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Biomedical subjects

J G Robson

Publications and source records attributed to J G Robson.

At least 19 recordsLinked to original sources

The photopic negative response of the flash electroretinogram in primary open angle glaucoma.

PURPOSE: To determine whether the photopic negative response (PhNR) of the electroretinogram (ERG) is reduced in patients with primary open angle glaucoma (POAG). METHODS: ERGs were recorded with DTL electrodes from 62 normal subjects (16 to 82 years), 18 POAG patients (47 to 83 years) and 7 POAG suspects (46 to 73 years) to brief flashes (<6 ms), and also in a few subjects to long (200 ms) red, full-field ganzfeld flashes delivered on a rod-saturating blue background. At the time of ERG measurements, the intraocular pressures of most of the patients were controlled medically. Visual field sensitivities were measured with the Humphrey C24-2 threshold test and optic nerve head cup-to-disc ratio (C/D) was determined by binocular indirect ophthalmoscopy. RESULTS: ERGs of normal subjects contained a slow negative potential following the a- and b-waves, the PhNR, that increased slightly in latency with age. The a- and b-wave amplitudes and implicit times of POAG patients were similar to age-matched controls. In contrast, their PhNRs were small or virtually absent. PhNR amplitudes were reduced even when visual sensitivity losses were small, and were correlated significantly (P < 0.05) with mean deviation (MD), corrected pattern SD (CPSD), and C/D across the population of POAG patients whose MD losses ranged from 1 to 13 dB, CPSDs from 0 to 11 dB and C/Ds from 0.6 to 0.9. PhNRs of most POAG suspects also were small. CONCLUSIONS: PhNR amplitudes in POAG patients are smaller than those of normal subjects. PhNR amplitudes are reduced when visual field sensitivity losses are mild and become even smaller as sensitivity losses increase. There is a potential role for the PhNR in early detection and possibly in monitoring the progression of glaucomatous damage.

Adolescent↗

Effects of experimental glaucoma in macaques on the multifocal ERG. Multifocal ERG in laser-induced glaucoma.

Multifocal ERGs (MERGs) of 5 adult monkeys (Macaca mulatta) with inner retinal defects caused by laser-induced glaucoma were compared to MERGs from 3 monkeys with inner retinal activity suppressed pharmacologically. MERGs were recorded with DTL fiber electrodes from anesthetized monkeys. Stimuli consisted of 103 equal size hexagons within 17 degrees of the fovea. Stimuli at each location passed through a typical VERIS m-sequence of white (200 cd/m2) and black (12 cd/m2) presentations. In animals with laser-induced glaucoma, visual field sensitivity was assessed by static perimetry using the Humphrey C24-2 full-threshold program modified for animal behavior. Inner retinal (amacrine and ganglion cell) activity was suppressed by intravitreal injection of TTX (4.7-7.6 microM) and NMDA (1.6-5 mM). In normal eyes the first order response (1st order kernel) was larger and more complex, with more distinct oscillations (>60 Hz) in central than in peripheral locations. The 2nd order kernel also was dominated by oscillatory activity. There were naso-temporal variations in both kernels. Pharmacological suppression of inner retinal activity reduced or eliminated the oscillatory behavior, and naso-temporal variations. The 1st order kernel amplitude was increased most and was largest at the fovea. Removed inner retinal responses also were largest at the fovea. The 2nd order kernel was greatly reduced at all locations. In eyes with advanced glaucoma, the effects were similar to those produced by suppressing inner retinal activity, but the later portion of the 1st order kernel waveform was different, lacking a dip after the large positive wave. Visual sensitivity losses and MERG changes both increased over the timecourse of glaucoma, with changes in the MERG being more diffusely distributed across the visual field. We conclude that 1st and 2nd order responses of the primate MERG can be identified that originate from inner retina and are sensitive indicators of glaucomatous neuropathy.

Animals↗

The uniform field and pattern ERG in macaques with experimental glaucoma: removal of spiking activity.

PURPOSE: To determine whether the uniform field and pattern ERGs that are reduced in macaque eyes with experimental glaucoma have the same inner-retinal origins. METHODS: ERGs were recorded from 14 anesthetized adult macaques using DTL electrodes. Six monkeys had laser-induced experimental glaucoma, and two others received intravitreal injections of tetrodotoxin (TTX, 6 microM) to block spiking activity of inner-retinal neurons. The remaining 6 animals were normal. Uniform fields and grating patterns (0.1-3 cpd) were square-wave modulated at 1.7 Hz (transient) and 8 Hz (steady state). The test field (42 degrees x 32 degrees) had a mean luminance of 44 cd/m2 and a contrast of 10% to 82%. RESULTS: In normal eyes transient ERGs to uniform fields contained photopic negative responses (PhNR) after the b-wave and after the d-wave. Transient pattern electroretinograms (PERGs) at each contrast reversal showed positive (P50) potentials followed by negative (N95) potentials of time course similar to that of the PhNR. The PhNR and N95 were greatly reduced or eliminated by experimental glaucoma and by TTX. Summing responses to luminance increments and decrements of the uniform field could simulate the PERG to low spatial frequency stimuli. Further, the PERG responses to high spatial frequencies were similar to the simulation in shape but slightly delayed in time. Experimental glaucoma and TTX had similar effects on the N95 of the simulated PERG as to those on the actual PERG. However, P50 was more reduced by experimental glaucoma than by TTX, indicating a nonspiking contribution to P50. For the steady state condition, the uniform field ERG, the simulated PERG, and the actual PERG all were affected by experimental glaucoma and TTX, indicating that they contained contributions from the spiking activity of ganglion cells. CONCLUSIONS: The changes in the uniform field and PERG responses produced by experimental glaucoma are related and are largely a consequence of reduced spiking activity of ganglion cells and their axons. These findings raise the possibility that the uniform field ERG could serve as a useful alternative to the PERG in the assessment of clinical glaucomatous neuropathy.

Animals↗

Identifying inner retinal contributions to the human multifocal ERG.

Contributions to the multifocal electroretinogram (ERG) from the inner retina (i.e. ganglion and amacrine cells) were identified by recording from monkeys before and after intravitreal injections of n-methyl DL aspartate (NMDLA) and/or tetrodotoxin (TTX). Components similar in waveform to those removed by the drugs were identified in the human multifocal ERG if the stimulus contrast was set at 50% rather than the typically employed 100% contrast. These components were found to be missing or diminished in the records from some patients with glaucoma and diabetes, diseases which affect the inner retina.

Adult↗

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

PURPOSE: To investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. METHODS: Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (< or = 5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3.8-8 p.M) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. RESULTS: Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as -6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. CONCLUSIONS: The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy.

Adult↗

Effects of background light on the human dark-adapted electroretinogram and psychophysical threshold.

We compared the effects of background light on the sensitivities of two components of the human electroretinogram, the cornea-negative scotopic threshold response (STR) and the cornea-positive PII (beta wave), as well as on the psychophysical sensitivity in a ganzfeld. The background illuminance necessary to reduce the STR (an inner retinal signal) measurably was approximately five times greater than that needed to raise the psychophysical threshold. A background illuminance at least 1 log unit greater still was needed to reduce PII (a signal-reflecting activity of bipolar cells). These findings suggest (1) that the weakest backgrounds that reduce retinal sensitivity have their effect at a site that is proximal to the bipolar cells, a site that involves amacrine or ganglion cells, and (2) that very weak backgrounds have their effect on visual sensitivity at a site more proximal than the scotopic threshold response generator and perhaps more central than the retina.

Adult↗

Photoreceptor and bipolar cell contributions to the cat electroretinogram: a kinetic model for the early part of the flash response.

The time course of the initial negative wave of the flash electroretinogram of the dark-adapted cat has been found to be critically dependent of contributions from cells of the inner retina, not only for very low-intensity flashes for which the negative scotopic threshold response is dominant but also when the stimulus is sufficiently intense for the rods themselves to contribute directly to the electroretinogram. However, if the inner-retinal responses are blocked pharmacologically or are suppressed by a steady adapting background, the initial negative wave of the remaining electroretinogram (the alpha wave) can be explained as the sum of photoreceptor and bipolar-cell components that can be modeled as described by Lamb and Pugh [J. Physiol. (London) 449, 717 (1992)] and Robson and Frishman [Vis. Neurosci. 12, 837 (1995)], respectively.

Animals↗

The scotopic electroretinogram of macaque after retinal ganglion cell loss from experimental glaucoma.

PURPOSE: This study describes the dark-adapted electroretinograms (ERGs) of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension. METHODS: Monocular experimental glaucoma was produced by argon laser trabeculoplasty, and visual fields were assessed with behavioral static perimetry. Electroretinographic responses to brief ganzfeld flashes under fully dark-adapted conditions were recorded using DTL fiber electrodes in anesthetized animals. The authors quantified retinal layer thickness and cell loss in 1-micron radial sections and inspected optic nervous under the light microscope. RESULTS: At the lowest intensities, a sensitive negative component of the scotopic ERG, which normally peaks approximately 200 msec after stimulus onset, was present in the control eyes but was reduced greatly or was virtually absent in the experimental eyes of monkeys with severe visual field loss. A previously unreported sensitive positive component of the scotopic ERG remained in both eyes. In the control eyes, the positive component gave rise to a sharp peak approximately 120 msec after stimulus onset, but in the experimental eyes, because of the absence of the more delayed sensitive negative potential, it was sustained, lasting as long as 700 msec. Scotopic a- and b-waves and oscillatory potentials in the experimental eyes were not consistently different from control eyes. Ganglion cell and optic nerve loss in the experimental eyes was substantial, and there was little other obvious retinal damage. CONCLUSIONS: A sensitive negative component is reduced or absent from the dark-adapted ERGs of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension.

Animals↗

Steady discharges of X and Y retinal ganglion cells of cat under photopic illuminance.

The discharges of ON- and OFF-center X and Y retinal ganglion cells in the presence of stationary patterns or of a uniform field of photopic luminance were recorded from urethane-anesthetized adult cats. The interval statistics and power spectra of these discharges were determined from these discharge records. The patterned stimuli were selected and positioned with respect to a cell's receptive field so as to generate steady discharges that were different in mean discharge rate from that cell's discharge for the diffuse field. The interval statistics of discharges recorded for diffuse or patterned illumination for all cell types can be modeled, approximately, as coming from renewal processes with gamma-distributed intervals. The gamma order of the interval distributions was found to be nearly proportional to the mean discharge rate for X cells, but not for Y cells. Typical values for the gamma orders and their dependence on mean rate for different cell types are given. The same model of a renewal process with gamma-distributed intervals is used to model the measured power spectra and performs well. When the gamma order is proportional to mean rate, the power spectral density at low temporal frequencies is independent of discharge rate. Gamma order was proportional to mean rate for X cells but not for Y cells. Nonetheless, the power spectral densities of both cell types at low frequencies were approximately independent of discharge rate. Hence, noise in this band of frequencies can be considered additive. The consequences of departures from the renewal process and of the gamma order not being proportional to mean rate are considered. The significance of different rates of discharge for signaling is discussed.

Action Potentials↗

Organization of suppression in receptive fields of neurons in cat visual cortex.

1. The response to an optimally oriented stimulus of both simple and complex cells in the cat's striate visual cortex (area 17) can be suppressed by the superposition of an orthogonally oriented drifting grating. This effect is referred to as cross-orientation suppression. We have examined the spatial organization and tuning characteristics of this suppressive effect with the use of extracellular recording techniques. 2. For a total of 75 neurons, we have measured the size of each cell's excitatory receptive field by use of rectangular patches of drifting sinusoidal gratings presented at the optimal orientation and spatial frequency. The length and width of these grating patches are varied independently. Receptive-field length and width are determined from the dimensions of the smallest grating patch required to elicit a maximal response. 3. The extent of the area from which cross-orientation suppression originates has been measured in an analogous manner. Each neuron is excited by a patch of drifting grating the same size as the receptive field. The response to this stimulus is modulated by a superimposed patch of grating having an orthogonal orientation. After selecting the spatial frequency that produces maximal suppression, the response of each cell is examined as a function of the length and width of the orthogonal (suppressive) grating patch. Results from 29 cells show that the dimensions of the orthogonal grating patch required to elicit maximal suppression are similar to, or smaller than, the dimensions of the excitatory receptive field. Thus cross-orientation suppression originates from within the receptive field. 4. For some cells the spatial frequency tuning of the suppressive effect is much broader than the spatial frequency tuning for excitation. In these cases it is possible to find a spatial frequency that produces suppression but not excitation. With the use of a suppressive stimulus having this spatial frequency, we examined the strength of suppression as a function of orientation for 11 cells. These tests show that suppression occurs at all orientations, including the preferred orientation for excitation. In some cases, suppression is somewhat stronger at the preferred orientation for excitation than at any other orientation. 5. For 12 cells we varied the relative spatial phase between the optimally oriented and orthogonal gratings. In all cases the magnitude of suppression is largely independent of the relative spatial phase. 6. For three binocular cells we examined whether the suppressive effect of a grating oriented orthogonal to the optimum could be mediated dichoptically.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Responses to sinusoidal gratings of two types of very nonlinear retinal ganglion cells of cat.

Perhaps 35% of all of the ganglion cells of the cat do not have classical center-surround organized receptive fields. This paper describes, quantitatively, the responses of two such cell types to stimulation with sinusoidal luminance gratings, whose spatial frequency, mean luminance, contrast, and temporal frequency were varied independently. The patterns were well-focused on the retina of the anesthetized and paralyzed cat. In one type of cell, the maintained discharge was depressed or completely suppressed when a contrast pattern was imaged onto the receptive field (suppressed-by-contrast cell). In the other type of cell, the introduction of a pattern elicited a burst of spikes (impressed-by-contrast cell). When stimulated with drifting gratings, the cell's mean rate of discharge was reduced (suppressed-by-contrast cell) or elevated (impressed-by-contrast cell) over a limited band of spatial frequencies. There was no significant modulated component of response. The reduction in mean rate of suppressed-by-contrast cells caused by drifting gratings had a monotonic dependence on contrast, a relatively low-pass temporal-frequency characteristic and was greater under photopic than mesopic illuminance. If grating of spatial frequency, that when drifted evoked a response from these cells, were instead held stationary and contrast-reversed, the mean rate of a suppressed-by-contrast cell was also reduced and that of an impressed-by-contrast cell increased. But, for contrast-reversed gratings, the discharge contained substantial modulation at even harmonic frequencies, the largest being the second harmonic. The amplitude of this second harmonic did not depend on the spatial phase of the grating, and its dependence on spatial frequency, at least for suppressed-by-contrast cells, was similar to that of the reduction in mean rate of discharge. Our results suggest that the receptive fields of suppressed-by-contrast and impressed-by-contrast cells can be modeled with the general form of the nonlinear subunit components of Hochstein and Shapley's (1976) Y cell model.

Action Potentials↗

Summation of very close spatial frequencies: the importance of spatial probability summation.

In accounting for pattern thresholds it is necessary to consider probability summation (or equivalent nonlinear pooling) not only across detectors selective for different spatial frequencies but also across detectors in different spatial positions. Interestingly, calculation on this basis shows that the amount of summation between components of closely similar spatial frequency in a large grating is primarily determined by the variation in sensitivity of detectors at different spatial locations and is little affected by the spatial-frequency bandwidths of the detectors. To test this conclusion, we have measured the amount of summation between two components with spatial frequencies very close to 6 c/deg in two regions of the visual field: in the fovea (a region where sensitivity is very non-uniform) and in the periphery (where sensitivity is nearly uniform). As predicted, there was less summation between components of very closely similar frequencies in the nearly-uniform peripheral region than in the non-uniform foveal region. Measurements in the fovea of the summation of two components with spatial frequencies very near to either 1.5, 6 or 24 c/deg showed, as expected, that the amount of summation depends upon the ratio of the frequencies rather than their absolute difference, indicating that probability summation takes place over an area related to spatial frequency rather than over a fixed area.

Female↗

Nature of the maintained discharge of Q, X, and Y retinal ganglion cells of the cat.

Cat retinal ganglion cells with center-surround receptive fields have an irregular discharge whose rate is altered by visual stimulation. In assessing the detectability of stimulus-induced changes in the discharge, a consideration of the power spectral density of the discharge is helpful. The power spectral density of Q, X, and Y cells is flat at low frequencies, rises to a peak at the mean frequency of firing, and then decays away at higher frequencies in an oscillatory manner to an asymptotic level equal to the mean rate of discharge. Measured spectra correspond closely with spectra predicted by a renewal-point process with gamma-distributed intervals. When the rate of the discharge is altered by visual stimulation, the spectral density at low frequencies remains roughly constant. Assuming that it is the noise power at these frequencies that is effective in limiting the detectability of visual stimuli, it appears that at the retinal level the irregularity of the discharge can be treated as an additive noise.

Action Potentials↗

Spatio-temporal interactions in cat retinal ganglion cells showing linear spatial summation.

The spatio-temporal characteristics of cat retinal ganglion cells showing linear summation have been studied by measuring both magnitude and phase of the responses of these cells to drifting or sinusoidally contrast-modulated sinusoidal grating patterns. It has been demonstrated not only that X cells behave approximately linearly when responding with amplitudes of less than about 10 impulses/sec to stimuli of low contrast but also that cells of another type with larger receptive field centres (Q cells) behave approximately linearly under the same conditions. These Q cells appear to form a homogeneous group which is probably a subset of the tonic W cells (Stone & Fukuda, 1974) or sluggish centre-surround cells (Cleland & Levick, 1974). The over-all spatio-temporal frequency characteristics of cells showing linear spatial summation are not separable in space and time. The form of the spatial frequency responsivity function of these cells depends upon the temporal frequency at which it is measured while the temporal phase of their resonse measured at any constant temporal frequency depends upon the spatial frequency of the stimulus. The behaviour of X and Q cells is quite well explained by an extension of the model in which signals from centre and surround mechanisms with radially Gaussian weighting functions are summed to provide the drive to the retinal ganglion cell. While the general form of the temporal frequency response characteristics of these ganglion cells are probably provided by the characteristics of elements common to the centre and surround pathways, the spatio-temporal interactions can be explained by assuming that the surround signal is delayed relative to the centre signal by a few milliseconds.

Animals↗

A new approach to the study of binocular interaction in visual cortex: normal and monocularly deprived cats.

Retinal disparity sensitivity was examined for cells in areas 17 and 18 of the cat's visual cortex. As a stimulus, we used drifting sinusoidal gratings which were spatially phase-shifted in one eye with respect to the other. The gratings were of high contrast (80%) and optimal values of spatial and temporal frequencies and orientations were used. In the normal cat cortex, binocular cells in areas 17 and 18 were all sensitive to phase shifts, but only minimal effects were observed for monocular cells. Recordings were also made from monocularly deprived cats, but no binocular influence was found from the silent eye.

Animals↗