On December 22, 2021, a 62-year-old man named Philip O’Keefe logged on to Twitter and sent a tweet for the first time in his life. It would have been unremarkable except for the fact that O’Keefe had written his message by linking his brain directly with his computer. “No need for keystrokes or voices,” O’Keefe tweeted. “I created this tweet just by thinking it.”

O’Keefe is living with amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, a rare neurological condition that results in progressive paralysis. Since receiving his diagnosis, O’Keefe has gradually lost the ability to speak, eat, and type on a computer. While ALS is a fatal disease with no known cure, people with the disease often live with it for years as their brain slowly destroys their ability to interact with the outside world. 

O’Keefe managed to break out of his solitude thanks to an exquisitely delicate mesh of electrodes clinging to the inside of a single blood vessel traversing his brain’s motor cortex. This device, known as a “Stentrode,” was developed by an Australian company called Synchron that has spent the past decade pioneering a radical new approach to brain-computer interfaces (BCIs). The Stentrode monitors electrical activity in the brain’s motor area and translates it into a digital signal that allows people to directly interact with digital devices. The Stentrode allows individuals to tweet, write emails, and even play computer games just by thinking about the actions they want to perform.

Today, O’Keefe is one of a half-dozen people to have a Stentrode implanted. But if U of M alum Riki Banerjee (Ph.D. ’05) has her way, millions of others may be able to benefit from the technology in the not-so-distant future. 

Some smart money is betting that the company is onto something. Synchron announced a completed $75 million financing in December 2022. The investment firms of Microsoft’s Bill Gates and Amazon’s Jeff Bezos participated in the round.

A new BCI from Down Under

Banerjee joined Synchron as its executive vice president of research and development just a few months before O’Keefe sent his historic tweet. Her mandate: lead the company to commercializing its revolutionary BCI technology. At the time, Synchron had about a dozen researchers in Australia and the company was wrapping up the first clinical trial of its Stentrodes in humans. 

That program, called SWITCH, resulted in O’Keefe and three other individuals with paralysis receiving a Stentrode implant. It was a successful early-stage demonstration that the device was safe and effective for humans.

Australia was a natural starting point for trialing Synchron’s brain-computer interface. The company had been launched from the lab of Thomas Oxley, a neuroscientist at the University of Melbourne who now serves as Synchron’s CEO. The swift launch of a clinical trial was enabled by Australia’s unique regulations around new medical devices. But to get its device into the heads of the millions of people living with paralysis around the world, Synchron needs the blessing of the U.S. Food and Drug Administration, whose review process is considered the gold standard for new devices.

In 2020, the FDA granted Synchron’s Stentrode “Breakthrough Device” status, which put it on a fast track for a first clinical trial in the U.S. In 2021, the company was granted an Investigational Device Exemption, which allowed it to move forward with tests in humans. That trial, called COMMAND, launched in 2022 with the goal of implanting a Stentrode in six American patients.

It’s the first step toward a much larger “pivotal” trial: the final hurdle a new medical device must clear before the FDA allows it to be made commercially available to patients. And as far as Oxley is concerned, Banerjee is just the person to spearhead such a monumental effort.

It’s all in your head

Synchron has been, in many respects, a major shift in Banerjee’s career. She’d spent the previous 12 years working on neuromodulation technologies—therapeutic systems that change the way neurons behave by delivering small doses of electricity to the brain—at Medtronic, the largest medical device manufacturer in the world. 

When she arrived at Synchron’s brand new lab in Brooklyn, however, she found a handful of employees working in a mostly empty warehouse using tabletops stacked on top of cardboard boxes as desks. The walls were bare and the wi-fi had only been connected a few days prior—a quintessential startup environment. 

“My role is to build the team and work with them to develop a product to start clinical work in the U.S.,” Banerjee says. “For the past 18 months we built the office from the ground up. It’s been a real whirlwind.”

Although Banerjee hadn’t worked on brain-computer interface technology at Medtronic, she’s uniquely suited for the task ahead of her at Synchron. Her doctoral work at the U of M with Professor of Electrical Engineering Rhonda Franklin focused on finding ways to fit sophisticated electronic devices into ever smaller packages, while using just a small fraction of the energy required to power a modern smartphone. And when it comes to BCI technology—and Synchron’s Stentrode in particular—miniaturization is the name of the game.

A wholly new approach

Today, most BCI technologies are used exclusively in research settings, and fewer than 100 people in the world have a BCI implant. Except for the handful of patients who have participated in Synchron’s trials, all of the existing BCI technologies operate according to the same basic principle. An opening is made in a person’s head and an array of ultra-thin electrode needles—much finer than a human hair—are inserted directly into the person’s motor cortex. These needles capture the electrical activity of hundreds of individual motor neurons and relay it into a computer, where the activity is translated into a digital signal that allows the person to operate a computer.

Synchron’s Stentrode is different. Rather than inserting multiple needles directly into a person’s brain through the top of their head, the Stentrode is surgically implanted into the brain’s blood vessels by taking a “back door” through the jugular vein. The Stentrode is delivered to the brain’s blood vessels using a catheter carrying a much smaller stent. Once the stent reaches the brain, a delicate mesh of 16 electrodes that looks like microscopic chicken wire is deployed into a blood vessel overlaying the brain’s motor cortex. Here the electrodes monitor the aggregate electrical activity of the neurons in the motor cortex and relay that electrical information to a device implanted in the person’s chest, which wirelessly sends the information to a computer. There the electrical impulses are translated into keystrokes and mouse clicks.

“The idea is that your blood vessels are going everywhere, so if you want to get into different regions of the brain, the vasculature will allow that,” says Banerjee. “We’re riding along with this wave of innovation in the neurovascular space that allows access to those blood vessels and the place the Stentrode is situated is right up against the motor cortex, where a person’s motor intention can be recorded.”

In a conventional BCI, a module typically is permanently grafted to the back of a person’s head. If you look at one of Synchron’s patients, you’d never know they had an implant. Not only is this approach to BCI less invasive than currently available alternatives, it uses common techniques that doctors already use to treat strokes. This means that once Synchron receives FDA approval, most major hospitals in the U.S. should already have the experience and technology needed to implant the devices in patients.

A challenging, rewarding journey

Synchron’s SWITCH trial in Australia was the first time that a vascular BCI had ever been tested in humans. Banerjee and her team hope the recently launched COMMAND trial will replicate these results in the U.S. In the meantime, her focus is on developing processes for scaling the manufacture of the devices: a challenge that will draw on her decade of previous experience at Medtronic and her ability to lead a diverse team of researchers from domains such as chemistry, materials science, electrical and mechanical engineering, and software development.

For Banerjee, the opportunity to lead a team of gifted scientists is one of the major perks of her job. “I’m not the smartest person in the room, but I love that I can kind of interact with these people on a journey that has such an impactful outcome,” she says. Another perk is seeing patients with Synchron’s implants regain their autonomy.

Last summer, the first U.S. patient received a Stentrode implant at Mount Sinai West in New York. Banerjee hopes as many as five other American patients will receive an implant in the near future.

“These are paralyzed patients, and it’s a very rewarding experience seeing the hope this gives them and their family that their connection can be maintained,” Banerjee says. “One of our patients told us they felt comforted that they can always tell their partner they love them. It’s those kinds of things that make this work so meaningful.”