An Innovative Clinical Trial Breaks New Ground in ALS Research

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, affects the nerve cells that control movement throughout the body. Eventually, it leads to a gradual loss of the ability to stand, walk and use one's hands.

It can also impair the muscles used for speech, resulting in a loss of understandable communication.

For the past 20 years, the BrainGate clinical trials have pioneered and tested new approaches to help restore communication and mobility for people with paralysis, including people with spinal cord injury, brainstem stroke, and ALS.

In a new study published in the New England Journal of Medicine, the BrainGate team at the University of California Davis placed four small microelectrode arrays into the motor cortex of a 45-year-old man with severe dysarthria (problems producing speech) from ALS, hoping this would allow the man to communicate more quickly and easily simply by attempting to speak.

In this Q&A, you'll hear from Leigh Hochberg, MD, PhD, the lead investigator in the BrainGate project and the director of the Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital.

Dr. Hochberg dives into the BrainGate project and discusses this latest test of a brain-computer interface (BCI).

1. Can you briefly describe the BrainGate clinical trial and its primary objective?

Our BrainGate clinical trials have been developing and testing approaches to restore communication and mobility for people with paralysis, including people with spinal cord injury, brainstem stroke, muscular dystrophy, or ALS.

Like all early clinical trials of investigational medical devices, we study the safety of these systems. In addition, most of our team is focused on creating novel and ever-better methods for our participants to use these investigational systems to improve communication and mobility.

2. Can you explain the brain-computer interface (BCI) used in the trial and how it works?

One can consider many diseases and injuries resulting in paralysis as having caused a “disconnection” between the brain and the muscles that permit movement and speech. Spinal cord injury is a direct example of this--a disconnection occurs between the otherwise healthy brain and body.

An implantable brain-computer interface (iBCI) records brain signals associated with the intention to move, “decodes” that neural activity, and reconnects those signals (and thus, the original intent) toward the control of an external device or another implanted system.

For example, people who are able-bodied commonly control a computer by moving their hand to control a mouse. With an iBCI, the user simply thinks about using their hand--in the same manner that they did before the onset of weakness or paralysis--and we convert the associated brain signals in real-time into the movement of a cursor on a computer screen.

The original demonstrations of this were about 20 years ago, and the progress made since then has been incredible.

3. How did the BCI allow a man with ALS to ”speak” again?

Although we and others have traditionally recorded from areas of the brain that primarily control voluntary movement of the hand, more recently researchers have focused on decoding attempted speech from parts of the brain that control the muscles of articulation.

In this current study, the BrainGate team at University of California Davis placed four small microelectrode arrays into the motor cortex of a 45-year-old man with severe dysarthria from ALS.

As he attempted to speak, the neuronal ensemble activity associated with that attempted speech was first processed by an artificial neural network, which identified the most likely phonemes—the building blocks of words—being spoken.

Those phonemes were then additionally processed by language models such as those used by cellphone and smart speaker-based systems for interpreting audible speech. Here, they allowed the brain signals to be turned into text on a screen.

The user could then elect whether to have that text read aloud by the computer, which used a voice built from recordings of the user’s own voice prior to the onset of ALS.

He was able to speak about 32 words per minute, enabling far richer and faster interactions with his family, friends, care partners and colleagues. He’s even been using it for Zoom meetings.

4. Could you elaborate on the development process of the brain-computer interface?

More than 50 years ago, the National Institutes of Health (NIH) established the Neural Prosthesis Program, a precursor to today’s NIH BRAIN Initiative.

Seminal work in the late 1960s and 1970s showed that it was possible to record single neurons or small groups of neurons from the cortex and to predict the movement of an external device based only on those recordings.

With thanks to NIH, the Department of Veterans Affairs, and other federal and philanthropic support, we’ve been testing the investigational BrainGate system in our participants’ place of residence – their home, or their assisted care facility – since we launched the research in 2004.

Doing so has allowed us to develop and test a system where it actually needs to work – for example, in the user’s living room.

5. Can you expand on the collaboration aspect of this work? How were multidisciplinary fields involved? 

One of the great privileges of directing the BrainGate consortium is to help provide the infrastructure and environment that enables such an extraordinary multidisciplinary and multi-institutional team to work seamlessly. Our consortium benefits every day from Mass General Brigham’s deeply experienced research infrastructure - which really means the incredibly dedicated and thoughtful people who review, administer, and support research.

Our team from Mass General, Brown, Providence VA Healthcare, Stanford, UC-Davis and Emory includes neurologists, neurosurgeons, neuroscientists, neuroengineers, speech and language pathologists, computer scientists, and many others.

Undergrads, grad students, postdocs, research staff, and faculty from across the institutions are simultaneously engaged, with individual laboratories pursuing their own research hypotheses within a unified clinical trial - all permitting rapid iteration and the expansion of research from one clinical site to another. Just as importantly – we are all learning from each other every day.

6. What are some of the next steps in your research?

In our own BrainGate research, we’re excited about the potential for around-the-clock, intuitive, robust communication through both speech and the control of tablet computers, as well as the reanimation of paralyzed limbs through wearable, soft robotics.

What academic research does best in this field is making the breakthrough demonstrations of what is possible, and for doing the rigorous, fundamental human brain research and applied neuroengineering that informs the next generation of breakthroughs.

At the same time, our BrainGate and others’ academic BCI research has substantially de-risked the field, leading to the creation of multiple new BCI companies over the past few years. I’m excited about the new technologies that they’ll develop and their associated clinical trials. In support of those efforts, Mass General Brigham’s Data Science Office (MGB AI) recently convened the Implantable BCI Collaborative Community (iBCI-CC).

This is the first Collaborative Community with FDA participation in the clinical neurosciences, and I think it will have an important role in shaping the evolution of this field from today’s (and tomorrow’s) critical academic research through to its required translation to industry and, hopefully, the eventual demonstrations of safety and efficacy leading to market approval of multiple novel iBCIs that will help our patients.

The iBCI-CC is a forum for a diverse group of stakeholders including people with lived experience of paralysis, care partners, industry representatives, clinicians, researchers, foundations, ethicists, representatives from federal agencies and others that play such an important role in medical device translation.

There are many interesting, open questions about these technologies, and the iBCI-CC will help to create consensus opinions in a pre-competitive space, lowering the barrier for successful devices being made available to our patients as soon as possible.

The iBCI field is incredibly exciting, so now we need to make sure there’s a runway for these technologies not only to get to market, but to become available to our patients – in our own NeuroICU, and around the world.

When I’m attending in our NeuroICU, and I meet a patient who has just lost the ability to move or the ability to speak, I want nothing more than to be able to provide a technology that restores that lost function. Through our own BrainGate research and other ongoing neuroengineering R&D in academia and industry, I’m confident that implantable BCIs are on a path to becoming incredible restorative neurotechnologies.

CAUTION: Investigational Device. Limited by Federal Law to investigational use.