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Day #169: Know your spinal cord – The central pattern generator

V0008396 Brain and spinal cord: dissection, back view. Coloured line

Day (or really post) twelve on knowing your spinal cord. We have a whole category for the posts, neuroanatomy. Today we are going to talk about the curious case of the central pattern generators (CPG’s). Unfortunately, we cannot talk about them without talking about the experiments that found them, meaning we will be covering animal studies. In particular, some animal studies that might not sit well with some people. I attempted to be general where I can, just know that it is coming.

First let’s talk about what a central pattern generator does. A CPG is a neurological circuit that produces a rhythmic output. This is a fancy way of saying a CPG is what is activated when you’re walking (maybe, we will explain the disclaimer in a moment). It isn’t just walking that is rhythmic either, heartbeat, breathing, swimming, flying, swallowing, these are just a few examples of a rhythmic output.

Central pattern generators do not require higher brain functions, they are their own systems and the output of this circuit is not fixed. One of the defining characteristics of the CPG circuit is its flexibility in response to sensory input. This is to say that if you run, you’re still using the same CPG that controls walking, just like you’re activating the same CPG when you’re riding a bicycle. The difference is the sensory input from the muscle spindles and golgi tendon organs (your proprioceptive inputs).

Now for the disclaimer I mentioned, we KNOW that CPG’s exist in all sorts of different animals and we will get into that in just a moment. We even have a good idea these circuits exist in humans, but that is the extent of the existence in humans. We expect they exist, we would not be surprised if they exist, we even have evidence to support the existence of a CPG involved in human walking, but we have not definitely found it (despite what the wikipedia page suggests). Finding the human CPG would actually be a rather big deal for a lot of reasons, but for now we only have evidence that it exists, nothing definitive.

If this all sounds rather complex, that is because it is, CPG are incredibly complex circuits that one are activated can maintain very computationally intensive behaviors (like walking for example). Let’s look at one model of a CPG network called the 3FBL (for FeedForward and Feedback Based Locomotion), you can read the paper that I am pulling this figure from called, “The contribution of a central pattern generator in a reflex-based neuromuscular model.” The opening sentence agrees that the presence of CPG’s in human locomotion is still open to debate. Below is Fig. 3 from the study, showing the model they created, I won’t go into detail about it, but this is to illustrate how complex the circuit we’re talking about can be.

CPG

Fig. 3 in the study referenced in the above paragraph showing the proposed CPG based on their research and previous models.

We first came to the realization that CPG’s existed sometime around 1911. One of the first researchers who studied them was named Thomas Graham Brown. He realized that the basic pattern of stepping can be produced by the spinal cord without the need of descending commands from the cortex. His work involved decerebrate animals and I’m sorry to say we still use this practice today to study spinal cord behavior.

A brief side note: I am a researcher and an animal lover. I understand the need to study this and the reason decerebrate animals are used. I (probably) could not do this particular type of research, but I am not opposed to it because it has the potential to be extremely helpful in the repair and recovery of spinal cord injury and other neurological disorders. I sincerely wish there was a better way, but as of now there is not. If this makes me a bad person in your eyes, then so be it, but just know that I do not take the sacrifice these animals make lightly and neither do the researchers who do these studies.

We should probably define decerebrated, this means that the cerebellum has been severed or in some cases removed. This eliminates the connection to the brain, but still leaves the spinal cord itself functioning. This animal model was first used to show that the CPG even exists. Brown’s research was far ahead of its time and his mentor, Sir Charles S. Sherrington (who also was doing similar research) disagreed with his findings saying that they were actually observing a chain of reflexes caused by proprioceptive feedback. Brown later used deafferented animals to show this was not the case. This work would not be recognized for its implications until almost 50 years later when CPG research started to take off again.

By now you may be wondering why we are talking about CPG’s when we don’t even know they exist in humans. The answer is spinal cord stimulation. That’s right, the research I do (somewhat) relies on the CPG’s existence in humans. When someone has an incomplete spinal cord injury, they may be able to move, but depending on what level the injury occurred they will be unable control the lower limbs enough to walk or even support themselves. We are still trying to understand what happens when the spinal cord is injured and the work I’m doing in particular is trying to find that answer.

Based on what we do know, we have a good idea what is happening (although I cannot stress this enough, we do not know for sure). The neural signal that travels from the brain to the lumbar enlargement is reduced because of a spinal cord injury. This makes it more difficult to activate the spinal circuitry and possibly, if it exists, the central pattern generator that create the cyclical motion we do when we walk. When we stimulate the spinal cord, and we can do this non-invasively, we lower the threshold for those circuits to fire.

In particular my mentor (Co-PI) thinks we are stimulating the dorsal root ganglion and the type 1a afferent fibers. By lowering the firing threshold this reduced signal coming from the spinal cord can now activate the circuitry needed for walking. We can also over stimulate by increasing the amplitude and cause spontaneous activation of the muscles or even muscle lock. This is not what we want because we are no longer stimulating the spinal circuitry, so we have a limit to how high an amplitude we can stimulate with and that value is very person specific. There has even been video posted showing the effect non-invasive spinal cord stimulation has on the ability to move. I will end this post with that video and this brief word.

We don’t know for sure that CPG’s exist in humans, but we have a good idea and this work help supports that idea. I do not know when or if we will find them in humans. However, I wanted to include this post in the series I’m doing because it is important to know where we are in our understanding of the spinal cord.

Now, check out this video showing a person with spinal cord injury. What you are seeing is a device that is fully supporting their legs. The person fully controlling their limbs on their own, with no input from people so keep that in mind. You can clearly see the effect the stimulation has on spinal cord circuitry and how this can be used as a treatment to restore some function. This video is evidence that we probably have a CPG, and that is a good thing in this case.

Until next time, don’t stop learning!

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