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[Preprint]. 2023 Dec 26:2023.12.26.23300405.
doi: 10.1101/2023.12.26.23300405.

Portable Multi-focal Visual Evoked Potential Diagnostics for Multiple Sclerosis/Optic Neuritis patients

S Mohammad Ali Banijamali  1 , Craig Versek  2 , Kristen Babinski  3 , Sagar Kamarthi  1 , Deborah Green-LaRoche  3 , Srinivas Sridhar  4
Affiliations

Portable Multi-focal Visual Evoked Potential Diagnostics for Multiple Sclerosis/Optic Neuritis patients

S Mohammad Ali Banijamali et al. medRxiv. .

Abstract

Purpose: Multiple Sclerosis (MS) is a neuro-inflammatory disease of the Central Nervous System (CNS) in which the body's immune system attacks and destroys myelin sheath that protects nerve fibers and causes disruption in axonal signal transmission. Demyelinating Optic Neuritis (ON) is often a manifestation of MS and involves inflammation of the optic nerve. ON can cause vision loss, pain and discomfort in the eyes, and difficulties in color perception.In this study, we developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from near the O1, Oz, O2, O9 and O10 locations on the scalp (extended 10-20 system) using custom electroencephalography (EEG) electrodes.

Methods: Each test session is constituted by a short 2.5-minute full-field visual evoked potentials (ffVEP) test, followed by a 12.5-minute multifocal VEP (mfVEP) test. The ffVEP test evaluates the integrity of the visual pathway by analyzing the P1 (also known as P100) component of responses from each eye, while the mfVEP test evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEP responses. The results of the ffVEP test for patients were evaluated against normative data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification.

Results: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging (MRI) and Optical Coherence Tomography (OCT) findings.

Conclusion: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.

Keywords: Full-Field Visual Evoked Potential (ffVEP); Machine Learning; Multi-Focal Visual Evoked Potential (mfVEP); Multiple Sclerosis (MS); Optic Neuritis; Portable Diagnostics; Signal Processing; Support Vector Machine (SVM).

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Figures

Figure 1.
Figure 1.
Portable wireless NeuroVEP system. A. NeuroVEP device prototype integrating NeuroVEP sensor with visual stimulus headset, B. Closeup of NeuroVEP EFEG sensor arrays, C. Location of electrodes on the scalp over the visual cortex, D. Dichoptic stimulus and typical neuroelectric response, Visual pathway. Image in part D: Derived from (https://commons.wikimedia.org/wiki/File:Human_visual_pathway.svg)
Figure 2.
Figure 2.
A. ffVEP dartboard pattern-reversal visual Stimulus, B. mfVEP 36 sectors visual stimulus.
Figure 3.
Figure 3.
Full-Field Stimulus Data Analysis Steps.
Figure 4.
Figure 4.
Arrangement of the electrodes and calculation of left, center and right array responses.
Figure 5.
Figure 5.
Full-field test reports of a representative normal subject from NeuroVEP Device.
Figure 6.
Figure 6.
Multi-focal Stimulus Data Analysis Steps.
Figure 7.
Figure 7.
A. Multi-focal test electrode arrangement and calculation of derived signals. B. Calculation of SNR for mfVEP responses: Signal window [45:150] ms and Noise window [325:430] ms.
Figure 8.
Figure 8.
Schematic of the stimuli used for creating the “artificial defect” evaluation dataset. In each case, only sectors on one ring were unmasked (stimulating).
Figure 9.
Figure 9.
Overlay of training data A. Normal class vs. B. Abnormal class.
Figure 10.
Figure 10.
Full-field test reports of a MS/ON subject from A. NeuroVEP Device (note, positive peaks point upward) and B. Tufts SOC device (note, positive peaks point downward).
Figure 11.
Figure 11.
mfVEP custom stimuli, responses, and per eye visual function classifications for A. full stimulus 0–22.25° ecc. B. Artificially masked mid-peripheral ring stimulus 2.72–8.58° ecc., and C. Artificially masked outermost peripheral ring stimulus 8.58–22.25° ecc. Scores between 0 to 100 represent the quality of the response based on the classification probabilities and are linearly gray-scaled (White: Normal, Black: Abnormal); therefore, mid-gray sectors may be marked as “ambiguous”, requiring further analysis.
Figure 12.
Figure 12.
NeuroVEP’s results for subject S10 with right eye (OD) optic neuritis. A. ffVEP results with delayed right eye (OD) and abnormal interhemispheric amplitude ratio, B. mfVEP results which show a scotoma in the right eye.
Figure 13.
Figure 13.
A. HVF Central 30–2 Threshold Test with mfVEP sectors’ locations overlayed on top, B. NeuroVEP mfVEP test for right eye (OD) of an ON subject. Brain MRI Results: Optic Neuritis Optometrist Notes: Vision loss in right eye (OD), can see some colors, not shapes. HVF: Cecocentral Scotoma. NeuroVEP ffVEP: Abnormal waveform for the right eye (OD). Probably a prechiasmatic dysfunction. NeuroVEP mfVEP: Very poor or loss of vision in the black area.
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