Realistic retinal modeling unravels the differential role of excitation and inhibition to starburst amacrine cells in direction selectivity

Retinal direction-selectivity originates in starburst amacrine cells (SACs), which display a centrifugal preference, responding with greater depolarization to a stimulus expanding from soma to dendrites than to a collapsing stimulus. Various mechanisms were hypothesized to underlie SAC centrifugal preference, but dissociating them is experimentally challenging and the mechanisms remain debatable. To address this issue, we developed the Retinal Stimulation Modeling Environment (RSME), a multifaceted data-driven retinal model that encompasses detailed neuronal morphology and biophysical properties, retina-tailored connectivity scheme and visual input. Using a genetic algorithm, we demonstrated that spatiotemporally diverse excitatory inputs–sustained in the proximal and transient in the distal processes–are sufficient to generate experimentally validated centrifugal preference in a single SAC. Reversing these input kinetics did not produce any centrifugal-preferring SAC. We then explored the contribution of SAC-SAC inhibitory connections in establishing the centrifugal preference. SAC inhibitory network enhanced the centrifugal preference, but failed to generate it in its absence. Embedding a direction selective ganglion cell (DSGC) in a SAC network showed that the known SAC-DSGC asymmetric connectivity by itself produces direction selectivity. Still, this selectivity is sharpened in a centrifugal-preferring SAC network. Finally, we use RSME to demonstrate the contribution of SAC-SAC inhibitory connections in mediating direction selectivity and recapitulate recent experimental findings. Thus, using RSME, we obtained a mechanistic understanding of SACs’ centrifugal preference and its contribution to direction selectivity.

Virtual reality validation of naturalistic modulation strategies to counteract fading in retinal stimulation

Objective: Temporal resolution is a key challenge in artificial vision. Several prosthetic approaches are limited by the perceptual fading of evoked phosphenes upon repeated stimulation from the same electrode. Therefore, implanted patients are forced to perform active scanning, via head movements, to refresh the visual field viewed by the camera. However, active scanning is a draining task, and it is crucial to find compensatory strategies to reduce it. Approach: To address this question, we implemented perceptual fading in simulated prosthetic vision using virtual reality. Then, we quantified the effect of fading on two indicators: the time to complete a reading task and the head rotation during the task. We also tested if stimulation strategies previously proposed to increase the persistence of responses in retinal ganglion cells to electrical stimulation could improve these indicators. Main results: This study shows that stimulation strategies based on interrupted pulse trains and randomisation of the pulse duration allows significant reduction of both the time to complete the task and the head rotation during the task. Significance: The stimulation strategy used in retinal implants is crucial to counteract perceptual fading and to reduce active head scanning during prosthetic vision. In turn, less active scanning might improve the patient's comfort in artificial vision.

Organic semiconductors for light-mediated neuromodulation

Organic semiconductors have generated substantial interest in neurotechnology and emerged as a promising approach for wireless neuromodulation in fundamental and applied research. Here, we summarise the range of applications that have been proposed so far, including retinal stimulation, excitation and inhibition of cultured neurons and regulation of biological processes in other non-excitable cells from animal and plant origins. We also discuss the key chemical and physical phenomena at the basis of the interaction between materials and cells. Finally, we provide an overview of future perspectives, exciting research opportunities and the remaining challenges hampering the translation of this blooming technology into the clinic and industry.

Spatial Resolution of Suprachoroidal–Transretinal Stimulation Estimated by Recording Single-Unit Activity From the Cat Lateral Geniculate Nucleus

Retinal prostheses are devices used to restore visual sensation in patients suffering from photoreceptor degeneration, such as retinitis pigmentosa. Suprachoroidal–transretinal stimulation (STS) is a prosthesis with retinal electrodes located in the sclera. STS has the advantage that it is safer than epiretinal or subretinal prostheses, as the implant is not directly attached to the retinal tissue. We have previously reported feasibility of STS with animal experiments and clinical trials. However, functional evaluation with neurophysiological experiments is still largely missing. To estimate the spatial resolution of STS, single-unit activities in response to STS were recorded from relay cells in the dorsal lateral geniculate nucleus of cats, and the response probability of the units was analyzed in relation to the distance between the stimulus location and the receptive field of each recorded unit. A platinum electrode was attached to the sclera after lamellar resection, and the return electrode was placed in the vitreous. The stimulating current, which ranged from 50 to 500 μA, was applied between these electrodes, and the probability of spike responses occurring just after retinal stimulation was measured. The distance at half-maximum of response was determined from the collected response probabilities as a function of stimulus intensity for all units characterized by their distances from the receptive field center to the stimulation point. As the stimulation became weaker, this distance decreased to 1.8° at 150 and 100 μA. As another estimation, the radius of 25% response probability was 1.4° at 100 μA. The diameter of the stimulated cat retinal area, 3.6° or 2.8°, corresponds to human visual acuity of 0.005 or 0.007, or finger counting. Considering the lower hazard to the retina of STS and its potentially large visual field coverage, STS is an attractive method for retinal prosthetic device development.

Evaluation and Optimization of Methods for Generating High-Resolution Retinotopic Maps Using Visual Cortex Voltage-Sensitive Dye Imaging

The localization and measurement of neuronal activity magnitude at high spatial and temporal resolution are essential for mapping and better understanding neuronal systems and mechanisms. One such example is the generation of retinotopic maps, which correlates localized retinal stimulation with the corresponding specific visual cortex responses. Here we evaluated and compared seven different methods for extracting and localizing cortical responses from voltage-sensitive dye imaging recordings, elicited by visual stimuli projected directly on the rat retina by a customized projection system. The performance of these methods was evaluated both qualitatively and quantitatively by means of two cluster separation metrics, namely, the (adjusted) Silhouette Index (SI) and the (adjusted) Davies-Bouldin Index (DBI). These metrics were validated using simulated data, which showed that Temporally Structured Component Analysis (TSCA) outperformed all other analysis methods for localizing cortical responses and generating high-resolution retinotopic maps. The analysis methods, as well as the use of cluster separation metrics proposed here, can facilitate future research aiming to localize specific activity at high resolution in the visual cortex or other brain areas.

Changes in neural activity around the time of saccades: Separate contributions of visual and non-visual signals on MEG alpha and theta band activity

Visual processing mainly occurs during fixation, periods separated by saccadic eye movements, necessitating a close coordination between sensory and motor systems. It has been suggested that the intention to make a saccade can modulate neural activity, including predictive changes, suppression of peri-saccadic retinal input and trans-saccadic integration. Consistent with this idea, modulations of neural activity around the time of saccades have been reported in non-human species, showing non-visually mediated, extraretinal responses in specific brain regions. In humans, however, peri-saccadic whole-brain activity has mainly been studied in the context of a perceptual task, making it difficult to disentangle activity related to the task, visual transients from retinal stimulation and non-visual (saccade-related) responses. We measured magnetoencephalography (MEG) theta (3–7 Hz) and alpha (8–12 Hz) activity during voluntary horizontal saccade execution between two fixation points. To distinguish between visually and non-visually mediated activity, participants engaged in three tasks: voluntary saccades in near-darkness, fixation with visual input shifted to simulate the saccade, and volitional saccades in total darkness. Using correlational analyses, we found that patterns of neural activity are consistent with contributions of two separate mechanisms, one related to saccades (non-visual/extraretinal) and the other linked to the processing of visual input at the beginning of the new fixation (visual/retinal). Changes in occipital alpha power and instantaneous frequency showed a similar time course in near-dark and simulated saccade conditions, suggesting an effect of visually evoked responses. In contrast, alterations in parietal-occipital theta power and phase clustering were consistent with a non-visually-driven (extraretinal) mechanism, with similar multivariate patterns for near-dark and full-darkness conditions. Some effects, such as theta phase reset and alterations in alpha power, showed separable contributions of both the saccade and visual transient, with differing time courses. This combination of visual and non-visual mechanisms may support sensorimotor integration during active vision.

Hubungan Penggunaan Smartphone terhadap Ketajaman Penglihatan

Visual acuity is the ability of a person's eyes to distinguish the shapes and details of objects at a certain distance. Decreased visual acuity is still a health problem in society. A person's visual acuity is influenced by refraction, pupil size, light intensity, exposure time, retinal stimulation area, eye adaptation, and eye movement. The use of smartphones has become a necessity of everyday life in society. Several studies have shown that smartphone use can lead to decreased visual acuity. This study aimed to determine whether there is a relationship between smartphone use and visual acuity and the factors that can affect visual acuity due to smartphone use. The research design used was a literature review with journals that can be accessed free full text through PubMed and ClinicalKey. As a result, the smartphone use can lead to DED, myopia, dan blurred vision. In conclusion, there is a relationship between smartphone use and visual acuityKeywords: smartphone, visual acuity Abstrak: Ketajaman penglihatan adalah kemampuan mata seseorang untuk membedakan bentuk dan detail objek pada jarak tertentu. Penurunan ketajaman penglihatan masih menjadi masalah kesehatan dalam masyarakat. Ketajaman penglihatan seseorang dipengaruhi oleh refraksi, ukuran pupil, intensitas cahaya, waktu pemaparan, area stimulasi retina, adaptasi mata, dan gerakan mata. Penggunaan smartphone sudah menjadi kebutuhan kehidupan sehari-hari dalam masyarakat. Beberapa penelitian menunjukkan bahwa penggunaan smartphone dapat menyebabkan penurunan ketajaman penglihatan. Tujuan penelitian untuk mengetahui apakah terdapat hubungan penggunaan smartphone terhadap ketajaman penglihatan dan faktor-faktor yang dapat mempengaruhi ketajaman penglihatan karena penggunaan smartphone. Desain penelitian yang dipakai adalah literature review dengan jurnal-jurnal yang dapat diakses secara gratis melalui PubMed dan ClinicalKey. Hasilnya menunjukkan bahwa penggunaan smartphone dapat mengakibatkan DED, miopia dan penglihatan kabur. Sebagai simpulan, terdapat hubungan penggunaan smartphone terhadap ketajaman penglihatanKata Kunci: smartphone, ketajaman penglihatan

Photovoltaic retinal prosthesis restores high-resolution responses to single-pixel stimulation in blind retinas

Retinal prostheses hold the promise of restoring vision in totally blind people. However, a decade of clinical trials highlighted quantitative limitations hampering the possibility of reaching this goal. A key challenge in retinal stimulation is to independently activate retinal neurons over a large portion of the subject’s visual field. Reaching such a goal would significantly improve the perception accuracy in retinal implants’ users, along with their spatial cognition, attention, ambient mapping and interaction with the environment. Here we show a wide-field, high-density and high-resolution photovoltaic epiretinal prosthesis for artificial vision (POLYRETINA). The prosthesis embeds 10,498 physically and functionally independent photovoltaic pixels, allowing for wide retinal coverage and high-resolution stimulation. Single-pixel illumination reproducibly induced network-mediated responses from retinal ganglion cells at safe irradiance levels. Furthermore, POLYRETINA allowed response discrimination with a high spatial resolution equivalent to the pixel pitch (120 µm) thanks to the network-mediated stimulation mechanism. This approach could allow mid-peripheral artificial vision in patients with retinitis pigmentosa.