▎ WuXi AppTec content team editor
You lie in bed and you hear your relatives surrounding you, talking about your condition. You want to participate in their conversations, but even with all your might, you can't make a sound, you can't open your eyes, and you can't even control your facial muscles to make even a slight expression. Your consciousness is very clear, but you have completely lost the ability to control your body and express itself to the outside world...
This is not a nightmare, but a true portrayal of people with amyotrophic lateral sclerosis (ALS), commonly known as frostbite, who are in a closed state. As a rare but fatal neurodegenerative disease, patients with ALS gradually lose control of their muscles, and some patients eventually lose control even of the eyeball and facial muscles, and they lose the ability to communicate completely locked in their bodies until they reach the end of their lives.
In Germany, a 36-year-old man faced such a situation. He was diagnosed with ALS in August 2015 and has since seen a sharp turn in health. After only 4 months, he lost the ability to speak and walk; the next year, the patient was unable to breathe on his own and needed to survive with a ventilator.
The patient from Germany communicates with the outside world through a brain-computer interface (Image source: Wyss Center)
As the disease progresses, the patient's communication with others becomes a problem. In the early days, he was also able to use eye tracking devices to group words and sentences through eye movements. But since August 2017, with the decline of control over the eyes, he has been unable to use the device, and can only answer the question of "yes" and "no" by whether the eyeball is moving.
Due to the inevitable complete loss of eye movements, the patient told the research team at the University of Tübingen that he wanted to implant brain-computer interfaces to maintain communication with his family, especially his young son. In 2016, such devices already helped a female ALS patient communicate with the outside world with her mind, but when the brain has completely lost control of the body, no one knows the answer to whether such a strategy works.
After the family signed, the research team implanted two electrode arrays with only 3 millimeters of edge length into the patient's motor cortex. Each array contains 64 needle-like electrodes for detecting neural signals.
▲ This device consisting of electrodes is used to record the patient's brain activity (Image source: Reference[1])
Although the patient is no longer able to move his body, his brain can tell the body how to move, and the electrodes capture the signals of brain activity produced by this process. Theoretically, two different neural signals can correspond to a "yes" or "no" answer.
But after surgery, neither asking the patient to imagine moving hands, feet, or eyes translates into clear enough answers. It wasn't until 3 months later that the research team found an effective way to respond. They used the auditory neurofeedback system of the patient's brain, and the trained patient could control the firing rate of the neuron after hearing the sound, so that the frequency of the feedback sound matched the target tone. If the discharge rate is above a higher threshold and persists for more than 0.25 seconds, the patient says "yes"; conversely, if the discharge rate is 0.25 seconds below the lower threshold continuously, the patient says "no".
Video demonstrates how patients respond to sound (Video Source: Reference[1])
Based on this process, a spelling program reads out the letters of the alphabet, and the patient selects a specific letter by giving a yes or no answer by a neural signal. Of course, predictably, the process is rather slow, with patients being able to select only one letter per minute. In addition, the accuracy of the technique was limited: during the 135-day trial, patients were able to match the target tone for 107 days, of which only 44 days produced meaningful statements.
Dr Jonas Zimmermann, one of the paper's corresponding authors, from the Wyss Center for Biological and Neural Processes, also said the technology is still flawed: not only expensive, but also time- and energy-consuming. For example, caregivers need to be trained to familiarize themselves with the system and confirm patient feedback. In this way, the patient can use the implanted device to communicate with others.
But for such a patient who is completely closed in his own world, being able to communicate with his family and doctors through meaningful sentences is a huge leap in itself. For the first time after using the system for 3 weeks, he "said" meaningful sentences and asked caregivers to help him move his body.
In the year that followed, he generated many more complete sentences. He expresses affection to his family ("I love my cool son"), tells caregivers what he wants to eat through his esophagus ("Hungarian beef soup and pea soup"), and also gives advice to the system ("turn on word recognition")... For the patient, this is the only window through which he expresses his inner world to others.
▲The situation of patients using this device to generate statements (Image source: Reference [1])
Unfortunately, over time, the device's effectiveness has diminished. Now, he can only use this device to answer the question of "yes" and "no". The researchers say this may be because the scar tissue around the implant blocks the transmission of nerve signals; in addition, another possible reason is the weakening of the patient's brain's own thinking.
At present, the system is still in the preclinical stage, and the authors hope to conduct clinical trials in the near future. Before it can be extended to clinical use, it is necessary to further demonstrate its long-term, applicability and safety in other patients. The paper was published in the journal Nature Communications. "This study shows that you can write sentences even when you are completely paralyzed and unable to use your eyes and muscles to communicate with the outside world." The leader of the study, Professor Niels Birbaumer of the University of Tübingen in Germany, said.