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Artificial vision.

Outer retinal degenerations such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) lead to blindness because of photoreceptor degeneration. To test whether controlled electrical stimulation of the remaining retinal neurons could provide form vision, we electrically stimulated the inner retinal surface with micro-electrodes inserted through the sclera/eye wall of 14 of these patients (12 RP and 2 AMD). This procedure was performed in the operating room under local anaesthesia and all responses were recorded via a video camera mounted on the surgical microscope. Electrical stimulation of the inner retinal surface elicited visual perception of a spot of light (phosphene) in all subjects. This perception was retinotopically correct in 13 of 14 patients. In a resolution test in a subject with no light perception, the patient could resolve phosphenes at 1.75 degrees centre-to-centre distance (i.e. visual acuity compatible with mobility; Snellen visual acuity of 4/200).

Blindness↗

The site of saccadic suppression.

During rapid eye movements, or saccades, stable vision is maintained by active reduction of visual sensitivity. The site of this saccadic suppression remains uncertain. Here we show that phosphenes--small illusory visual perceptions--induced by transcranial magnetic stimulation (TMS) to the human occipital cortex are immune to saccadic suppression, whereas phosphenes induced by retinal stimulation are not, thus providing direct physiological evidence that saccadic suppression occurs between the retina and the occipital visual cortex.

Adult↗

Pattern recognition with the optic nerve visual prosthesis.

A volunteer with retinitis pigmentosa and no residual vision was chronically implanted with an optic nerve electrode connected to an implanted neurostimulator and antenna. An external controller with telemetry was used for electrical activation of the nerve which resulted in phosphene perception. Open-loop stimulation allowed the collection of phosphene attributes and the ability to elicit perception of simple geometrical patterns. Low perception thresholds allowed for large current intensity range within safety limits. In a closed-loop paradigm, the volunteer was using a head-worn video camera to explore a projection screen. The volunteer underwent performance evaluation during the course of a training program with 45 simple patterns. After learning, the volunteer reached a recognition score of 63% with a processing time of 60 s. Mean performance in orientation discrimination reached 100% with a processing time of 8 s.

Electric Stimulation↗

Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine.

Between attacks, migraine patients are characterized by potentiation instead of habituation of stimulation-evoked cortical responses. It is debated whether this is due to increased or decreased cortical excitability. We have studied the changes in visual cortex excitability by recording pattern-reversal visual evoked potentials (PR-VEP) after low- and high-frequency repetitive transcranial magnetic stimulation (rTMS), known respectively for their inhibitory and excitatory effect on the cortex. In 30 patients (20 migraine without, 10 with aura) and 24 healthy volunteers, rTMS of the occipital cortex was performed with a focal figure-of-eight magnetic coil (Magstim). Nine hundred pulses were delivered randomly at 1 or 10 Hz in two separate sessions. Stimulus intensity was set to the phosphene threshold or to 110% of the motor threshold if no phosphenes were elicited. Before and after rTMS, PR-VEP were averaged sequentially in six blocks of 100zztieresponses during uninterrupted 3.1 Hz stimulation. In healthy volunteers, PR-VEP amplitude was significantly decreased in the first block after 1 Hz rTMS and the habituation normally found in successive blocks after sustained stimulation was significantly attenuated. In migraine patients, 10 Hz rTMS was followed by a significant increase of first block PR-VEP amplitude and by a reversal to normal habituation of the potentiation (or dishabituation) characteristic of the disorder. This effect was similar in both forms of migraine and lasted for at least 9 min. There were no significant changes of PR-VEP amplitudes after 1 Hz rTMS in migraineurs and after 10 Hz rTMS in healthy volunteers, nor after sham stimulation. The recovery of a normal PR-VEP habituation pattern after high-frequency rTMS is probably due to activation of the visual cortex and the dishabituation in healthy volunteers to cortical inhibition. We conclude, therefore, that the deficient interictal PR-VEP habituation in migraine is due to a reduced, and not to an increased, pre-activation excitability level of the visual cortex.

Adult↗

Spreading photoparoxysmal EEG response is associated with an abnormal cortical excitability pattern.

Photosensitivity or photoparoxysmal response (PPR) is a highly heritable electroencephalographic trait characterized by an abnormal cortical response to intermittent photic stimulation (IPS). In PPR-positive individuals, IPS induces spikes, spike-waves or intermittent slow waves. The PPR may be restricted to posterior visual areas (i.e. local PPR with occipital spikes only) or spread to anterior non-visual cortical regions (i.e. PPR with propagation). The mechanisms underlying the PPR and causing its spread remain to be clarified. In unmedicated PPR-positive individuals and PPR-negative control participants without any history of previous seizures, we used focal transcranial magnetic stimulation (TMS) to investigate the excitability of the visual or primary motor cortex (M1). In the first experiment [18 healthy control subjects (i.e. without PPR in electroencephalography: 6 females, mean age 26.5 +/- 7.34 years) and 17 healthy participants with PPR (7 females, mean age 25.18 +/- 12.2 years) were studied], occipital TMS was used to elicit phosphenes or to suppress the visual perception of letter trigrams. PPR-positive individuals with propagation had lower phosphene thresholds and steeper stimulus-response curves than individuals without PPR or with occipital spikes only. Occipital TMS also induced a stronger suppression of visual perception in PPR-positive subjects with propagation relative to subjects without PPR or with occipital spikes. In the second experiment, we applied TMS over the right M1 without concurrent IPS and measured the motor threshold, the stimulus response curve, and the duration of the cortical silent period (CSP) in PPR positive individuals with propagation and in PPR-negative control participants [15 right-handed healthy subjects without PPR (3 males, mean age 17.7 +/- 3.6 years) and 14 right-handed healthy individuals showing a PPR with propagation (3 males, mean age 17.4 +/- 3.9 years)]. PPR-positive individuals showed no changes in these excitability measures relative to the PPR-negative control participants. We also measured the modifiability of the CSP by continuous IPS at a frequency of 18 or 50 Hz. While IPS reduced the duration of the CSP in PPR-negative control subjects, IPS had no effect on the duration of the CSP in PPR-positive individuals. Our results provide first time evidence that the propagation of the PPR is associated with increased excitability of the occipital but not the motor cortex. The stronger inhibitory effect of TMS on visual perception and the failure of IPS to shorten the CSP in PPR-positive participants may possibly reflect adaptive changes that prevent the provocation of seizures during the PPR.

Adolescent↗

Interaction of low frequency electric fields with the nervous system: the retina as a model system.

The retina provides an example of effects, the visually perceived 'phosphenes', being generated in nervous tissue by external electric or magnetic fields of low frequency and intensity. What is known about the cellular mechanisms by which the phosphenes are generated is reviewed, whether they provide useful information for setting limits on the magnitude of induced electric fields to which nervous tissue can be safely exposed is assessed, and some difficulties in translating these values of internal fields into safe values of external electric or magnetic fields are considered.

Animals↗

Image processing strategies dedicated to visual cortical stimulators: a survey.

Multi-electrode devices are constantly evolving toward a state where complexity and reliability are adequate for providing a breakthrough in visual cortical stimulation allowing the blind to recover partial vision. Yet few research teams have focused on the development of the front-end subsystem that transforms an input image from a camera into stimulation commands. This article collects state-of-the-art knowledge about the appearance and organization of phosphenes, and previous work in image processing dedicated to visual cortical stimulation. Observations and hypothesis about important issues are highlighted, and six image processing strategies that could be used in such a subsystem are presented, from the most optimistic that use brightness modulation to emulate grayscale to the most conservative that use only on/off phosphene evocation.

Blindness↗

Visual cortex excitability in migraine evaluated by single and paired magnetic stimuli.

OBJECTIVE: To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single- and paired-pulses. METHODS: Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti-migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS with an interstimulus interval of 50 ms. RESULTS: The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%) (P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired-pulse stimulation than with single pulses (P < .001). CONCLUSIONS: PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single-pulse TMS, paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.

Adolescent↗

Modulatory effects of low- and high-frequency repetitive transcranial magnetic stimulation on visual cortex of healthy subjects undergoing light deprivation.

The aim of the present study was to explore further the effects of light deprivation (LD) on visual cortex excitability. Healthy subjects reporting reliable induction of phosphenes by occipital transcranial magnetic stimulation (TMS) underwent 60 min of complete LD. Phosphene threshold (PT) was measured before (T0), after 45 min (T1) and 60 min (T2) of LD, and then every 10 min after light re-exposure until recovery to T0 values. Repetitive TMS (rTMS) (at 1 or 10 Hz) was applied in separate sessions during the last 15 min of LD. PTs significantly decreased after 45 min of LD. rTMS differentially modified the effects of 60 min LD on PTs depending on stimulation frequency. One hertz rTMS did not change the decreasing of PT values as observed in baseline condition, but significantly prolonged the time to recover T0 PT values after light re-exposure. By contrast, 10 Hz rTMS significantly increased PT and the time to recover T0 PT values after light re-exposure was shortened. The results of this study show that the modulatory effects of different rTMS frequencies on visual cortex critically depend on the pre-existing excitability state of inhibitory and facilitatory circuits, and provide novel insights into the neurophysiological changes that take place in the visual cortex following functional visual deafferentation.

Adult↗

Flashing lights in thyroid eye disease: a new symptom described and (possibly) explained.

BACKGROUND/AIMS: Some patients with restrictive thyroid ophthalmopathy, referred for consideration of extraocular muscle surgery, complained of flashing lights in the superior visual field on upgaze. The frequency was assessed and the pathogenesis of this previously unreported symptom explored. METHODS: 30 patients were recruited, all of whom had tight inferior recti and were in the burnt out phase of thyroid eye disease. They were directly questioned regarding any symptoms of photopsia and their records were examined with respect to disease status and treatment, ocular motility, intraocular pressure, retinal status, and surgical intervention. Magnetic resonance imaging (MRI) and cine MRI scans were reviewed for evidence of globe compression. The frequency of symptoms was compared with an age and sex matched control group. RESULTS: Three patients spontaneously complained of flashing lights. A further nine patients had this symptom when directly questioned. 18 patients had no symptoms. None of the 33 control patients had symptoms on direct questioning. Sagittal MRI and cine MRI failed to demonstrate globe compression by the inferior rectus muscle even in cases that showed an intraocular pressure rise in upgaze. CONCLUSION: A new symptom of flashing lights in upgaze has been identified in thyroid eye disease patients with tight inferior recti. It is suggested that the lights are likely to be phosphenes as a result of either compression of the globe by a tight inferior rectus or traction on the insertion of the inferior rectus. The small amount of globe compression required to produce phosphenes seems to be beyond the resolution limit of MRI.

Adult↗

Stimulation of the human frontal eye fields modulates sensitivity of extrastriate visual cortex.

The precise role of frontal eye fields (FEF) in vision independent of their role in eye movements remains a matter of debate. One proposal is that the FEF exert top-down influences on the extrastriate visual cortex prior to eye movement preparation. Here we establish, by use of transcranial magnetic stimulation (TMS), that activity in the human FEFs has a direct effect on the sensitivity of extrastriate visual area MT/V5, and that the spatial organization of this top-down effect is lateralized in the human brain. We show that phosphene threshold-the TMS intensity required to elicit a visual perception-for MT/V5 stimulation changes as a function of the delay between the application of TMS over FEF and MT/V5. The effects were specific to the location and time of stimulation. Stimulation of FEF 20-40 ms prior to stimulation of MT/V5 decreased the intensity of MT/V5 stimulation required to elicit phosphenes: TMS of the right FEF changed the sensitivity of left and right MT/V5 whereas TMS of the left FEF changed the sensitivity only of the left MT/V5. Thus, the sensitivity of human extrastriate cortex is modulated by activity in the FEF.

Brain Mapping↗

Facial recognition using simulated prosthetic pixelized vision.

PURPOSE: To evaluate a model of simulated pixelized prosthetic vision using noncontiguous circular phosphenes, to test the effects of phosphene and grid parameters on facial recognition. METHODS: A video headset was used to view a reference set of four faces, followed by a partially averted image of one of those faces viewed through a square pixelizing grid that contained 10x10 to 32x32 dots separated by gaps. The grid size, dot size, gap width, dot dropout rate, and gray-scale resolution were varied separately about a standard test condition, for a total of 16 conditions. All tests were first performed at 99% contrast and then repeated at 12.5% contrast. RESULTS: Discrimination speed and performance were influenced by all stimulus parameters. The subjects achieved highly significant facial recognition accuracy for all high-contrast tests except for grids with 70% random dot dropout and two gray levels. In low-contrast tests, significant facial recognition accuracy was achieved for all but the most adverse grid parameters: total grid area less than 17% of the target image, 70% dropout, four or fewer gray levels, and a gap of 40.5 arcmin. For difficult test conditions, a pronounced learning effect was noticed during high-contrast trials, and a more subtle practice effect on timing was evident during subsequent low-contrast trials. CONCLUSIONS: These findings suggest that reliable face recognition with crude pixelized grids can be learned and may be possible, even with a crude visual prosthesis.

Adult↗

Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine.

OBJECTIVES: We hypothesized that the hyperexcitability of occipital cortex neurons may predispose migraine subjects to develop spreading depression, the putative basis of migraine with aura (MwA). To date there is no direct physiologic correlate confirming this in patients. Accordingly, we evaluated the differences in the threshold of occipital cortex excitation between MwA patients and normal controls (C) using transcranial magnetic stimulation (TMS). METHODS: TMS was performed using the Cadwell MES 10 stimulator. A circular coil 9.5 cm in 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 just visualized. RESULTS: Eleven MwA patients, mean age 37 +/- 7 years, were compared with 11 C, mean age 37.7 +/- 7 years. The difference in the proportion of subjects with phosphene generation between MwA patients and C was significant (MwA patients 100% versus C 27.3%, p = 0.001). The mean threshold level for MwA patients was 44.2 +/- 8.6 versus 68.7 +/- 3.1 for C (p = 0.0001). All threshold levels for MwA patients were lower than the lowest threshold for C; the MwA patient with the lowest threshold had an aura after stimulation. CONCLUSIONS: The threshold for excitability of occipital cortex is lower in MwA patients compared with C. This is a direct neurophysiologic correlate for clinical observations that have indicated hyperexcitability of the occipital cortex in migraineurs.

Adult↗

Transcranial magnetic stimulation in migraine: a review of facts and controversies.

There is compelling evidence that cortical excitability is modified in migraine patients between attacks. Transcranial magnetic stimulation (TMS) is a non-invasive tool to investigate this abnormality. Repetitive transcranial magnetic stimulation (rTMS) activates the underlying cortex at high, but inhibits it at low stimulation frequencies. This is a review of published results obtained in migraineurs with TMS and rTMS over motor or visual cortices. Prevalence and/or threshold data of phosphenes induced by single pulse TMS of the visual cortex are contradictory, some favouring increased, others decreased interictal excitability. The discrepancies may be due to differences in methodology and poor reliability of phosphene reporting. In a recent rTMS study of the occipital cortex we have found evidence in favour of an interictal decrease of the preactivation excitability level by using amplitude of visual evoked potentials and its habituation during sustained stimulation as indices of cortical excitability. The hypothesis of increased cortical excitability, taken in its strict physiological sense of a decreased response threshold and/or an increased response to a single suprathreshold stimulus, may thus not be any longer tenable. The long lasting effects of rTMS allow in future studies to assess metabolic changes of the cortex and subcortical structures with functional imaging methods and to explore novel therapeutic strategies for migraine.

Cerebral Cortex↗

[Electrophysiological diagnosis in partial optic nerve atrophy syndrome].

Vision conduction routes were examined in 75 patients with the syndrome of optic nerve partial atrophy by recording the visual evoked potentials, threshold of electric sensitivity emergence, critical frequency of phosphene disappearance, electroretino- and electroneurograms. The findings of these examinations correlated best of all with the clinical picture when visual evoked potentials (latency increase, decrease of the amplitude with atrophy augmentation, interhemispheric asymmetry in chiasmal and retro-chiasmal involvement) or the critical frequency of phosphene disappearance (reliably reduced if a disease was developing) were recorded. Introduction of electrodes with therapeutic and diagnostic purpose permitted assessment of optic nerve function from the electroneurogram amplitude and time parameters.

Electrophysiology↗

J.E. Purkynĕ's contributions to the physiology of the visual, the vestibular and the oculomotor systems.

J.E. Purkynĕ (1787-1869) was one of the leading physiologists in the first half of the 19th century, became the founder of the "exact subjectivism", and remained during his entire life a very careful observer in psychophysical experiments. He made moreover many important discoveries in anatomy, neuroanatomy, embryology and pharmacology. Despite his outstanding contributions to science, he remained in his general philosophy and feelings deeply attached to the Romantic spirit of the age. After Purkynĕ returned to Prague in 1849 he played an important role in his nation's search for a national identity and became a leading figure in the cultural and social life of Prague. Purkynĕ's contributions to the physiology of vision, the oculomotor and the vestibular systems are reviewed. In vision Purkynĕ discovered the Purkynĕ-tree, flicker patterns seen in diffuse light, moving light nebula in the Eigengrau, spatially patterned structures in pressure phosphenes, the antagonistic properties of Galvanic phosphenes with respect to current polarity, periodic afterimages, the Troxler effect for colour perception with the peripheral retina and the principle of the ophthalmoscope. The Purkynĕ-shift in chromatic sensitivity when the adaptation level shifts from scotopic to photopic vision was rediscovered by Purkynĕ. Purkynĕ was the first to describe the "Purkynĕ images" of the anterior and posterior surfaces of the cornea and the lens and the changes in the third Purkynĕ image when the eye accommodates. He described optokinetic nystagmus and optokinetic after-nystagmus and explained movement aftereffects as a habituation of the gaze motor system. Important contributions were made by Purkynĕ to the physiology of the vestibular system, but he did not propose the existence of peripheral receptors for this system. He believed that direct mechanical effects on certain parts of the brain (especially the cerebellum) are responsible for the mechanisms of vertigo. Purkynĕ's five categories of vertigo are still valid today (vertigo of motion, Galvanic vertigo, vertigo caused by general brain ischemia, height vertigo and vertigo caused by alcohol and other narcotics). Purkynĕ's contribution to sensory physiology can be considered as one of the essential foundations on which modern sensory physiology and psychophysics are built.

Adaptation, Ocular↗

[The effects of electric stimulation of the visual cortex of the cat in a behavior model of placing reaction].

In 5 alert cats, the dependence of latency and probability of placing reaction on the parameters of electrical stimulation of visual cortex (the pulse duration and frequency in a series, number of pulses in a series) was studied. The values of current parameters were analogous to those that aroused human phosphens. The results revealed the conformity of the dependence of phosphens and cat's motor reaction on the current parameters. An addition of sound or electrocutaneous stimuli to the current stimulation decreases the threshold of the motor reaction and increases its probability. It is particularly obvious in case of weak and middle intensity currents when the probability of correct reactions to the current is insignificant.

Animals↗

Specific features of the electroretinogram of vertebrates induced by X-rays.

The net electroretinograms of dark-adapted retinas of the common frog in situ were investigated on an automated experimental system with programmed control and electronic differentiation of biopotentials with respect to the first and second derivatives. It was demonstrated that X-rays elicit an electroretinogram consisting of two components, provisionally called the first and second X-ray reactions (X-1 and X-2), which differ with respect to their parameters from electroretinograms elicited under the same conditions by red and blue light. The administration of sodium azide, sodium nitrate, monoiodo-acetate and other substances alter the X-1 and X-2 as well as the photo-induced ERGs in different ways; this indicates their relative independence and different mechanisms of the occurrence and passing of excitation across the structures of the retina, and makes it possible to partially isolate these for individual study. Thus, the assertion of a number of investigators regarding the absence of specific features in the X-ray induced electroretinograms becomes problematical. The discovery of X-ray-specific reactions in the retina makes it possible to hope that the radiological phosphene (the X-ray phosphene) may serve as a test for the determination of the individual radiational excitability of the central nervous system.

Animals↗