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PubMed2006

Phosphene induction by microstimulation of macaque V1.

Non-human primates are being used to develop a cortical visual prosthesis for the blind. We use the properties of electrical microstimulation of striate cortex (area V1) of macaque monkeys to make inferences about phosphene induction. Our analysis is based on well-established properties of V1: retino-cortical magnification factor, receptive-field size, and the characteristics of hypercolumns. We argue that phosphene size is dependent on the amount of current delivered to V1 and on the retino-cortical magnification factor. We suggest that to improve the correspondence between the site of stimulation within V1 and the visual field location of an elicited phosphene both eyes must be put under experimental control given that phosphene location is retinocentric and given that the vergence angle between the eyes might affect the position of a phosphene in depth. Knowing how electrical microstimulation interacts with cortical tissue to evoke percepts in behaving macaque monkeys is fundamental to the establishment of an effective cortical visual prosthesis for the blind.

Animals↗
PubMed2001

Motor and phosphene thresholds: a transcranial magnetic stimulation correlation study.

OBJECTIVE: To investigate the stability of visual phosphene thresholds and to assess whether they correlate with motor thresholds. BACKGROUND: Currently, motor threshold is used as an index of cortical sensitivity so that in transcranial magnetic stimulation (TMS) experiments, intensity can be set at a given percentage of this value. It is not known whether this is a reasonable index of cortical sensitivity in non-motor and hence whether it should be used in experiments where other cortical areas are targeted. Previous studies have indicated that phosphene threshold might be a suitable alternative in TMS studies of the visual system. METHOD: Using single pulse TMS visual phosphene and motor thresholds were measured in 15 subjects. Both thresholds were retested in seven of these subjects a week later. RESULT: Visual phosphene thresholds, though stable within subjects across the two sessions, showed greater variability than motor thresholds. There was no correlation between the two measures. CONCLUSION: TMS motor thresholds cannot be assumed to be a guide to visual cortex excitability and by extension are probably an inappropriate guide to the cortical excitability of other non-motor areas of the brain. Phosphene thresholds are proposed as a potential standard for inter-individual comparison in visual TMS experiments.

Adult↗
PubMed1999

Phosphenes and transient scotomas induced by magnetic stimulation of the occipital lobe: their topographic relationship.

Transcranial magnetic stimulation (TMS) of the visual cortex is known to induce phosphenes and is able to suppress visual perception. To address the topographic relationship of phosphenes and transient scotomas, the visual field of 10 normal subjects was investigated using a perimetric approach. The central visual field (diameter: 20 degrees) was tested at 32 sites. Perceptual thresholds were determined by presenting 1 ms test spots flashed with varying intensity in random order. TMS was applied with a focal figure-of-eight coil placed over the inion. All subjects perceived phosphenes, mostly restricted to one of the lower quadrants within the visual field. In 13 out of 15 investigations, a magnetic stimulus triggered 100 ms after the visual target resulted in a relative scotoma with threshold changes of 8 dB or more. In 9 of 13 investigations, scotomas coincided spatially with sketches of phosphenes made by subjects in a separate test. Scotomas covered only a small percentage of the total visual field, which may explain the failure of previous studies to find perceptual suppression with the focal coil. The present result demonstrates that phosphenes evoked during TMS can serve as a guide for optimal visual stimulus alignment in neuropsychological experiments.

Adult↗
PubMed2005

Intraocular pressure measurement in patients with previous LASIK surgery using pressure phosphene tonometer.

PURPOSE: To compare intraocular pressure (IOP) assessment in post-LASIK patients using non-contact tonometry, pressure phosphene tonometry and applanation tonometry. METHODS: Sixty-two consecutive LASIK patients were analysed preoperatively and postoperatively with non-contact, pressure phosphene and applanation tonometry. Comparisons among these values were assessed with paired sample Student t-test, Pearson's correlation test and Bland-Altman plotting. RESULTS: There was no significant difference for preoperative IOP measurement between non-contact, pressure phosphene and applanation tonometry. The mean +/-SD difference between the preoperative non-contact tonometry and postoperative pressure phosphene tonometry IOP measurements was 0.80 +/- 2.77 mmHg (P < 0.01). Postoperative applanation tonometry significantly underestimated IOP measurement by 5.45 +/- 2.96 mmHg (P < 0.001) and postoperative non-contact tonometry significantly underestimated IOP measurement by 9.96 +/- 2.25 mmHg (P < 0.001). CONCLUSION: Pressure phosphene tonometry may provide an alternative method for the assessment of IOP in post-LASIK patients.

Adult↗
PubMed2004

Consecutive transcranial magnetic stimulation: phosphene thresholds in migraineurs and controls.

OBJECTIVE: To characterize the temporal course of transcranial magnetic stimulation-induced phosphene thresholds in subjects with migraine and in controls. METHODS: Eleven subjects with migraine with aura, 10 subjects with migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no history of migraine and without migraine during the study) were studied. Subjects were not on preventive medication. Transcranial magnetic stimulation was performed, and a phosphene threshold was measured 3 times a week over 3 weeks in a manner timed to incorporate the menstrual period in females. A headache calendar was kept during the study. RESULTS: Mean transcranial magnetic stimulation thresholds were lower for each migraine group compared with controls (P <.001) for each comparison. There was a trend for lower thresholds among subjects with migraine with aura compared with subjects with migraine without aura (P <.10), but not subjects with menstrual migraine. There was consistent lowering of thresholds from the first to the last stimulation in all migraine groups and in the controls. Maximum and minimum thresholds did not predict headache occurrence, nor did the occurrence of headache predict an ensuing maximum or minimum phosphene threshold. CONCLUSIONS: Transcranial magnetic stimulation thresholds are lower in subjects with migraine compared with controls. The reported phosphene threshold is lowered with repeated measurement. Neither high nor low phosphene thresholds predict a subsequent headache, nor do migraines predict a subsequent high or low threshold.

Electric Stimulation↗
PubMed2006

Phosphenes electrically evoked with DTL electrodes: a study in patients with retinitis pigmentosa, glaucoma, and homonymous visual field loss and normal subjects.

PURPOSE: To develop an improved, easy, and safe method for reliably eliciting electrical phosphenes and to compare reported perceptions and values of chronaxie and rheobase in healthy individuals and patients with distinct ophthalmic diseases. METHODS: DTL electrodes were used with a four-alternative, forced-choice method to determine psychophysically the strength-duration curves by using the Weiss model of electrical tissue stimulation in 47 subjects: healthy individuals (n = 17; n = 6 under light- and dark-adapted conditions), patients with open-angle glaucoma (n = 9), retinitis pigmentosa (RP; n = 14), amblyopia (n = 3), or homonymous visual field loss (n = 4). RESULTS: In all subjects, thresholds were safely determined without side effects. Subjects reported a homogenous, central, white, steady phosphene. The rheobase was higher in glaucoma and patients with RP than in healthy subjects (0.1129 +/- 0.0314 and 0.6868 +/- 0.1054 vs. 0.0383 +/- 0.0057 mA; P = 0.05 and <0.00001, respectively), and it increased with age (r = 0.51; P = 0.038). The rheobase was lower in light- than in dark-adapted conditions (difference 0.015 mA; P = 0.016). In patients with RP, no correlation was found between rheobase or chronaxie and retinal thickness (in OCT) or number of years after reading loss, but there was a correlation between rheobase and visual acuity (P = 0.014). In patients with RP or glaucoma, no inhomogeneity of phosphenes was reported, but all patients with homonymous visual field loss reported lateralization of the phosphene into the area of visual loss. CONCLUSIONS: Use of DTL electrodes to elicit electrical phosphenes is safe, fast, and reliable. It bears significant advantages over corneal electrodes and provides a valuable tool to elucidate ophthalmologic disease processes and to screen candidates for retinal prostheses.

Adult↗
PubMed2002

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.

Electric Conductivity↗
PubMed1992

Simulation of a phosphene-based visual field: visual acuity in a pixelized vision system.

A visual prosthesis for the blind using electrical stimulation of the visual cortex will require the development of an array of electrodes. Passage of current through these electrodes is expected to create a visual image made up of a matrix of discrete phosphenes. The quality of the visual sense thus provided will be a function of many parameters, particularly the number of electrodes and their spacing. We are conducting a series of psychophysical experiments with a portable "phosphene" simulator to obtain estimates of suitable values for electrode number and spacing. The simulator consists of a small video camera and monitor worn by a normally sighted human subject. To simulate a discrete phosphene field, the monitor is masked by an opaque perforated film. The visual angle subtended by images from the masked monitor is 1.7 degrees or less, depending on the mask, and falls within the fovea of the subject. In the study presented here, we measured visual acuity as a function of the number of pixels and their spacing in the mask. Visual acuity was inversely proportional to pixel density, and trained subjects could achieve about 20/26 visual acuity with a 1024 pixel image. We conclude that 625 electrodes implanted in a 1 cm by 1 cm area near the foveal representation of the visual cortex should produce a phosphene image with a visual acuity of approximately 20/30. Such an acuity could provide useful restoration of functional vision for the profoundly blind.

Blindness↗
PubMed2006

Effects of theta burst stimulation protocols on phosphene threshold.

OBJECTIVE: We investigated the effects on occipital cortex, of two newly developed methods of repetitive transcranial magnetic stimulation (rTMS): continuous and intermittent theta burst stimulation (cTBS and iTBS), that lead to long lasting changes in excitability when applied over primary motor cortex. METHODS: Phosphene threshold to a single TMS pulse was measured before and after application of either continuous or intermittent theta burst stimulation (cTBS/iTBS; 600 total pulses at 80% phosphene threshold). RESULTS: In our cohort, cTBS increased phosphene threshold by an average of 10%. In contrast, iTBS, which transiently increases motor cortex excitability, had no effect on phosphene threshold. CONCLUSIONS: cTBS can be applied successfully to non-motor areas of cortex, but iTBS may need modification to produce maximal effects. SIGNIFICANCE: cTBS maybe a new useful tool in disorders characterized by an abnormal state of activity of the visual cortex.

Adult↗
PubMed2003

Modulation of moving phosphene thresholds by transcranial direct current stimulation of V1 in human.

Small moving sensations, so-called moving phosphenes are perceived, when V5, a visual area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if only V5 takes part in movement perception or other visual areas are also involved in this process. In this study we tested the involvement of V1 in the perception of moving phosphenes by applying transcranial direct current stimulation (tDCS) to this area. tDCS is a non-invasive stimulation technique known to modulate cortical excitability in a polarity-specific manner. Moving and stationary phosphene thresholds (PT) were measured by TMS before, immediately after and 10, 20 and 30 min after the end of 10 min cathodal and anodal tDCS in nine healthy subjects. Reduced PTs were detected immediately and 10 min after the end of anodal tDCS while cathodal stimulation resulted in an opposite effect. Our results show that the excitability shifts induced by V1 stimulation can modulate moving phosphene perception. tDCS elicits transient, but yet reversible effects, thus presenting a promising tool for neuroplasticity research.

Adult↗
PubMed2000

Magnetically induced phosphenes in sighted, blind and blindsighted observers.

Direct stimulation of visual cortex can produce illusory flashes of light, called phosphenes. Here we describe the spatial and motion properties of phosphenes produced by transcranial magnetic stimulation in normal subjects and in two subjects with peripheral or cortical blindness. The totally retinally blind subject experienced normal phosphenes, apart from their concentration in the centre of the visual field, whereas the hemianopic subject, lacking area V1, did not experience phosphenes when his surviving extrastriate visual areas were stimulated. In the absence of V1, magnetically induced activity was unable to generate a conscious visual percept in the field defect.

Adult↗
PubMed2004

No correlation between moving phosphene and motor thresholds: a transcranial magnetic stimulation study.

The aim of this study was to investigate the temporal stability of moving phosphenes and to assess whether moving phosphene thresholds (PTs) correlate with motor thresholds (MTs). Small moving sensations, so-called moving phosphenes, are perceived when V5, an area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if V5 phosphenes are stable sensations across measurements and if they are a reasonable index of the cortical excitability of V5. Currently, MT is more commonly used as an index of global cortical excitability. However, previous studies have indicated that stationary PTs are suitable alternatives when the primary visual cortex is stimulated by TMS. Using paired-pulse TMS, stationary and moving PTs and applying single pulse TMS, MTs were measured in 11 subjects. PTs were retested in nine subjects 5-7 days later. Stationary and moving PTs were stable within subjects across the two sessions and showed a high inter-correlation. Conversely, PTs and MTs did not correlate. Our results are in agreement with previous studies showing that excitatory measurements of one specific cortex cannot be generalized to the excitability of the whole cortex. Thus, we propose specific measures for cortices of interest: PT for visual experiments and MT for motor experiments.

Adult↗
PubMed2006

A clinical evaluation of proview pressure phosphene tonometry in children.

PURPOSE: The Proview tonometer measures intraocular pressure by inducing a pressure phosphene through the eyelid and, if reliable and valid, may offer a quick, nonthreatening and noninvasive alternative method of obtaining intraocular pressures (IOPs) without the use of eye drops. This study compares the IOP measurements obtained in children using Proview pressure phosphene tonometry (PPPT) and Goldmann tonometry (GT). METHODS: One hundred four 5- to 12-year-old patients of the University Optometric Center/SUNY College of Optometry participated in the study. Subjects were randomized to receive, by different investigators, either PPPT or GT first. Two measurements with each instrument were attempted on each eye of all subjects. A subgroup of 41 subjects was asked which of the two methods was preferred. RESULTS: Seven percent of the subjects did not report a pressure phosphene response compared with 12% of the subjects on whom the investigators were unable to perform GT. The remaining 85 subjects completed the subject protocol. Of the 41 subjects asked, 56% preferred PPPT, 24% had no preference, and 20% preferred GT. The coefficient of repeatability between the two readings was higher for PPPT (3-4 mm Hg) than for GT (1 mm Hg). Mean IOP was 4 mm Hg higher for PPPT than GT with the difference in readings between the two instruments increasing with higher IOPs (r >19%, p < 0.005). CONCLUSIONS: In our study of healthy young subjects, PPPT measurements of IOP appear to be repeatable within a few millimeters of mercury in most children, but for some children, variability in repeat measurements can be substantial. Our data showed a mean difference in readings of 4 mm Hg with a 95% confidence interval that the PPPT reading was between 12 mm Hg above GT and 4 mm Hg below GT. This wide range of values indicates that PPPT is not comparable to GT. However, because our study found that children can appreciate pressure phosphenes and most prefer PPPT over GT, the Proview monitor may have value as a noninvasive, portable screener in pediatric patients. To fully evaluate this potential, further studies are needed that include patients with high IOPs.

Child↗
PubMed2005

Clinical evaluation of the pressure phosphene tonometer in patients with glaucoma.

AIM: To evaluate the reliability of the pressure phosphene tonometer in comparison with the Goldmann applanation tonometer. METHODS: 45 consecutive patients with glaucoma (78 eyes) participated in the study. Eyes with previous eye surgery, a documented peripheral visual field defect, a refractive error of more than 5 dioptres, and patients who were unable to understand the procedure were excluded from the study. Intraocular pressure was measured with a pressure phosphene tonometer by one examiner and with a Goldmann applanation tonometer by two other examiners no more than 15 minutes apart. A second series of measurements was performed several weeks later on 34 patients (59 eyes). There was no communication between examiners or between examiner and patient regarding test results. RESULTS: No statistically significant correlation was found between the applanation tonometry values and those obtained with a pressure phosphene tonometer. CONCLUSION: The pressure phosphene tonometer is not suitable for reliably measuring intraocular pressure.

Adult↗
PubMed2003

Evaluation of cortical excitability by motor and phosphene thresholds in transcranial magnetic stimulation.

Motor threshold (MT), as determined by transcranial magnetic stimulation (TMS), is used as a parameter of cortex excitability. In TMS with single or repetitive pulses, stimulus intensities in general are referred to the individual MT, although it is unclear whether MT also reflects the excitability of nonmotor cortical areas such as the visual cortex. Visual cortex excitability can be assessed by thresholds for eliciting phosphenes (phosphene threshold, PT) following TMS over the occipital cortex. The question of a different efficacy of TMS pulses in distinct cortical areas was approached by comparing motor and phosphene thresholds using single-pulse TMS applied to the primary motor and visual cortex. The aim of the study was to clarify, whether MT and PT correlate with each other and whether MT possibly serves as a reasonable measure for the excitability of the visual cortex. In 32 healthy volunteers, TMS with biphasic single pulses was applied over the motor and visual cortex with a figure of eight-shaped coil connected to a Dantec MagPro stimulator. MT and PT were individually measured (percent of maximal stimulator output). Mean PT (61.4+/-11.7%) was significantly higher than mean MT (39.4+/-5.9%) (p=0.01). MT and PT did not correlate significantly (r=0.29, p>0.1). These findings suggest that the MT does not reflect the excitability of the visual cortex. Regarding excitatory effects, the efficacy of TMS may be different over the motor and visual cortex, likely related to a different excitability of these cortical areas. This should be considered in planning and execution of TMS studies of nonmotor cortical areas.

Adult↗
PubMed2004

Evaluation of intraocular pressure change after laser in situ keratomileusis using the pressure phosphene tonometer.

PURPOSE: To evaluate the applicability of pressure phosphene tonometry in measuring intraocular pressure (IOP) after laser in situ keratomileusis (LASIK). SETTING: Baptist Eye Clinic, Kyoto, Japan. METHODS: Thirty-six eyes of 22 consecutive patients who had had LASIK for myopia were enrolled in this prospective comparative study. The mean age of the patients was 32.6 years +/- 9.0 (SD). The IOP was measured using the pressure phosphene tonometer (FPT), Goldmann applanation tonometry (GAT), and noncontact tonometry (NCT). The patients themselves took measurements with the FPT before and 1 week after surgery. One-way analysis of variance followed by a Bonferroni/Dunn multiple comparison post hoc test was administered to compare the preoperative and postoperative measurements with each tonometer. These data were represented graphically using a method described by Bland and Altman. The relationship between each tonometric change and the central corneal thickness (CCT) or keratometry (K) changes after LASIK were evaluated with by Pearson correlation coefficient. RESULTS: Statistically significant differences were found between preoperative and postoperative measurements with GAT and NCT but not with FPT. Preoperative and postoperative FPT readings conformed to the British Standard for reproducibility of a standard test method for IOP estimation. No significant correlation between FPT changes and CCT or K changes was found. CONCLUSIONS: Pressure phosphene tonometry measures IOP through the upper eyelid, and changes in corneal shape do not appear to have an effect on the IOP. The IOP measurements with FPT were constant before and after LASIK.

Adult↗
PubMed2003

The threshold for phosphenes is lower in migraine.

We have reported a preliminary study confirming hyperexicitability 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 hyperexicitability of the occipital cortex in migraineurs.

Adult↗
PubMed2005

Reproducibility of self-measured intraocular pressure with the phosphene tonometer in patients with ocular hypertension and early to advanced glaucoma.

PURPOSE: To evaluate the reproducibility of self-measured intraocular pressure with the Proview tonometer in ocular hypertensives and early to advanced glaucoma patients. PATIENTS AND METHODS: Thirty-three patients with glaucoma and three with ocular hypertension (72 eyes) were prospectively enrolled. History of cornea surgery was the only exclusion criterion. A trainer took a set of three readings first. Subsequently, the patient (after successful training) took one set of three readings and a physician took two sets of three Goldmann readings. One hour later this was repeated. RESULTS: 72% of patients could see the phosphene in both eyes, 8% could see it in one eye, and 19% could not see it in either eye. Patients who could not see the Phosphene had an average mean deviation of -10.9 compared with -3.4 for those who could see it (P = 0.01). Eyes that could not see the phosphene were excluded from further analysis. The average absolute difference between two Proview measurements one hour apart was 1.76 +/- 1.76 mm Hg (r = 0.71). The measurement error (difference between Goldmann and Proview readings) tended to remain constant between sets of measurements taken one hour apart (average error was 2.4 +/- 2.1 mm Hg, r = 0.85). No adverse event was recorded. CONCLUSIONS: Repeated self-tonometry measurements showed very good reproducibility. The systematic, reproducible error between Proview and Goldmann readings may be clinically acceptable and suggests that a baseline "calibration" should be obtained for each patient before the Proview values are used clinically. Self-administered tonometry can play a role in the clinical care of ocular hypertensive and glaucoma patients with the possible exception of very advanced cases.

Adolescent↗