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PubMed2002

Changes in visual cortex excitability in blind subjects as demonstrated by transcranial magnetic stimulation.

Any attempt to restore visual functions in blind subjects with pregeniculate lesions provokes the question of the extent to which deafferented visual cortex is still able to generate conscious visual experience. As a simple approach to assessing activation of the visual cortex, subjects can be asked to report conscious subjective light sensations (phosphenes) elicited by focal transcranial magnetic stimulation (TMS) over the occiput. We hypothesized that such induction of phosphenes can be used as an indicator of residual function of the visual cortex and studied 35 registered blind subjects after partial or complete long-term (>10 years) deafferentation of the visual cortex due to pregeniculate lesions. TMS was applied over the visual cortex in 10 blind subjects with some residual vision (visual acuity <20/400; Group 1), 15 blind subjects with very poor residual vision (only perception of movement or light; Group 2), 10 blind subjects without any residual vision (Group 3) and 10 healthy controls. A stimulation mapping procedure was performed on a 1 x 1 cm skull surface grid with 130 stimulation points overlying the occipital skull. We analysed the occurrence of phosphenes at each stimulation point with regard to frequency and location of phosphenes in the visual field. Previous experiments have shown that repetitive TMS reliably elicits brief flashes of white or coloured patches of light. Therefore, stimulation was performed with short trains of seven consecutive 15 Hz stimuli applied with an intensity of 1.3 times the motor threshold. Under such conditions, phosphenes occurred in 100% of subjects in Group 1, in 60% of Group 2 and in 20% of Group 3. Phosphene thresholds were normal, but the number of effective stimulation sites was significantly reduced in Groups 2 and 3. The results indicate that in blind subjects there is alteration in TMS-induced activation of the deafferented visual cortex or processes engaged in bringing the artificial cortex input to consciousness. The ability to elicit phosphenes is reduced in subjects with a high degree of visual deafferentation, especially in those without previous visual experience.

Adolescent↗
PubMed2005

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.

Adult↗
PubMed2000

Enhanced excitability of the human visual cortex induced by short-term light deprivation.

Long-term deprivation of visual input for several days or weeks leads to marked changes in the excitability and function of the occipital cortex. The time course of these changes is poorly understood. In this study, we addressed the question whether a short period of light deprivation (minutes to a few hours) can elicit such changes in humans. Noninvasive transcranial magnetic stimulation (TMS) of the human occipital cortex can evoke the perception of flashes or spots of light (phosphenes). To assess changes in visual cortex excitability following light deprivation, we measured the minimum intensity of stimulation required to elicit phosphenes (phosphene threshold) and the number of phosphenes elicited by different TMS stimulus intensities (stimulus-response curves). A reduced phosphene threshold was detected 45 min after the onset of light deprivation and persisted for the entire deprivation period (180 min). Following re-exposure to light, phosphene thresholds returned to predeprivation values over 120 min. Stimulus-response curves were significantly enhanced in association with this intervention. In a second experiment, we studied the effects of light deprivation on functional magnetic resonance imaging (fMRI) signals elicited by photic stimulation. fMRI results showed increased visual cortex activation after 60 min of light deprivation that persisted following 30 min of re-exposure to light. Our results demonstrated a substantial increase in visual cortex excitability. These changes may underlie behavioral gains reported in humans and animals associated with light deprivation.

Adult↗
PubMed2004

Retinotopy with coordinates of lateral occipital cortex in humans.

OBJECT: The lateral occipital cortex in humans is known as the "extrastriate visual cortex." It is, however, an unexplored field of research, and the anatomical nomenclature for its surface has still not been standardized. This study was designed to investigate whether the lateral occipital cortex in humans has retinotopic representation. METHODS: Four right-handed patients with a diagnosis of intractable epilepsy from space-occupying lesions in the occipital lobe or epilepsy originating in the occipital lobe received permanently implanted subdural electrodes. Electrical cortical stimulation was applied directly applied to the brain through metal electrodes by using a biphasic stimulator. The location of each electrode was measured on a lateral skull x-ray study. Each patient considered a whiteboard with vertical and horizontal median lines. The patient was asked to look at the midpoint on the whiteboard. If a visual hallucination or illusion occurred, the patient recorded its outline, shape, color, location, and motion on white paper one tenth the size of, and with vertical and horizontal median lines similar to those on, the whiteboard. Polar angles and eccentricities of the midpoints of the phosphenes from the coordinate origin were measured on the paper. On stimulation of the lateral occipital lobe, 44 phosphenes occurred. All phosphenes were circular or dotted, with a diameter of approximately 1 cm, except one that was like a curtain in the peripheral end of the upper and lower visual fields on stimulation of the parietooccipital region. All phosphenes appeared in the visual field contralateral to the cerebral hemisphere stimulated. On stimulation of the lateral occipital lobe, 22 phosphenes moved centrifugally or toward a horizontal line. From three-dimensional scatterplots and contour maps of the polar angles and eccentricities in relation to the x-ray coordinates of the electrodes, one can infer that the lateral occipital cortex in humans has retinotopic representation. CONCLUSIONS: The authors found that phosphenes induced by electrical cortical stimulation of the lateral occipital cortex represent retinotopy. From these results one can assert that visual field representation with retinotopic relation exists in the extrastriate visual cortex.

Adult↗
PubMed1968

The sensations produced by electrical stimulation of the visual cortex.

1. An array of radio receivers, connected to electrodes in contact with the occipital pole of the right cerebral hemisphere, has been implanted into a 52-year-old blind patient. By giving appropriate radio signals, the patient can be caused to experience sensations of light (;phosphenes') in the left half of the visual field.2. The sensation caused by stimulation through a single electrode is commonly a single very small spot of white light at a constant position in the visual field; but for some electrodes it is two or several such spots, or a small cloud.3. For weak stimuli the map of the visual field on the cortex agrees roughly with the classical maps of Holmes and others derived from war wounds. With stronger stimuli, additional phosphenes appear; these follow a map that is roughly the classical map inverted about the horizontal meridian.4. The phosphenes produced by stimulation through electrodes 2.4 mm apart can be easily distinguished. By stimulation through several electrodes simultaneously, the patient can be caused to see predictable simple patterns.5. The effects of the duration and frequency of stimulating pulses on the threshold have been explored.6. For cortical phosphenes there is no sharp flicker fusion frequency, and probably no flicker fusion frequency at all.7. During voluntary eye movements, the phosphenes move with the eyes. During vestibular reflex eye movements they remain fixed in space.8. Phosphenes ordinarily cease immediately when stimulation ceases, but after strong stimulation they sometimes persist for up to 2 min.9. Our findings strongly suggest that it will be possible, by improving our prototype, to make a useful prosthesis.

Accommodation, Ocular↗
PubMed2001

Visual cortex excitability in migraine with and without aura.

OBJECTIVES: Previous research using transcranial magnetic stimulation has produced equivocal findings concerning thresholds for the generation of visual phosphenes in migraine with aura. These studies were methodologically varied and did not systematically address cortical excitability in migraine without aura. We therefore studied magnetophosphene thresholds in both migraine with aura and migraine without aura compared with headache-free controls. METHODS: Sixteen subjects with migraine with aura and 12 subjects with migraine without aura were studied and compared with 16 sex- and age-matched controls. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the threshold stimulation intensity at which subjects just perceived phosphenes via a method of alternating course and fine-tuning of stimulator output. RESULTS: There were no significant differences across groups in the proportion of subjects seeing phosphenes. However, the mean threshold at which phosphenes were reported was significantly lower in both migraine groups (migraine with aura=47%, migraine without aura=46%) than in controls (66%). Moreover, there was no significant correlation between individual phosphene threshold and the time interval to the closest migraine attack. CONCLUSION: Our findings confirm that the occipital cortex is hyperexcitable in the migraine interictum, both in migraine with and without aura.

Adolescent↗
PubMed2002

Transcranial magnetic stimulation of visual area V5 in migraine.

OBJECTIVE: To examine visual cortical excitability in persons with migraine using transcranial magnetic stimulation (TMS) over an extrastriate area of the brain, area V5. BACKGROUND: Previous studies found that persons with migraine have a lower phosphene threshold than healthy control subjects with TMS delivered over the primary visual cortical area V1. The result suggests that the occipital cortex in migraineurs between migraine attacks is hyperexcitable. However, it is not known whether interictal cortical hyperexcitability is also present in areas of the association visual cortex. METHOD: To investigate this, single-pulse TMS was delivered over visual area V5, the motion cortex, to 16 persons with migraine and visual aura, nine migraineurs without visual aura, and 16 healthy control subjects. TMS was delivered at intensities ranging from 30 to 100% of maximum stimulator output or until the participant reported seeing phosphenes (visual illusions characterized by flashes of light). Thresholds to phosphenes were obtained for each participant using a staircase procedure. RESULT: Significantly lower phosphene thresholds for TMS delivered over V5 were found in migraineurs as compared with control subjects. Qualitatively, the migraineurs' experience of phosphenes were more vivid, florid, and sustained compared with that of control subjects. CONCLUSION: Results of this study indicate that hyperexcitability of the visual cortex in migraine goes beyond visual area V1 and demonstrates for the first time a significant difference in threshold for excitability of visual area V5 in persons with migraine.

Adolescent↗
PubMed1996

Visual perception elicited by electrical stimulation of retina in blind humans.

OBJECTIVE: To evaluate the feasibility of bypassing damaged photoreceptors and electrically stimulating the remaining viable retinal layers to provide limited visual input to patients who are blind because of severe photoreceptor degeneration. METHODS: In the operating room with the patient under local anesthesia, focal electrical stimulation of the retinal surface with brief biphasic pulses was performed using small probes inserted through the sclera. The procedure was performed in five subjects who had little or no light perception. Three subjects had retinitis pigmentosa, one had age-related macular degeneration, and one had unspecified retinal degeneration from birth. RESULTS: Stimulation elicited visual perception of a spot of light (phosphene). Subjects who previously had useful vision accurately localized the phosphenes according to the retinal area stimulated. Two subjects could track the movement of the stimulating electrode by reporting movement of the elicited phosphene, and could perceive two simultaneous phosphenes on independent stimulation with two electrodes. In a resolution test, one of the subjects with no light perception in his left eye resolved phosphenes at 1.75 degrees center-to-center distance (ie, 4/200 OS visual acuity). CONCLUSIONS: Local electrical stimulation of the retinal surface in patients blind from outer retinal disease results in focal light perception that seems to arise from the stimulated area. Such findings in an acute experiment warrant further research into the possibility of prolonged retinal stimulation, improved resolution, and ultimately, an intraocular visual prosthesis.

Adult↗
PubMed1984

Coloured patterns in hemianopic fields.

In a group of 96 patients with homonymous hemianopia or quadrantanopia from various causes, usually vascular lesions, 14 experienced coloured patterns in the hemianopic field. A questionnaire was used in an attempt to obtain as much information as possible on these phosphenes. They appeared in four major colours--red, green, blue and yellow--usually in fields that joined to form horizontally and vertically orientated geometric patterns. They demonstrated translocation related to ocular movement but otherwise were not influenced in any way by ocular movement or by opening and closing the eyes. The patients experiencing these phosphenes constituted a homogeneous group in relation to neurological findings, cause of hemianopia, CT findings and prognosis. All had sustained cerebral infarction, and CT studies revealed small circumscribed lesions, usually subcortically in the striate area of the interhemispheric fissure and the adjacent white matter in the occipital lobes. The visual defects resolved completely or to a considerable extent in many cases, which suggests that the phosphenes are associated with hemianopia due to a functional disorder rather than to tissue loss. Coloured patterns are therefore a prognostically favourable symptom. The geometric structure of the phosphenes and the fact that the same four colours consistently reappear must reflect the neuronal organization of the visual cortex. It can be postulated that this functional unit is organized on the basis of pyramids and tetrahedrons. The similarity of the geometric structures to the fortification lines encountered in migraine raises the possibility that the patterns are generated in the striate cortex. Absence of alteration in size with increasing distance from the fovea suggests that these phosphenes originate in a prestriate area. The colours reported indicate stimulation of intact colour-coding neurons in the prestriate area.

Adolescent↗
PubMed1972

Electrical stimulation of the human eye in different adaptational states.

1. Experiments are described in which the phosphene produced by passing alternating current of frequency 100 Hz through the eye is matched with a patch of light having the same apparent size.2. Matches of this type have been made against different background light intensities, and at various times after a strong retinal bleach.3. To match the phosphene under particular conditions of this type, it is found that the patch must be set some 1.5 log td brighter than its own threshold under the same conditions. Exceptions to this rule occur with very bright backgrounds, or very soon after bleaching.4. The increment threshold for a small spot of light on the phosphene in the dark is some 0.5 log td higher than for the same spot on a patch of light matched in appearance to the phosphene under the same conditions.5. The process linking electrical stimulation of the eye to firing of fibres in the optic nerve is deduced to be substantially unaffected by the state of adaptation of the eye, save perhaps in the exceptional conditions described in (3).6. It is therefore argued that this phosphene is the result of stimulation both of the retinal visual pathways lying central to the variable-gain element commonly accepted to explain the facts of dark adaptation, and also of the input to this element that is supposed to alter its gain.

Adaptation, Ocular↗
PubMed2006

Motor and occipital cortex excitability in migraine patients.

OBJECTIVE: We evaluated motor and occipital cortex excitability in migraine patients using transcranial magnetic stimulation. METHODS: 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. RESULTS: 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. CONCLUSION: Our findings indicate that the occipital cortex, but not the motor cortex, is hyperexcitable in migraine patients.

Action Potentials↗
PubMedDate not supplied

The occipital cortex is hyperexcitable in migraine: experimental evidence.

OBJECTIVES: Threshold for generation of magnetophosphenes has been reported to be lower in migraine. We compared the threshold for eliciting phosphenes by transcranial magnetic stimulation and the ability to visually trigger headache in a select group of individuals with migraine with and without aura to normal controls. METHODS: Transcranial magnetic stimulation 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. Stimulator intensity was then fine-tuned to determine the threshold at which phosphenes were seen. In the same subjects, visual stimulation was given in 3.0 T MRI and if a headache occurred the response was recorded. RESULTS: Fifteen subjects with migraine were compared to 8 controls. A significant proportion of the migraineurs (86.7%) developed phosphenes compared to the controls (25%) (P = .006). The probability of triggering a headache was also higher in the migraineurs (53%); no headache was triggered in the controls (P = .019). A significant correlation was found between the threshold for phosphenes on transcranial magnetic stimulation and visually triggered headache (P = .002). When only migraine was considered, there was again a significant trend (P = .084). CONCLUSIONS: There is a difference in threshold for excitability of occipital cortex in migraineurs and controls. The hyperexcitable visual cortex in migraine is predisposed to visually triggered headache.

Adult↗
PubMed2005

[Intraocular pressure measurement using the Proview tonometer].

PURPOSE: To evaluate a new ocular tonometer (Proview) which functions by visualizing a phosphene after putting pressure on the upper eyelid. To ascertain its accuracy and reproducibility with respect to the Goldmann tonometer (GT). METHODS: A study on both eyes of 110 non-selected patients was performed. One measurement with GT and three subsequent measurements with Proview were taken by the same investigator. The number of failed attempts to visualize the phosphene was recorded. We evaluated each eye separately to observe the possible learning effect. RESULTS: The intraocular pressure (IOP) mean with Proview is 5 mm Hg higher than the GT (p < 0.001). The coefficient of correlation between both instruments is low (R = 0.67; R(2) = 0.45) in the right eye (RE). The difference between maximum and minimum values of the 3 measurements taken with the Proview was 3.21 (SD: 1.73) mm Hg in RE. The failed attempts to see the phosphene were 5.14 (SD: 2.39) in RE and 4.93 (SD: 2.78) in left eye (p > 0.05). CONCLUSIONS: The Proview(R) tonometer showed low accuracy and reproducibility in comparison with the GT. This tonometer requires a long learning process before phosphene visualization. The results demonstrated that this tonometer is not clinically useful, except in patients with serious corneal diseases which make measurement with GT very difficult.

Female↗
PubMed1992

[Examination of the visual system with transcranial magnetic stimulation].

The influence of transcranially applied magnetic stimuli on the function of the afferent (sensory) and efferent (motor) parts of the visual system have been discussed. Excitatory (positive) phenomena are subjective photic sensations (phosphenes) which can be elicited by transcranial magnetic stimulation over occipital parts of the skull. The phosphenes appear on the left or right side of the visual field depending upon the direction of the coil currents, which determines whether the visual cortex of the right or the left hemisphere is activated. The configuration of the phosphene fields hints at an excitation of the primary visual cortex (Brodmann's area 17). However, magnetic brain stimulation also produces inhibitory (negative) phenomena. When strong magnetic field pulses are applied over the primary visual cortex, foveally presented visual stimuli cannot be identified even when no phosphenes are perceived at the same time. Depending on the position of the stimulation coil, this suppression of perception can be restricted to visual stimuli presented on the right, or left of, above or below the fixation point. No generation or disturbance of eye movements by transcranial magnetic stimulation has been reported before, except for a delay of saccades within a reaction time paradigm.

Animals↗
PubMed2006

Enhanced performance with brain stimulation: attentional shift or visual cue?

The premotor theory of visual spatial attention proposes that the same brain activity that prepares for saccades to one part of the visual field also facilitates visual processing at that same region of the visual field. Strong support comes from improvements in performance by electrical stimulation of presaccadic areas, including the frontal eye field and superior colliculus (SC). Interpretations of these stimulation experiments are hampered by the possibility that stimulation might be producing an internal visual flash or phosphene that attracts attention as a real flash would. We tested this phosphene hypothesis in the SC by comparing the effect of interchanging real visual stimuli and electrical stimulation. We first presented a veridical visual cue at the time SC stimulation improved performance; if a phosphene improved performance at this time, a real cue should do so in the same manner, but it did not. We then changed the time of SC visual-motor stimulation to when we ordinarily presented the veridical visual cue, and failed to improve performance. Last, we shifted the site of SC stimulation from the visual-motor neurons of the SC intermediate layers to the visual neurons of the superficial layers to determine whether stimulating visual neurons produced a larger improvement in performance, but it did not. Our experiments provide evidence that a phosphene is not responsible for the shift of attention that follows SC stimulation. This added evidence of a direct shift of attention is consistent with a key role of the SC in the premotor theory of attention.

Animals↗
PubMed2002

Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz repetitive transcranial magnetic stimulation.

Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS.

Adult↗
PubMed2005

Transcranial magnetic stimulation in the visual system. I. The psychophysics of visual suppression.

When applied over the occipital pole, transcranial magnetic stimulation (TMS) disrupts visual perception and induces phosphenes. Both the underlying mechanisms and the brain structures involved are still unclear. The first part of the study characterizes the suppressive effect of TMS by psychophysical methods. Luminance increment thresholds for orientation discrimination were determined in four subjects using an adaptive staircase procedure. Coil position was controlled with a stereotactic positioning device. Threshold values were modulated by TMS, reaching a maximum effect at a stimulus onset asynchrony (SOA) of approx. 100 ms after visual target presentation. Stronger TMS pulses increased the maximum threshold while decreasing the SOA producing the maximum effect. Slopes of the psychometric function were flattened with TMS masking by a factor of 2, compared to control experiments in the absence of TMS. No change in steepness was observed in experiments using a light flash as the mask instead of TMS. Together with the finding that at higher TMS intensities, threshold elevation occurs even with shorter SOAs, this suggests lasting inhibitory processes as masking mechanisms, contradicting the assumption that the phosphene as excitatory equivalent causes masking. In the companion contribution to this one we present perimetric measurements and phosphene forms as a function of the stimulation site in the brain and discuss the putative generator structures.

Adult↗
PubMed2005

Hypo-excitability of cortical areas in patients affected by Friedreich ataxia: a TMS study.

The aim of the study was to explore excitability of a motor and a non-motor (visual) area in patients affected by Friedreich ataxia and to correlate neurophysiological data with clinical parameters. Seven patients (3M/4F) and ten healthy controls (5M/5F) participated in the study. The hot-spot for activation of right abductor pollicis brevis was checked by means of a figure-of-eight coil and the motor threshold (MT) on this point was recorded. The phosphene threshold (PT) was measured by means of a focal coil over the occipital cortex as the lower intensity of magnetic stimulation able to induce the perception of phosphenes. The patients showed a significantly higher mean PT (p<.03) and MT values (p<.001) than controls. In all but one patient unable to perceive phosphenes (42% vs. 50% of controls), TMS at 100% intensity did not elicit motor response at rest. The difference in percentage of patients (57.1%) and controls (100%) with motor responses was nearly significant. The size of GAA1 expansion showed significant correlations with PT and MT values. The results of our study showed that FA patients had reduced cortical activation, involving both the motor and the visual cortex. The cortical involvement in these patients seems to be mainly genetically determined. The study provides the first evidence of cortical dysfunction in patients with genetically defined Friedreich ataxia.

Adolescent↗