Four advanced ALS (amyotrophic lateral sclerosis) patients who were “completely locked in” (totally unable to communicate) for years have suddenly broken through in a lab at the Wyss Center for Bio and Neuroengineering in Geneva, Switzerland — communicating a “yes” or “no” by simply thinking the answers.

The brain–computer interface (BCI) system achieved this remarkable breakthrough by using functional near-infrared spectroscopy (fNIRS) to measure changes in blood oxygen levels in the frontal lobes of the brain.

Patients suffering from ALS paralysis, but with preserved awareness, cognition, eye movements and blinking, are classified as having “locked-in syndrome” and can communicate via a BCI by looking at a computer screen, for example. But when the disorder progresses until the patient loses control of the last muscular response, usually the eye muscles, the condition is known as “completely locked-in state” (CLIS), with no possibility of communication. For most of us: a nightmare world.

“Are you happy?”

But surprisingly, when the researchers asked the question, “Are you happy?,” the answer from all four was consistently “yes,” repeated over weeks of questioning. In response to the researchers’ statement, “I love to live,” three of the four replied yes. The researchers asked other personal questions that required “yes” or “no” answers, such as: “Your husband’s name is Joachim?”

They found the questions elicited correct responses in 70% of the trials. In one case, a family requested that the researchers asked the patient whether he would agree for his daughter to marry her boyfriend, Mario. The answer: “no” nine times out of ten.

Overturning previous theories, the research was published in an open-access paper January 31 in PLoS Biology. It was conducted by a multinational team led by Professor Niels Birbaumer, affiliated with the University of Tübingen in Germany; Ospedale San Camillo, IRCCS, Venice, Italy; and the Wyss Center for Bio and Neuroengineering. “If we could make this technique widely clinically available, it could have a huge impact on the day-to-day life of people with completely locked-in syndrome,” said Birbaumer.

“Restoring communication for completely locked-in patients is a crucial first step in the challenge to regain movement,” said Professor John Donoghue, Director of the Wyss Center. “The Wyss Center plans to build on the results of this study to develop clinically useful technology that will be available to people with paralysis resulting from ALS, stroke, or spinal cord injury. The technology used in the study also has broader applications that we believe could be further developed to treat and monitor people with a wide range of neuro-disorders.”

How fNIRS detected “yes” and “no”



The brain-computer interface in the study was based on functional near-infrared spectroscopy (fNIRS), which measures blood oxygenation (O 2 Hb). While other brain-computer interfaces have previously enabled some paralyzed patients to communicate, near-infrared spectroscopy is, so far, the only successful approach to restore communication to patients suffering from completely locked-in syndrome, according to the researchers.

After training a classifier separating “yes” from “no” answers for several days, the patients were given feedback of their affirmative or negative response to questions with known answers and open questions over a period of weeks. To measure relative change in oxygenated hemoglobin in the blood (indicating neural changes), the researchers used a NIRSport functional near-infrared spectroscopy system, which provides eight near-infrared sources and eight detectors, and placed these “optodes” over the frontocentral brain region.

To measure changes in O 2 Hb, the fNIRS system shined two wavelengths (760 nm and 850 nm) of pulsed near-infrared light. The blood component hemoglobin scatters light, and the ratio of infrared light absorbed to light scattered depends on the amount of hemoglobin binding with oxygen. NIRS measures the change of this ratio and infers the change in O 2 Hb concentration from that change. The NIRS device can reach to about 3 centimeters in the brain, with a resolution on the order of 5–10 mm, according to NIRX.

The work was supported by Deutsche Forschungsgemeinschaft; Stiftung Volkswagenwerk; German Ministry of Education and Research; Baden-Wuerttemberg Stiftung EMOIO from the Federal Ministry of Education and Research; Eva and Horst Koehler-Stiftung; National Natural Science Foundation of China; EU grant LUMINOUS; San Camillo hospital; and NINDS, NIH.



Brain-computer interface allows completely locked-in people to communicate