Phosphene Threshold Research Articles

Mapping the routes of perception: Hemispheric asymmetries in signal propagation dynamics.

The visual system has long been considered equivalent across hemispheres. However, an increasing amount of data shows that functional differences may exist in this regard. We therefore tried to characterize the emergence of visual perception and the spatiotemporal dynamics resulting from the stimulation of visual cortices in order to detect possible interhemispheric asymmetries. Eighteen participants were tested. Each of them received 360 transcranial magnetic stimulation (TMS) pulses at phosphene threshold intensity over left and right early visual areas while electroencephalography was being recorded. After each single pulse, participants had to report the presence or absence of a phosphene. Local mean field power analysis of TMS-evoked potentials showed an effect of both site (left vs. right TMS) of stimulation and hemisphere (ipsilateral vs. contralateral to the TMS): while right TMS determined early stronger activations, left TMS determined later stronger activity in contralateral electrodes. The interhemispheric signal propagation index revealed differences in how TMS-evoked activity spreads: left TMS-induced activity diffused contralaterally more than right stimulation. With regard to phosphenes perception, distinct electrophysiological patterns were found to reflect similar perceptual experiences: left TMS-evoked phosphenes are associated with early occipito-parietal and frontal activity followed by late central activity; right TMS-evoked phosphenes determine only late, fronto-central, and parietal activations. Our results show that left and right occipital TMS elicits differential electrophysiological patterns in the brain, both per se and as a function of phosphene perception. These distinct activation patterns may suggest a different role of the two hemispheres in processing visual information and giving rise to perception.

Influence of dark adaptation on the perceptual threshold of electrically evoked phosphenes

Aims/Purpose: Phosphenes are light phenomena in the eye that have been studied since the 18th century. They can be evoked mechanically or by electrostimulation, for example. The perception of phosphenes and their threshold, the limit of phosphene perception, has been the subject of numerous studies. In this work, the dynamics of the threshold shift of electrically evoked phosphenes during dark adaptation is recorded. Statistically it was tested whether the phosphene thresholds differ before and after dark adaptation.Methods: A study was conducted on 16 healthy subjects (7 w, 9 m, 28.5 ± 6.8 yr). Each subject sat approximately 30 cm in front of a black cloth‐covered semi‐circular screen placed on a table. On the table was a signal generator (33250A, Agilent Technologies Inc, Santa Clara, CA, USA) with a rotary control for the subject's own setting of the current intensity for the current stimulation (sinusoidal, 20 Hz) using a transcranial electrical stimulator (DC‐Stimulator PLUS, neuroConn GmbH, Ilmenau, Germany). The electrodes were a ring electrode at one eye and a rectangular electrode at the back of the head. After the subject had been instructed, and the electrodes had been attached, the subject had to set the phosphene threshold in room light conditions (125 cd/sqm) 10 times in succession (baseline B1, bright adapted). Lightproof glasses were then worn. For 40 min, each subject adjusted the threshold at intervals of 2 min. After 40 min, 10 more threshold values were recorded (baseline B2, dark adapted). Means were calculated for each subject for both baselines B1 and B2 and tested for discrimination using the Wilcoxon signed‐rank test.Results: All subjects were able to successfully complete the test. The global thresholds before and after dark adaptation were 132.3 ± 13.8 μA and 329.5 ± 38.0 μA respectively. The difference between the conditions B1 and B2 is significant (p = 0.0002). All measurement curves of the threshold progression show an increasing behaviour with a pronounced plateau after approximately 15 min.Conclusions: We successfully performed a study on the generation of phosphenes during current stimulation. The dynamics of the threshold progression from light to dark adaptation could be recorded. A significant threshold shift is shown for all subjects.

Changes in Thresholds of Electrically Evoked Phosphene and Electrical Lability of the Optic Nerve in the Ground Station Crew in the International Experiment SIRIUS 20/21

In the ground sealed station crew, during the 8 months international experiment SIRIUS 20/21 simulating an interplanetary flight, electrically induced phosphene (EIP) thresholds, which reflected the electrical sensitivity (ES) of the retina, and the optic nerve. ES&L was assessed using the “ESOM” device (“Neuron”, Ufa, Russia) once a month, twice a day (morning/evening), under mesopic conditions. An increase in ES and other patterns of changes in ES&L parameters during period of isolation were established, reflecting the adaptation of the crew to the conditions of the experiment and the reaction of the visual system to physical and psycho-emotional stress. Further study of the thresholds of the EIP and L of the optic nerve in experiments of increasing duration will make it possible to determine the biomarkers that differentiate the individual adaptive reaction of astronauts from dysfunction of the retina and optic nerve under real space flight conditions. The L of the optic nerve showed greater resistance to experimental conditions than the ES of the retina. The results suggest that the determination of the L in the ES&L test can become an express test on board the ISS to assess the functional state of the papillomacular bundle of optic nerve fibers, the risk of developing or diagnosing SANS (flight-associated neuro-ocular syndrome) in long-term space missions.

Continuous and intermittent theta burst stimulation of primary visual cortex do not modulate resting state functional connectivity: A sham-controlled multi-echo fMRI study.

Theta burst stimulation (TBS) is a type of rTMS protocol which has the advantage of a shorter delivery time over traditional rTMS.When applied to motor cortex, intermittent TBS (iTBS) has been shown to yield excitatory aftereffects, whereas continuous TBS (cTBS) may lead to inhibitory aftereffects, both lasting from minutes to hours. The majority of TBS research has targeted motor, frontal, and parietal regions, and to date very few studies have examined its efficacy at visual areas. We designed a sham-controlled study to investigate the immediate poststimulation and short-term (1 h post-stimulation) effects of iTBS and cTBS to V1. Using multiecho functional magnetic resonance imaging, we measured the direct and indirect effects of TBS by comparing resting state functional connectivity (FC) before and after stimulation in whole brain networks, and seeds from V1 (stimulation site) and neighboring occipital and parietal visual networks. In addition, we also measured pre- and post-TBS phosphene thresholds (PTs) to examine the modulatory effects of TBS on cortical excitability. We found no changes in FC for iTBS, cTBS or sham stimulation conditions from baseline to poststimulation timepoints. Additionally, cTBS and iTBS had no effect on visual cortical excitability. Our results indicate that unlike our previous low frequency rTMS to V1 study, which resulted in widespread FC changes up to at least 1 h after stimulation, TBS to V1 does not affect FC.Contrary to the studies showing comparable TBS and rTMS aftereffects in motor and frontal regions,our findings suggest that a single session of cTBS or iTBS to V1 at 80% PT using a standard protocol of 600 pulses may not be effective in targeting FC, especially in clinical settings where therapy for pathological networks is the goal.

Monocular transcorneal electrical stimulation induces ciliary muscle thickening in contralateral eye

Transcorneal electrical stimulation (TES) is used as therapy for retinal diseases such as retinitis pigmentosa (RP) and was suggested for assessing retinal sensitivity by determining phosphene thresholds, subjective luminance impressions caused by retinal stimulation. Further applications concerned the accommodation process, revealing an improved accommodative amplitude in presbyopic eyes after TES treatment. The respective changes of the ciliary muscle (CM), the structure most important for near vision, during TES are yet unknown. In a pilot study, we aimed to assess whether monocular TES leads to morphological and functional CM changes and whether central accommodation control is affected. Ten healthy, near-emmetropic adults participated in the trial (4 females, age 26.3 ± 3.6 years). Using a wavefront and a stimulus generator, a biphasic square-wave stimulus (2 s positive and 6 s negative amplitude) of 0 μA average current was produced and transferred to the eye by means of a Dawson-Trick & Litzkow electrode. Prior to the stimulation, an individual determination of phosphene thresholds served to define individual TES current amplitudes, which ranged between 60 and 100 μA. Optical coherence tomography (OCT) imaging of the right eye's temporal ciliary muscle was performed before and during ipsi- as well as contralateral monocular TES in randomized order in the morning and afternoon of the same day. During imaging, subjects fixated a target at 4 m distance and refraction was simultaneously recorded via eccentric infrared photorefraction. OCT images were assessed using previously published custom-developed software, allowing the definition of selective CM thickness (CMT) readings, and plotting of continuous CMT profiles along the muscle border. CMT profiles revealed that both stimulations, on the ipsi- and contralateral eye, induced a thickening of the CM compared to the non-stimulated state. The selective CMT readings confirmed a significant increase with ipsi- (31 ± 30 μm; p = 0.010) and contralateral (25 ± 16 μm; p = 0.001) TES. However, refraction during far vision was not significantly affected by either stimulation (ipsilateral [n = 5]: median Δw/-w/o = 0 D; contralateral [n = 7]: Δw/-w/o = 0.13 D). Pupil size on average increased during TES, but without reaching significance (ipsilateral [n = 5] median Δw/-w/o = 0.23 mm, contralateral [n = 7] Δw/-w/o = 0.39 mm). Ipsilateral CM thickening could be explained by local changes within the stimulated ciliary muscle, such as increased blood flow or interstitial fluid rise induced by TES. However, the CMT increase in the right eye when TES was performed contralaterally, on the left eye, indicates an involvement of the central control circuit of accommodation. Further possible explanations for this finding are a synchronization of neuronal activities in the visual pathway, the release of vasoactive neuropeptides, or effects on the central blood pressure regulation. Given a neuromodulation effect on the CM function, TES might have implications for children with accommodation insufficiencies and as additional therapy in myopia control management, e.g. in combination with multifocal contact lens treatment. Our study is important for the clinical application of TES, and the outcome might add crucial knowledge to the current understanding of the accommodation process and inform research and treatment of both myopia and presbyopia.

Excitability Changes in Occipital Cortex After Continuous Theta-Burst Stimulation.

Modulation of visual cortical structures by repetitive transcranial magnetic stimulation is rarely observed in literature. In this study; the researchers aimed to investigate the neurophysiological alterations by using continuous theta burst stimulation (cTBS) protocol over the occipital cortex in healthy subjects. Twenty-five (15 female, 10 male) (mean age 29.84±4.7 years) healthy individuals were included in sham and real cTBS occipital stimulation sessions. Before and after each session, neurophysiological studies including phosphene threshold and visual evoked potential (VEP) responses were recorded. The P100 latency values and maximum amplitude values between N75-P100 peaks of 100 responses of 1000 uninterrupted continuous visual stimuli were measured. The VEP habituation and phosphene thresholds were compared in sham and real cTBS sessions. The phosphene threshold values increased to statistically significant levels after the real cTBS session. Visual evoked potential habituation was observed in both sham and real cTBS sessions in individuals without significant differences. Also, no difference between the P100 latencies and N75-P100 amplitude values in the sham and real cTBS sessions was observed. Phosphene threshold measurements demonstrated the modulation of the occipital cortex excitability via cTBS in healthy subjects.

Metabolic long‐term monitoring of transcorneal electrical stimulation in retinitis pigmentosa

AbstractPurpose: Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyse oxygen saturation in retinal vessels and has shown promising short‐term results as a therapy monitoring tool for TES. The aim of our study was to measure the long‐term effects of TES on RO parameters over a period of 3 years (3Y).Methods: A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0–1.5 optic‐disc diameters from the disc margin, in retinal arterioles (A‐SO2) and venules (V‐SO2) were measured and their difference (A‐V SO2) was calculated. In addition, we recorded the diameters in the main arterioles (D‐A) and venules (D‐V). ANOVA‐based linear mixed‐effects models were employed for statistical analysis using SPSS®.Results: After 3Y of TES treatment both the mean A‐SO2 (from 96.35 ± 12.76% to 100.89 ± 5.87%, p = 0.22) and V‐SO2 (from 62.20 ± 11.55% to 64.55 ± 8.24%, p = 0.77) increased slightly. The A‐V SO2, which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance (p = 0.27). TES also did not appear to alter the vascular diameter parameters, D‐A and D‐V (p > 0.05).Conclusions: Our long‐term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow‐up study and to confirm this trend reflecting a possible benefit of TES for RP.

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.

Effect of ambient lighting on frequency dependence in transcranial electrical stimulation-induced phosphenes

Inconsistencies have been found in the relationship between ambient lighting conditions and frequency-dependence in transcranial electric stimulation (tES) induced phosphenes. Using a within-subjects design across lighting condition (dark, mesopic [dim], photopic [bright]) and tES stimulation frequency (10, 13, 16, 18, 20 Hz), this study determined phosphene detection thresholds in 24 subjects receiving tES using an FPz-Cz montage. Minima phosphene thresholds were found at 16 Hz in mesopic, 10 Hz in dark and 20 Hz in photopic lighting conditions, with these thresholds being substantially lower for mesopic than both dark (60% reduction) and photopic (56% reduction), conditions. Further, whereas the phosphene threshold-stimulation frequency relation increased with frequency in the dark and decreased with frequency in the photopic conditions, in the mesopic condition it followed the dark condition relation from 10 to 16 Hz, and photopic condition relation from 16 to 20 Hz. The results clearly demonstrate that ambient lighting is an important factor in the detection of tES-induced phosphenes, and that mesopic conditions are most suitable for obtaining overall phosphene thresholds.

Continuous and intermittent theta burst stimulation to the visual cortex do not alter GABA and glutamate concentrations measured by magnetic resonance spectroscopy.

BackgroundTheta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), uses repeated high‐frequency bursts to non‐invasively modulate neural processes in the brain. An intermittent TBS (iTBS) protocol is generally considered “excitatory,” while continuous TBS (cTBS) is considered “inhibitory.” However, the majority of work that has led to these effects being associated with the respective protocols has been done in the motor cortex, and it is well established that TMS can have variable effects across the brain.Objectives and methodWe investigated the effects of iTBS and cTBS to the primary visual cortex (V1) on composite levels of gamma‐aminobutyric acid + co‐edited macromolecules (GABA+) and glutamate + glutamine (Glx) since these are key inhibitory and excitatory neurotransmitters, respectively. Participants received a single session of cTBS, iTBS, or sham TBS to V1. GABA+ and Glx were quantified in vivo at the stimulation site using spectral‐edited proton magnetic resonance spectroscopy (1H‐MRS) at 3T. Baseline pre‐TBS GABA+ and Glx levels were compared to immediate post‐TBS and 1 h post‐TBS levels.ResultsThere were no significant changes in GABA+ or Glx following either of the TBS conditions. Visual cortical excitability, measured using phosphene thresholds, remained unchanged following both cTBS and iTBS conditions. There was no relationship between excitability thresholds and GABA+ or Glx levels. However, TBS did alter the relationship between GABA+ and Glx for up to 1 h following stimulation.ConclusionsThese findings demonstrate that a single session of TBS to the visual cortex can be used without significant effects on the tonic levels of these key neurotransmitters; and add to our understanding that TBS has differential effects at visual, motor, and frontal cortices.

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.

Transcorneal electrical stimulation reduces the annual rate of visual field decline in retinitis pigmentosa

AbstractPurposeIn retinitis pigmentosa (RP) the visual field area (VFA) declines exponentially. We investigated whether the annual decline rate (ADR) can be slowed by transcorneal electrical stimulation (TcES).MethodsWe conducted an a posteriori analysis of data from 51 adult patients with RP who participated in an interventional, randomized, single‐masked study (clinicaltrials.gov: NCT01837901; Schatz et al., 2017, IOVS 58(1)). Patients were randomized into 3 groups stimulated with 0 mA (sham stimulation), 150% or 200% of their phosphene threshold, respectively. Over one year, TcES was applied monocularly, 30 min per week with biphasic current pulses (OkuStim, 5 ms each phase, 20 Hz, 0.2 to 1.0 mA). VFA were repeatedly assessed in both eyes (Octopus 900, target V4e). VFA values were normalized to percentage of baseline value, transformed into the natural logarithm, averaged within groups, and subjected to a weighted linear regression analysis. ADR was calculated from the slope of best fit line for both eyes in the sham group (n = 20) and in the treated group (n = 31, 150% and 200% groups pooled).ResultsIn the sham group, for the stimulated eyes the ADR was 8.0% (F‐test for slope: p = 0.011) while for the non‐stimulated eyes it was 9.6% (p = 0.005). In the treated group, for the stimulated eyes the ADR was 3.4% (p = 0.276), and for the non‐stimulated eyes it was 7.0% (p = 0.035). The difference between the ADR in the stimulated and non‐stimulated eyes was evident when only eyes stimulated with >0.8 mA (n = 9) were included. The progression in the stimulated eyes had almost stopped, the ADR was 2.7% (p = 0.397) compared to 9.2% (p = 0.022) in the non‐stimulated eyes. The analysis is limited by data variability, sample size and observation period.ConclusionThe analysis showed that the ADR can be markedly slowed by TcES in a dose‐dependent manner. Thus, regular use of TcES is an effective therapeutic method for slowing or arresting disease progression in RP.

Amplitude modulated transcranial alternating current stimulation (AM-TACS) efficacy evaluation via phosphene induction

Amplitude modulated transcranial alternating current stimulation (AM-tACS) is a novel method of electrostimulation which enables the recording of electrophysiological signals during stimulation, thanks to an easier removable stimulation artefact compared to classical electrostimulation methods. To gauge the neuromodulatory potential of AM-tACS, we tested its capacity to induce phosphenes as an indicator of stimulation efficacy. AM-tACS was applied via a two-electrode setup, attached on FpZ and below the right eye. AM-tACS waveforms comprised of different carrier (50 Hz, 200 Hz, 1000 Hz) and modulation frequencies (8 Hz, 16 Hz, 28 Hz) were administered with at maximum 2 mA peak-to-peak stimulation strength. TACS conditions in the same frequencies were used as a benchmark for phosphene induction. AM-tACS conditions using a 50 Hz carrier frequency were able to induce phosphenes, but with no difference in phosphene thresholds between modulation frequencies. AM-tACS using a 200 Hz or 1000 Hz carrier frequency did not induce phosphenes. TACS conditions induced phosphenes in line with previous studies. Stimulation effects of AM-tACS conditions were independent of amplitude modulation and instead relied solely on the carrier frequency. A possible explanation may be that AM-tACS needs higher stimulation intensities for its amplitude modulation to have a neuromodulatory effect.

Metabolic Long-Term Monitoring of Transcorneal Electrical Stimulation in Retinitis Pigmentosa

Introduction: Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyze oxygen saturation in retinal vessels and has shown promising short-term results as a therapy monitoring tool for TES. The aim of our study was to measure the long-term effects of TES on RO parameters over a period of 3 years (3Y). Methods: A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0–1.5 optic-disc diameters from the disc margin, in retinal arterioles (A-SO₂) and venules (V SO₂) were measured and their difference (A-V SO₂) was calculated. In addition, we recorded the diameters in the main arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were employed for statistical analysis using SPSS®. Results: After 3Y of TES treatment both the mean A-SO₂ (from 96.35 ± 12.76% to 100.89 ± 5.87%, p = 0.22) and V SO₂ (from 62.20 ± 11.55% to 64.55 ± 8.24%, p = 0.77) increased slightly. The A-V SO₂, which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance (p = 0.27). TES also did not appear to alter the vascular diameter parameters, D-A and D-V (p > 0.05). Conclusion: Our long-term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow-up study and to confirm this trend reflecting a possible benefit of TES for RP.

Клінічна ефективність комплексного лікування хворих на початкову стадію аксіальної діабетичної оптичної нейропатії

Мета. Вивчення клінічної ефективності комплексного лікування із застосуванням тіоктової кислоти, комбінації вітамінів В1, В6, В12, етилметилгідроксипіридину сукцинату та бримонідину тартрату у хворих на початкову стадію аксіальної діабетичної оптичної нейропатії. Матеріали та методи. Аналіз здійснювався на основі даних спостереження 40 хворих (63 ока) з початковою стадією аксіальної діабетичної оптичної нейропатії. Основну групу становили 20 хворих (33 ока), яким на фоні гіпоглікемічної терапії повторними курсами 2 рази на рік призначали: тіоктову кислоту (берлітіон) по 1 табл. (300 мг) 1 раз на добу впродовж 42 днів; комбінацію вітамінів В1, В6, В12 (мільгама) по 2 мл внутрішньом’язово 1 раз на 3 доби впродовж 21 дня з подальшим переходом на пероральний прийом по 1 табл. 3 рази на день впродовж 21 дня; етилметилгідроксипіридину сукцинат (армадин) по 100 мг внутрішньом’язово впродовж 14 днів, а також місцеве використання бримонідину тартрату 0,2% у вигляді очних крапель по 1–2 краплі 2 рази на день постійно. До контрольної групи увійшли 20 хворих (30 очей), яким проводили тільки гіпоглікемічну терапію. Крім стандартних, методи офтальмологічного дослідження включали електрофізіологічні дослідження та оптичну когерентну томографію сітківки й зорового нерва. Обстеження хворих проводили до лікування, через 1,5, 6, 7,5, 12, 13,5, 18, 19,5, 24 та 25,5 місяця після лікування. Результати. Внаслідок проведених досліджень було виявлено покращення структурно-функціональних характеристик зорового нерва у 72,7 % хворих, що проявлялось більшою (на 43,8 %) гостротою зору, меншим (на 118,9 %) порогом чутливості за фосфеном, меншим (на 37,0 %) показником локального витончення комплексу гангліонарних клітин сітківки, меншою (на 34,8 %) товщиною решітчастої пластинки порівняно з контрольною групою в динаміці спостереження через 25,5 місяця. Висновки. З огляду на отримані результати запропонований спосіб комплексного лікування хворих із початковою стадією аксіальної діабетичної оптичної нейропатії покращує структурно-функціональні характеристики зорового нерва, що обґрунтовує його клінічну ефективність.

Ефективність і доцільність використання нутрицевтиків з ресвератролом у пацієнтів з високою ускладненою міопією

The paper is dedicated to the study of the efficiency of nutraceutical with resveratrol and vitamins and antioxidants of AREDS (Age-Related Eye Disease Studies) formula in patients with high myopia. Seventy-five patients (150 eyes) with high axial myopia (–7.0 to –20.0 diopters) and chorioretinal dystrophy were examined. Group I included 21 patients (42 eyes) who received conservative nootropic and metabolic therapy; group II included 34 patients (68 eyes) who received a nutraceutical containing 60 mg of trans-resveratrol combined with components of AREDS formula, omega-3 fatty acid and vitamin D (Resvega®Forte) at the end of nootropic and metabolic therapy; group III included 20 patients (40 eyes) who did not receive conservative treatment. The effectiveness of treatment was evaluated based on maximal corrected visual acuity (MCVA), phosphene threshold (PT) and the findings of optical coherence tomography of the macula (foveal thickness (FT) and subfoveal choroidal thickness (SCT)) every 6 months before and after treatment. In patients of group II, the MCVA increase during the first year was 29.8% versus baseline (p=0.005), and the achieved therapeutic effect was maintained until the end of the second year of the follow-up period. The patients of group III showed MCVA decrease by 19.1% after 24 months from the start of the follow-up period. Despite the absence of statistical difference in baseline MCVA in all the groups, MCVA in patients of group III was lower than that in patients of group II after 12 months and lower than that in patients of group I (p˂0.0002) after 24 months. There was a 4.7 % increase in FT in patients of group III versus baseline (p˂0.05). The patients of group III showed a 34.4% decrease in SCT versus baseline (p<0.05). Thus, the use of nutraceuticals with resveratrol and antioxidants of AREDS formula in the comprehensive treatment of patients with myopic chorioretinal dystrophies allows to achieve good functional results with stable foveal thickness without signs of myopic choroidal vascularization and preservation of subfoveal choroidal thickness.

Reduced Occipital Cortex Excitability in Amyotrophic Lateral Sclerosis.

In addition to motor cortex involvement, sensory abnormalities have been demonstrated in amyotrophic lateral sclerosis (ALS), including structural and metabolic alterations in the occipital cortex. The aim of this study was to examine occipital excitability changes in ALS. Twenty-one patients with ALS and 16 healthy subjects were enrolled into the study. Phosphene experience and phosphene threshold were studied to assess occipital excitability. Cognitive function was evaluated in both groups by means of Montreal Cognitive Assessment and Addenbrooke's Cognitive Examination-Revised visuospatial score tests. Phosphene was experienced in 13 (81.3%) healthy subjects and 9 (42.9%) patients with ALS ( P = 0.04). The mean phosphene threshold was not significantly different between the two groups. No correlation existed between phosphene threshold and motor cortical excitability parameters, ALS Functional Rating Scale Revised, Montreal Cognitive Assessment, and Addenbrooke's Cognitive Examination-Revised scores. Visual cortex is affected, and the occipital excitability is reduced in ALS, without any relation to motor cortical excitability changes, providing another clue suggestive of sensory involvement in ALS.

Retinal and Cortical Contributions to Phosphenes During Transcranial Electrical Current Stimulation.

It is generally believed that the phosphenes induced by transcranial electric current stimulation (tECS) are a product of retinal activation, even when electrode placement is directly over the primary visual cortex. However, the origins of these tECS-induced phosphenes have not yet been conclusively determined. In this study, phosphene detection thresholds using an FPz-Oz montage were compared with those from (i) an Oz-Cz montage to determine whether prefrontal regions, such as the retina, contribute to phosphenes and (ii) an FPz-Cz montage to determine whether the visual cortex in the occipital lobe contributes to phosphenes. Twenty-two participants received transcranial current stimulation with each of these montages (as well as a T3-T4 montage included for exploratory purposes) at 6, 10, 16, 20, 24, 28, and 32 Hz. To estimate differences in current density at the retina and occipital lobe across montages, modeling of current density at phosphene thresholds was measured across 20 head models. Consistent with the proposal that tECS-induced phosphenes are generated in the retina, increasing current density near the retina (FPz-Oz relative to Oz-Cz montage) reduced phosphene thresholds. However, increasing current density near the occipital cortex (FPz-Oz relative to FPz-Cz montage) also reduced phosphene thresholds while also requiring less current density at the retina according to the modeling estimates. This suggests that tECS of this occipital cortex also contributed to phosphene perception. © 2020 Bioelectromagnetics Society.

Evaluating Current Density Modeling of Non-Invasive Eye and Brain Electrical Stimulation Using Phosphene Thresholds.

Because current flow cannot be measured directly in the intact retina or brain, current density distribution models were developed to estimate it during magnetic or electrical stimulation. A paradigm is now needed to evaluate if current flow modeling can be related to physiologically meaningful signs of true current distribution in the human brain. We used phosphene threshold measurements (PTs) as surrogate markers of current-flow to determine if PTs, evoked by transcranial alternating current stimulation (tACS), can be matched with current density estimates generated by head model-based computer simulations. Healthy, male subjects (n=15) were subjected to three-staged PT measurements comparing six unilateral and one bilateral stimulation electrode montages according to the 10/20 system: Fp2-Suborbital right (So), Fp2-right shoulder (rS), Fp2-Cz, Fp2- O2, So-rS, Cz-F8 and F7-F8. The stimulation frequency was set at 16 Hz. Subjects were asked to report the appearance and localization of phosphenes in their visual field for every montage. Current density models were built using multi-modal imaging data of a standard brain, meshed with isotropic conductivities of different tissues of the head using the SimBio and SCIRun software packages. We observed that lower PTs were associated with higher simulated current levels in the unilateral montages of the model head, and shorter electrode distances to the eye had lower PTs. The lowest mean PT and the lowest variability were found in the F7-F8 montage (95±33 μA). Our results confirm the hypothesis that phosphenes are primarily of retinal origin, and they provide the first in vivo evidence that computer models of current flow using head models are a valid tool to estimate real current flow in the human eye and brain.

Nonlinear interaction between stimulation intensity and initial brain state: Evidence for the facilitatory/suppressive range model of online TMS effects

The effects of online Transcranial Magnetic Stimulation (TMS) can qualitatively vary as a function of brain state. For example, TMS intensities which normally impair performance can have a facilitatory effect if the targeted neuronal representations are in a suppressed state. These phenomena have been explained in terms of the existence of distinct facilitatory and suppressive ranges as a function of TMS intensity which are shifted by changes in neural excitability. We tested this model by applying TMS at a low (60 % of phosphene threshold) or high (120 % of phosphene threshold) intensity during a priming paradigm. Our results show that state-dependent TMS effects vary qualitatively as a function of TMS intensity. Whereas the application of TMS at 120 % of participants’ phosphene threshold impaired performance on fully congruent trials (in effect, reducing the benefit of priming), TMS applied at a lower intensity (60 % of phosphene threshold), facilitated performance on congruent trials. These results demonstrate that behavioral effects of TMS reflect a nonlinear interaction between initial activation state and TMS intensity. They also provide support for the existence of facilitatory/suppressive ranges of TMS effects which shift when neural excitability changes.