Visual adaptation and the cone flicker electroretinogram

This study examined the hypothesis that changes in the response properties of the human cone ERG during light adaptation represent the recovery of cone system responsiveness toward a dark-adapted value after an initial decrease in responsiveness at adapting field onset. The electroretinographic (ERG) responses to 31.1 Hz flicker were obtained under both dark-adapted and light-adapted conditions for stimulus luminances ranging from -1.42(-)+0.82 log cd sec/m2. At low stimulus luminances, flicker ERG amplitudes were larger under dark-adapted than under light-adapted conditions, consistent with the hypothesis. However, at high stimulus luminances, flicker ERG amplitudes obtained under light-adapted conditions were approximately double those recorded from the dark-adapted eye. Therefore, the increase in cone ERG amplitude that occurs during light adaptation at high stimulus luminances does not represent a return toward a dark-adapted level but instead entails a substantial enhancement above the dark-adapted value, by a mechanism that is presently unidentified.     

Harmonic analysis of the cone flicker ERG of rabbit

Harmonic analysis was used to characterize the rabbit flicker ERG elicited by sinusoidally modulated full-field stimuli under light-adapted conditions. The frequency-response function for fundamental amplitude, derived from Fourier analysis of the ERG waveforms, exhibited two limbs, with an amplitude minimum at approximately 30Hz, and a high-frequency region peaking at around 45Hz and extending to more than 100Hz at higher adapting levels. At low frequencies (<20Hz), the fundamental response amplitude was independent of mean luminance (Weber law behavior), whereas the response amplitude at high stimulus frequencies varied nonlinearly with mean luminance. At low frequencies, intravitreal administration of L-AP4, which blocks ON-pathway activity, reduced the fundamental response amplitude and produced a phase shift. On the other hand, PDA, which reduces OFF-pathway activity, had a minimal effect on both the response amplitude and phase at low frequencies. At high frequencies, L-AP4 increased the fundamental response amplitude at low mean luminances, whereas PDA had only a small effect on amplitude and phase. Both pharmacologic agents removed the minimum in the amplitude-frequency function as well as the abrupt change in phase at stimulus frequencies near 30Hz. The results suggest that there is a nonlinear interaction between ON- and OFF-pathway activity over the entire stimulus frequency range examined in this study. These findings provide a basis for formulating protocols to evaluate the effect of pharmacologic agents and/or disease on the cone flicker ERG of rabbit.     

The influence of cone adaptation upon rod mediated flicker

The influence of annular fields on sensitivity to sinusoidal flicker was assessed in the dark adapted parafoveal retina. Test stimuli were 2 degrees 20' in diameter; annuli had a 2 degrees 20' inner and 7 degrees 30' outer diameter. Rod flicker was studied with a "green" stimulus too dim to influence cones. Selective cone flicker was obtained using red and green flicker in counterphase and yoked together in modulation depth and scotopic illuminance. Results showed the following. (1) Annular stimulation of rods slightly facilitated rod-mediated flicker sensitivity to frequencies less than 10 Hz. In contrast, annular stimulation of cones greatly facilitated rod-mediated sensitivity, particularly for flicker frequencies greater than 7 Hz. We designate this effect, cone-rod interaction. (2) Annular stimulation of cones has a negligible influence upon sensitivity to cone-mediated flicker frequencies less than 15 Hz. In contrast, annular stimulation of rods has a large influence upon sensitivity to cone-mediated flicker, an effect we designate rod-cone interaction. (3) Within limits, both rod-cone and cone-rod interaction increase as the annular illuminance increases and as flicker frequency increases; the limiting frequency and illuminance values, however, are different for the two forms of interaction. Results are compared with prior evidence that rod and cone signals summate to produce an absolute threshold or flicker sensation. We suggest that there are at least three mechanisms for interaction between rod- and cone-related signals.     

Characteristics of period doubling in the rat cone flicker ERG

When the eye is stimulated by a flickering light, the electroretinogram (ERG) and other electrophysiological responses in the visual pathway often exhibit period doubling. This phenomenon is manifested as an alternation in the shape of the response waveform from cycle to cycle, and also as spectral components at the half-fundamental frequency (F/2) and its odd multiples. Although period doubling has been described in humans as well as in other animals, its features in the rodent flicker ERG have not been characterized. We investigated the properties of period doubling in the rat cone flicker ERG elicited with full field, sinusoidal photic stimuli. Period doubling was observed when the temporal frequency of the stimulus was in the range of 20-30 Hz. The F/2 component of the Fourier spectrum of the ERG was more pronounced than its odd harmonics. The magnitude of the cycle-to-cycle variation in amplitude differed depending on whether measurements were based on peak-to-trough or trough-to-peak amplitudes, owing to the relative phase relationship between F/2 and F as a function of stimulus frequency. The frequency-response characteristics of period doubling varied with stimulus contrast, such that reducing the contrast shifted the peak F/2 amplitude to a lower stimulus frequency. Period doubling was evident in rat eyes in which PDA was administered intravitreally, indicating that the phenomenon can occur independently of OFF pathway activity in the rat retina. The period doubling properties we observed in the flicker ERG response of the rat cone system provide constraints on the nature of the nonlinear feedback mechanism presumed to underlie the period doubling phenomenon.     

Stimulation of rods can increase cone flicker ERGs in man

Recent psychophysical studies in man and electrophysiological studies in lower vertebrates show that dark adapted, unstimulated rods inhibit cone mediated flicker. This investigation uses comparable psychophysical and ERG procedures in man to demonstrate rod-cone interaction of this type. With either procedure the rod cone interaction cannot be demonstrated with Ganzfeld stimulation. A single small, red, flickering test field, which is a common psychophysical stimulus for testing rod-cone interaction, elicits an immeasurably small cone ERG. But an array of many such targets, flickering synchronously, is an effective psychophysical stimulus and produces an ERG with larger cone than rod components. With such an array, it can be shown that a steady, rod-stimulating background selectively enhances cone ERG components.     

Chromatic suppression of cone inputs to the luminance flicker mechanism

Eisner and MacLeod [J. opt. Soc. Am. 71, 705-718 (1981)] showed that intense green and red chromatic adapting fields may suppress respectively the M and L cone input to the luminance mechanism by a factor considerably greater than Weber's law. We obtained evidence for such chromatic suppression by measuring complete detection contours for different ratios of red and green test lights presented in rapid flicker in the center of a uniform field. The detection contours represent thresholds as the quantal modulation of the M and L cones normalized by the quantal catch owing to the field. Luminance flicker mechanisms were identified by sections of the contours where detection was controlled by a linear sum of the M and L cone test signals. The slope of these sections indicated that intense red fields selectively suppressed the L cone input to the luminance mechanism by a factor greater than Weber's law; evidence was much less firm for an analogous suppression of the M cone input by intense green fields. The shape of the detection contours also suggests that intense red fields, which differentially light-adapt the M and L cones, may produce a moderate temporal phase-shift between the M and L cone signals. The shape of the temporal MTF of the M cone and the L cone input to the luminance mechanism may be determined at the cone stage, with the absolute sensitivity (vertical scaling) being partially dependent on selective chromatic suppression of the cone inputs owing to the intense chromatic field. Luminance and red-green chromatic temporal sensitivity functions are presented in terms of the M and L cone quantal modulations. Chromatic sensitivity progressively rises above luminance sensitivity as temporal frequency is gradually lowered below 15 Hz, with the consequence that 'contrast sensitivity' may be much higher for color than for luminance.     

Characteristics of period doubling in the human cone flicker electroretinogram

Electroretinogram (ERG) responses of the cone system to a flickering stimulus can exhibit a cyclic variation in amplitude. This phenomenon of synchronous period doubling has been attributed to a nonlinear feedback mechanism within the retina that alters response gain. The aim of the present study was to investigate intersubject variability in period doubling in the ERG of the human cone system, and to assess the implications of this variability for signal processing within the retina. Period doubling was examined in a group of 12 visually normal subjects, using sinusoidal full-field flicker and harmonic analysis of the ERG waveforms. For all subjects, the ERG responses to 32-Hz flicker (a frequency commonly used clinically) were characterized by a harmonic component at the stimulus frequency and at higher harmonics that were integral multiples of the stimulus frequency, as expected. In addition, six of the subjects showed period doubling at 32 Hz, characterized by harmonic components at integer multiples of a frequency that was half the stimulus frequency (the subharmonic). However, the subharmonic itself did not exceed the noise level. These findings suggest that the subharmonic is generated prior to or at the site that produces the nonlinear higher harmonics of the ERG response, and that a subsequent band-pass filter attenuates this subharmonic. Examination of harmonic components of the subjects' ERG waveforms at other stimulus frequencies, as well as a cycle-by-cycle analysis of the ERG waveforms, suggested that individual differences in period doubling may be due to intersubject variation in the strength of the hypothesized feedback signal and/or the time constant of its decay.     

Perimetry of critical flicker frequency in human rod and cone vision

Photopic critical flicker frequency (CFF) to green and yellow-red targets became independent of visual field location when the decrease in the density of retinal ganglion cells and increase in their receptive-field size towards the retinal periphery were compensated for by increasing stimulus area in inverse proportion to the human cortical magnification factor squared (M-scaling) and by reducing stimulus luminance in inverse proportion to Ricco's area (F-scaling). In mesopic and scotopic vision CFF to green targets increased monotonically with eccentricity despite MF-scaling. Instead, CFF to MF-scaled yellow-red targets that predominantly stimulated cones was independent of eccentricity at all luminance levels tested.     

Rod influence on cone flicker detection: variation with retinal eccentricity

Previous studies have shown that cone flicker thresholds are influenced by the adaptation state of the rod system. We have examined how the properties of this rod-cone flicker interaction differ with retinal eccentricity. The threshold for detecting 25 Hz flicker was measured in the dark-adapted eye, against a rod-saturating Ganzfeld background and following a Ganzfeld bleach. The magnitude of the interaction, defined as the difference between light- and dark-adapted flicker thresholds, covaries with changes in rod absolute threshold across the visual field. At a given eccentricity, the magnitude of the interaction is constant for test diameters ranging from 7' to 1.7 degrees, indicating that variations in magnitude with eccentricity do not result from changes in spatial summation properties. The measurement of cone flicker thresholds during bleaching recovery provides evidence that variations in the magnitude of the rod-cone flicker interaction with retinal eccentricity may result from differences in the channel capacity of the pathway carrying the threshold-elevating signal from rods.     

Comparison of spectral measures of period doubling in the cone flicker electroretinogram

Purpose Under certain conditions, the full-field flicker electroretinogram (ERG) of the cone system can show period doubling, such that the shape of the ERG waveform alternates from cycle to cycle. The purpose of this study was to determine the relationship between stimulus temporal frequency and the amplitudes of the spectral components of the ERG that correspond to period doubling. Method ERGs were recorded from 10 visually normal subjects in response to full-field sinusoidal flicker presented at frequencies ranging from 12.5 to 100 Hz. Period doubling was apparent over the stimulus frequency range from 25 to 100 Hz and was quantified in terms of the amplitudes of spectral components of the ERG waveform that corresponded to half the stimulus frequency (f/2) and three and five times that frequency (3f/2 and 5f/2). Results At stimulus frequencies between 30 and 40 Hz, the amplitude of f/2 was significantly lower than either 3f/2 or 5f/2, which themselves did not differ significantly. At stimulus frequencies between 40 and 60 Hz, all three response components were equivalent in amplitude. At stimulus frequencies above 60 Hz, however, the amplitudes of 3f/2 and 5f/2 were reduced significantly compared to f/2. Conclusion There is a frequency-dependent relationship among the spectral components of the flicker ERG that correspond to period doubling. The amplitude of f/2 underestimates the magnitude of period doubling at stimulus frequencies between 30 and 40 Hz, whereas the amplitudes of 3f/2 and 5f/2 underestimate the degree of period doubling at stimulus frequencies above 60 Hz. The explanation for the frequency dependence of these spectral components remains to be resolved.     

Stimulus chromatic properties affect period doubling in the human cone flicker ERG

Period doubling in the full-field cone flicker electroretinogram (ERG) refers to an alternation in waveform amplitude and/or shape from cycle to cycle, presumably owing to the operation of a nonlinear gain control mechanism. This study examined the influence of stimulus chromatic properties on the characteristics of period doubling in order to better understand the underlying mechanism. ERGs were acquired from 5 visually normal subjects in response to sinusoidally modulated flicker presented at frequencies from 25 to 100 Hz. The test stimuli and the pre-stimulus adaptation were either long wavelength (R), middle wavelength (G), or an equal combination of long and middle wavelengths (Y), all equated for photopic luminance. Fourier analysis was used to obtain the response amplitude at the stimulus frequency F and at a harmonic frequency of 3F/2, which was used as the index of period doubling. The frequency-response function for 3F/2 typically showed two peaks, occurring at approximately 33.3 and 50 Hz. However, the magnitude of period doubling within these frequency regions was dependent on the chromatic properties of both the test stimulus and the pre-stimulus adaptation. Period doubling was generally smallest when an R test was used, even though the stimuli were luminance-equated and the amplitude of F did not differ between the various conditions. The pattern of results indicates that the mechanism that generates period doubling is influenced by chromatic signals from both the test stimulus and the pre-stimulus adaptation, even though the high stimulus frequencies presumably favor the achromatic luminance system.     

Activation phase of cone phototransduction and the flicker electroretinogram in retinitis pigmentosa

This study examined the relationship between the activation phase of cone phototransduction and the flicker electroretinogram (ERG) in 15 patients with retinitis pigmentosa (RP) and 12 age-equivalent, visually normal control subjects. Values of Rmp3 (maximum amplitude of P3, the massed cone photoreceptor response) and S (sensitivity of cone phototransduction) were derived from a delayed Gaussian model applied to the leading edge of the ERG a-wave. Fundamental amplitude and phase of the flicker ERG were derived from responses to sinusoidal flicker presented at temporal frequencies ranging from 7.8 to 100 Hz. Patients with RP who had a reduced value of Rmp3 alone had an overall reduction in flicker ERG amplitude with a normal response phase across temporal frequency. Patients with RP who had a reduced value of S, whether or not Rmp3 was reduced, had the greatest amplitude reduction at temporal frequencies above 40 Hz and phase lags across a range of temporal frequencies. At high temporal frequencies, the amplitude reduction of the flicker ERG was predicted by the product of Rmp3 and S for all of the subjects except the three patients with RP who had the lowest fundamental amplitudes. The results indicate that there is a systematic relationship between the derived parameters of the activation phase of cone phototransduction and the characteristics of the flicker ERG in patients with RP, although the phase changes in the flicker ERG were generally greater than predicted by the derived parameters alone.     

Light adaptation, rods, and the human cone flicker ERG.

During the course of light adaptation, the amplitude and implicit time of the human cone ERG change systematically. In the present study, the effect of adapting field luminance on these ERG changes was assessed, and the hypothesis that light adaptation of the rod system is the primary determining factor was evaluated. Cone ERG responses, isolated through the use of 31.1-Hz flicker, were obtained from two visually normal subjects, initially under dark-adapted conditions and then repeatedly for 30 min following the onset of each of a series of ganzfeld adapting fields with luminances that ranged from -1.2 to 2.1 log cd/m2. The increase in flicker ERG amplitude and decrease in implicit time during light adaptation were greatest at the highest adapting field luminances. Photopically equivalent achromatic and long-wavelength adapting fields induced comparable increases in flicker ERG amplitude, while scotopically equivalent adapting fields had considerably different effects. This latter finding demonstrates that the rod system is not a major determinant of the adaptation-induced increase in cone ERG amplitude.     

Estimates of L:M cone ratio from ERG flicker photometry and genetics

Estimates of L:M cone ratio for males with normal color vision were derived using the flicker-photometric electroretinogram (ERG). These were obtained by best fitting ERG spectral sensitivity functions to a weighted sum of long (L)- and middle (M)-wavelength-sensitive cone spectral absorption curves. Using the ERG, measurements can be made with extremely high precision, which leaves variation in the wavelength of maximal sensitivity (lambda(max)) of the cone photopigments as the major remaining source of inaccuracy in determining the ratio of cone contributions. Here that source of inaccuracy was largely eliminated through the use of individualized L-cone spectral absorption curves deduced from L-pigment gene sequences. The method was used on 62 normal males as part of an effort to obtain a true picture of how normal variations in L:M cone ratio are distributed. The percentage of L cones in the average eye was 65%L [where %L = 100 X L / (L+M)]. There were huge individual differences ranging from 28%-93%L, corresponding to more than a 30-fold range in L:M ratio (0.4-13). However, the most extreme values were relatively rare; 80% of the subjects fell within +/-15 %L of the mean, corresponding to a 4-fold range in L:M ratio (1-4). The method remedies major weaknesses inherent in earlier applications of flicker photometry to estimate cone ratio; however, it continues to depend on the assumption that the average L cone produces a response with an identical amplitude to that of the average M cone. A comparison of the ERG results with the distribution of cone ratios estimated from cone pigment messenger RNA in cadaver eyes indicates that the assumption generally holds true. However, there may be a small number of exceptions in which individuals have normally occurring (but relatively rare) amino acid substitutions in one of their pigments that significantly affect the physiology of the cone class containing that pigment, so as to reduce the amplitude of its contribution to the ERG. Consistent with this possibility, extreme cone contribution ratios were found to be associated with atypical L-pigment amino acid combinations.     

Dark-adapted rod suppression of cone flicker detection: Evaluation of receptoral and postreceptoral interactions

Dark-adapted rods in the area surrounding a luminance-modulated field can suppress flicker detection. However, the characteristics of the interaction between rods and each of the cone types are unclear. To address this issue, the effect that dark-adapted rods have on specific classes of receptoral and postreceptoral signals was determined by measuring the critical fusion frequencies (CFF) for receptoral L-, M-, and S-cone and postreceptoral luminance ([L+M+S] and [L+M+S+Rod]) and chromatic ([L/(L+M)]) signals in the presence of different levels of surrounding rod activity. Stimuli were generated with a two-channel photostimulator that has four primaries for a central field and four primaries for the surround, allowing independent control of rod and cone excitation. Measurements were made either with adaptation to the stimulus field after dark adaptation or during a brief period following light adaptation. The results show that dark-adapted rods maximally suppressed the CFF by approximately 6 Hz for L-cone, M-cone, and luminance modulation. Dark-adapted rods, however, did not significantly alter the S-cone CFF. The [L/(L+M)] postreceptoral CFF was slightly suppressed at higher surround illuminances, that is, higher than surround luminances resulting in suppression for L-cone, M-cone, or luminance modulation. We conclude that rod-cone interactions in flicker detection occurred strongly in the magnocellular pathway.     

Absence of ocular interaction in flicker ERG responses reflecting cone opponent and luminance signals

The aim of the study was to investigate whether there is an ocular interaction in the flicker ERG responses reflecting luminance and cone opponency in normal human subjects. Flicker ERGs were recorded from one dilated eye of 10 healthy volunteers. Each subject was tested twice: once with and once without occluding the opposite eye. Red and green LEDs were modulated in counterphase in a Ganzfeld stimulator. ERG responses were recorded for different ratios of the modulation in the red and green LEDs and at 12 and 36 Hz. The amplitudes and phases of the fundamental components were compared between the conditions with and without occlusion. The 12-Hz flicker ERGs reflected activity of the cone opponent channel, whereas the 36-Hz data reflected luminance activity. There were no significant differences between the conditions with and without occluding the opposite eye for any of the stimulus protocols. Ocular interaction is absent in flicker ERGs reflecting cone opponent and luminance activity.     

Regional cone dysfunction in retinitis pigmentosa evaluated by flicker ERGs: relationship with perimetric sensitivity losses

PURPOSE: To evaluate regional cone dysfunction in retinitis pigmentosa (RP) by recording focal electroretinograms (FERGs) from the central and paracentral retinal regions and to correlate the FERG with perimetric sensitivity losses. METHODS: Twenty-three typical patients with RP (age, 18-65 years; visual acuity, 20/100 to 20/20; kinetic visual field by size II/4e, 20-40 degrees ) and eight age-matched control subjects were evaluated. FERGs were recorded in response to either a central (eccentricity, 0-2.25 degrees ) or a paracentral annular (2.25-9 degrees ) field, presented on a light-adapting background. Fields' luminances (mean: 80 cd/m(2)) were sinusoidally modulated at different temporal frequencies (TFs; 10.3, 14, 21, 32, 41, and 52 Hz). Amplitude and phase of the responses' fundamental harmonic (1F) were measured. Perimetric sensitivity was measured by a visual field perimeter. For each patient, mean sensitivity losses were calculated for both the central (0-2.25 degrees ) and paracentral (2.25-9 degrees ) regions. RESULTS: On average, central and paracentral FERGs of patients with RP were reduced in amplitude (P 相似文献