Phosphene Generation Research Articles

A Phosphenotron Device for Sensoric Spatial Resolution of Phosphenes within the Visual Field Using Non-Invasive Transcranial Alternating Current Stimulation.

This study presents phosphenotron, a device for enhancing the sensory spatial resolution of phosphenes in the visual field (VF). The phosphenotron employs a non-invasive transcranial alternating current stimulation (NITACS) to modulate brain activity by applying weak electrical currents to the scalp or face. NITACS's unique application induces phosphenes, a phenomenon where light is perceived without external stimuli. Unlike previous invasive methods, NITACS offers a non-invasive approach to create these effects. The study focused on assessing the spatial resolution of NITACS-induced phosphenes, crucial for advancements in visual aid technology and neuroscience. Eight participants were subjected to NITACS using a novel electrode arrangement around the eye orbits. Results showed that NITACS could generate spatially defined phosphene patterns in the VF, varying among individuals but consistently appearing within their VF and remaining stable through multiple stimulations. The study established optimal parameters for vibrant phosphene induction without discomfort and identified electrode positions that altered phosphene locations within different VF regions. Receiver Operating characteristics analysis indicated a specificity of 70.7%, sensitivity of 73.9%, and a control trial accuracy of 98.4%. These findings suggest that NITACS is a promising, reliable method for non-invasive visual perception modulation through phosphene generation.

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.

Prediction of phosphenes occurrence in patients undergoing photon irradiation to ocular structures due to brain tumor.

Phosphenes are visual light phenomena that are experienced when there is no apparent light that stimulates the eye. In oncology, phosphenes are also present during radiation therapy for patients with tumors of the central nervous system, eyes, head and neck. Due to the discomfort of patients treated with irradiation to the head regions, research is conducted to determine whether the dose to the ocular structures is predictive for the occurrence of phosphenes. The objective was to demonstrate the relationship between the doses of the retina and vitreous humour with the appearance of phosphenes. A descriptive study was carried out in a prospective cohort in 25 patients older than 18 years, with malignant tumours located at the level of the brain, both of primary and secondary origin, subjected to irradiation in 6 MV linear accelerators, during February 2020 to January 2021. As independent variables: Retinal dose and vitreous humour dose, and as dependent variables: Light flashes and stable light. Logistic regression analysis was used for prediction, using the SPSS statistical program (version 26.0). A final date of 380 external radiotherapy treatments. The presence of any of the events in a prevalence of 58.7% of the total of fractions. The distribution for the presence of both events, flash of light and stable light, was 69.1%, 20.6% and 10.3% respectively. In the logistic regression analysis, for the light flare, only the dose factor in vitreous was significant (OR: 1.74, IC [1.059-2.419] p: 0.001). For stable light, the dose in the retina (OR: 1.73, IC [1.121-2.341] p: 0.005), and dose in the vitreous humor (OR: 1.82, IC [1.335-2.315] p: 0.003). There is a predictive relationship between the doses of irradiation of the retina and vitreous humour, for the generation of phosphenes. These results help radiotherapy centres take these anatomical structures into account to reduce the presence of phosphenes in patients. Likewise, it would help to reduce phosphenes, keeping the bunker area illuminated during the treatment.

End-to-end optimization of prosthetic vision.

Neural prosthetics may provide a promising solution to restore visual perception in some forms of blindness. The restored prosthetic percept is rudimentary compared to normal vision and can be optimized with a variety of image preprocessing techniques to maximize relevant information transfer. Extracting the most useful features from a visual scene is a nontrivial task and optimal preprocessing choices strongly depend on the context. Despite rapid advancements in deep learning, research currently faces a difficult challenge in finding a general and automated preprocessing strategy that can be tailored to specific tasks or user requirements. In this paper, we present a novel deep learning approach that explicitly addresses this issue by optimizing the entire process of phosphene generation in an end-to-end fashion. The proposed model is based on a deep auto-encoder architecture and includes a highly adjustable simulation module of prosthetic vision. In computational validation experiments, we show that such an approach is able to automatically find a task-specific stimulation protocol. The results of these proof-of-principle experiments illustrate the potential of end-to-end optimization for prosthetic vision. The presented approach is highly modular and our approach could be extended to automated dynamic optimization of prosthetic vision for everyday tasks, given any specific constraints, accommodating individual requirements of the end-user.

Predicción de ocurrencia de fosfenos en pacientes sometidos a irradiación con fotones a estructuras oculares por tumor cerebral

Background and objectivePhosphenes are visual light phenomena that are experienced when there is no apparent light that stimulates the eye. In oncology, phosphenes are also present during radiation therapy for patients with tumors of the central nervous system, eyes, head and neck. Due to the discomfort of patients treated with irradiation to the head regions, research is conducted to determine whether the dose to the ocular structures is predictive for the occurrence of phosphenes. The objective was to demonstrate the relationship between the doses of the retina and vitreous humor with the appearance of phosphenes. Material and methodA descriptive study was carried out in a prospective cohort in 25 patients older than 18 years, with malignant tumors located at the level of the brain, both of primary and secondary origin, subjected to irradiation in 6MV linear accelerators, during February 2020 to January 2021. As independent variables: Retinal dose and vitreous humor dose, and as dependent variables: Light flashes and stable light. Logistic regression analysis was used for prediction, using the SPSS statistical program (version 26.0). ResultA final date of 380 external radiotherapy treatments. The presence of any of the events in a prevalence of 58.7% of the total of fractions. The distribution for the presence of both events, flash of light and stable light, was 69.1%, 20.6% and 10.3% respectively. In the logistic regression analysis, for the light flare, only the dose factor in vitreous was significant (OR: 1.74; 95% CI: 1.059-2.419; p: 0.001). For stable light, the dose in the retina (OR: 1.73; 95% CI: 1.121-2.341; p: 0.005), and dose in the vitreous humor (OR: 1.82; 95% CI: 1.335-2.315; p: 0.003). ConclusionsThere is a predictive relationship between the doses of irradiation of the retina and vitreous humor, for the generation of phosphenes. These results help radiotherapy centers take these anatomical structures into account to reduce the presence of phosphenes in patients. Likewise, it would help to reduce phosphenes, keeping the bunker area illuminated during the treatment.

Parametric study of transcranial alternating current stimulation for brain alpha power modulation.

Transcranial alternating current stimulation, a non-invasive brain stimulation technique, has been used to increase alpha (8–12 Hz) power, the latter being associated with various brain functions and states. Heterogeneity among stimulation parameters across studies makes it difficult to implement reliable transcranial alternating current stimulation protocols, explaining the absence of consensus on optimal stimulation parameters to modulate the alpha rhythm. This project documents the differential impact of controlling for key transcranial alternating current stimulation parameters, namely the intensity, the frequency and the stimulation site (anterior versus posterior). Phase 1:20 healthy participants underwent 4 different stimulation conditions. In each experimental condition, stimulation via 2 electrodes was delivered for 20 min. Stimulation conditions were administered at PO7-PO8 or F3-F4 at individual’s alpha frequency, or at individual’s theta frequency or sham. Stimulation intensity was set according to each participant’s comfort following a standardized unpleasantness scale (≤ 40 out of 100) and could not exceed 6 mA. All conditions were counterbalanced. Phase 2: participants who tolerated higher intensity of stimulation (4–6 mA) underwent alpha-frequency stimulation applied over PO7–PO8 at 1 mA to investigate within-subject modulation of stimulation response according to stimulation intensity. Whether set over posterior or anterior cortical sites, alpha-frequency stimulation showed greater increase in alpha power relative to stimulation at theta frequency and sham stimulation. Posterior alpha-frequency stimulation showed a greater increase in alpha power relative to the adjacent frequency bands over frontal and occipito-parietal brain areas. Low intensity (1 mA) posterior alpha stimulation showed a similar increase in alpha power than at high (4–6 mA) intensity when measured immediately after stimulation. However, when tested at 60 min or 120 min, low intensity stimulation was associated with significantly superior alpha power increase relative to high intensity stimulation. This study shows that posterior individual’s alpha frequency stimulation at higher intensities is well tolerated but fails to increase stimulation aftereffects recorded within 2 h of stimulation on brain oscillations of the corresponding frequency band. In sharp contrast, stimulating at 1 mA (regardless of phosphene generation or sensory perception) effectively and selectively modulates alpha power within that 2-h time window, thus validating that it as a reliable stimulus intensity for future studies. This study also shows that posterior alpha-frequency stimulation preferentially modulates endogenous brain oscillations of the corresponding frequency band. Moreover, our data suggest that posterior alpha-frequency transcranial alternating current stimulation is a reliable and precise non-invasive brain stimulation technique for persistent modulation of both frontal and occipito-parietal alpha power.

Methods to Compare Predicted and Observed Phosphene Experience in tACS Subjects.

Background Phosphene generation is an objective physical measure of potential transcranial alternating current stimulation (tACS) biological side effects. Interpretations from phosphene analysis can serve as a first step in understanding underlying mechanisms of tACS in healthy human subjects and assist validation of computational models. Objective/Hypothesis This preliminary study introduces and tests methods to analyze predicted phosphene occurrence using computational head models constructed from tACS recipients against verbal testimonies of phosphene sensations. Predicted current densities in the eyes and the occipital lobe were also verified against previously published threshold values for phosphenes. Methods Six healthy subjects underwent 10 Hz tACS while being imaged in an MRI scanner. Two different electrode montages, T7-T8 and Fpz-Oz, were used. Subject ratings of phosphene experience were collected during tACS and compared against current density distributions predicted in eye and occipital lobe regions of interest (ROIs) determined for each subject. Calculated median current densities in each ROI were compared to minimum thresholds for phosphene generation. Main Results All subjects reported phosphenes, and predicted median current densities in ROIs exceeded minimum thresholds for phosphenes found in the literature. Higher current densities in the eyes were consistently associated with decreased phosphene generation for the Fpz-Oz montage. There was an overall positive association between phosphene perceptions and current densities in the occipital lobe. Conclusions These methods may have promise for predicting phosphene generation using data collected during in-scanner tACS sessions and may enable better understanding of phosphene origin. Additional empirical data in a larger cohort is required to fully test the robustness of the proposed methods. Future studies should include additional montages that could dissociate retinal and occipital stimulation.

Mechanisms of phosphene generation in ocular proton therapy as related to space radiation exposure

Particle therapy provides an opportunity to study the human response to space radiation in ground-based facilities. On this basis, a study of light flashes analogous to astronauts’ phosphenes reported by patients undergoing ocular proton therapy has been undertaken. The influence of treatment parameters on phosphene generation was investigated for 430 patients treated for a choroidal melanoma at the proton therapy centre of the Institut Curie (ICPO) in Orsay, France, between 2008 and 2011. 60% of them report light flashes, which are predominantly (74%) blue. An analysis of variables describing the patient’s physiology, properties of the tumour and dose distribution shows that two groups of tumour and beam variables are correlated with phosphene occurrence. Physiology is found to have no influence on flash triggering. Detailed correlation study eventually suggests a possible twofold mechanism of phosphene generation based on (i) indirect Cerenkov light in the bulk of the eye due to nuclear interactions and radioactive decay and (ii) direct excitation of the nerve fibres in the back of the eye and/or radical excess near the retina.

Optimized single pulse stimulation strategy for retinal implants

Retinal implants offer prospects of vision restoration for some blind patients by eliciting visual percepts of spots of light called ‘phosphenes’. Recently, a mathematical model has been developed that predicts patients' perception of phosphene brightness for current-driven electrical stimulation of the retina. This model is explored for different stimulation parameters on a single electrode, including safety and hardware limitations, to produce phosphenes of specified brightness. We describe a procedure to derive stimulation parameters to account for such constraints, and describe methods to construct optimal stimuli in terms of producing maximal perceived brightness and efficient generation of phosphenes of a given brightness by employing minimal energy. In both cases, it is found that the resulting optimized stimulation waveforms consist of a long stimulation period, and interphase delays between initial and charge-balancing phases.

Computational analysis of thresholds for magnetophosphenes

In international guidelines, basic restriction limits on the exposure of humans to low-frequency magnetic and electric fields are set with the objective of preventing the generation of phosphenes, visual sensations of flashing light not caused by light. Measured data on magnetophosphenes, i.e. phosphenes caused by a magnetically induced electric field on the retina, are available from volunteer studies. However, there is no simple way for determining the retinal threshold electric field or current density from the measured threshold magnetic flux density. In this study, the experimental field configuration of a previous study, in which phosphenes were generated in volunteers by exposing their heads to a magnetic field between the poles of an electromagnet, is computationally reproduced. The finite-element method is used for determining the induced electric field and current in five different MRI-based anatomical models of the head. The direction of the induced current density on the retina is dominantly radial to the eyeball, and the maximum induced current density is observed at the superior and inferior sides of the retina, which agrees with literature data on the location of magnetophosphenes at the periphery of the visual field. On the basis of computed data, the macroscopic retinal threshold current density for phosphenes at 20 Hz can be estimated as 10 mA m−2 (−20% to + 30%, depending on the anatomical model); this current density corresponds to an induced eddy current of 14 μA (−20% to + 10%), and about 20% of this eddy current flows through each eye. The ICNIRP basic restriction limit for the induced electric field in the case of occupational exposure is not exceeded until the magnetic flux density is about two to three times the measured threshold for magnetophosphenes, so the basic restriction limit does not seem to be conservative. However, the reasons for the non-conservativeness are purely technical: removal of the highest 1% of electric field values by taking the 99th percentile as recommended by the ICNIRP leads to the underestimation of the induced electric field, and there are difficulties in applying the basic restriction limit for the retinal electric field.

Consistent Phosphenes Generated by Electrical Microstimulation of the Visual Thalamus. An Experimental Approach for Thalamic Visual Neuroprostheses

Most work on visual prostheses has centered on developing retinal or cortical devices. However, when retinal implants are not feasible, neuroprostheses could be implanted in the lateral geniculate nucleus (LGN) of the thalamus, the intermediate relay station of visual information from the retina to the visual cortex (V1). The objective of the present study was to determine the types of artificial stimuli that when delivered to the visual thalamus can generate reliable responses of the cortical neurons similar to those obtained when the eye perceives a visual image. Visual stimuli {Si} were presented to one eye of an experimental animal and both, the thalamic {RThi} and cortical responses {RV1i} to such stimuli were recorded. Electrical patterns {RThi*} resembling {RThi} were then injected into the visual thalamus to obtain cortical responses {RV1i*} similar to {RV1i}. Visually- and electrically generated V1 responses were compared. Results: During the course of this work we: (i) characterized the response of V1 neurons to visual stimuli according to response magnitude, duration, spiking rate, and the distribution of interspike intervals; (ii) experimentally tested the dependence of V1 responses on stimulation parameters such as intensity, frequency, duration, etc., and determined the ranges of these parameters generating the desired cortical activity; (iii) identified similarities between responses of V1 useful to compare the naturally and artificially generated neuronal activity of V1; and (iv) by modifying the stimulation parameters, we generated artificial V1 responses similar to those elicited by visual stimuli. Generation of predictable and consistent phosphenes by means of artificial stimulation of the LGN is important for the feasibility of visual prostheses. Here we proved that electrical stimuli to the LGN can generate V1 neural responses that resemble those elicited by natural visual stimuli.

Simultaneous TMS-fMRI of the Visual Cortex Reveals Functional Network, Even in Absence of Phosphene Sensation

Phosphene sensation is commonly used to measure cortical excitability during transcranial magnetic stimulation (TMS) of the occipital cortex. However, some individuals lack this perception, and the reason for it is still unknown. In this work, we used functional magnetic resonance imaging (fMRI) to detect brain activation during local TMS of the occipital cortex in twelve healthy subjects. We found that TMS modulated brain activity in areas connected to the stimulation site, even in people unable to see phosphene. However, we observed a trend for a lower blood-oxygenation-level dependent (BOLD) signal, and smaller brain-activation clusters near the stimulated site than in the interconnected brain areas, suggesting that TMS pulse is more effective downstream than at its application site. Furthermore, we noted prominent differences in brain activation/deactivation patterns between subjects who perceived phosphene and those who did not, implying a functional distinction in their neuronal networks that might explain the origin of differences in phosphene generation.

Interhemispheric transfer of phosphenes generated by occipital versus parietal transcranial magnetic stimulation

Phosphenes represent a perceptual effect of transcranial magnetic stimulation (TMS) or electric stimulation of visual cortical areas. One likely neural basis for the generation of static phosphenes is the primary visual cortex (V1) although evidence is controversial. A peculiar feature of V1 is that it has sparse callosal connections with the exception of a central portion of visual field representation. In contrast, visually responsive cortical areas in the parietal lobe have widespread callosal connections. Thus, interhemispheric transfer (IT) time of off-centre phosphenes should be slower when generated by V1 than by visual parietal areas. To verify this possibility, in Exp. 1 we measured IT of phosphenes generated by TMS applied to V1 and in Exp. 2 we measured IT of phosphenes obtained by TMS applied to posterior parietal cortex. In both experiments, we obtained static bright circular phosphenes appearing in the contralateral hemifield. We measured IT time behaviorally by comparing unimanual simple reaction time to the onset of a phosphene under crossed or uncrossed hemifield-hand condition (Poffenberger paradigm). In keeping with our prediction, we found a substantially longer IT time for V1 than for parietal phosphenes. Additionally, an IT similar to that obtained with V1 stimulation was found when participants were asked to imagine the phosphenes previously experienced during TMS. In conclusion, the present results suggest that IT of phosphenes either generated by V1 TMS or imagined is subserved by slower callosal channels than those of real visual stimuli or parietal phosphenes.

Masking visual stimuli by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) applied over the occipital pole can suppress visual perception. Since its first description in 1989 by Amassian et al., this technique has widely been used to investigate visual processing at the cortical level. This article presents a review of experiments masking visual stimuli by TMS. The psychophysical characterization of TMS masking, the dependence on stimulus onset asynchrony between visual stimulus and TMS pulse, and the topography of masking within the visual field are considered. The relation between visual masking and the generation of phosphenes is discussed as well as the underlying physiological mechanisms.

Motor and Occipital Cortex Excitability in Migraine Patients

We evaluated motor and occipital cortex excitability in migraine patients using transcranial magnetic stimulation. In this study, we included 15 migraine patients with aura (MwA), 15 patients without aura (MwoA) between attacks, and 31 normal healthy controls. Motor thresholds at rest, amplitudes of motor evoked potentials, central motor conduction time and cortical silent period were measured by stimulation of the motor cortex by using 13.5 cm circular coil and recording from abductor digiti minimi muscle. Additionally, phosphene production and the threshold of phosphene production was determined by stimulation of the visual cortex with the same coil. No significant differences were observed between the groups with respect to the motor thresholds, Motor evoked potential max/compound muscle action potential max (MEPmax/Mmax) amplitudes, central motor conduction times and duration of cortical silent period. Although not statistically significant, the proportion of the migraineurs with phosphene generation (90%) was found to be higher than that of normal controls (71%). Phosphene threshold levels in migraine patients, however, were significantly lower than those of the controls with MwA patients having the lowest levels. Our findings indicate that the occipital cortex, but not the motor cortex, is hyperexcitable in migraine patients.

Investigation of the primary visual cortex using short-interval paired-pulse transcranial magnetic stimulation (TMS)

Previous studies using short-interval paired-pulse TMS have provided valuable insights into physiology of human motor cortex. Depending on the interstimulus interval (ISI) between the two pulses intra-cortical facilitation (ICF) or intra-cortical inhibition (ICI) can be observed. Similar patterns of inhibition and facilitation have also been demonstrated in prefrontal and parietal cortices. In order to prove whether principles that govern cortical excitability in the motor system also extend to the visual system and to further characterize possible neural correlates of phosphene generation, we applied short-interval paired-pulse TMS to the occipital cortex. In addition, we examined the effect of different coil orientations on perception of phosphenes induced by paired-pulse TMS. In all of 10 healthy subjects, a general facilitation of phosphene perception could be observed for interstimulus intervals of 2–12 ms (conditioning stimulus (CS) 90% and test stimulus (TS) 100% of subject's phosphene threshold) compared to TS alone. With CS intensity decreasing to 80% or less, the effect diminished. No significant changes occurred when TS intensity was increased to 110%. Phosphene perception was enhanced with an induced current direction from lateral to medial at an ISI of 12 ms. Inhibition was not observed in any condition. Our results indicate that the mechanisms underlying phosphene induction in the visual cortex are different from those underlying intracortical inhibition and facilitation in the motor cortex.

MIGRAINE: PATHOPHYSIOLOGY

We have reported a preliminary study confirming hyperexcitability of occipital cortex in migraine with aura (MwA) using transcranial magnetic stimulation (TMS). We have now completed a blinded study to investigate the occipital cortex in MwA and without aura (MwoA) compared with normal controls (NC) using TMS. TMS was performed using the Caldwell MES‐10 stimulator. A circular coil 9.5 cm diameter was applied to the occipital scalp (7 cm above the inion). Stimulator intensity was increased in 10% increments until subjects reported visual phenomena or 100% intensity was reached. Stimulation intensity was then fine tuned to determine the threshold at which phosphenes were seen. Fisher's exact t‐test and logrank test were used for statistical comparisons. Ten subjects with MwA and MwoA were compared to 10 NC. The difference in the proportion of subjects with phosphene generation was statistically significant (MwA 100%, MwoA 60% and NC 30%) [P= 0.003]. The difference in threshold levels for phosphenes was also significant for MwA 42.8%, and controls 57.3%[P= 0.0001]. There is a difference in threshold for excitability of occipital cortex in MwA and MwoA compared to NC. This is a direct neurophysiological correlate for clinical observations, which have inferred hyperexcitability of the occipital cortex in migraineurs. Comment.—Dr. Michael Welch has stated that the occipital lobe is to migraine as the temporal lobe is to epilepsy, and this study is further corroboration of his aphorism. SJT

Electrical phosphenes: on the influence of conductivity inhomogeneities and small-scale structures of the orbita on the current density threshold of excitation.

Electrical and magnetic phosphenes, perceptions of light as a result of non-adequate stimulation of the eye by electrical current or magnetic induction, respectively, are one of the cornerstones to justify limit values for extreme low-frequency fields specified by statutory regulations. However, the mechanism and place of action, as well as the excitation threshold, remain unknown until now. We suggest that the origin of phosphene excitation is the synaptic layer of the eye. The current density threshold value for electrical phosphene excitation was numerically quantified for this area on the basis of a detailed geometrical model in original submillimetre resolution and specifically measured conductivities in the LF range. The threshold values found were 1.8 A m-2 at 60 Hz and 0.3 A m-2 at 25 Hz. These values are comparable with values of other excitable tissues. It has been shown that the current density threshold for phosphene generation depends on small-scale structures not taken into account by previous models.

A model of the electrical volume conductor in the region of the eye in the ELF range

Electrical and magnetic phosphenes are irritations of the eye caused by electric currents or magnetic fields. These are well known effects initially investigated in the early 1900s. Available estimations of the current densities in the eye, based on the assumption of a homogeneous volume conductor, show low thresholds. These outdated thresholds are still an important cornerstone when justifying today's limit values for extremely low-frequency (ELF) fields specified by statutory regulations. In vitro measurements of the complex conductivity of cattle eye are carried out for the ELF range (5–2000 Hz) separated for the different tissues of the eyeball. They do not show peculiarities at 20 Hz which is the threshold minimum for the phosphene generation. The reported conductivity data of the eye region show variations of two orders of magnitude regarding the electrical conductivity of the individual tissue layers. Starting with these new data, a model of the orbita is introduced describing the eye and its periphery as an electrically inhomogeneous volume conductor. This model contains small-scale structures which are expected to behave as good electrical conductors yielding regions of higher field values within the eye. Therefore, earlier models assuming a homogeneous volume conductor can be regarded as oversimplistic.

The pathophysiology of migraine.

Migraine results from episodic changes in central nervous system physiologic function in hyperexcitable brain manifested by abnormal energy metabolism, lowered threshold for phosphene generation, and increased contingent negative variation. Human functional magnetic resonance imaging and magnetoencepholography data strongly suggest that aura is caused by cortical spreading depression. Brain hyperexcitability may be caused by low magnesium levels, mitochondrial abnormalities with abnormal phosphorylation of adenosine 5'-diphosphate, a dysfunction related to nitric oxide, or calcium channelopathy. Low magnesium can result in opening of calcium channels, increased intracellular calcium, glutamate release, and increased extracellular potassium, which may in turn trigger cortical spreading depression. Mitochondrial dysfunction has been suggested by a low phosphocreatine:Pi ratio and a possible response by migraine patients to riboflavin prophylaxis. Nitroglycerine administration results in a delayed migraine-like headache in migraine patients but not in control patients, and a nonspecific nitric oxide synthase inhibitor aborted migraine at 2 hours in the majority of tested migraine patients compared to controls. Many patients with familial hemiplegic migraine have a missense mutation in the P/Q calcium channel, so that this form of migraine, at least, is associated with a demonstrable calcium channelopathy. The generation of migraine occurs centrally in the brain stem, sometimes preceded by cortical spreading depression and aura. Activation of the trigeminovascular system stimulates perivascular trigeminal sensory afferent nerves with release of vasoactive neuropeptides, resulting in vasodilation and transduction of central nociceptive information. There is then a relay of pain impulses to central second- and third-order neurons and activation of brain stem autonomic nuclei to induce associated symptoms.