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An Epilepsy Drug May Have Treatment Potential for Migraines

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The migraine—a common but debilitating brain disorder characterized by severe headaches, often with accompanying nausea and visual auras—has perplexed neurologists for decades. There are so many types of migraine, and each person’s physiology responds differently to the few drugs and treatments available.

In the hunt for an umbrella drug to treat all migraines, researchers at the University of British Colombia have investigated a potential new treatment for migraine with aura, which affects about one-third of migraine sufferers: pregabalin (brand name Lyrica). In a class of drugs called gabapentinoids, pregabalin is an anticonvulsant used to treat epilepsy, neuropathic pain, and fibromyalgia. The researchers published their results today in Proceedings of the National Academy of Sciences (PNAS).

Migraines begin in the brain before they’re ever visualized as an aura or felt as an intense headache. Researchers believe migraines are triggered by a brain pattern known as cortical spreading depression, or SD. Though triggers can be numerous, the SD starts in the brain as a “depolarization of neurons in a particular area of the brain,” Stuart Cain, lead author and a neurophysiologist at University of British Columbia, Vancouver tells mental_floss. “This causes a wave of excitation that travels across the brain.”

After the excitation period, there’s a long period of inactivity in which the neurons become stuck in this inactive state. “It’s this wave of inactivity that is actually causing spreading depression, and that causes the migraine aura,” he explains. Though the mechanisms are still not fully understood, they also believe this SD triggers the trigeminal nerve, one of the most widely distributed nerves in the head. That is what causes the headache pain.

As the SD travels slowly through the brain, it may go into the visual cortex and stimulate visual hallucinations, or even the auditory cortex, causing auditory hallucinations. In regular mice, the SD is constrained to the cortex, known as cortical spreading depression, which is typical migraine without aura. But in the mutant mice they used for the study, genetically modified to exhibit high susceptibility to the familial hemiplegic migraine (FHM) gene, FHM-1, which are associated with migraines accompanied by a visual aura, the SD enters the subcortical structures of the hippocampus, causing this type of migraine.

Migraines, strokes, and epilepsy are all known as calcium channel disorders; among other things, calcium channels play a role in cell depolarization and excitability. The FHM-1 patients have mutations in the P2 voltage-gated calcium channel. Pregabalin has been shown in previous studies to bind to the alpha-2 delta subunit of voltage-gated calcium channels, modulating the amount of calcium coming into the cell through this channel. When pregabalin inhibits the calcium, it also suppresses SD, which can stop migraines from starting.

To test the effects of pregabalin on the mutant mice, the researchers anesthetized the mice and induced migraine through implanted carbon fiber electrodes in the occipital cortex. Then, they injected them with a dose of pregabalin mixed with saline. (Humans would take an oral dose.)

“Mice have very fast metabolism, so you can’t wait too long,” Cain says. So 45 minutes later, they took eight consecutive image slices using a special form of MRI known as “diffusion weighted” MRI or “DW-MRI” over 13 minutes to track the SD in the mouse brains. “When SD occurs, the brain cells swell, and this changes the brightness of intensity on the MRI image. So we can view it as a movie traveling through the brain,” Cain says.

As they theorized, the pregabalin did indeed have an effect on SD. It slowed the speed and intensity of the SD waves. It also helped clear up a question neurologists have had about whether SD ever goes into the cerebellum, a structure in the very back of the brain that controls movement. “We were excited to see if the SD went into that structure in mutant mice, but it never did, so that was quite a big finding for the field," he says. "We now know that ataxia [a loss of voluntary muscle control] has nothing to do with SD.”

While they can’t recreate this same study design in human trials, since that would require inserting electrodes into the brain, they do have plans to combine MRI diagnostics with administration of pregabalin to attempt to improve outcomes for migraine patients. Cain is optimistic about the drug’s possibilities. “What the study shows is that more clinical trials are definitely warranted so we can properly validate its use for migraines,” he says.

For migraine patients, any new treatment in the already limited arsenal may bring hope.

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Man Buys Two Metric Tons of LEGO Bricks; Sorts Them Via Machine Learning
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iStock // Ekaterina Minaeva

Jacques Mattheij made a small, but awesome, mistake. He went on eBay one evening and bid on a bunch of bulk LEGO brick auctions, then went to sleep. Upon waking, he discovered that he was the high bidder on many, and was now the proud owner of two tons of LEGO bricks. (This is about 4400 pounds.) He wrote, "[L]esson 1: if you win almost all bids you are bidding too high."

Mattheij had noticed that bulk, unsorted bricks sell for something like €10/kilogram, whereas sets are roughly €40/kg and rare parts go for up to €100/kg. Much of the value of the bricks is in their sorting. If he could reduce the entropy of these bins of unsorted bricks, he could make a tidy profit. While many people do this work by hand, the problem is enormous—just the kind of challenge for a computer. Mattheij writes:

There are 38000+ shapes and there are 100+ possible shades of color (you can roughly tell how old someone is by asking them what lego colors they remember from their youth).

In the following months, Mattheij built a proof-of-concept sorting system using, of course, LEGO. He broke the problem down into a series of sub-problems (including "feeding LEGO reliably from a hopper is surprisingly hard," one of those facts of nature that will stymie even the best system design). After tinkering with the prototype at length, he expanded the system to a surprisingly complex system of conveyer belts (powered by a home treadmill), various pieces of cabinetry, and "copious quantities of crazy glue."

Here's a video showing the current system running at low speed:

The key part of the system was running the bricks past a camera paired with a computer running a neural net-based image classifier. That allows the computer (when sufficiently trained on brick images) to recognize bricks and thus categorize them by color, shape, or other parameters. Remember that as bricks pass by, they can be in any orientation, can be dirty, can even be stuck to other pieces. So having a flexible software system is key to recognizing—in a fraction of a second—what a given brick is, in order to sort it out. When a match is found, a jet of compressed air pops the piece off the conveyer belt and into a waiting bin.

After much experimentation, Mattheij rewrote the software (several times in fact) to accomplish a variety of basic tasks. At its core, the system takes images from a webcam and feeds them to a neural network to do the classification. Of course, the neural net needs to be "trained" by showing it lots of images, and telling it what those images represent. Mattheij's breakthrough was allowing the machine to effectively train itself, with guidance: Running pieces through allows the system to take its own photos, make a guess, and build on that guess. As long as Mattheij corrects the incorrect guesses, he ends up with a decent (and self-reinforcing) corpus of training data. As the machine continues running, it can rack up more training, allowing it to recognize a broad variety of pieces on the fly.

Here's another video, focusing on how the pieces move on conveyer belts (running at slow speed so puny humans can follow). You can also see the air jets in action:

In an email interview, Mattheij told Mental Floss that the system currently sorts LEGO bricks into more than 50 categories. It can also be run in a color-sorting mode to bin the parts across 12 color groups. (Thus at present you'd likely do a two-pass sort on the bricks: once for shape, then a separate pass for color.) He continues to refine the system, with a focus on making its recognition abilities faster. At some point down the line, he plans to make the software portion open source. You're on your own as far as building conveyer belts, bins, and so forth.

Check out Mattheij's writeup in two parts for more information. It starts with an overview of the story, followed up with a deep dive on the software. He's also tweeting about the project (among other things). And if you look around a bit, you'll find bulk LEGO brick auctions online—it's definitely a thing!

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Why Your iPhone Doesn't Always Show You the 'Decline Call' Button
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When you get an incoming call to your iPhone, the options that light up your screen aren't always the same. Sometimes you have the option to decline a call, and sometimes you only see a slider that allows you to answer, without an option to send the caller straight to voicemail. Why the difference?

A while back, Business Insider tracked down the answer to this conundrum of modern communication, and the answer turns out to be fairly simple.

If you get a call while your phone is locked, you’ll see the "slide to answer" button. In order to decline the call, you have to double-tap the power button on the top of the phone.

If your phone is unlocked, however, the screen that appears during an incoming call is different. You’ll see the two buttons, "accept" or "decline."

Either way, you get the options to set a reminder to call that person back or to immediately send them a text message. ("Dad, stop calling me at work, it’s 9 a.m.!")

[h/t Business Insider]

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