“The possibility to restore mobility to patients could have tremendous benefits,” says Mitchell Elkind, chief clinical science officer of the American Heart Association (AHA), and a tenured professor of neurology and epidemiology at Columbia University (New York City, USA), outlining the significant potential held by brain-computer interface (BCI) technologies in conversation with NeuroNews. “For those with limited function, even small gains can be life-altering. These gains may lead not only to increased ability to go out of the home, interact with friends and neighbours, and enjoy life; but they may also lead to positive mental health benefits, as patients may then be less depressed.”
In recent weeks and months, a number of breakthroughs involving BCIs have been made public. Late last year, the Wyss Center for Bio and Neuroengineering in Geneva, Switzerland presented positive animal-model results with its implantable Ability BCI system—describing this as an “important step” on the road to eventual human trials of the device.
More recently, Onward Medical and Precision Neuroscience have shared major updates in this space. In May, Onward published a paper in Nature detailing how its spinal cord stimulation (SCS) therapy had been used alongside a wireless BCI to give a patient augmented control over movement of his paralysed legs. The following month, Precision announced the successful completion of first-in-human implantations of its Layer 7 Cortical Interface as part of a pilot study evaluating the device.
And, over the past year, Synchron has provided several updates regarding its endovascular BCI offering—including completed enrolment for its US COMMAND trial earlier this month, with a total of six severe quadriparesis patients having been implanted with the company’s motor neuroprosthesis technology to date. Another innovation that has perhaps featured in more mainstream media coverage than any other is Neuralink’s N1 implant—on 19 September, the company announced recruitment had opened for its first-in-human PRIME study following review-board approval.
However, despite once again asserting that BCIs hold “a great deal of promise for neurological disorders in general, including stroke as well as spinal cord injury [SCI]”, Elkind feels it is appropriate to distinguish between the different conditions and instances in which these innovative devices could—in theory—be used.
A bridge too far?
According to Elkind, fundamental distinctions between stroke, and conditions like SCI or amyotrophic lateral sclerosis (ALS), create “certain challenges” when it comes to restoring physical function.
“That is because stroke primarily affects the brain itself,” he explains. “When the brain and the primary nerve tissue are injured—as is usually [the case] with a stroke—the neural connections that underpin the ability to move are the ones that are affected. [In those instances], a BCI may be less successful in capturing brain activity to trigger physical function, and I think we have more to learn about how to interpret the brain signals in stroke patients to allow them to regain movement.
“Where these technologies probably work best—at least right now—is by [creating] a bridge between the brain, where the signal originates, and the lower spine or the peripheral nervous system, where the movement is carried out. It is one thing to bridge two parts of the nervous system, each of which is working relatively normally. But, when the originator of the neural information, the brain itself, is damaged because of a stroke, that is a [bigger] problem. It is like the difference between having a fuse blown versus a wire in an electrical system cut.”
However, Elkind does highlight one relatively small stroke subset in which logic dictates BCIs may carry more promise: those affecting the brain stem, in between the base of the brain and the spinal cord. Brain stem strokes can be ischaemic or haemorrhagic in nature, and like spinal cord injuries can involve weakness on one or both sides of the body. The complex array of symptoms associated with brain stem strokes may also include vertigo, dizziness and severe imbalance, as well as double vision, slurred speech, and decreased consciousness.
“[The brain stem] is an area that does act more like a bridge, similar to the spinal cord, and so injury to the brain stem may be able to be bypassed by one of these BCIs,” Elkind notes. “And, for patients who have the most feared type of brain stem stroke—locked-in syndrome, where the pons (which literally means bridge) is damaged by a stroke and messages cannot get through—these devices may be very helpful. We need to see more evidence supporting that, but this could potentially be a gamechanger for these specific patients.”
Complexity of the problem
The degree of recovery that can be achieved in patients with reduced movement and function is dependent, Elkind adds, on both the location and the severity of the damage suffered. A further consideration he points to is the fact that “disabilities after neural injury come in many different shapes and sizes”.
“For patients who are locked in, and unable to move anything from the face down, the ability to use a computer independently is a great leap forward. Affected individuals have written beautiful books using lesser systems,” he avers. “The mechanical adaptations that will allow movement would likely come later and seem less technically challenging than the ability to interpret neural activity using a computer interface in the first place.”
Here, Elkind alludes to another key variable when it comes to enabling functional recovery: the extent of the patient’s impairment, but also the exact type of functionality that is being targeted. Fundamentally, he feels, BCI technologies in their current form are likely best-suited to restoring movements involving the hips and legs—because the signals sent to those larger muscle groups to facilitate walking, for example, are “much simpler”.
“You can imagine it is easier, at this stage, to develop computers that can make walking happen at the level of the spinal cord,” he goes on. “To move the hands and the fingers is a lot more complicated. A lot more of the space in our brains is devoted to the movement of our fingers, and our mouths, and our tongues, compared to the hips and the shoulders. So, to help people who have speech difficulty, as well as people with weakness of the hands and the fingers, [is more challenging], and I think we are a long way from somebody being able to play the piano or perhaps even write with a pen [using a BCI technology].
“Recent studies have been in very small numbers of patients with particular types of injuries. These are baby steps, and I expect it will be at least five years before technical kinks are worked out and larger trials are being done; and it may be 10 years before they begin to enter clinical practice; and another 10 years before they become an established standard of care. We know that medications shown to be effective take 15–17 years to make their way into clinical practice, so this may take as long or longer. Epilepsy surgery has had similarly slow uptake. These treatments will likely be expensive, and it will be important for them to demonstrate significant clinical effects.”