Roman

Project Title

Simulation of Cone Responses for Photosensitive Epilepsy

Introduction

Photosensitive epilepsy occurs in patients who experience seizures when presented with flashing lights. In 1997, thousands of children reported being affected by watching a pokemon episode in Japan. While many these symptoms did not turn out to be seizures, 700 of these children did experience epileptic seizures caused by flashing lights in this pokemon episode [1].

Background

Epidemiology

Photosensitive epilepsy affects 10% of children who have been diagnosed with epilepsy, while only 4% of adults affected by epilepsy suffer seizures triggered by visual stimuli [2]. Not all visual stimuli are equally linked to photosensitive epilepsy. Rapid red lights flashing are more likely to trigger photosensitive epileptic seizures, perhaps due to how they stimulate red cones [3]. Additionally, multicolor modulations are also highly epileptic, specially red and blue modulations at 15 hz [2].

Electrophysiology

Using EEG, doctors can non-invasively record brain activity in epileptic patients. The photoparoxysmal response (PPR) is an abnormal and amplified pattern of brain activity observed only in epileptic patients while observing flashing stimuli [4]. Recent unpublished data shows that PPRs are observed in more patients when observing a red light flashing stimulus compared to when observing other light colors [5].

Research Goals

While researchers have identified the stimuli and brain responses associated with epilepsy, elucidating the mechanisms that transform epileptic stimuli into epileptic cortical responses is a challenging task. Studying how the human eye processes stimuli and transforms them into electrical signals is difficult without using invasive methods. However, recent tools are designed to carry out computer simulations of the human eye.

Questions

Using the Image System Engineering Toolbox for Biology (ISETBIO), a toolbox to simulate processes at the front-end of the visual system [6], we ask:

1. How does the human eye process stimuli that may trigger epileptic seizures?

2. Could cone activity intensify when processing epileptic stimuli (i.e. red lights)?

Hypotheses

More specifically, we test the following hypotheses:

1. Compared to M-cones and S-cones, L-Cones absorb more photons in red stimuli.

2. PPRs caused by colored stimuli are correlated with cone absorption levels.

3. Red flashing stimuli will trigger Photocurrents with a larger dynamic range in L-Cones compared to M-cones and S-cones.

Methods

The Wikipede edits Myriapoda.

To test our hypotheses, we used ISETBIO to simulate how the human eye process stimuli delivered by a xenon light source.

Stimuli

Six different colored filters were applied to the xenon light source. The figure on the right shows the spectral power distributions (SPDs) for the filtered xenon light (solid lines; the black SPD corresponds to the white light), and the cone sensitivity curves (dashed lines; red: L-cones, green: M-cones, blue: S-cones) as reference. Stimuli had an average luminance of 100 $cd/m^2$.

Eye simulations

We used the ISETBIO toolbox to process the xenon light stimuli with the default human optics. To create flashing stimuli we generated sequences where the xenon light filters were sinusoidally modulated by a black screen.

Measurements

To characterize cone absorptions, we calculated the cone absorptions for each type of cone and each stimulus color with duration of 5ms.

To positively correlate PPR incidence in epileptic patients and levels of cone absorption for different stimuli colors, we found the least squares linear regression coefficients that explain such positive correlation.

To characterize the transduction of colored stimuli over time, we calculated photocurrents while cones processed 1.5Hz flashing stimuli of different colors for 1.2 seconds.

Results

L-cones absorb more photons in red light compared to M-cones and S-cones

When assessing how different cone types absorbed light colors, we found that red light was absorbed the most by L cones. The figure bellow shows how other light colors (black line corresponds to white light) were absorbed by L, M, and S cones. Note that L-cones also absorbed orange, yellow, green and white colors more than M-cones and S-cones.

PPRs do not linearly correlate with absorption levels

We plotted cone absorptions vs PPR percentages in order to assess whether a linear relationship between cone absorption and PPRs exists. The plots bellow show L, M, and S cones absorptions vs PPR percentage for each color (black line corresponds to white light). The rightmost plot shows the absorptions for all three types of cones summed vs PPR percentages.

As a next step, we tried finding a weighted sum of L, M, and S cones that could explain a linear relation between cone absorptions and PPR percentages. The goal was then to find a vector $x\in {𝐑}^{\mathbf{(}\mathrm{𝟑}𝐱\mathrm{𝟏}\mathbf{)}}$ that would minimize the squared error between ${\hat{y}}_{PPR}=Ax$ and <mathj> y_{PPR}</math>, where $A\in {𝐑}^{(6,3)}$ is a matrix whose columns are the absorptions for L, M, and S cones.

Appendix

Presentation Slides

Acknowledgements

Thanks to Dora Hermes for her mentorship while carrying out this project.

Thanks to Trisha Lian for her help with project and coursework as TA in the class.

References

[1] Radford, B., & Bartholomew, R. (2001). Pokémon contagion: photosensitive epilepsy or mass psychogenic illness?. Southern medical journal, 94(2), 197-204.

[2] Parra, J. (2017). Epileptic Photosensitivity: Towards Implementation of Preventative Measures. In Converging Clinical and Engineering Research on Neurorehabilitation II(pp. 103-106). Springer International Publishing.

[3] Harding, G. R. (1998). TV can be bad for your health. Nature medicine, 4(3), 265-267.

[4] Fisher, R. S., Harding, G., Erba, G., Barkley, G. L., & Wilkins, A. (2005). Photic‐and pattern‐induced seizures: a review for the Epilepsy Foundation of America Working Group. Epilepsia, 46(9), 1426-1441.

[5] Kasteleijn-Nolst-Trenité, unpublished data.

[6] Brainard, D. H., Jiang, H., Cottaris, N. P., Rieke, F., Chichilnisky, E. J., Farrell, J. E., & Wandell, B. A. (2015, June). Isetbio: Computational tools for modeling early human vision. In Imaging Systems and Applications (pp. IT4A-4). Optical Society of America.