Retinal Phosphenes Research Articles

Amplitude modulating frequency overrides carrier frequency in tACS-induced phosphene percept.

The amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM-tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects (four females, aged from 20-44 years old) under tACS that paired carrier waves (10, 14, 18, 22 Hz) with different envelope conditions (0, 2, 4Hz) over the mid-occipital and left facial areas. We also examined the phosphene source by adopting a high-density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM-tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM-tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper-left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near-eye electrodermal activity (EDA) measured under the threshold-level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM-tACS-induced phosphene.

Magneto- and electrophosphene thresholds in the retina: a dosimetry modeling study

Objective. Sensations of flickering light produced by time-varying magnetic fields or electric currents are called magneto- or electrophosphenes. Phosphene thresholds have been used in international guidelines and standards as an estimate of the thresholds of exposure that produce effects in the central nervous system (CNS). However, the estimated threshold values have a large range of uncertainty. Approach. Phosphene thresholds were approximated by simulating five phosphene threshold experiments. Retinal electric fields and currents induced by electric and magnetic stimulation were calculated using the finite element method and 14 anatomically realistic computational models of human heads. Main results. The radial component of retinal current density was determined to be in the range of 6.0–20.6 mA m−2. This study produces more accurate estimates for threshold current density in the retina using detailed anatomical models and the estimates had a reduced range of uncertainty compared to earlier studies. Significance. The results are useful for studying the mechanisms of retinal phosphenes and for the development of exposure limits for the CNS.

P189 Transcranial modulation of visually induced gamma power: a concurrent TACS-MEG study

Introduction Alpha oscillations (8–12 Hz) are proposed to mediate ‘attentional gating’ by suppressing neuronal processing in task-irrelevant sensory regions, reflected by ‘pulsed-inhibition’ of stimulus-induced gamma-band activity (40–100 Hz). Concurrent TACS-MEG has the potential to reveal TACS entrainment of alpha oscillations at the stimulation site and thus their causal impact on neuronal activity representing stimulus processing. Objectives We aimed to provide evidence that TACS can entrain the phase of alpha oscillations in the visual cortex by assessing its modulatory impact on the power of visual stimulus-induced gamma oscillations via simultaneous MEG recordings. Materials & methods TACS was applied during MEG in intermingled 5.4s trials either in Oz-Cz or FPz-Cz montage. Montage and stimulation frequency were randomized across trials, applying either individual alpha frequency (IAF), IAF−4 Hz, IAF+4 Hz, or no stimulation, resulting in a 2 (Montage) × 3 (Frequency) design plus a ‘NoStim’ condition. Stimulation intensity for both montages was adjusted separately to 95% retinal phosphene threshold. Participants performed a simple visual detection task, attending an inward moving grating, known to induce strong occipital gamma responses. TACS artifacts were reduced via regression methods, LCMV beamformer time-course extraction from the visual cortex, and high-pass filtering. Importantly, the gamma frequency of interest (∼50–60 Hz) was largely unaffected by TACS artifacts. We compared TACS-to-gamma phase-power coupling (PAC) for the respective experimental conditions. Results We found a rhythmic modulation of stimulus-induced gamma power by TACS at IAF (i.e., TACS-gamma phase-amplitude coupling) for the Oz-Cz montage, but not for the FPz-Cz montage which was introduced to control for subthreshold retinal entrainment effects. Conclusion Our findings (i) demonstrate that concurrent TACS-MEG can principally be used to study cross-frequency-coupling between transcranially entrained slower and spontaneous or stimulus-related faster oscillations, (ii) cannot merely result from subthreshold retinal entrainment, and (iii) suggest that alpha oscillations are indeed a possible means for top-down suppression of bottom-up sensory processing.

Cutaneous retinal activation and neural entrainment in transcranial alternating current stimulation: A systematic review

Transcranial alternating current stimulation (tACS) applies exogenous oscillatory electric field potentials to entrain neural rhythms and is used to investigate brain-function relationships and its potential to enhance perceptual and cognitive performance. However, due to current spread tACS can cause cutaneous activation of the retina and phosphenes. Several lines of evidence suggest that retinal phosphenes are capable of inducing neural entrainment, making the contributions of central and peripheral stimulation to the effects in the brain difficult to disentangle. In this literature review, the importance of this issue is further illustrated by the fact that photic stimulation can have a direct impact on perceptual and cognitive performance. This leaves open the possibility that peripheral photic stimulation can at least in part explain the central effects that are attributed to tACS. The extent to which phosphene perception contributes to the effects of exogenous oscillatory electric fields in the brain and influence perception and cognitive performance needs to be examined to understand the working mechanisms of tACS in neurophysiology and behaviour.

Computational analysis shows why transcranial alternating current stimulation induces retinal phosphenes

Objective. Transcranial alternating current stimulation (tACS), which is a novel technique for the manipulation of cortical oscillations, can generate subjective visual sensations (phosphenes). In this work, we computationally investigate the current that reaches the eyes from tACS electrodes in order to show that phosphenes induced by tACS are retinal in origin. Approach. The finite-element method is used for modelling the path of the current in an anatomically realistic model of the head for various electrode montages. The computational results are used for analysing previous experimental data to investigate the sensitivity of the eye to electrical stimulation. Main results. Depending on the locations of both the stimulating and reference electrodes, a small portion of the stimulation current chooses a path that goes through the eyes. Due to the sensitivity of the retina to electrical stimulation, even distant electrodes can produce a sufficiently strong current at the eyes for inducing retinal phosphenes. Significance. The interference from retinal phosphenes needs to be considered in the design of tACS experiments. The occurrence of phosphenes can be reduced by optimizing the locations of the electrodes, or potentially increasing the number of reference electrodes to two or more. Computational modelling is an effective tool for guiding the electrode positioning.

Transcranial alternating current stimulation (tACS)

Transcranial alternating current stimulation (tACS) seems likely to open a new era of the field of noninvasive electrical stimulation of the human brain by directly interfering with cortical rhythms. It is expected to synchronize (by one single resonance frequency) or desynchronize (e.g., by the application of several frequencies) cortical oscillations. If applied long enough it may cause neuroplastic effects. In the theta range it may improve cognition when applied in phase. Alpha rhythms could improve motor performance, whereas beta intrusion may deteriorate them. TACS with both alpha and beta frequencies has a high likelihood to induce retinal phosphenes. Gamma intrusion can possibly interfere with attention. Stimulation in the “ripple” range induces intensity dependent inhibition or excitation in the motor cortex (M1) most likely by entrainment of neuronal networks, whereas stimulation in the low kHz range induces excitation by neuronal membrane interference. TACS in the 200 kHz range may have a potential in oncology.

Biophysical visual virtual reality in retinotopic visual areas

AbstractPreviously, we have pointed out that biophoton production can be a controlled process that originates from regulated redox/radical reactions. Our biophoton experiments support the notion that various visual related phenomena such as discrete retinal noise, retinal phosphenes as well as negative afterimages are due to biophotons. We have also suggested a new model, stating that the brain is able to create biophysical pictures in retinotopic visual areas via redox regulated biophotons of synchronized neurons. According to our interpretation, visualization (imagery) is a special kind of representation i.e., visual imagery requires peculiar inherent biophysical processes. Our idea of biophysical visual virtual reality in retinotopic areas may be a possible biophysical basis of Kosslyn's reality simulation principle in the case of visual imagery. Long-term visual memories are not stored as biophysical pictures but as epigenetic codes. During visual imagery, top-down processes control the epigenetic encoded long-term visual information. Then, according to retrieved epigenetic information, synchronized retinotopic neurons generate dynamic patterns of biophotons via redox reactions that can produce biophysical pictures. We have also presented an iterative model involving a biophysical picture-representation without homunculus during visual imagery.

Spontaneous and visible light-induced ultraweak photon emission from rat eyes

Here, we present the first experimental in vitro evidence of the existence of spontaneous and visible light-induced ultraweak photon emission from freshly isolated whole eye, lens, vitreous humor, and retina samples from rats. These results suggest that the photochemical source of retinal discrete noise, as well as retinal phosphenes, may originate from natural bioluminescent photons within the eyes. During normal vision, the eyes are continuously exposed to ambient powerful photons that pass through various parts of the eyes, which can produce ultraweak delayed bioluminescent photons that arise from diverse parts of the eyes. Although the importance and possible role of ambient light-induced permanent delayed photons (within different parts of the eyes) during vision requires further investigation, our study may provide evidence of an origin of discrete dark noise and retinal phosphenes.

Retinal phosphenes and discrete dark noises in rods: A new biophysical framework

Spontaneous rhodopsin activation produces discrete noises indistinguishable from single-photon responses. However, there is a serious discrepancy between the apparent energy barrier of thermal events compared with that of the photon-driven process. Current estimates of the activation energies of discrete dark noises in vertebrate rod and cone pigments are ∼40–50 kcal/mol for activation by photon and ∼20–25 kcal/mol for activation by heat. To reconcile this discrepancy, it was assumed that thermal activation and photon activation of rhodopsin follow different molecular mechanisms. The most convincing hypothesis for a separate low-energy thermal pathway is that the discrete dark noises of rods arise in a small subpopulation of rhodopsins, where the Schiff base linking the chromophore to the protein part has been deprotonated. According to Narici et al.’ experiments (2009, Radiation Measurements), phosphene perception in space travel is due to the ionizing radiation-induced free radicals that generate chemiluminescent photons from lipid peroxidation. These photons are absorbed by the photoreceptors chromophores, which modify the rhodopsin molecules (bleaching) and start the photo-transduction cascade resulting in the perception of phosphenes. Here, we point out that not only retinal phosphenes but also the discrete dark noise of rods can be due to the natural redox related (free radical) bioluminescent photons in the retina. In other words, under regulated conditions, lipid peroxidation is a natural process in cells and also in retinal membranes. Since the natural lipid peroxidation is one of the main sources of bioluminescent photons and the photoreceptors have the highest oxygen demand and polyunsaturated fatty acid (PUFA) concentration, there is a continuous, low level bioluminescent photon emission in the retina without any external photonic stimulation. During photopic or scotopic vision, evanescent bioluminescent photon emission is negligible. In contrast, in dark-adapted retinal cells this evanescent bioluminescent photon emission is not negligible. Therefore, our hypothesis is that the discrete dark noise of rods can be due to these bioluminescent photons.

Retina or visual cortex? The site of phosphene induction by transcranial alternating current stimulation

Retina or visual cortex? The site of phosphene induction by transcranial alternating current stimulation

Extremely low frequency (ELF) electric and magnetic field exposure limits: Rationale for basic restrictions used in the development of an Australian standard

There are large disparities between basic restrictions for exposure to extremely low-frequency (0-3 kHz) Electric and Magnetic Fields set by two major international bodies. Both bodies agree that these basic restrictions should prevent neuro-stimulatory effects: the retinal phosphene at frequencies up to a few hundred Hertz and peripheral nervous stimulation (PNS) at higher frequencies. The disparity arises from differences in estimated thresholds and frequency dependence, and whether restrictions should be of tissue induced current density or electric field. This paper argues that the latter metric more directly relates to neurostimulatory processes. By analysing available literature, a threshold for retinal phosphenes occurrence is found to be 56 mV/m (95% Confidence Interval 2-1330 mV/m), with a characteristic frequency of 20 Hz. Similarly, the smallest PNS sensation threshold is identified at 2 V/m (characteristic frequency above 3 kHz). In the case of the former, the large range of uncertainty suggests a 'power of ten' value of 100 mV/m. For the latter, because of the small margin between sensation and pain threshold, and because of the large individual variation, the smallest estimate of sensation threshold (2 V/m) represents a basic restriction with precaution incorporated.