Resting state electroretinography: An innovative approach to intrinsic retinal function monitoring.

The electroretinogram (ERG) represents the biopotential evoked by the retina in response to a light stimulus. The flash evoked ERG (fERG) is the ERG modality most frequently used clinically to diagnose and monitor retinal disorders. We hereby present a new method to record spontaneous retinal activity, without the use of a flash stimulus, that we named the resting-state ERG (rsERG). The recordings were done in normal subjects under light- and dark-adaptation and with different background light conditions (i.e., variations of wavelength and intensity). Additionally, rsERG recordings were obtained in five patients with retinopathies. The signals were subsequently analyzed in the frequency domain, extracting both periodic (i.e., frequency peaks) and aperiodic (i.e., background trend) components of the signal. The later was further assessed through a multifractal analysis using Wavelet Leaders. Results show that, irrespective of the recording conditions used, the rsERG always includes the same 90 Hz component; a frequency component also present in the fERG response, suggesting a retinally-intrinsic origin. However, in addition, the fERGs also includes a low-frequency component which is absent in the rsERGs, a finding supporting a retinally-induced origin. Comparing rsERGs with fERGs in selected patients with various retinal disorders indicates that the two retinal signals are not always similarly affected (either as a result of underlying retinal pathology or otherwise), suggesting an added value in the assessment of retinal function. Thus, the rsERG could have a similar role in clinical visual electrophysiology as that of the resting-state EEG in neurology namely, to quantify changes in spontaneous activity that result from a given disease processes.

Discrete Wavelet Transform Analysis of the Electroretinogram in Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder.

Background: To evaluate the electroretinogram waveform in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) using a discrete wavelet transform (DWT) approach. Methods: A total of 55 ASD, 15 ADHD and 156 control individuals took part in this study. Full field light-adapted electroretinograms (ERGs) were recorded using a Troland protocol, accounting for pupil size, with five flash strengths ranging from -0.12 to 1.20 log photopic cd.s.m-2. A DWT analysis was performed using the Haar wavelet on the waveforms to examine the energy within the time windows of the a- and b-waves and the oscillatory potentials (OPs) which yielded six DWT coefficients related to these parameters. The central frequency bands were from 20-160 Hz relating to the a-wave, b-wave and OPs represented by the coefficients: a20, a40, b20, b40, op80, and op160, respectively. In addition, the b-wave amplitude and percentage energy contribution of the OPs (%OPs) in the total ERG broadband energy was evaluated. Results: There were significant group differences (p < 0.001) in the coefficients corresponding to energies in the b-wave (b20, b40) and OPs (op80 and op160) as well as the b-wave amplitude. Notable differences between the ADHD and control groups were found in the b20 and b40 coefficients. In contrast, the greatest differences between the ASD and control group were found in the op80 and op160 coefficients. The b-wave amplitude showed both ASD and ADHD significant group differences from the control participants, for flash strengths greater than 0.4 log photopic cd.s.m-2 (p < 0.001). Conclusion: This methodological approach may provide insights about neuronal activity in studies investigating group differences where retinal signaling may be altered through neurodevelopment or neurodegenerative conditions. However, further work will be required to determine if retinal signal analysis can offer a classification model for neurodevelopmental conditions in which there is a co-occurrence such as ASD and ADHD.

Multi-Angular Electroretinography (maERG): Topographic Mapping of the Retinal Function Combining Real and Virtual Electrodes.

GOAL: The full-field electroretinogram (ffERG) is an objective tool to assess global retinal function, though as it is currently done, it is unable to localize sources of retinal dysfunction or damage. To overcome this, we have developed a new way to record multiple spatial derivations of the ERG using the rotating capability of the eye, thus creating "virtual electrodes". We have termed this the multi-angular ERG (or maERG). With only 3 real electrodes and 11 varying gaze positions, we create 33 "virtual electrodes". METHODS: We created a realistic electrophysiological and anatomical eye model (i.e., forward model) to reconstruct the retinal activity (i.e., inverse problem) from the 33 virtual electrodes. We simulated 2 pathological scenarios (central and peripheral scotomas), which were compared to their respective theoretical source configurations using an Area under Receiver Operator Characteristic curve metric. RESULTS: Our simulations show that the low-resolution brain electromagnetic tomography algorithm (LORETA) is the best method tested to reconstruct retinal sources when compared to the Minimum Norm Estimate algorithm. Furthermore, a signal to noise ratio of 50 dB is needed to accurately reconstruct the retina's functional map. CONCLUSION: Our proposed maERG recording method, combined with our solution to the electromagnetic inverse problem enables us to reconstruct the functional map of the human retina. SIGNIFICANCE: We believe that this new functional retinal imaging technique will permit earlier detection of retinal malfunction and consequently optimize the clinical monitoring of patients affected with retinopathies.

The effects of bandpass filtering on the oscillatory potentials of the electroretinogram.

PURPOSE: In order to study the OPs, the ERG signal must be filtered to eliminate the low-frequency waves known as the a- and b-waves. Unfortunately, the ISCEV ERG standard does not give clear guidelines on how to proceed apart from indicating that frequencies below 75 Hz should be filtered out when recording scotopic OPs, while no suggestions are offered for the photopic OPs. The purpose of this study was thus to characterize more extensively the effects of various digital filters on the photopic OP waveforms in order to suggest the most appropriate filtering method to record them. METHODS: Filtered OPs (N = 9600 tracings) were extracted from a photopic ERG databank of 40 normal subjects [intensity: 4.4 cd s m-2; background: 30 cd m-2] using 240 different combinations of five digital filters types (Bessel; Butterworth; Elliptic; Chebyshev type 1 and 2), eight bandwidth ranges (50-300; 75-300; 100-300; 125-300; 50-1000; 75-1000; 100-1000; 125-1000 Hz), three filter orders (1, 2 and 5) and with/without phase lag corrections that were generated using MATLAB 2015b. The peak time and the percentage of OPs (sum of OP amplitudes on the b-wave amplitude) were calculated in the time domain (TD%OP). RESULTS: The timing of the OPs was less affected than the amplitude by the different filters used. Depending on the filter used, the resulting OPs were either severely depressed (16.16% of broadband OP content) or slightly reduced (93.63%). The filters that most successfully eliminated the slow components of the ERG (i.e., < 12% of broadband value) were the Bessel, the Butterworth and the Chebyshev type 1 filters and out of the latter, the Butterworth filter was that which most faithfully reproduced the high-frequency OPs (i.e., > 96%). CONCLUSION: Our results vividly demonstrate the need to better define the characteristics of the filter that is used to record the OPs as it does have a significant impact on the resulting waveform.

Assessing the Contribution of the Oscillatory Potentials to the Genesis of the Photopic ERG with the Discrete Wavelet Transform.

The electroretinogram (ERG) is composed of slow (i.e., a-, b-waves) and fast (i.e., oscillatory potentials: OPs) components. OPs have been shown to be preferably affected in some diseases (such as diabetic retinopathy), while the a- and b-waves remain relatively intact. The purpose of this study was to determine the contribution of OPs to the building of the ERG and to examine whether a signal mostly composed of OPs could also exist. DWT analyses were performed on photopic ERGs (flash intensities: -2.23 to 2.64 log cd·s·m-2 in 21 steps) obtained from normal subjects (n = 40) and patients (n = 21) affected with a retinopathy. In controls, the %OP value (i.e., OPs energy/ERG energy) is stimulus- and amplitude-independent (range: 56.6-61.6%; CV = 6.3%). In contrast, the %OPs measured from the ERGs of our patients varied significantly more (range: 35.4%-89.2%; p < 0.05) depending on the pathology, some presenting with ERGs that are almost solely composed of OPs. In conclusion, patients may present with a wide range of %OP values. Findings herein also support the hypothesis that, in certain conditions, the photopic ERG can be mostly composed of high-frequency components.