Retinal electrophysiology in central nervous system disorders. A review of human and mouse studies

Abstract

The retina and brain share similar neurochemistry and neurodevelopmental origins, with the retina, often viewed as a “window to the brain.” With retinal measures of structure and function becoming easier to obtain in clinical populations there is a growing interest in using retinal findings as potential biomarkers for disorders affecting the central nervous system. Functional retinal biomarkers, such as the electroretinogram, show promise in neurological disorders, despite having limitations imposed by the existence of overlapping genetic markers, clinical traits or the effects of medications that may reduce their specificity in some conditions. This narrative review summarizes the principal functional retinal findings in central nervous system disorders and related mouse models and provides a background to the main excitatory and inhibitory retinal neurotransmitters that have been implicated to explain the visual electrophysiological findings. These changes in retinal neurochemistry may contribute to our understanding of these conditions based on the findings of retinal electrophysiological tests such as the flash, pattern, multifocal electroretinograms, and electro-oculogram. It is likely that future applications of signal analysis and machine learning algorithms will offer new insights into the pathophysiology, classification, and progression of these clinical disorders including autism, attention deficit/hyperactivity disorder, bipolar disorder, schizophrenia, depression, Parkinson’s, and Alzheimer’s disease. New clinical applications of visual electrophysiology to this field may lead to earlier, more accurate diagnoses and better targeted therapeutic interventions benefiting individual patients and clinicians managing these individuals and their families.

Group comparisons of the individual electroretinogram time trajectories for the ascending limb of the b-wave using a raw and registered time series

“…To identify the optimal time interval in which to examine group differences, the region where there is greatest separation of the confidence interval boundaries could be used to localize the most suitable time or registered time point or interval. Thus, this report introduces the potential analysis of the ERG waveform using elements of FDA theory as an additional tool with which to analyze the ERG in retinal and neurological disorders [ 17 , 46 – 48 ].…”

“…FDA has been implemented to aid diagnosis in cardiology using electrocardiogram signals [ 49 ], gait patterns in Parkinson’s disease [ 50 ] and electroencephalograph recordings to assess driver fatigue [ 51 ]. Here our focus is on the ERG, and this method may therefore assist in expanding the application of the ERG to not only retinal [ 46 ] but also in the classification neurological disorders where multiple genetic and environmental factors may interact to hinder the identification of distinct phenotypical entities based on conventional ERG measures [ 38 , 48 , 49 , 52 , 53 ].…”

Enhancing Electroretinogram Classification with Multi-Wavelet Analysis and Visual Transformer

“…By analyzing the ERG waveform, potential biomarkers can be identified for the early detection of ADHD and bipolar disorder. Researchers have applied signal analysis techniques, such as wavelets and variable frequency complex demodulation, to studies in ASD [3] and ADHD [46] to fully leverage the potential of ERG in classifying or detecting CNS disorders at an earlier stage. These initial studies have identified the potential for identifying features extracted from signal analysis to improve ML classification models.…”

Reduced contrast sensitivity, pattern electroretinogram ratio, and diminished a-wave amplitude in patients with major depressive disorder

“…The ERG is a non-invasive ophthalmological examination method of the retina, which is increasingly applied in the field of neuropsychiatric research [10][11][12][13]. Given its embryological origin as part of the central nervous system [14], the retina is often regarded as an easily accessible "window to the brain" [15].…”