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I have just read about a visual effect called a scintillating scotoma.

Many variations occur, but scintillating scotoma usually begins as a spot of flickering light near or in the center of the visual field, which prevents vision within the scotoma area. The affected area flickers but is not dark. It then gradually expands outward from the initial spot. Vision remains normal beyond the borders of the expanding scotoma(s), with objects melting into the scotoma area background similarly to the physiological blind spot, which means that objects may be seen better by not looking directly at them in the early stages when the spot is in or near the center.

[...]The visual anomaly results from abnormal functioning of portions of the occipital cortex at the back of the brain, not in the eyes nor any component thereof, such as the retinas.3 This is a different disease from retinal migraine, which is monocular (only one eye).

It is a phenomenon that is believed to occur in the brain.

Scintillating scotomas are most commonly caused by cortical spreading depression, a pattern of changes in the behavior of nerves in the brain during a migraine.

That article is short and includes an impressive looking GIF of an optical image of the brain showing a wave-like pattern of blood volume which seems to come from the YouTube video Spreading Depolarization viewed using IOS. Santos et al. Neuroimage 2014 which links to Santos, E. et al. Radial, spiral and reverberating waves of spreading depolarization occur in the gyrencephalic brain NeuroImage, 99, 1 Oct. 2014, pp244-255.

The first Wikipedia article also says:

Symptoms typically appear gradually over 5 to 20 minutes and generally last fewer than 60 minutes, leading to the headache in classic migraine with aura, or resolving without consequence in acephalgic migraine. Many migraine sufferers change from scintillating scotoma as a prodrome to migraine to scintillating scotoma without migraine. Typically the scotoma resolves spontaneously within the stated time frame, leaving no subsequent symptoms, though some report fatigue, nausea, and dizziness as sequelae.

I don't completely understand the language there; I am not sure if it means that scintillating scotoma is always associated with some kind of migraine, or if they also occur as isolated events.

QUESTION: Why is it believed, or how is it known (if it is) that scintillating scotomas are caused by cortical spreading depression? Are these always related to some kind of migraine?

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The primary visual cortex is topographic, which means that specific parts of that brain region correspond exactly to specific parts of your visual field. In order to prove that a scotoma (literally a blind spot in your vision) is due to dysfunctional neurons, all you need to do is show that the neurons responsible for that spot in your vision are not working but the rest of them are. We can do this with a variety of tools, the most common one these days being fMRI. In addition to showing that the area of neuronal dysfunction maps onto the area subserving vision in that area where the scotoma is located, a spreading depression does exactly that: it spreads, at a predictable rate, from the location of its onset to adjacent brain tissue. fMRI will show you not only the area of brain dysfunction, but will allow you to "follow" the neuronal dysfunction as it moves over time, and show that it corresponds to the location of the scotoma in your visual field, which will also move in correspondence. HTH. See: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31895/ for first reference to this type of research (more in pubmed with keywords fMRI and migraine aura).

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    $\begingroup$ This looks like a good answer - it would be an excellent answer if it included a citation to some work showing or reviewing this. $\endgroup$
    – Bryan Krause ♦
    Commented Nov 8, 2019 at 22:47
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    $\begingroup$ Welcome to Stack Exchange and thank you for your answer. As the other comment points out it's generally recommended to support statements of facts with supporting links or citations so that readers can better judge the validity of an answer. In this case citing and linking to an example of fMRI demonstrating the movement of a spreading depression would be an excellent way of doing that. Thanks! $\endgroup$
    – uhoh
    Commented Nov 8, 2019 at 23:13
  • $\begingroup$ Also, there is a different but related question in Medical Sciences SE that you might be interested in: What things can trigger scintillating scotomas? Are they sometimes classified benign and not a reflection of a condition requiring further treatment? $\endgroup$
    – uhoh
    Commented Nov 8, 2019 at 23:14

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