Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.
Medscape spoke with the trial's principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University in Philadelphia, about the trial's initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
How did you first get involved with implanting electrodes to help stroke patients with recovery?
I was involved in the first human application of a microelectrode array in a young man who had quadriplegia due to a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.
I was naive and thought that this would soon be a widely available clinical medical device. Now it's nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.
A few years ago I spoke with Dr Robert Rosenwasser, chairman of the department of neurosurgery here, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said, "Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke." And that's what we did.
Multielectrode array manufactured by Blackrock Microsystems
Image courtesy of Blackrock Microsystems
How did the idea of using computer brain electrode interfaces begin?
Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they're trying to move their limbs, you want a motor control signal.
In someone who has end-stage ALS or a brain stem stroke, you can't even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.
It's important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They're just recording the endogenous activity that the brain makes. In comparison, a deep-brain stimulator is usually not recording anything; it's just delivering energy to the brain and hoping for the best.
But what we're doing is asking, if the person is trying to move the paralyzed limb but can't, can we get to the source of the signal and then do something with it?
What's the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?
The first step is a scan. People have been doing functional MRI (fMRI) on patients who have had a stroke as long as we've had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it's been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.
So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it's so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
The Cortimo Trial's Enticing Findings
What are the most striking results that you've seen so far with the device?
The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn't do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we're recording.
Obviously, that's very encouraging and gives us hope that many months or years after a stroke, people's brains are able to maintain this representation of all these different movements and plans. It's almost like it's trapped on the other side of the stroke and some of the signals can't get out.
The other discovery we're pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That's very different from all the prior research with brain array interfaces.
Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
What are the next steps for this technology before it can potentially become available in the clinic?
For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia due to, for example, spinal cord injury or end-stage ALS, who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.
Also, when you're recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it's certainly an engineering challenge. It's not just a single channel that you occasionally query; it's hundreds of thousands of channels of this complicated data stream.
But these are solvable challenges. People have been making a lot of progress. It's really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.
With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who've had a stroke, if they're motivated and there's no real contraindication.
Creating a Novel Device
On that point, are you partnering with engineering and technology companies?
The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab science type of project.
We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle — a better sensor or a better wireless transmitter.
The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don't need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the US Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it's actually reasonable and necessary.
How long will an implantable device last?
That's a key question and concern. If you have someone like our participant, who's in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There's a macro electrode that's just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.
One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they've already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
Are there any final messages you'd like to share with Medscape's clinician audience?
Regardless of our specialty, we're always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and un-paralyze your limbs may be available in the coming 5 or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.
Patients and their families need to be part of the conversation of where this is all going. That's one thing that's totally different for brain devices vs other devices, where a person's psychological state doesn't necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep — the way you think about and approach it — actually changes to the structure of the brain pretty dramatically.
I don't want to cause unreasonable hope that we're going to snap our fingers and it's going to be cured. But I do think it's fair to raise a possibility as a way to say that keeping oneself really healthy is justified.
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Cite this: 'Living Brain Implants' May Restore Stroke Mobility - Medscape - Feb 22, 2021.