Artificial sharp-wave-ripples to support memory and counter neurodegeneration.

Information processed in our sensory neocortical areas is transported to the hippocampus during memory encoding, and between hippocampus and neocortex during memory consolidation, and retrieval. Short bursts of high-frequency oscillations, so called sharp-wave-ripples, have been proposed as a potential mechanism for this information transfer: They can synchronize neural activity to support the formation of local neural networks to store information, and between distant cortical sites to act as a bridge to transfer information between sensory cortical areas and hippocampus. In neurodegenerative diseases like Alzheimer's Disease, different neuropathological processes impair normal neural functioning and neural synchronization as well as sharp-wave-ripples, which impairs consolidation and retrieval of information, and compromises memory. Here, we formulate a new hypothesis, that artificially inducing sharp-wave-ripples with noninvasive high-frequency visual stimulation could potentially support memory functioning, as well as target the neuropathological processes underlying neurodegenerative diseases. We also outline key challenges for empirical tests of the hypothesis.

Increased ocular dopamine levels in rabbits after blue light stimulation of the optic nerve head.

The purpose was to quantify ocular dopamine in rabbits after stimulation of the optic nerve head with short-wavelength (blue) light to activate melanopsin expressed in the axons of intrinsically photosensitive retinal ganglion cells (ipRGCs). Dopamine levels in tears, aqueous humor, vitreous body, and retina (including choroid) were quantified after blue light stimulation of the optic nerve head of 15 rabbits with an optical fiber for 1 min, 10 min, or no stimulation (n = 5, each group). The left eye of all rabbits was operated on to introduce the optical fiber and stimulate the optic nerve, while the contralateral eye served as internal control. One minute of blue light stimulation significantly increased dopamine concentration in the vitreous body of the treated eyes compared to the contralateral ones (P = 0.015). Stimulation for 10 min significantly increased dopamine concentration in the vitreous body, as well as the aqueous humor (P < 0.05). Therefore, using an optical fiber approach to stimulate the optic nerve head with blue light significantly increased dopamine concentration in the aqueous humor and the vitreous body. This likely reflects an upregulation of retinal dopamine synthesis that could be attributed to ipRGC activation. However, the data provided in this study fell short of establishing a definitive link between dopamine release and ipRGC activation, mainly due to the lack of evidence supporting the expression of the melanopsin photopigment in the optic nerve.

Blue-light stimulation of the blind-spot constricts the pupil and enhances contrast sensitivity.

Short- and long-wavelength light can alter pupillary responses differently, allowing inferences to be made about the contribution of different photoreceptors on pupillary constriction. In addition to classical retinal photoreceptors, the pupillary light response is formed by the activity of melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC). It has been shown in rodents that melanopsin is expressed in the axons of ipRGCs that bundle at the optic nerve head, which forms the perceptual blind-spot. Hence, the first aim of this study was to investigate if blind-spot stimulation induces a pupillary response. The second aim was to investigate the effect of blind-spot stimulation by using the contrast sensitivity tests. Fifteen individuals participated in the pupil response experiment and thirty-two individuals in the contrast sensitivity experiment. The pupillary change was quantified using the post-illumination pupil response (PIPR) amplitudes after blue-light (experimental condition) and red-light (control condition) pulses in the time window between 2 s and 6 s post-illumination. The contrast sensitivity was assessed using two different tests: the Freiburg Visual Acuity Test and Contrast Test and the Tuebingen Contrast Sensitivity Test, respectively. Contrast sensitivity was measured before and 20 minutes after binocular blue-light stimulation of the blind-spot at spatial frequencies higher than or equal to 3 cycles per degree (cpd) and at spatial frequencies lower than 3 cpd (control condition). Blue-light blind-spot stimulation induced a significantly larger PIPR compared to red-light, confirming a melanopsin-mediated pupil-response in the blind-spot. Furthermore, contrast sensitivity was increased after blind-spot stimulation, confirmed by both contrast sensitivity tests. Only spatial frequencies of at least 3 cpd were enhanced. This study demonstrates that stimulating the blind-spot with blue-light constricts the pupil and increases the contrast sensitivity at higher spatial frequencies.

A review of the current state of research on artificial blue light safety as it applies to digital devices.

Light is necessary for human health and well-being. As we spend more time indoors, we are being increasingly exposed to artificial light. The development of artificial lighting has allowed us to control the brightness, colour, and timing of our light exposure. Yet, the widespread use of artificial light has raised concerns about the impact of altering our light environment on our health. The widespread adoption of personal digital devices over the past decade has exposed us to yet another source of artificial light. We spend a significant amount of time using digital devices with light-emitting screens, including smartphones and tablets, at close range. The light emitted from these devices, while appearing white, has an emission spectrum with a peak in the blue range. Blue light is often characterised as hazardous as its photon energy is higher than that of other wavelengths of visible light. Under certain conditions, visible blue light can cause harm to the retina and other ocular structures. Blue light can also influence the circadian rhythm and processes mediated by melanopsin-expressing intrinsically photosensitive retinal ganglion cells. While the blue component of sunlight is necessary for various physiological processes, whether the low-illuminance artificial blue light emitted from digital devices presents a risk to our health remains an ongoing area of debate. As technological advancements continue, it is relevant to understand how new devices may influence our well-being. This review examines the existing research on artificial blue light safety and the eye, visual performance, and circadian functions.

Increase in b-wave amplitude after light stimulation of the blind spot is positively correlated with the axial length of myopic individuals.

Altered retinal dopamine and ON-pathway activity may underlie myopia development. It has been shown that the stimulation of the blind spot with short-wavelength light increases the electroretinogram (ERG) b-wave amplitude of myopic eyes and may engage the retinal dopaminergic system. This study evaluated the impact of various durations of blind spot stimulation on the electrophysiological response of the myopic retina and their relationship to axial length. Six myopic individuals underwent three short-wavelength blue light blind spot stimulation protocols (10 s, 1 min, 10 min) using a virtual reality headset. As a control condition, no stimulation was shown for 1 min. The b-wave amplitude of the photopic full-field ERG was measured at baseline and 10, 20, 30, 40, 50, and 60 min after each condition. A significant increase in b-wave amplitude was observed for all stimulation protocols compared to the control. The peak b-wave amplitude was observed 20 min after the 1-min stimulation protocol and 60 min after the 10-min stimulation protocol. A significant positive correlation was found between axial length of the eye and percent change in b-wave amplitude for the 10-min stimulation protocol. A rapid and a delayed b-wave time course responses were observed following 1 min and 10 min of blind spot stimulation, respectively. Overall, these results indicate that light stimulation of the blind spot for various durations elevates ON-bipolar cell activity in the retina and as such is assumed to reduce the myopic response. These findings could have implications for future myopia treatment.

Blue light blind-spot stimulation upregulates b-wave and pattern ERG activity in myopes.

Upregulation of retinal dopaminergic activity may be a target treatment for myopia progression. This study aimed to explore the viability of inducing changes in retinal electrical activity with short-wavelength light targeting melanopsin-expressing retinal ganglion cells (ipRGCs) passing through the optic nerve head. Fifteen healthy non-myopic or myopic young adults were recruited and underwent stimulation with blue light using a virtual reality headset device. Amplitudes and implicit times from photopic 3.0 b-wave and pattern electroretinogram (PERG) were measured at baseline and 10 and 20 min after stimulation. Relative changes were compared between non-myopes and myopes. The ERG b-wave amplitude was significantly larger 20 min after blind-spot stimulation compared to baseline (p < 0.001) and 10 min (p < 0.001) post-stimulation. PERG amplitude P50-N95 also showed a significant main effect for 'Time after stimulation' (p < 0.050). Implicit times showed no differences following blind-spot stimulation. PERG and b-wave changes after blind-spot stimulation were stronger in myopes than non-myopes. It is possible to induce significant changes in retinal electrical activity by stimulating ipRGCs axons at the optic nerve head with blue light. The results suggest that the changes in retinal electrical activity are located at the inner plexiform layer and are likely to involve the dopaminergic system.

Responses of Neurons in Lateral Intraparietal Area Depend on Stimulus-Associated Reward During Binocular Flash Suppression.

Discovering neural correlates of subjective perception and dissociating them from sensory input has fascinated neuroscientists for a long time. Bistable and multistable perception phenomena have exhibited great experimental potential to address this question. Here, we performed electrophysiological recordings from single neurons in lateral intraparietal area (LIP) of rhesus macaques during stimulus and perceptual transitions induced by binocular flash suppression (BFS). LIP neurons demonstrated transient bursts of activity after stimulus presentation and stimulus or perceptual switches but only a minority of cells demonstrated stimulus and perceptual selectivity. To enhance LIP neural selectivity, we performed a second experiment in which the competing stimuli were associated with asymmetric rewards. We found that transient and sustained activities substantially increased while the proportion of stimulus selective neurons remained approximately the same, albeit with increased selectivity magnitude. In addition, we observed mild increases in the proportion of perceptually selective neurons which also showed increase magnitude of selectivity. Importantly, the increased selectivity of cells after the reward manipulation was not directly reflecting the reward size per se but an enhancement in stimulus differentiation. Based on our results, we conjecture that LIP contributes to perceptual transitions and serves a modulatory role in perceptual selection taking into account the stimulus behavioral value.

Non-intrusive practitioner pupil detection for unmodified microscope oculars.

Modern microsurgery is a long and complex task requiring the surgeon to handle multiple microscope controls while performing the surgery. Eye tracking provides an additional means of interaction for the surgeon that could be used to alleviate this situation, diminishing surgeon fatigue and surgery time, thus decreasing risks of infection and human error. In this paper, we introduce a novel algorithm for pupil detection tailored for eye images acquired through an unmodified microscope ocular. The proposed approach, the Hough transform, and six state-of-the-art pupil detection algorithms were evaluated on over 4000 hand-labeled images acquired from a digital operating microscope with a non-intrusive monitoring system for the surgeon eyes integrated. Our results show that the proposed method reaches detection rates up to 71% for an error of ≈3% w.r.t the input image diagonal; none of the state-of-the-art pupil detection algorithms performed satisfactorily. The algorithm and hand-labeled data set can be downloaded at:: www.ti.uni-tuebingen.de/perception.

Binocular flash suppression in the primary visual cortex of anesthetized and awake macaques.

Primary visual cortex (V1) was implicated as an important candidate for the site of perceptual suppression in numerous psychophysical and imaging studies. However, neurophysiological results in awake monkeys provided evidence for competition mainly between neurons in areas beyond V1. In particular, only a moderate percentage of neurons in V1 were found to modulate in parallel with perception with magnitude substantially smaller than the physical preference of these neurons. It is yet unclear whether these small modulations are rooted from local circuits in V1 or influenced by higher cognitive states. To address this question we recorded multi-unit spiking activity and local field potentials in area V1 of awake and anesthetized macaque monkeys during the paradigm of binocular flash suppression. We found that a small but significant modulation was present in both the anesthetized and awake states during the flash suppression presentation. Furthermore, the relative amplitudes of the perceptual modulations were not significantly different in the two states. We suggest that these early effects of perceptual suppression might occur locally in V1, in prior processing stages or within early visual cortical areas in the absence of top-down feedback from higher cognitive stages that are suppressed under anesthesia.