first stimulus pulses. (iv) Finally, extending the study to asymmetric waveforms, our results predict a lower BCs threshold using asymmetric long anodic-first pulses compared to that of asymmetric short cathodic-first stimulation. Significance. This study predicts the effects of several stimulation parameters on spiking BCs response to electrical stimulation. Of importance, our findings shed light on mechanisms underlying the experimental observations from the literature, thus highlighting the capability of the methodology to predict and guide the development of electrical stimulation protocols to generate a desired biological response, thereby constituting an ideal testbed for the development of electroceutical devices.

The Lightness/Pitch Crossmodal Correspondence Modulates the Rubin Face/Vase Perception

We examine whether crossmodal correspondences (CMCs) modulate perceptual disambiguation by considering the influence of lightness/pitch congruency on the perceptual resolution of the Rubin face/vase (RFV). We randomly paired a black-and-white RFV (black faces and white vase, or vice versa) with either a high or low pitch tone and found that CMC congruency biases the dominant visual percept. The perceptual option that was CMC-congruent with the tone (white/high pitch or black/low pitch) was reported significantly more often than the perceptual option CMC-incongruent with the tone (white/low pitch or black/high pitch). However, the effect was only observed for stimuli presented for longer and not shorter durations suggesting a perceptual effect rather than a response bias, and moreover, we infer an effect on perceptual reversals rather than initial percepts. We found that the CMC congruency effect for longer-duration stimuli only occurred after prior exposure to the stimuli of several minutes, suggesting that the CMC congruency develops over time. These findings extend the observed effects of CMCs from relatively low-level feature-based effects to higher-level object-based perceptual effects (specifically, resolving ambiguity) and demonstrate that an entirely new category of crossmodal factors (CMC congruency) influence perceptual disambiguation in bistability.

Optogenetic stimulation of primate V1 reveals local laminar and large-scale cortical networks related to perceptual phosphenes

Developing optogenetics in non-human primates (NHPs) is essential for translating its successful implementation in rodents to clinical applications in humans. However, information about how optogenetics influences the primate cortex remains limited. Here, we evaluate how optogenetic stimulation of the primate primary visual cortex (V1) affects local and large-scale network activation concerned with visual perception. To this end we injected an optogenetic construct (AAV9-hSyn-ChR2-eYFP) into the V1 cortex of four macaque monkeys (macaca mulatta) and measured the effects of optogenetic V1 stimulation using functional magnetic resonance imaging (fMRI), laminar electrophysiology, and behavioural assessment. In three macaques, blood-oxygen-dependent (BOLD) fMRI activity could be reliably elicited with optogenetic stimulation in V1 and several connected extrastriate brain areas, including V2/V3, motion-sensitive area MT and the frontal-eye-fields (FEF), in particular when pulsed stimulation at 40 Hz was applied. BOLD modulation was associated with consistent neural spiking activity measured in V1 of two macaques. More detailed analysis revealed strongest neuronal activation in layer 4B and infragranular layers, which tightly reflected the histological expression pattern of the optogenetic construct in V1. Driving this visual network proved sufficient to elicit a visual percept (phosphene) in one macaque during a perceptual choice task. Taken together, our findings reveal the laminar and large-cortical activation pattern related to visual phosphene generation and emphasize the need for further improving optogenetic methods in NHPs as a step towards applications in humans.

Pictorial balance is a bottom-up aesthetic property mediated by eye movements

Pictures evoke both a top down and a bottom-up visual percept of balance. Through its effect on eye movements, balance is a bottom-up conveyor of aesthetic feeling. Eye movements are predominantly influenced by the large effects of saliency and top-down priorities; it is difficult to separate out the much smaller effect of balance. Given that balance is associated with a unified and harmonious picture and that there is a pictorial effect known to painters and historically documented that does just that, it was thought that such pictures are perfectly balanced. Computer models of these pictures were created by the author and were found to have bilateral quadrant luminance symmetry with a lower half lighter by a factor of ~1.07 +/- ~0.03. A top weighted center of quadrant luminance calculation is proposed to measure balance. To show that this effect exists, two studies were done that compared identical pictures in two different frames with respect to whether they appeared different given that the sole difference is balance. Results show that with observers, mostly painters, there was a significant correlation between average pair imbalance and observations that two identical pictures appeared different indicating at a minimum that the equation for calculating balance was correct. A conventional study of preference could not be done because of the necessity of using LED pictures that increase overall salience, and so decrease the aesthetic effect while retaining the effects on eye movements. The effect is the result of the absence of balancing forces on eye movements. With painters who can disregard salience, the effect results from the absence of forces drawing attention to any part of the image. All parts of the picture including that in peripheral vision receive attention, and the eye seems to slide through rather than to jump from objet to object. The effect is being called pictorial coherency. Large tonally contrasting forms, geometric forms or many different forms that cannot be visually combined prevent the effect from being seen. Pictorial balance, an unaccustomed visual force, explains why viewing pictures cause fatigue. That pictures can evoke such a low level percept based on luminance would indicate that it belongs to a much earlier evolutionary development of the visual stream where it was possibly used to follow movement by defining a complex object as a simple vector.

Representation of conscious percept without report in the macaque face patch network

A powerful paradigm to identify the neural correlates of consciousness is binocular rivalry, wherein a constant visual stimulus evokes a varying conscious percept. It has recently been suggested that activity modulations observed during rivalry could represent the act of report rather than the conscious percept itself. Here, we performed single-unit recordings from face patches in macaque inferotemporal (IT) cortex using a no-report paradigm in which the animal’s conscious percept was inferred from eye movements. We found high proportions of IT neurons represented the conscious percept even without active report. Population activity in single trials, measured using a new 128-site Neuropixels-like electrode, was more weakly modulated by rivalry than by physical stimulus transitions, but nevertheless allowed decoding of the changing conscious percept. These findings suggest that macaque face patches encode both the physical stimulus and the animal’s conscious visual percept, and the latter encoding does not require active report.

Model-Based Recommendations for Optimal Surgical Placement of Epiretinal Implants

A major limitation of current electronic retinal implants is that in addition to stimulating the intended retinal ganglion cells, they also stimulate passing axon fibers, producing perceptual ‘streaks’ that limit the quality of the generated visual experience. Recent evidence suggests a dependence between the shape of the elicited visual percept and the retinal location of the stimulating electrode. However, this knowledge has yet to be incorporated into the surgical placement of retinal implants. Here we systematically explored the space of possible implant configurations to make recommendations for optimal intraocular positioning of the electrode array. Using a psychophysically validated computational model, we demonstrate that better implant placement has the potential to reduce the spatial extent of axonal activation in existing implant users by up to ∼55 %. Importantly, the best implant location, as inferred from a population of simulated virtual patients, is both surgically feasible and is relatively stable across individuals. This study is a first step towards the use of computer simulations in patient-specific planning of retinal implant surgery.

Vizuální nevědomí: vizuální organizace nevizuálního města

This article focuses on the organization of space. The practices through which we grasp and conceive space are the paper’s concern. Practices emanating from the visual organization of space are usually so commonplace for seeing people so that these practices are only poorly reflected in seeing people’s understandings of space. This is why we turn to the experience of visually impaired people. Our understanding of this experience is based on interviews with 16 communication partners from Prague and Brno in 2014 and 2015. We use the poststructuralist approach of philosopher Gilles Deleuze, psychoanalyst Félix Guattari and geographer Marcus Doel to interpret the interviews and we show that visual impairment is not about non-seeing, but about becoming seeing differently – via the non-visual percept. Yet, such practices of seeing space differently are still shaped by the modern collective optical unconscious. Doel asserts that this unconscious has been structured by the medium of film, among others, and the film technique of montage. This has made the optical unconscious obscene. Montage unbound time and space from their firm coordinates and enabled seeing beyond screened frames. This strengthened the incorporeality of spatial experience. Visually impaired people’s practices of seeing and dealing with the optical unconscious accentuate the corporeality of sight again, however. Their practices fuse the seeing via non-visual percept and the optical unconscious into new configurations, demonstrating that no way of seeing can be incorporeal.

Visual Objects in the Auditory System in Sensory Substitution: How Much Information Do We Need?

Sensory substitution devices such as The vOICe convert visual imagery into auditory soundscapes and can provide a basic ‘visual’ percept to those with visual impairment. However, it is not known whether technical or perceptual limits dominate the practical efficacy of such systems. By manipulating the resolution of sonified images and asking naïve sighted participants to identify visual objects through a six-alternative forced-choice procedure (6AFC) we demonstrate a ‘ceiling effect’ at 8 × 8 pixels, in both visual and tactile conditions, that is well below the theoretical limits of the technology. We discuss our results in the context of auditory neural limits on the representation of ‘auditory’ objects in a cortical hierarchy and how perceptual training may be used to circumvent these limitations.