• A dim view of M-cone onsets

      Parry, Neil R.A.; McKeefry, Declan J.; Kremers, Jan; Murray, I.J. (2016-03)
      We investigated the brightness (i.e., perceived luminance) of isolated L- and M-cone pulses to seek a perceptual correlate of our previous reports that M-on electroretinograms resemble L-off responses, implying the operation of post-receptoral opponent processing. Using triple silent substitutions, cone increments were generated in a 4-primary ganzfeld, masked by random positive or negative luminance bias. The results show that M-cone increments decrease in brightness, while L-cone increments increase. These differences became smaller as field size reduced; this was not eccentricity or area dependent. We speculate about early retinal input into brightness perception.
    • Human S-cone electroretinograms obtained by silent substitution stimulation

      Maguire, John; Parry, Neil R.A.; Kremers, Jan; Murray, I.J.; McKeefry, Declan J. (2018-01-29)
      We used triple silent substitution stimuli to characterize human S-cone electroretinograms (ERGs) in normal trichromats. Short-wavelength-cone (S-cone) ERGs were found to have different morphological features and temporal frequency response characteristics compared to ERGs derived from L-cones, M-cones, and rod photoreceptors in normal participants. Furthermore, in two cases of retinal pathology, blue cone monochromatism (BCM) and enhanced S-cone syndrome (ESCS), S-cone ERGs elicited by our stimuli were preserved and enhanced, respectively. The results from both normal and pathological retinae demonstrate that triple silent substitution stimuli can be used to generate ERGs that provide an assay of human S-cone function.
    • Incremental and decremental L- and M-cone driven ERG responses: I. Square-wave pulse stimulation.

      McKeefry, Declan J.; Kremers, Jan; Kommanapalli, Deepika; Challa, Naveen K.; Murray, I.J.; Maguire, John; Parry, Neil R.A. (2014-04)
      Electroretinograms (ERGs) elicited by transient, square-wave L- and M-cone isolating stimuli were recorded from human trichromatic (n=19) and dichromatic (n=4) observers. The stimuli were generated on a 4 primary LED stimulator and were equated in terms of cone modulation (cone contrast = 0.11) and retinal illuminance (12,000 trolands). L- and M-cone isolated ERGs had waveforms similar to those observed for luminance responses. However, M-cone ERGs exhibited a phase reversal in their responses to onset and offset stimuli relative to the L-cone responses. This on-off response reversal was observed in trichromats but not dichromats. Simultaneous counter-phase and in-phase combinations of L- and M-cone isolating stimuli generated responses that reflected chromatic and luminance processing, respectively. We conclude that L- and M-cone specific ERGs provide a measure of how photoreceptors contribute to post-receptoral mechanisms.
    • Incremental and decremental L- and M-cone driven ERG responses: II. Sawtooth stimulation.

      Kremers, Jan; Pangeni, G.; Tsaousis, K.T.; McKeefry, Declan J.; Murray, I.J.; Parry, Neil R.A. (2014-04)
      L- and M-cone driven on- and off- ERG responses and their interactions were examined using full field stimuli with sawtooth temporal profiles. The effects of temporal frequency and contrast were studied. ERG recordings were obtained from 21 trichromatic, 1 protanopic, and 1 deuteranopic subjects. ERGs to L-cone increments and decrements resembled those to M-cone decrements and increments, respectively (i.e., of the opposite polarity). Temporal frequency and contrast had little effect on the implicit times. All response components varied linearly with contrast. When stimulated simultaneously, the responsivities of most components were larger for counterphase than for inphase modulation. The retinal processing leading to an ERG response is reversed for L- and M-cone driven responses.
    • The morphology of human rod ERGs obtained by silent substitution stimulation

      Maguire, John; Parry, Neil R.A.; Kremers, Jan; Murray, I.J.; McKeefry, Declan J. (2017-02)
      Purpose To record transient ERGs from the lightadapted human retina using silent substitution stimuli which selectively reflect the activity of rod photoreceptors. We aim to describe the morphology of these waveforms and examine how they are affected by the use of less selective stimuli and by retinal pathology. Methods Rod-isolating stimuli with square-wave temporal profiles (250/250 ms onset/offset) were presented using a 4 primary LED ganzfeld stimulator. Experiment 1: ERGs were recorded using a rodisolating stimulus (63 ph Td, rod contrast, Crod = 0.25) from a group (n = 20) of normal trichromatic observers. Experiment 2: Rod ERGs were recorded from a group (n = 5) using a rodisolating stimulus (Crod = 0.25) which varied in retinal illuminance from 40 to 10,000 ph Td. Experiment 3: ERGs were elicited using 2 kinds of nonisolating stimuli; (1) broadband and (2) rod-isolating stimuli which contained varying degrees of L- and M-cone excitation. Experiment 4: Rod ERGs were recorded from two patient groups with rod monochromacy (n = 3) and CSNB (type 1; n = 2). Results The rod-isolated ERGs elicited from normal subjects had a waveform with a positive onset component followed by a negative offset. Response amplitude was maximal at retinal illuminances\100 ph Td and was virtually abolished at 400 ph Td. The use of non-selective stimuli altered the ERG waveform eliciting more photopic-like ERG responses. Rod ERGs recorded from rod monochromats had similar features to those recorded from normal trichromats, in contrast to those recorded from participants with CSNB which had an electronegative appearance. Conclusions Our results demonstrate that ERGs elicited by silent substitution stimuli can selectively reflect the operation of rod photoreceptors in the normal, light-adapted human retina.
    • Red-green and blue-yellow mechanisms are matched in sensitivity for temporal and spatial modulation.

      McKeefry, Declan J.; Murray, I.J.; Kulikowski, J.J. (2001)
      The spatial and temporal properties of human colour vision are examined using isoluminant, red¿green and blue¿yellow tritanopic gratings. Chromatic sensitivity is found to be low-pass as a function of both spatial and temporal frequency along all the chromatic axes investigated, including the tritanopic confusion lines employed to examine the properties of the S-cone driven mechanism. Comparison of sensitivity to on-off and contrast reversing stimuli indicates that transient mechanisms contribute to the detection of red¿green patterns but that the detection of S-cone specific patterns is governed by sustained mechanisms. By compensating for transient contributions to red¿green sensitivity, it is shown that sensitivity of chromatic mechanisms dominated by L- and M-cone input are closely matched to those with S-cone input.
    • Rod Electroretinograms Elicited by Silent Substitution Stimuli from the Light-Adapted Human Eye

      Maguire, John; Parry, Neil R.A.; Kremers, Jan; Kommanapalli, Deepika; Murray, I.J.; McKeefry, Declan J. (2016-08)
      Purpose: To demonstrate that silent substitution stimuli can be used to generate electroretinograms (ERGs) that effectively isolate rod photoreceptor function in humans without the need for dark adaptation, and that this approach constitutes a viable alternative to current clinical standard testing protocols. Methods: Rod-isolating and non-isolating sinusoidal flicker stimuli were generated on a 4 primary light-emitting diode (LED) Ganzfeld stimulator to elicit ERGs from participants with normal and compromised rod function who had not undergone dark-adaptation. Responses were subjected to Fourier analysis, and the amplitude and phase of the fundamental were used to examine temporal frequency and retinal illuminance response characteristics. Results: Electroretinograms elicited by rod-isolating silent substitution stimuli exhibit low-pass temporal frequency response characteristics with an upper response limit of 30 Hz. Responses are optimal between 5 and 8 Hz and between 10 and 100 photopic trolands (Td). There is a significant correlation between the response amplitudes obtained with the silent substitution method and current standard clinical protocols. Analysis of signal-to-noise ratios reveals significant differences between subjects with normal and compromised rod function. Conclusions: Silent substitution provides an effective method for the isolation of human rod photoreceptor function in subjects with normal as well as compromised rod function when stimuli are used within appropriate parameter ranges. Translational Relevance: This method of generating rod-mediated ERGs can be achieved without time-consuming periods of dark adaptation, provides improved isolation of rod- from cone-based activity, and will lead to the development of faster clinical electrophysiologic testing protocols with improved selectivity.
    • Simple reaction times in colour space: the influence of chromaticity, contrast and cone opponency.

      McKeefry, Declan J.; Murray, I.J.; Parry, Neil R.A. (2003)
      PURPOSE. This study examined the influence of stimulus chromaticity on simple reaction times (RTs) to determine the stage of chromatic processing that is most influential in their generation. METHODS. Simple RTs were measured in response to the cosinusoidally ramped onset of small, equiluminant, colored Gaussian spots. The chromaticity of these stimuli was varied, to modulate along a series of vectors in color space that included red-green (L-M) and blue-yellow (S-[L+M]) opponent axes. RESULTS. RTs are highly sensitive to small departures from subjective equiluminance. They are also dependent on stimulus chromaticity. The longest RTs are generated in response to equiluminant stimuli that isolate S-cone activity, whereas the shortest are generated by stimuli that modulate the L-M opponent axis. However, temporal processing differences are highly dependent on how the chromatic stimuli are scaled in relation to one another. The differences are reduced when scaling is based on detection threshold. The relationship between chromatic contrast and RT can be described by the modified Piéron equation RT = RT0 + k · C-1. CONCLUSIONS. Simple RTs generated in this study conform to the idea that they are largely determined by cone-opponency mechanisms. The use of cone contrast as a metric for scaling chromatic stimuli exaggerates differences between the temporal responsiveness of L-M and S-(L+M) opponency mechanisms.
    • Simultaneous chromatic and luminance human electroretinogram responses

      Parry, Neil R.A.; Murray, I.J.; Panorgias, A.; McKeefry, Declan J.; Lee, B.B.; Kremers, Jan (2012)
      The parallel processing of information forms an important organisational principle of the primate visual system. Here we describe experiments which use a novel chromatic-achromatic temporal compound stimulus to simultaneously identify colour and luminance specific signals in the human electroretinogram (ERG). Luminance and chromatic components are separated in the stimulus; the luminance modulation has twice the temporal frequency of the chromatic modulation. ERGs were recorded from four trichromatic and two dichromatic subjects (1 deuteranope and 1 protanope). At isoluminance, the fundamental (first harmonic) response was elicited by the chromatic component in the stimulus. The trichromatic ERGs possessed low-pass temporal tuning characteristics, reflecting the activity of parvocellular post-receptoral mechanisms. There was very little first harmonic response in the dichromats' ERGs. The second harmonic response was elicited by the luminance modulation in the compound stimulus and showed, in all subjects, band-pass temporal tuning characteristic of magnocellular activity. Thus it is possible to concurrently elicit ERG responses from the human retina which reflect processing in both chromatic and luminance pathways. As well as providing a clear demonstration of the parallel nature of chromatic and luminance processing in the human retina, the differences that exist between ERGs from trichromatic and dichromatic subjects point to the existence of interactions between afferent post-receptoral pathways that are in operation from the earliest stages of visual processing.
    • Temporal characteristics of L and M-cone isolating steady-state ERGs

      Kommanapalli, Deepika; Murray, I.J.; Kremers, Jan; Parry, Neil R.A.; McKeefry, Declan J. (2014-04)
      Cone isolating stimuli were used to assess the temporal frequency response characteristics of L- and M-cone electroretinograms (ERGs) in nine trichromatic and four dichromatic human observers. The stimuli comprised sinusoidal temporal modulations varying from 5 to 100 Hz. ERGs were recorded using corneal fiber electrodes and subjected to fast Fourier transform analysis. At low temporal frequencies (<10  Hz<10  Hz) the L- and M-cone ERGs had similar amplitude and exhibited minimal differences in apparent latency. At higher flicker rates (>20  Hz>20  Hz) L-cone ERGs had greater amplitudes and shorter apparent latencies than the M-cone responses. These differences between the L- and M-cone ERGs are consistent with their mediation by chromatic and luminance postreceptoral processing pathways at low and high temporal frequencies, respectively.
    • A Temporal White Noise Analysis for Extracting the Impulse Response Function of the Human Electroretinogram

      Zele, A.; Feigle, B.; Kambhampati, P.; Aher, A.; McKeefry, Declan J.; Parry, Neil R.A.; Maguire, John; Murray, I.J.; Kremers, Jan (2017-11)
      Purpose: We introduce a method for determining the impulse response function (IRF) of the ERG derived from responses to temporal white noise (TWN) stimuli. Methods: This white noise ERG (wnERG) was recorded in participants with normal trichromatic vision to full-field (Ganzfeld) and 39.38 diameter focal stimuli at mesopic and photopic mean luminances and at different TWN contrasts. The IRF was obtained by cross-correlating the TWN stimulus with the wnERG. Results: We show that wnERG recordings are highly repeatable, with good signal-tonoise ratio, and do not lead to blink artifacts. The wnERG resembles a flash ERG waveform with an initial negativity (N1) followed by a positivity (P1), with amplitudes that are linearly related to stimulus contrast. These N1 and N1-P1 components showed commonalties in implicit times with the a- and b-waves of flash ERGs. There was a clear transition from rod- to cone-driven wnERGs at ~1 photopic cd.m 2. We infer that oscillatory potentials found with the flash ERG, but not the wnERG, may reflect retinal nonlinearities due to the compression of energy into a short time period during a stimulus flash. Conclusion: The wnERG provides a new approach to study the physiology of the retina using a stimulation method with adaptation and contrast conditions similar to natural scenes to allow for independent variation of stimulus strength and mean luminance, which is not possible with the conventional flash ERG. Translational Relevance: The white noise ERG methodology will be of benefit for clinical studies and animal models in the evaluation of hypotheses related to cellular redundancy to understand the effects of disease on specific visual pathways.