Discovering an early symptom of the SOD1 mutation in rat motor behavior
This is as of my latest project, in collaboration with Dr. Paul Yarowsky from the  University of Maryland School of Medicine. Paul heard that we were working on this new algorithm for discovering very subtle effects on behavior, and he came to us with an interesting problem. He’s working with transgenic rats in which a mutation in the SOD1 gene was inserted. What is interesting about this mutation is that in humans it results in Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's Disease after a famous patient (actually, the most famous ALS patient nowadays is probably the theoretical physicist Stephan Hawking).

As with humans, SOD1 rats get the disease when they reach adulthood, and as with humans, no one knows how to diagnose the disease before adulthood. Young SOD1 rats look perfectly healthy and normal, and score normal in all the standard tests. If we could find some symptom in the movement of these young rats, even something very subtle, we could test if treatments can make it better (i.e., more like the behavior of normal rats) even at a young age. Treatments at a younger age may be more efficient, since they can delay and maybe even prevent the onset of the disease. In addition, discovering such a symptom may give us some insight into early diagnosis of ALS in human patients. 

We ran 12 young SOD1 rats and 12 wild-type controls in our
SEE open field arena, analyzed it with our algorithm, and we indeed found such a subtle pattern. The algorithm itself is not published yet, but I’ll show here some examples of this pattern. It is indeed very subtle – I could not see it with my eyes, nor any other difference in the behavior of these rats in comparison to the normal rats. But my algorithm reliably detects it at age 50 days old, about half the age of the adult-onset of the disease, and again at 80 days old.

This pattern is defined as follows: heavy braking while the rat is moving near the wall of the arena, but taking a slight turn away from it. The young SOD1 rats perform this movement pattern significantly less than the wild-type controls do, though we don’t have any idea why yet. Here are some animation examples of this pattern from our data. The arch is the wall of the arena, the circle represent the rat (it’s approximately rat size) and each animation shows 2 seconds of behavior in a loop, with the path coordinates that belong to the pattern highlighted in red.  To the right of each animation there’s also a speed profile of the same behavior.
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