Can the "vegetable" wake up as desired?
   Economic Daily·China Economic Net reporter Shen Hui

  Obviously close at hand, but blocked in a different world. For many family members of "vegetables" who have suffered misfortune, the farthest distance in the world may not be separated from each other, but I am standing in front of you, but unable to communicate with each other. Facing the eager call of their relatives, will they one day create miracles of awakening in the "sleeping"? This is a major challenge facing cognitive neuroscience. Nowadays, the advent of new diagnostic tools makes people see the light.

  In order to overcome the world-class problem of "vegetative" awakening, Chinese scientists have made unremitting efforts to extract neural representations related to language processing in patients with impaired consciousness, and combine them with machine learning methods to create a set of diagnostic and predictive models. Convenient clinical diagnosis and rehabilitation prediction for the consciousness level of "vegetable people", with an accuracy rate of 80%. Relevant research results were jointly completed by the Chinese Academy of Sciences Brain Science and Intelligent Technology Innovation Center (Institute of Neuroscience) and the Wang Liping Research Group of the Key Laboratory of Primate Neurobiology of the Chinese Academy of Sciences. They have been published online in the international authoritative scientific journal Nature -Neuroscience".

  Limitations of existing diagnostic methods

  According to incomplete statistics, nearly 100,000 patients in my country fall into a coma every year due to traumatic brain injury, stroke, ischemic hypoxic encephalopathy and other diseases, and then enter a state of long-term disturbance of consciousness, that is, the "vegetative" state in the traditional sense.

  In patients with impaired consciousness, two types of states are the most common. One is the unresponsive awakening syndrome in which the eyes can be opened and closed but there is no perception. This type of patient is usually difficult to recover; the other is the minimum consciousness state, that is, the patient has limited perception, such as eye contact with others, or eye contact Can track moving objects. Compared with patients with unresponsive arousal syndrome, patients with minimal consciousness have a higher level of residual consciousness and a higher possibility of recovery.

  However, the identification of the patient's status at this stage mainly relies on the observation and scale scores of doctors with clinical experience, such as observing the patient's response to instructions, seeing whether the patient's eyes can follow the doctor's hand, but this identification method is misdiagnosed. Up to 40%.

  Investigating the reason, the researchers believe that this identification method is subjective, and the doctor in charge of the examination needs to be professionally trained, otherwise it is easy to make wrong judgments. In addition, some "vegetables" may know exactly what the doctor asks them to do, but cannot respond. "This does not mean that their brains are not awake. If such patients are misjudged, many treatment opportunities will be missed in the follow-up." said Dr. Gui Peng, the co-first author of the study.

  In order to further improve the accuracy of diagnosis, in recent years, researchers have used EEG or magnetic resonance imaging to record the brain activity of patients, and then speculate on the degree of consciousness disorder. However, in Gui Peng’s opinion, the latter has many implementation limitations. For example, many patients will be connected to supportive equipment such as ventilators, which brings great inconvenience to related examinations. At the same time, it is often caused by supportive equipment and magnetic resonance. The incompatibility of the instrument makes it impossible to check or even accidents.

  "Not only that, due to the lack of neurological indicators, there is still room for improvement in the accuracy of using magnetic resonance imaging to detect the level of consciousness of patients." Gui Peng said.

  Can a more convenient and objective diagnosis method for consciousness disorders be developed? Wang Liping, who has been committed to the study of language-related mechanisms, decided to use EEG to combine the advanced cognitive function of language processing with the state of consciousness. In this regard, the team of Mao Ying/Wu Xuehai from the Department of Neurosurgery of Huashan Hospital hit it off, and the two sides have started cooperative research in 2016.

  In Wang Liping’s view, on the one hand, this move has important scientific value for studying the brain’s ability to process language processing and neural mechanisms in different states of consciousness; on the other hand, it uses language processing ability as an indicator of brain cognitive ability to judge the patient’s remaining consciousness Level, has extremely important clinical value and social significance for the diagnosis and rehabilitation of patients with consciousness disorders.

  The scientific principles underlying the research

  This new method is based on the brain's understanding and processing of language information. Ding Nai, a researcher at Zhejiang University and a collaborator of this research, discovered in his work that when healthy people listen to a sequence of Chinese phonetic sounds presented at a certain frequency, their brains correspond to different levels of language structures-words, words, phrases, and sentences.

  For example, when a 4-character sentence of "Little Horse Crossing the River" is played continuously at a rate of 4 words per second, the brain will track the words ("小", "马", "crossing" and "河", appearing at 4 Hz), words ("Little horse" and "crossing the river", appearing frequency is 2Hz) and sentence ("Little horse crossing the river", appearing frequency is 1Hz) structure, and it is reflected in nerve signals such as brain magnetism or EEG. Correspondingly, if a four-character phonetic sequence like "Gao Xue Shan Pao" does not exist in the word and sentence structure is presented, only the neural signals corresponding to the frequency of the word structure can be observed.

  On this basis, the team hypothesized that there may be a correlation between the remaining consciousness level of patients with impaired consciousness and the processing depth of the hierarchical structure in the language sequence, especially in the neural representation of the high-level language structure. In other words, the ability of patients with consciousness disorders to process three different levels of words, words, and sentences may represent different levels of consciousness. If the language information can be processed, the frequency of brain electrical activity generated by the brain corresponding to the words, words, and sentences will be different. "The research is based on the principle that only the more awake the brain can understand the more complex sentences." Wang Liping explained.

  Based on this, the researchers designed three language sequences with different levels: a single word sequence containing only the word level, a phrase sequence containing a word and word structure, and a sentence sequence containing the word, word, and sentence levels, and played them to No Response Patients with arousal syndrome and minimal consciousness, record their brain electrical activity when they are stimulated by speech. The results of comparison with healthy subjects showed that both the patient group and the healthy subject group showed significant neural responses to the hierarchical structure of words, but only the brain electrical activity of the healthy subject group significantly reflected the tracking of word and sentence structure .

  It is worth noting that in individual analysis, the researchers found that 15 patients showed neural activity tracking the structure of words and sentences. "Machine learning further shows that it is more effective to distinguish between the two types of patients by using neural activity under the condition of phrase sequence and sentence sequence." Wang Liping introduced.

  Or find a more universal evaluation index

  In terms of neural mechanism, consciousness is not a static brain function, but a real-time evolutionary process of dynamic change, self-preservation and working together with the whole brain.

  Because the previous experimental results are difficult to reflect the dynamic changes of the brain, based on the relationship between consciousness and higher cortical brain areas in the global working space theory of consciousness, the team further made the hypothesis that brain activities with high levels of consciousness will stay in the higher prefrontal lobes for a long time. —In the information loop of the parietal cortex, low-level brain activity is more often distributed in low-level information processing brain areas such as sensory. "To put it simply, the more complex the syntactic structure of the language sequence processed by the brain, the more high-level brain activities are involved." Wang Liping said.

  To this end, the researchers recorded the EEG microstates of three groups of subjects when they received three different levels of structured language sequences, and compared them with the resting state. The results showed that when dealing with multi-level language sequences, healthy subjects showed more EEG microstates related to high-level brain activity, and the brain activity of the patient group was more related to sensory cortex activity. A further comparison between the two groups of patient teams found that compared with the non-responsive arousal syndrome group, the minimal consciousness group had a shorter duration of low-level sensory-related microstates, and higher-level cognitive-related microstates appeared more frequently per unit time, and the patients The differences in the microstate of brain activity between the groups were more significant under high-level language tasks.

  The machine learning model established by comprehensively using EEG indicators under the above language paradigm is not only significantly better than clinical evaluation based on behavioral scales in diagnosis, but also can more accurately predict the recovery of individual patients after 100 days of EEG recording, and the accuracy rate is up to 80%. In the study, a 47-year-old male stroke coma patient only scored 5 points out of a total score of 23 according to the traditional behavior assessment scale, which indicates that the probability of awakening is extremely low. However, in the study of language processing stimulation on his brain, the patient had strong neural activity in words and sentences. The researchers combined with the judgment of the micro-state of his brain electricity, and he has a high probability of regaining consciousness-eventually, he regained consciousness.

  "This means that we may have found a universal brain consciousness level evaluation index, which has a wide range of potential applications in a series of brain state assessments related to consciousness level such as coma, sleep, anesthesia, etc." said Wang Liping.

  Gui Peng revealed that the team will further optimize the test plan in the research, combine multi-modal testing and recording methods, improve the clinical effect, adaptability and automation of the research results, and ultimately study the neural mechanism of consciousness disorders and the neural representation of consciousness activities. , And to provide experimental and theoretical basis for conducting relevant scientific research in patients with impaired consciousness.