Hence, an extensive study was performed on four ALS patients in CLIS to train them to communicate “yes” and “no.” In the present study, which is the first of its kind, fNIRS-based BCI was used for binary communication in four ALS patients in CLIS. The most devastating of motor neuron diseases is amyotrophic lateral sclerosis (ALS) [ 1 ], which is progressive and renders an individual motionless, severely affecting his or her communication ability [ 2 ]. We do not have a physiologically plausible explanation as to why fNIRS responses to “yes” and “no” are different, as they are in three patients showing oxygenation increase during the answering interval (ISI) for “yes” responses with negligible topographical differences and oxygenation decrease during negative answers, again without topographical differences throughout the frontal cortical area. Patients F, G, and B answered open questions containing quality of life estimation repeatedly with a “yes” response, indicating a positive attitude towards the present situation and towards life in general, as reported in larger samples of ALS patients [ 43 , 44 ]. https://doi.org/10.1371/journal.pbio.1002593.g006 
 
 Patients Patient F (female, 68 y old, completely locked-in state) was diagnosed with bulbar sporadic ALS in May 2007, was diagnosed as locked-in in 2009, and was diagnosed as completely locked-in May 2010, based on the diagnoses of experienced neurologists. An auditory paradigm was employed to (a) train patients on questions with known answers, termed as training sessions; (b) give feedback on questions with known answers, termed as feedback sessions (i.e., “Your husband’s name is Joachim,” and after classification during ISI: “your answer was recognized as ‘yes’/‘no’); and (c) answer open questions, termed as open question sessions (“You have back pain”). When the patients scored at least 70% on the training questions, the doctors moved on to more personal questions. To train the patients on the system, doctors asked them to think “yes” or “no” in response to a series of simple questions, such as “Your husband’s name is Joachim” and “Berlin is the capital of France.” 
 
 
 
 During the sessions, the patients wore a cap that uses infrared light to spot variations in blood flow in different regions of the brain. Open questions are general questions related to quality of life and questions of caretakers whose answers can only be known by the patient. As they answered the questions, a computer hooked up to the cap learned to distinguish the blood flow patterns for “yes” and “no” in each patient.
– Four paralyzed patients unable to communicate for years were finally able to do so through a potentially groundbreaking brain-reading system. And it turns out that one of them really didn't want his daughter to marry her boyfriend. The patients all had advanced ALS and were unable to control even their eyes, reports the Guardian. In other words, they had "locked-in syndrome," meaning total motor paralysis in spite of normal cognitive and emotional processing. Researchers at the University of Tübingen in Germany fitted the patients with caps through which they could observe changes in blood flow in different parts of the brain, they explain in the journal PLOS Biology. They first asked the patients to think yes or no in response to simple statements such as their spouse's name, and moved on to more personal questions when that was mastered. “It’s the first sign that completely locked-in syndrome may be abolished forever, because with all of these patients, we can now ask them the most critical questions in life,” says researcher Niels Birbaumer. The patients, all of whom are on ventilators and being cared for at home, range in age from 24 to 76. The team did stumble on a couple surprises. For instance, all four patients suggested they were "happy" with their lives in spite of being locked-in. (Birmbaumer suggests this might be because of something akin to meditation.) And one patient, who is 61, answered "no" nine times out of 10 when his 26-year-old daughter asked if she should marry her boyfriend Mario. "But they got married," one of the researchers tells the BBC. "Nothing can come between love." (Researchers can't explain how Stephen Hawking has lived this long.)