The Unreasonable Effectiveness of Deep Brain Stimulation Therapy and the Future of Neuromodulation

When DBS electrodes are properly placed the results are nothing short of a modern medical miracle.

However, in most patients the effectiveness wanes over time. There are a lot of theories as to why, below I will try to explain the one that makes the most sense to me, sometimes referred to as the Habituation Model. (I am going to try and do this as simply as I can but for more detail see this paper from Dr. Alfonso Fasano and Dr. Rick Helmich)

Think of the cells that surround these electrodes like any other living thing. All living things need to exchange information with their environment to survive, that is they need to be able to sense and respond to signals from their environment and then send signals back out that can have a predictable effect.

In DBS, we drop these alien probes into an environment where communication has gone awry. Those environments are often filled with all sorts of different cell types. At first the stimulator sends signals out to those cells and they in turn respond by sending signals back. However over time these cells realize that the thing that they’re communicating with isn’t responding in turn. They try and try and try again but they just can’t get any message across that produces any kind of predictable response. So each gradually pulls away to go talk to something else (kinda like humans no?), thus the messages in the network get jumbled again and the stimulation stops working as effectively as it could before.

What many patients then do is start turning up the dial on their stimulator. However, this must be done slowly and in close consultation with their physician as if it is turned up too quickly it can induce a long list of complications. (For more see this newly released paper from Dr. Michael Okun and colleagues)

Adaptive DBS should be a better solution than previous DBS systems because the electrodes both read and respond to signals from its environment.

The Future of Neuromodulation

While adaptive deep brain stimulation should be a giant leap forward for the field of neuromodulation and provide better care for people with neurodegenerative diseases, it will not be a cure. At best it will enable us to extend the lifetime efficacy of DBS systems by probably a few years, maybe a decade in some patients, if we get lucky.

This is because it does not slow the degenerative process (though I’m not sure that matters as much as we think, for more read Connectomic Deep Brain Stimulation from Dr. Andreas Horn. Though he does not explicitly state so I think his works makes a compelling case that with further refinements and better placements, DBS could be a much more effective symptomatic therapy and act as a functional cure for more patients.) And because the electrodes are still a rather clunky way to try and interact with and modulate signals in the brain.

I have been asked by a few organizations lately what I think could be done to further improve DBS. For one company I drew the picture above with the following description:

“For the future one on the right each of those little fibers should be dynamic, modular and adaptive. Ideally they should be guided by tiny nanobots and through machine learning algorithms slowly learn over time how to better innervate and stimulate whatever the target area is in each affected individual.”

Sounds easy enough, right? 😉

Here is another answer I gave just yesterday to a similar question:

“The future of DBS is in graphene based solution and personalized software applications for better patient and physician programmers.”

Graphene?

As it was explained to me, graphene is the thinnest, most conductive, most flexible and most durable material we will ever have. It was first made in 2004 but then rode the standard Gartner Hype cycle of all new inventions with promises that by now we would have space elevators ferrying us to the stars and neural laces for every boy and girl.

However, with our feet now firmly planted on the earth it does seem like graphene is about to hit the realistic bend in that hype curve. The most promising application for my money is better DBS from companies like INBRAIN Neuroelectronics for the rather simple reason that with graphene, as indicated above, we can develop something that looks and acts much more like a neuron.

Better Programmers & Better Data

The final key to improving DBS is the interface that patients and physicians see in their programmers and the kinds of information we can record from new DBS systems. I’m not going to go into any more detail for the moment as there are a lot of things happening in this area and I am still trying to wrap my head around it all for myself, but for more listen to the following from CEO of Rune Labs, Brian Pepin.

Well, the future certainly looks promising. Can’t wait till Wednesday (9/29) when we finally turn on the adaptive stimulation settings in my own device, which should coincidentally also be a pretty good test of the hypothesis mentioned above and give me some unique insights into adaptive DBS. Looking forward to sharing more of my impressions in the weeks and months to come.