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Characterization of interlimb interaction via transcutaneous spinal stimulation

A graphic hospital-PI put together to share our results. I made the figure on the left under the methods heading, which I’m still very proud of.

I was debating about talking about this because I’m “only” the second author on the paper. Apparently I’ve gotten picky now that I have a handful of first author papers in review/published. I’m joking, but seriously, this paper has a special place in my heart and today I want to talk a bit about the science, but also the story behind the paper, because it is an interesting one!

The story starts almost three years ago, when I first started working in hospital-PI’s lab. This paper was the very first project I assisted on and the first time I used the software he has an affinity towards. To be fair, we use labchart and if you’ve never used it before, it’s super easy to work with. As with almost every point in my life, the data collection for this project happened LITERALLY the day after I had shoulder surgery so I was a bit out of it, but since I don’t take pain medications (because they do less than nothing to help with the pain, as in cause side-effects) I was able to do the bulk of the work, albeit a little haphazardly.

You would think that data collection took so long and that’s why it only just recently got published, but that isn’t the case. We collected all the data we would use in this project within the week we started. I was also a participant in this experiment, since it’s a non-invasive lab, we tend to experiment on ourselves regularly, so that was fun. But things went slowly because we went back and forth on the statistics and what we wanted to show.

As if the universe is conspiring to help me drive this point home, we needed to get our story together and there were several different stories to tell with the dataset. So after doing the statistics over and over and over for different aspects of the story, we finally settled on what we wanted to share with the world.

The experiment was simple enough when you think about it. We evolved from quadrupeds even though we walk on two legs there are still connections between upper and lower limb (arm swing for example), so we wanted to see if we could use that to modulate (either increase or decrease the response) of spinal stimulation on the opposite enlargement.

For those who are new to the spinal cord, welcome! The spinal cord is an interesting creature and I’ve created what I believe to be the most comprehensive look at the spinal cord for someone just starting out (here). Briefly, there are two enlargements, the cervical (think neck area) that controls upper limb movement and lumbar (bottom of the rib cage back area) that control leg movement and they (probably) talk to each other.

When we use non-invasive stimulation of the spinal cord (TSS or transcutaneous spinal stimulation, transcutaneous is a fancy term for through the skin) we can activate motor pools that innervate (control) upper or lower limbs and adjusting the location of the stimulation higher or lower in the direction of the spinal cord (towards the head or feet) we can somewhat target specific muscles (the effect is pretty spread out, but it does work to a certain extent).

Unfortunately stimulation through tissues like that also activates nerves and muscles in the back, which can make TSS painful at very high intensities, but this is also dependant on the person. The theory we wanted to test in this paper was if we could activate the opposite enlargement to reduce the activation threshold of the enlargement we wanted to activate.

Put more succinctly, if we wanted to help someone with a spinal cord injury stand, we wanted to see if stimulating the cervical enlargement prior to the lumbar enlargement (the one controlling the legs) would reduce the intensity needed, making it more comfortable, but also producing a larger effect.

This experiment was done in neurologically intact participants, but the findings are important in both SCI populations and for other populations, like people who’ve had a stroke. We not only used the lumbar and cervical enlargement, but also peripheral nerve stimulation (PNS) of the arm (fibular nerve) or leg (ulnar nerve) to indirectly activate the opposite enlargement. In all we had four different tests (conditions), fibular stim -> Lumbar TSS, Cervical TSS -> Lumbar TSS, ulnar stim -> Cervical TSS, and Lumbar -> Cervical TSS.

Within each condition we changed the timing between stimuli from 10 ms to 110 ms (specifically 10, 20, 30, 40, 50, 60, 70, 80, 90 and 110 ms, we skipped 100 ms because it’s a long experiment and that is a long time between stimuli in nerve terms). So if we wanted to see changes in the lumbar enlargement we would stimulate the cervical enlargement then 10, 20, … 110 ms later we would stimulate the lumbar enlargement.

We repeated each condition 10 times, so A LOT of data since we had 16 participants ( 16 x 10 repeats x 12 different timings -including two controls x 4 conditions = 7,680 individual points if I did that math right). We measured responses from leg muscles: left and right vastus lateralis (VL), medial hamstrings (MH), soleus (SOL) and tibialis anterior (TA) muscles. And upper limb muscles: biceps (BIC) and triceps (TRIC) brachii, extensor carpi radialis (ECR), and flexor carpi radialis (FCR) of the non-dominant arm, and the BIC of the dominant arm for a total of 12 different muscles (times 7,680, so again a lot of data!!).

Ultimately we found some really cool things! Namely that we can facilitate (increase) the response in either the upper or lower limbs by stimulating either the peripheral nerve of the arm/leg or the opposite spinal enlargement. When stimulating the cervical enlargement anywhere from 20 – 50 ms before the lumbar enlargement, we found our first significant increase different leg muscles peaking anywhere from 70-90 ms (so Cervical TSS then 70-90 ms later -> Lumbar TSS). We found very similar timing going the other direction.

Using PNS we found very similar effects, which was interesting and makes sense if you think about it. Timing was very muscle dependant so I’m trying to be brief by giving the range instead of the exact value and muscle. From a statistical standpoint, we found p < 0.001 in some cases (specifically peak facilitation), so a very low chance that the effect was due to randomness.

To sum up what we found, we determined that we can influence the target spinal enlargement by activating the opposite enlargement either via TSS or PNS. We also determined timing to provide the largest effect.

This paper not only helps us better understand how the spinal cord is wired, but also helps us determine better ways to use electrical stimulation in rehabilitation. The fact that we can do this non-invasively still amazes me to this day and this paper was my hands on introduction to non-invasive spinal stimulation and helped spawn my love of neurophysiology.

I’ve learned a lot since this paper was first started and I’m excited to share the next few papers we have coming!

Unfortunately the paper is behind a paywall because our system is broken and awful. It makes me sad, but there’s not a lot I can do about it. However, I hope this post and the graphic at the top sums up the paper well enough for anyone interested.

Source:

Atkinson, Darryn A et al. “Characterization of interlimb interaction via transcutaneous spinal stimulation of cervical and lumbar spinal enlargements.” Journal of neurophysiology, 10.1152/jn.00456.2021. 23 Mar. 2022, doi: 10.1152/jn.00456.2021

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