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Auditory evoked visual awareness following sudden ocular blindness: an EEG and TMS investigation.

Neurophysiological and neuroanatomical studies have provoked controversy about whether the visual cortex may be more modifiable than previously believed. Auditory processing is enhanced in blind compared to sighted people, and the enhancement might reflect encroachment of auditory transmission onto visual cortex. To address this issue, we recorded the auditory event-related potentials (ERPs) correlated with auditory related paradoxical visual awareness in a subject with traumatic total late-onset blindness. We found that (1) there was auditory related brain activity over the occipital visual scalp regions starting from a very early stage (< 80 ms) and (2) this occipital activity was significantly different between "visually aware" and "visually unaware" responses in the P1 (40-80 ms) component following meaningful stimuli. There was also a significant difference between responses with and without visual awareness in the N1 (100-120 ms) component following either tones or meaningful stimuli. The phosphenes accompanying auditory stimuli in the ERP experiment were always perceived to be directly in front of the subject and this was reproduced by transcranial magnetic stimulation over the blind primary visual cortex and by sudden sounds delivered to the side or behind the subject. The TMS induced phosphenes were restricted to the central part of the space and were, at least qualitatively, the same as those induced by sounds. The results are clear evidence that human perceptual functions can be reorganized after sudden, late-onset, total ocular blindness.

Acoustic Stimulation↗

Observations of visual sensations produced by Cerenkov radiation from high-energy electrons.

Ten cancer patients whose eyes were therapeutically irradiated with 6-18 MeV electrons reported visual light sensations. Nine reported seeing blue light and one reported seeing white light. Controls reported seeing no light. Additionally, tests with patients ruled out the x-ray contamination of the electron beam as being important. The photon yield due to Cerenkov radiation produced by radium and its daughters for both electrons and gamma rays was calculated; it was found to account for a turn-of-the-century human observation of the "radium" phosphene. We conclude that the dominant mechanism of this phosphene is Cerenkov radiation, primarily from betas. From our own patient data, based on the color seen and the Cerenkov production rates, we conclude that the dominant mechanism is Cerenkov radiation and that high-energy electrons are an example of particle induced visual sensations.

Electrons↗

Motor and visual cortical excitability in migraineurs patients with or without aura: transcranial magnetic stimulation.

BACKGROUND AND PURPOSE OF STUDY: Controversy surrounds measures of visual and motor cortical excitability in migraineurs: some authors report that interictal excitability is increased, others decreased. The aim of this work was to provide further evidence about motor and visual cortical excitability in migraineurs between attacks. PATIENTS AND METHODS: Twenty-eight migraineurs patients, 18 with aura and 10 patients without aura and 20 healthy right-handed, age and sex matched volunteers were included in the study. Each subject underwent transcranial magnetic stimulation and was submitted to the following: determination of resting motor threshold (rMT), silent period (SP), MEP input-output curves, phosphene threshold (PT). RESULTS: Patients had lower rMT, shorter SP, and increased MEP recruitment compared with control group. There was an increased prevalence of phosphene (85%) as well as lower PT (63% of the stimulator output) in migraineurs compared with control group (75%, and 72%, respectively). There was a significant negative correlation between duration of attacks and PT (P = 0.02). No significant differences between patients with aura and without aura in different parameters of cortical excitability. CONCLUSION: Our findings confirm that the motor and visual cortexes are hyperexcitable and this appears partly to be consequent upon a failure of inhibitory circuits.

Adult↗

High-resolution two-dimensional spatial mapping of cat striate cortex using a 100-microelectrode array.

Much of our understanding of the visuotopic organization of striate cortex results from single-electrode penetrations and serial recording of receptive field properties. However, the quality of these maps is limited by imprecision in quantifying electrode position, combining data from multiple laminae, and eye drift during the measurement of the receptive field properties. We have addressed these concerns by using an array of 100 closely spaced microelectrodes to investigate the two-dimensional visuotopic organization of layer IV in cat striate cortex. This array allowed simultaneous measurement of the receptive field properties of multiple single units on a regularly spaced grid. We found the relationship between cortical and visual space to be locally non-conformal: the receptive field locations associated with a closely spaced line of electrodes appeared randomly scattered in visual space. To quantify the scatter, we fitted a linear transformation of electrode sites onto the associated receptive field locations. We found that the distribution of the difference between the predicted receptive field location and the measured location had standard deviations of 0.59 degrees and 0.45 degrees in the horizontal and the vertical axes, respectively. Although individual receptive field positions differed from the predicted locations in a non-conformal sense, the trend across multiple receptive fields followed the maps described elsewhere. We found, on average, that the 13 mm2 of cortex sampled by the array mapped onto a 5.8-degrees) region of visual space. From the scaling of this map and a combination of the statistics of the receptive field size (2.7+/-1.5 degrees) and scatter, we have explored the impact of electrode spacing on the completeness and redundancy in coverage of visual space sampled by an array. The simulation indicated an array with 1.2-mm spacing would completely sample the region of visual space addressed by the array. These results have implications for neuroprosthetic applications. Assuming phosphene organization resembles the visuotopic organization, remapping of visual space may be necessary to accommodate the scatter in phosphene locations.

Animals↗

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.

Animals↗

Creating a meaningful visual perception in blind volunteers by optic nerve stimulation.

A blind volunteer, suffering from retinitis pigmentosa, has been chronically implanted with an optic nerve visual prosthesis. Vision rehabilitation with this volunteer has concentrated on the development of a stimulation strategy according to which video camera images are converted into stimulation pulses. The aim is to convey as much information as possible about the visual scene within the limits of the device's capabilities. Pattern recognition tasks were used to assess the effectiveness of the stimulation strategy. The results demonstrate how even a relatively basic algorithm can efficiently convey useful information regarding the visual scene. By increasing the number of phosphenes used in the algorithm, better performance is observed but a longer training period is required. After a learning period, the volunteer achieved a pattern recognition score of 85% at 54 s on average per pattern. After nine evaluation sessions, when using a stimulation strategy exploiting all available phosphenes, no saturation effect has yet been observed.

Artificial Intelligence↗

Visual acuity measurement of prosthetic vision: a virtual-reality simulation study.

A virtual-reality simulation tested prosthetic visual acuity for both rectangular and hexagonal phosphene grids. Thirteen normally sighted, untrained subjects were required to identify the Landolt C optotype over ten sessions. Overall performance, performance by filter setting (image analysis), and performance by size and orientation of the Landolt C optotype are reported. The results indicated that the hexagonal grid had a slight (4.1%) but statistically significant (p < 0.0001) performance advantage over the rectangular grid for correct identification of the testing symbol. It was also observed that both the phosphene grids had distinct performance profiles relating to their respective spatial orientation. Over the course of the ten sessions, learning afforded subjects an averaged improved performance of 10%.

Artificial Intelligence↗

Excitability of human motor and visual cortex before, during, and after hyperventilation.

In humans, hyperventilation (HV) has various effects on systemic physiology and, in particular, on neuronal excitability and synaptic transmission. However, it is far from clear how the effects of HV are mediated at the cortical level. In this study we investigated the effects of HV-induced hypocapnia on primary motor (M1) and visual cortex (V1) excitability. We used 1) motor threshold (MT) and phosphene threshold (PT) and 2) stimulus-response (S-R) curves (i.e., recruitment curves) as measures of excitability. In the motor cortex, we additionally investigated 3) the intrinsic inhibitory and facilitatory neuronal circuits using a short-interval paired-pulse paradigm. Measurements were performed before, during, and after 10 min of HV (resulting in a minimum end-tidal Pco(2) of 15 Torr). HV significantly increased motor-evoked potential (MEP) amplitudes, particularly at lower transcranial magnetic stimulation (TMS) intensities. Paired-pulse stimulation indicated that HV decreases intracortical inhibition (ICI) without changing intracortical facilitation. The results suggestthat low Pco(2) levels modulate, in particular, the intrinsic neuronal circuits of ICI, which are largely mediated by neurons containing gamma-aminobutyric acid. Modulation of MT probably resulted from alterations of Na(+) channel conductances. A significant decrease of PT, together with higher intensity of phosphenes at low stimulus intensities, furthermore suggested that HV acts on the excitability of M1 and V1 in a comparable fashion. This finding implies that HV also affects other brain structures besides the corticospinal motor system. The further exploration of these physiological mechanisms may contribute to the understanding of the various HV-related clinical phenomenona.

Adult↗

Laminar variation in threshold for detection of electrical excitation of striate cortex by macaques.

Macaques were trained to signal their detection of electrical stimulation applied by a movable microelectrode to perifoveal striate cortex. Trains of < or =100 cathodal, 0.2-ms, constant current pulses were delivered at 50 or 100 Hz. The minimum current that could be reliably detected was measured at successive depths along radial electrode penetrations through the cortex. The lowest detection thresholds were routinely encountered when the stimulation was applied to layer 3, particularly just at the juncture between layers 3 and 4A. On the average, there was a twofold variation in threshold along the penetrations, with the highest intracortical thresholds being in layers 4C and 6. Variations as high as 20-fold were obtained in some individual penetrations, whereas relatively little change was observed in others. The minimum detectable current was 1 muA at a site in layer 3, i.e., 10-100 times lower than that for surface stimulation. Because macaques, as do human subjects, find electrical stimulation of striate cortex to be highly similar at all loci (a phosphene in the human case), it is puzzling as to how such uniformity of effect evolves from the exceedingly intricate circuitry available to the effective stimuli. It is hypothesized that the stimulus captures the most excitable elements, which then suppress other functional moieties, producing only the luminance of the phosphene. Lowest thresholds presumably are encountered when the electrode lies among these excitable elements that can, with higher currents, be stimulated directly from some distance or indirectly by the horizontal bands of myelinated axons, the stria of Baillarger.

Animals↗

Visual phenomena evoked by electrical stimulation of the human brain stem.

19 visual effects have been elicited out of 9,383 sites during stimulation mapping for physiological localization during stereotactic surgery. It is proposed that three visual pathways can be recognized during subcortical electrical stimulation in man. The optic tract and geniculocalcarine pathway, projecting to area 17, are recognizable by the production of contralateral coloured phosphenes. The tectopulvinar pathway projecting to areas 18 and 19 is recognizable by the eliciting of contralateral or bilateral colourless phosphenes or 'negative' visual effects, the latter presumably reflecting inhibitory collicular influences. Finally, deep responses, consisting of apparent movement of the visual fields, intermingled with 'negative' visual and oculomotor effects, suggest activation of a visual-oculomotor coordinating system.

Brain Mapping↗

Paragraph text reading using a pixelized prosthetic vision simulator: parameter dependence and task learning in free-viewing conditions.

PURPOSE: To investigate the feasibility of adequate reading by recipients of future prosthetic visual implants through simulation in sighted observers. METHODS: Four normally sighted subjects used a video headset to view short-story segments at a sixth grade reading level, presented in 6- to 11-word paragraphs through a pixelizing grid defined by five parameters (dot size, grid size, dot spacing, random dropout percentage, and gray-scale resolution). Grid parameters were varied individually, and four character sizes and two contrast levels were used. RESULTS: Reading speeds of 30 to 60 words per minute without errors were recorded for some parameter combinations. In general, reading accuracy and speed were influenced by all parameters. Reading accuracy exceeded 90% if the following conditions were met: At least 3 dots/charwidth were presented, and dropout did not exceed 50%. Reading speed deteriorated below 20 words per minute if accuracy fell below 90% and at low contrast if the grid spanned less than two characters. CONCLUSIONS: It is uncertain whether and to what extent retinal reorganization may limit the perception of multiple phosphenes by blind prosthesis recipients. If distinct phosphenes can be perceived, these results suggest that a 3 x 3-mm2 prosthesis with 16 x 16 electrodes should allow paragraph reading. The effects of stabilizing the dot grid on the retina must be investigated further.

Adult↗

Positive spontaneous visual phenomena limited to the hemianopic field in lesions of central visual pathways.

We prospectively studied 32 patients with ischemic infarction of the retrochiasmal visual pathways. Positive spontaneous visual phenomena (PSVP) in the blind hemifield were present in 13 patients (41%). The PSVP were subdivided into phosphenes, photopsias, visual hallucinations, palinopsia, and agitated delirium with hemianopia. PSVP were never associated with auditory or other sensory positive phenomena, except in patients with agitated delirium. Patients with photopsias, phosphenes, palinopsia, and visual hallucinations had similar lesions in MRI/CT, suggesting no anatomic area unique for these four phenomena. However, there was a significant difference in the severity of associated neurologic deficits between hemianopic patients with and without PSVP. Larger lesions destroying anteriorly located visual association areas precluded the development of PSVP, which may be related to release from inhibitory input of visual regions bordering the damaged area. Patients with the syndrome of agitated delirium and hemianopia had specific lesions involving the mesial aspect of the occipital lobe, the parahippocampal gyrus, and hippocampus.

Adult↗

Reading speed with a pixelized vision system.

A visual prosthesis based on electrical stimulation of the visual cortex with an array of penetrating electrodes is expected to produce pixelized visual images consisting of punctate spots of light (phosphenes). We measured reading speed in subjects viewing text with optically simulated phosphene fields in order to obtain estimates of the following design parameters for such an electrode array: pixel number, pixel spacing, and visual-field size. Comparisons were made between scanning the text with eye movements and scanning the text with head movements. The results indicate that a 25 x 25 array of pixels representing four letters of text projected on a foveal visual field of 1.7 degrees is sufficient to provide reading rates near 170 words/min with scrolled text and near 100 words/min with fixed text.

Humans↗

Artificial human vision.

Can vision be restored to the blind? As early as 1929 it was discovered that stimulating the visual cortex of an individual led to the perception of spots of light, known as phosphenes [1] . The aim of artificial human vision systems is to attempt to utilize the perception of phosphenes to provide a useful substitute for normal vision. Currently, four locations for electrical stimulation are being investigated; behind the retina (subretinal), in front of the retina (epiretinal), the optic nerve and the visual cortex (using intra- and surface electrodes). This review discusses artificial human vision technology and requirements, and reviews the current development projects.

Artificial Intelligence↗

Migraine with visual aura in developing age: visual disorders.

Visual disorders are an important symptom in the migraine of developing age. Different kinds of visual disturbances can precede, accompany or follow a migraine attack. These visual disturbances can be grouped into negative (hemianopsia, quadrantopsia, scotoma) and positive (phosphene, teicopsia, metamorphopsia, macropsia, micropsia, teleopsia, diplopia, dischromatopsia, hallucination disturbances) disorders. The pathogenetic mechanism of the visual phenomena of migraine has not yet been clarified. Various hypotheses have been proposed: vasospasm with consequent ischemia of some cerebral areas, the opening of arteriovenous shunts between the intra and extra cerebral circulation, the formation of microthrombi in arterioles and dopaminergic hypersensitivity of some nervous centers. We have studied 1787 children, affected by migraine with (13%) or without (87%) aura. Among the patients, 211 (12%) referred visual disorders, especially scotoma and phosphene. These data let us hypothesize that a relationship between migraine and visual disorders is present also in pediatric age. However this relationship is less important than in adults.

Adolescent↗

[Usefulness of establishing diagnosis and severity of the most frequent signs and symptoms in preeclamptic patients].

OBJECTIVE: Our aim was to determine that signs and symptoms are tools in establishing diagnosis and severity of preeclampsia. MATERIALS AND METHODS: Our study design was prolective, comparative, cross-sectional for evaluation of diagnosis. Our sample included 408 patients. The study employed classification criteria of the American College of Obstetricians and Gynecologists. One blinded family physician interrogated and examined each patient. The sample included patients with recent diagnosis and without treatment. Patients with HELLP syndrome, eclampsia, and those in Intensive Care were excluded. Clinical signs evaluated included headache, Phosphenes, acuphenes, tinnitus, vomiting, epigastric pain, right hypochondrium pain, ecchymosis, hematomas,and hyperreactive reflexes. RESULTS: A total of 192 patients without preeclampsia, 63 with mild, and 153 with severe preeclampsia were included. Clinical manifestations were absent in 60, 21 and 8% respectively of patients in each group. Presence of three or more signs or symptoms had sensitivity of 60% (CI95% 53-67), specificity of 84% (CI95% 79-89), and positive likelihood ratio of 3.8 and negative, 0.48. Most usefulness data for diagnosis of preeclampsia are hyperreactive reflexes, phosphenes, acuphenes, right hypochondrium pain, and epigastric pain. CONCLUSIONS: The symptoms and signs taken alone are tools for evaluation of severity but not for detection of preeclampsia. There is necessary to develop new way for it's diagnosis during prenatal care.

Cross-Sectional Studies↗

[Development of a new evaluation system for visual function].

Visual deterioration is caused principally by media opacity, by retinal damage, or by disorders of the higher visual system posterior to the optic nerve. In this article, we focused on media and retinal disorders and clinically evaluated a newly developed system for visual function. The decrease in visual function in cataract is subjectively well evaluated by contrast sensitivity, but is difficult to evaluate objectively. Recently, a wavefront sensor has been developed and ocular higher-order aberration (HOA) can now be measured objectively. We studied the relationship between age and HOA by wavefront sensor and found that HOA, especially spherical aberration in the lens, increased abruptly at the presbyopic age. We also found that the against-the-rule astigmatism in the lens increased at this age. Next, we investigated monocular diplopia which was presumably caused by HOA. Nine eyes with monocular triplopia and with mild nuclear cataract showed significant increase of trefoil aberration and negative spherical aberration (p<0.001). The simulated retinal Landolt's image from these two aberrations showed a triple configuration. Thus we confirmed that triplopia is caused by the combination of trefoil aberration and negative spherical aberration in early nuclear cataract. Next, we investigated whether Area under Log Contrast Sensitivity Function (AULCSF) can be predicted by HOA and light scattering. Backward light scattering (BLS) was evaluated by Schei mpflug image and the forward light scattering (FLS) by a spot size of the Hartmann image compensated for the effect of HOA. HOA was evaluated by root mean square (RMS) value from Hartmann image in a 4 mm pupil. Multiple linear regression revealed that AULCSF could be predicted from BLS, FLS, and HOA, in which each parameter contributed to the prediction significantly (p<0.01). By using this predicted value of AULCSF, the improvement of vision after cataract surgery can be predicted in cataract complicated by retinal disease. It has been reported that by fundus camera equipped with adaptive optics (AO), which is an application of wavefront analysis, photoreceptors could be visualized 2-dimensionally. We developed a compact AO fundus camera and demonstrated that cones were separately analyzed at retinal loci 1 degree temporal to the fovea centralis when the ocular aberration was reduced to less than 0.1 microm RMS in a 6 mm pupil. We are going to use this apparatus for eyes with retinal disease. The functional evaluation of residual retinal ganglion cells (RGCs) in the retina with damage to the photoreceptors is critically important for selecting candidates for artificial retina or regenerative therapy. Transcorneal electrical stimulation (TES) of the retina via contact lens electrodes evokes phosphene and indirect pupillary reflex. The threshold current for evoking phosphene in severely degenerated retinas with visual acuity worse than counting fingers showed a wide distribution, which suggested that TES was useful to evaluate residual RGCs functionally. TES also showed a neuroprotective effect. We suggest that the activation of glial cells by TES up-regulates the production of IGF-1, which eventually protects RGCs. The peripheral retina is important for walking even though the spatial resolution is not high. We developed an apparatus to measure stereopsis in the peripheral retina using a wide screen, and evaluated the peripheral stereopsis of 12 patients after macular translocation surgery and squint surgery. All three patients who showed peripheral stereopsis had only a small amount of squint angle. This method may be useful to evaluate stereopsis in patients with a central scotoma.

Cataract↗

Object localization, discrimination, and grasping with the optic nerve visual prosthesis.

PURPOSE: This study involved a volunteer completely blind from retinis pigmentosa who had previously been implanted with an optic nerve visual prosthesis. The aim of this two-year study was to train the volunteer to localize a given object in nine different positions, to discriminate the object within a choice of six, and then to grasp it. METHODS: In a closed-loop protocol including a head worn video camera, the nerve was stimulated whenever a part of the processed image of the object being scrutinized matched the center of an elicitable phosphene. The accessible visual field included 109 phosphenes in a 14 degrees x 41 degrees area. RESULTS: Results showed that training was required to succeed in the localization and discrimination tasks, but practically no training was required for grasping the object. The volunteer was able to successfully complete all tasks after training. The volunteer systematically performed several left-right and bottom-up scanning movements during the discrimination task. Discrimination strategies included stimulation phases and no-stimulation phases of roughly similar duration. CONCLUSION: This study provides a step towards the practical use of the optic nerve visual prosthesis in current daily life.

Blindness↗