Electroretinographic responses to luminance and cone-isolating white noise stimuli in macaques

Abstract

Electroretinograms (ERGs) are mass potentials with a retinal origin that can be measured non-invasively. They can provide information about the physiology of the retina. Often, ERGs are measured to flashes that are highly unnatural stimuli. To obtain more information about the physiology of the retina, we measured ERGs with temporal white noise (TWN) stimuli that are more natural and keep the retina in a normal range of operation. The stimuli can be combined with the silent substitution stimulation technique with which the responses of single photoreceptor types can be isolated. We characterized electroretinogram (ERG) responses driven by luminance activity or by the L- or the M-cones. The ERGs were measured from five anesthetized macaques (two females) to luminance, to L-cone isolating and to M-cone isolating stimuli in which luminance or cone excitation were modulated with a TWN profile. The responses from different recordings were correlated with each other to study reproducibility and inter-individual variability. Impulse response functions (IRFs) were derived by cross-correlating the response with the stimulus. Modulation transfer functions (MTFs) were the IRFs in the frequency domain. The responses to luminance and L-cone isolating stimuli showed the largest reproducibility. The M-cone driven responses showed the smallest inter-individual variability. The IRFs and MTFs showed early (high frequency) components that were dominated by L-cone driven signals. A late component was equally driven by L- and M-cone activity. The IRFs showed characteristic similarities and differences relative to flash ERGs. The responses to TWN stimuli can be used to characterize the involvement of retinal cells and pathways to the ERG response. It can also be used to identify linear and non-linear processes.

Luminance white noise electroretinograms (wnERGs) in mice

“…They were remotely similar to standard flash ERGs. An initial (awave-like) negative deflection (N1) was followed by a positive (b-wave-like) peak (P1), and resembled IRFs obtained by other groups in human subject (Saul and Still, 2016;Zele et al, 2017;Adhikari et al, 2019), mice (Wang et al, 2019), and macaques (Kremers et al, 2022). OP-like components were not present.…”

“…Such a stimulus is highly unnatural in a dark-adapted state and may push the retina in an extreme mode of operation where nonlinear mechanisms may become apparent that are not active under more natural stimuli (even when the stimulus is not hazardous). We previously proposed that OPs may be the result of such a non-linearity (Zele et al, 2017;Kremers et al, 2022).…”

“…Stimuli with white noise temporal profiles are more closely to natural stimuli as they have less regular statistics than most stimuli used in experimental procedures. Although used in other types of vision research (Chichilnisky, 2001;Chichilnisky and Rachel, 2002) they were, until recently, rarely employed in ERG recordings (Saul and Still, 2016;Zele et al, 2017;Adhikari et al, 2019;Wang et al, 2019;Kremers et al, 2022). Temporal white noise (TWN) stimuli have several advantages in comparison with flashes.…”

“…The cross-correlation of the wnERGs with the TWN stimulus is used to extract the impulse response function (IRF). In human subjects and in non-human primates, the impulse response functions (IRFs) resemble standard flash ERGs (Zele et al, 2017;Kremers et al, 2022) with an initial a-wave-like negativity that is followed by a positive deflection similar to the b-wave and by a component that resembles the PhNR. In contrast to the typical flash ERG response, the IRFs showed no oscillatory potential (OP)-like components in both humans and non-human primates (Zele et al, 2017;Kremers et al, 2022).…”

“…The Fourier transform of the IRF results in the modulation transfer function (MTF) that describes how signals of different temporal frequencies are processed by the linear approximation. We will discuss the analysis of wnERGs obtained in mice and compare the received IRFs of the luminance modulation and standard flash ERGs and IRFs of mice (Wang et al, 2019), macaques (Kremers et al, 2022), and human subjects (Zele et al, 2017).…”