In 2020, Ujwal Chaudhary, then a biomedical engineer at the University of Tübingen and the Wyss Center for Bio and Neuroengineering in Geneva, looked at his computer in amazement when an experiment he had spent years on revealed itself. A 34-year-old paralyzed man lay on his back in the lab, his head connected to a computer by a cable. A synthetic voice pronounced letters in German: “E, A, D…”
The patient had been diagnosed with amyotrophic lateral sclerosis a few years earlier, leading to the progressive degeneration of brain cells involved in movement. The man had lost the ability to even move his eyeballs and was totally unable to communicate; in medical terms, he was in a completely incarcerated state.
Or so it seemed. Dr. Chaudhary’s experiment had taught the man – not directly with his eyes, but by imagining his eyes moving – to select individual letters from the steady stream the computer spoke aloud. Letter by minute letter, one every 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: “For food I want curry with potato then Bolognese and potato soup.”
dr. Chaudhary and his colleagues were dumbfounded. “I couldn’t believe this was possible myself,” recalls Dr. Chaudhary, who is now director of ALS Voice gGmbH, a neurobiotechnology company based in Germany, and who no longer works with the patient.
The study, published Tuesday in Nature Communications, provides the first example of a patient in a fully confined state communicating with the outside world for extended periods, said Niels Birbaumer, the study’s leader and a former neuroscientist at the University of Tübingen. who is now retired.
dr. Chaudhary and Dr. Birbaumer conducted two similar experiments in 2017 and 2019 on patients who were completely confined and reported being able to communicate. Both studies were withdrawn after an investigation by the German Research Foundation concluded that the researchers had only partially videotaped their patients’ examinations, failed to properly show the details of their analyses, and made false statements. The German Research Foundation, which found that Dr. Birbaumer had committed scientific misconduct, imposed some of her strictest sanctions, including a five-year ban from submitting proposals and acting as a reviewer for the foundation.
The agency found that Dr. Chaudhary also committed scientific misconduct and imposed the same sanctions for a period of three years. Both he and Dr. Birbaumer were asked to withdraw their two papers, but they refused.
The investigation came after a whistleblower, Martin Spüler, a researcher, raised concerns about the two scientists in 2018.
dr. Birbaumer stuck to the conclusions and has taken legal action against the German Research Foundation. The results of the lawsuit are expected to be published in the next two weeks, said Marco Finetti, a spokesman for the German Research Foundation. dr. Chaudhary says his lawyers expect to win the case.
The German Research Foundation has no knowledge of the publication of the current study and will investigate it in the coming months, Mr Finetti said. In an email, a representative from Nature Communications who asked not to be named declined to comment on the details of how the study was vetted, but expressed confidence in the process. “We have a strict policy of safeguarding the integrity of the research we publish, including ensuring that research has been conducted to a high ethical standard and is reported transparently,” the representative said.
“I’d say it’s a solid study,” said Natalie Mrachacz-Kersting, a brain-computer interface researcher at the University of Freiburg in Germany. She was not involved in the investigation and was aware of the previously withdrawn papers.
But Brendan Allison, a researcher at the University of California at San Diego, expressed reservations. “This work, like other work by Birbaumer, should be taken with a huge mountain of salt given its history,” said Dr. Allison. He noted that his own team had described in a paper published in 2017 that he was able to communicate with fully incarcerated patients with standard “yes” or “no” answers.
The results show promise for patients in similarly unresponsive situations, including minimally unconscious and comatose states, as well as the rising number of people diagnosed with ALS each year worldwide. That number is expected to reach 300,000 by 2040.
“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 implications in discussions of euthanasia for patients in confined or vegetative states, he added: “It’s really great to see this moving forward, giving patients a voice” in their own decisions.
Numerous methods have been used to communicate with unresponsive patients. Some use basic pen-and-paper methods invented by family members. In other cases, a caregiver points to or speaks the names of items and looks for micro-responses – blinking, finger twitching of the patient.
In recent years, a new method has taken center stage: brain-computer interface technologies, which aim to convert 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 are mixed but compelling: patients moving prosthetic limbs using only their thoughts, and patients with stroke, multiple sclerosis and other conditions re-communicating with loved ones.
What scientists haven’t been able to do so far, though, is communicate extensively with people like the man in the new study who showed no movement at all.
In 2017, before becoming fully incarcerated, the patient had used eye movements to communicate with his family. Expecting that he would soon lose even this ability, the family requested an alternative communication system and approached Dr. Chaudhary and Dr. Birbaumer, a pioneer of brain-computer interface technology, both of whom worked nearby.
With the man’s permission, Dr. Jens Lehmberg, a neurosurgeon and author of the study, placed two small electrodes in the man’s brain regions involved in controlling movement. Then, for two months, the man was asked to imagine moving his hands, arms and tongue to see if they would generate a clear brain signal. But the effort yielded nothing reliable.
dr. Birbaumer then suggested using auditory neurofeedback, an unusual technique that trains patients to actively manipulate their own brain activity. The man first got a note – high or low, corresponding to yes or no. This was his “target tone” – the note he had to match.
He was then played a second note, which mapped to brain activity detected by the implanted electrodes. By concentrating — and imagining moving his eyes, to effectively turn his brain activity up or down — he was able to match the pitch of the second tone to the first. As he did so, he got real-time feedback on how the note was changing, 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 the man tried, he was able to change the second tone. Twelve days later, he managed to pair the second with the first.
“Then everything became consistent and he was able to reproduce those patterns,” said Jonas Zimmermann, a neuroscientist at the Wyss Center and an author of the study. When the patient was asked what he imagined to alter his own brain activity, he replied, “Eye movement.”
The following year, the man applied this skill to generate words and sentences. The scientists borrowed a communication strategy that the patient had used with his family when he could still move his eyes.
They grouped letters into sets of five colors. A computer voice first listed the colors and the man answered “yes” or “no,” depending on whether the letter he wanted to select was in that set. The voice then listed each letter, which it selected in the same way. He repeated these steps, set by set, letter by letter, to formulate complete sentences.
On the second day of his spelling attempt, he wrote: “First I want to thank Niels and his birbaumer.”
Some of his sentences include instructions: “Mama head massage” and “everyone should use gel on my eyes more often.” Others described cravings: “Goulash soup and sweet pea soup.”
Of the 107 days the man spent on spelling, 44 resulted in understandable sentences. And while there was great variability in speed, he was writing at about one character per minute.
“Wow, I was amazed,” said Dr. Mrachacz-Kersting. She speculated that incarcerated patients who can keep their minds stimulated could live longer and healthier lives.
dr. However, Mrachacz-Kersting stressed that the study was based on one patient and would need to be tested on many others.
Other researchers also expressed caution in embracing the findings.
Neil Thakur, chief mission officer of the ALS Association, said, “This approach is experimental, so there’s still a lot to learn.”
At this stage, the technology is also far too complex for patients and families to operate. Making it more user-friendly and speeding up communication speed will be crucial, said Dr. chaudhary. Until then, he said, a patient’s relatives will likely be happy.
“You have two options: no communication or communication at one character per minute,” he said. “What do you choose?”
Perhaps the biggest concern is time. Three years have passed since the implants were first inserted into the patient’s brain. Since then, his answers have become significantly slower, less reliable and often impossible to discern, said Dr. Zimmermann, who now cares for the patient at the Wyss Center.
The cause of this decline is unclear, but Dr. Zimmermann thought it probably stemmed from technical issues. The electrodes are thus approaching the end of their service life. However, replacing it now would be unwise. “It’s a risky procedure,” he said. “Suddenly you are exposed to new types of bacteria in the hospital.”
dr. 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 in non-retained patients. “As much as we want to help people, I think it’s also very dangerous to create false hopes,” said Dr. Zimmermann.
At the same time, Dr. Laureys of the Coma Science Group says there’s no point in cultivating a sense of “false despair” when viable innovations appear on the horizon.
“I’m extremely excited as a caregiver, as a doctor,” he said. “I think it’s wonderful that we are bringing these new scientific insights and technology to very vulnerable and dramatic circumstances.”