In 2020, Ujwal Chaudhary, a biomedical engineer then at the University of Tübingen (Germany) and the Wyss Center for Bio and Neuroengineering in Geneva (Switzerland), watched his computer in amazement as an experiment he had invested years in came to light. A 34-year-old paralyzed man was lying on his back in the laboratory, his head connected by a cable to a computer. A synthetic voice in German pronounced letters: “E, A, D…”.
The patient had been diagnosed a few years earlier with ALS (amyotrophic lateral sclerosis), a disease that causes the progressive degeneration of brain cells involved in movement. Man had lost the ability to even move his eyeballs, and was totally unable to communicate; in medical terms, he had the syndrome of incarceration (when the body is paralyzed but mental function is maintained).
Or so it seemed. Through Chaudhary’s experiment, man learned to select—not directly with his eyes, but by imagining his eyes moving—individual letters from the constant stream that the computer pronounced aloud. Letter by letter, one a minute or so, he formulated words and sentences.
“Wegen essen da wird ich erst mal des curry mit kartoffeln haben und dann bologna und dann gefuellte und dann kartoffeln suppe”, he wrote at one point: “To eat, I want curry with potato, then bologna and potato soup”.
Chaudhary and his colleagues were stunned. “I myself couldn’t believe it was possible,” recalled Chaudhary, who is now managing director of ALS Voice gGmbH, a neurobiotechnology company based in Germany, and no longer works with the patient.
The study, published Tuesday in Nature Communications, offers the first example of a totally paralyzed patient communicating extensively with the outside world, said Niels Birbaumer, study leader and former neuroscientist at the University of Tübingen, now retired.
Chaudhary and Birbaumer performed two similar experiments in 2017 and 2019 on patients who were completely paralyzed. and reported that they were able to communicate. Both studies were rejected after an investigation by the German Research Foundation concluded that researchers only partially videotaped their patients’ examinations, did not adequately show the details of their analyses, and made false claims.
The German Research Foundation, upon finding that Birbaumer committed scientific misconduct, imposed some of its harshest sanctions, including a ban on submitting proposals and serving as the foundation’s reviewer for five years.
The agency concluded that Chaudhary also committed scientific misconduct and imposed the same sanctions for a period of three years. Both he and Birbaumer were asked to revoke their two works, and they refused.
The investigation came after a whistleblower, researcher Martin Spuler, raised doubts about the two scientists in 2018.
Birbaumer upheld the study’s findings and took legal action against the German Research Foundation. The results of the process should be published in the next two weeks, said Marco Finetti, a spokesman for the foundation. Chaudhary said his lawyers hope to win the case.
The German Research Foundation is unaware of the publication of the current study and will investigate it in the coming months, Finetti said. In an email, a representative for Nature Communications, who asked not to be named, declined to comment on the details of how the study was judged, but expressed confidence in the process.
“We have strict policies to safeguard the integrity of the research we publish, including ensuring that it is conducted to a high ethical standard and reported transparently,” the representative said.
“I would say it’s a solid study,” said Natalie Mrachacz-Kersting, a brain-computer interface researcher at the University of Freiburg in Germany. She did not participate in the study and was aware of the previously rejected documents.
But Brendan Allison, a researcher at the University of California at San Diego, expressed reservations. “This work, like others by Birbaumer, should be viewed with great suspicion given his track record,” said Allison. He noted that in an article published in 2017, the researcher’s team had described that he was able to communicate with completely paralyzed patients. with basic answers, “yes” and “no”.
The results are promising for patients in similar unresponsive situations, including minimally conscious and comatose states, as well as the increasing number of people diagnosed with ALS worldwide each year. That number will reach 300,000 in 2040, according to projections.
“It’s a game-changer,” said Steven Laureys, a neurologist and researcher who leads the Coma Science Group at the University of Liège in Belgium, and was not involved in the study. The technology could have ethical ramifications in discussions around physician-assisted suicide for patients in vegetative states or with incarceration syndrome, he added. “It’s great to see this moving forward, giving patients a voice” to make their own decisions.
Various methods have been used to communicate with unresponsive patients. Some involve basic pen-and-paper methods created by relatives. In others, a caregiver points out or speaks the names of items and looks for microresponses—eye blinking, twitching the patient’s fingers.
In recent years, a new method has gained precedence: brain-computer interface technologies, which aim to translate a person’s brain signals into commands. Research institutes, private companies and entrepreneurial billionaires like Elon Musk have invested heavily in the technology.
The results were mixed but compelling: Patients moved prosthetic limbs using only their thoughts, and those with strokes, multiple sclerosis and other conditions communicated again with their loved ones.
What scientists haven’t been able to do so far, however, is communicate extensively with people like the man in the new study, who showed no movement.
In 2017, before becoming totally paralyzed, the patient used eye movements to communicate with the family. Anticipating that he would soon lose this ability, the family asked for an alternative communication system and turned to Chaudhary and Birbaumer, pioneers in the field of brain-computer interface technology, both of whom worked nearby.
With the patient’s approval, Dr. Jens Lehmberg, a neurosurgeon and author of the study, implanted two tiny electrodes in him in regions of the brain involved in controlling movement. Then, for two months, the man was asked to imagine moving his hands, arms and tongue to see if that would generate a clear brain signal. But the attempt yielded nothing credible.
Birbaumer then suggested using auditory neurofeedback, an unusual technique by which patients are trained to actively manipulate their own brain activity. The man was first stimulated with a sound note—high or low, corresponding to yes or no. That was his “white tone” — the note he had to imitate.
Then he played a second note, which mapped the brain activity that the implanted electrodes had detected. By concentrating and imagining moving his eyes, to effectively increase or decrease his brain activity, he was able to change the pitch of the second note to match the first. In doing so, he got real-time feedback on how the note changed, allowing him to raise the pitch when he wanted to say yes or lower it for no.
This approach had immediate results. On the first day of trials, the patient was able to change the second tone. Twelve days later, he managed to combine the second with the first.
“That’s when it all came together and he was able to reproduce these patterns,” said Jonas Zimmermann, a neuroscientist at the Wyss Center and co-author of the study. When the patient was asked what he imagined to alter his own brain activity, he replied, “Eye movement.”
For a year, the man applied this technique to generate words and sentences. The scientists took advantage of a communication strategy the patient had used with his family when he was still able to move his eyes.
At this stage, the technology is too complex for patients and family members to work with. Making it easier to use and accelerating the speed of communication will be crucial, Chaudhary said. Until then, he said, relatives of patients are likely to be satisfied.
“You have two options: no communication or communication at one character per minute,” he said. “What’s better?”
Perhaps the biggest concern is time. Three years have passed since the implants were first inserted into the patient’s brain. Since then, their responses have become significantly slower, less reliable and often impossible to discern, said Zimmermann, who now cares for the patient at the Wyss Center.
The cause of this decline is unclear, but Zimmermann thought it likely stemmed from technical issues. For example, electrodes are nearing the end of their lifespan. Replacing them now, however, would be unwise. “It’s a risky procedure,” he said. “Suddenly, the person is exposed to new types of bacteria in the hospital.”
Zimmermann and others at the Wyss Center are developing wireless microelectrodes that are safer to use. The team is also exploring other non-invasive techniques that have proven fruitful in previous studies with patients who are not paralyzed. “As much as we want to help people, I also think it’s very dangerous to create false hope,” Zimmermann said.
Translated by Luiz Roberto M. Gonçalves
