Written by Yang Yi

Editor in charge ︱ Wang Sizhen

Editor︱Yang Binwei

The development of brain-computer interface (BCIs) technology has established a new information transmission channel between the brain and external devices [1]

On August 8, 2022, He Jianghong's team from Beijing Tiantan Hospital Affiliated to Capital Medical University published online in the journal Neuroscience Bulletin "Brain-Computer Interfaces in Disorders of Consciousness" on the cutting-edge progress of brain-computer interface technology in the diagnosis and treatment of disorders of consciousness The perspective article (Insight) systematically reviews the application areas of BCIs in patients with DoCs, with a view to developing new paradigms and new ideas to promote BCIs

1.

In terms of diagnosis, the main goal of applying BCIs is to screen EEG characteristic waveforms related to compliance activities as evidence of the existence of consciousness [6]

2.

The feasibility of EEG-based BCIs system for communication has been preliminarily validated in healthy people and patients with amyotrophic lateral sclerosis (ALS) [10]

In addition to visual or auditory paradigms, Guger et al.
used a touch-based P300 BCI to assess compliance and communication in patients with DoCs [17]
.

This required the patient to silently count the number of vibrations in the heart and record the EEG signal from 100 ms before stimulation to 600 ms after stimulation
.

Significant changes in the mu rhythm (8–12 Hz, sensorimotor rhythm youyou (SMR)) and beta band (13–30 Hz) of the motor area during imaginary limb movements can serve as control signals for BCIs [ 18]
.

A significant decrease in SMR in the contralateral motor cortex during preparation for or during exercise is often referred to as event-related desynchronization, whereas a significant increase in ipsilateral SMR at the end of exercise is often referred to as event-related synchronization
.

Studies have shown that 19% of patients with MCS or VS have sensory and motor rhythm activation, and some patients demonstrate sustained attention, response selection, working memory, and language comprehension
.

Cruse et al also studied the possibility of motor imagery in the diagnosis of DoCs, and the results showed that the diagnostic accuracy was 53% [19]
.

However, since motor imagery-based BCIs require long-term training and are affected by volitional fluctuations, it is difficult to achieve consistent performance, and motor imagery-based BCIs still need further research in the field of DoCs
.

3.
Application in DoCs Rehabilitation Process

From the discovery of the self-organization phenomenon of sponge cells, organoid research has experienced decades of development from concept to application
.

Gradually mature culture systems and advanced analytical techniques have enhanced the application of organoids in biomedicine
.

Although the problems in organoid research remain to be resolved, their potential value for future biomedical research is undeniable
.

In future organoid studies, the combination of tissue engineering techniques and organoids for organoid co-culture

---

Essentially, DoCs are loss of function in some functional areas, and the remaining functional areas lack sufficient connectivity or integration to support arousal and awareness [20]
.

Based on this definition, it is believed that the restoration of consciousness depends in part on the remodeling of the central nervous system
.

Regarding neural electrical stimulation, it is generally believed that cervical spinal cord stimulation at the C2-C5 level or deep brain stimulation of key central nuclei can improve the condition of patients, especially DoCs caused by traumatic brain injury
.

Electrical stimulation based on BCIs feedback can be used to improve the condition of patients.
Closed-loop deep brain stimulation and cervical spinal cord stimulation are the main research directions of BCIs for DoCs rehabilitation, which requires neural circuit-based research to explore its mechanism
.

Due to the complex mechanisms of recovery after brain injury, further clinical validation is required to determine whether training with multimodal BCIs can promote neural remodeling and improve outcomes more rapidly in patients with DoCs
.

4.
Opportunities and challenges in application

From the discovery of the self-organization phenomenon of sponge cells, organoid research has experienced decades of development from concept to application
.

Gradually mature culture systems and advanced analytical techniques have enhanced the application of organoids in biomedicine
.

Although the problems in organoid research remain to be resolved, their potential value for future biomedical research is undeniable
.

In future organoid studies, the combination of tissue engineering techniques and organoids for organoid co-culture

---

Although many studies have shown that BCIs have been successfully applied to patients with DoCs, the high false-negative rate of BCIs cannot be ignored
.

When BCIs are used to diagnose DoCs, more precise techniques for judging the patient's state of consciousness should be considered
.

At the same time, since patients may be in the same state for a long time, long-term stable results should be obtained as much as possible to avoid fluctuations in the level of consciousness in repeated measurements
.

Many patients with DoCs are cared for by their families most of the time, and it may be necessary to implement BCIs for automated and portable measurements
.

In fact, DoCs patients, especially in the MCS state, often experience fluctuations in arousal, fatigue, and difficulty concentrating
.

The complexity of the experimental paradigm (stimuli and instructions), duration, and reproducibility of test results are important factors to consider when applying BCIs systems for diagnosis and evaluation
.

At the same time, it is difficult for patients with VS to communicate or give answers, and patients with MCS may experience delirium, and the paradigm of BCIs that do not require training may be more suitable for these patients
.

In addition, brain injury often leads to sensorimotor dysfunction, such as cortical deafness, blindness, and eye movement disorders
.

Most patients with DoCs cannot concentrate for long periods of time, which may result in a negative BCI classification result
.

Therefore, when developing BCIs systems, a personalized paradigm for patients with various sensory deficits is needed to reduce false-negative results
.

At present, there are few researches on BCIs algorithms for DoCs patients, and enhancing the signal-to-noise ratio helps to improve the detection accuracy of DoCs patients[21–23]
.

There are also studies suggesting that machine learning-based BCIs may be helpful in diagnosis, which requires further research [24]
.

When interpreting BCIs results, patients with implicit awareness may have negative results
.

Likewise, a positive result should not be regarded as clear evidence of the existence of consciousness, but merely to represent a possible better clinical outcome [25] (Table 1)
.

Table 1 Researches related to brain-computer interface in patients with impaired consciousness

(Table source: He Q, et al.
, Neurosci Bull, 2022)

V.
Summary and Outlook

From the discovery of the self-organization phenomenon of sponge cells, organoid research has experienced decades of development from concept to application
.

Gradually mature culture systems and advanced analytical techniques have enhanced the application of organoids in biomedicine
.

Although the problems in organoid research remain to be resolved, their potential value for future biomedical research is undeniable
.

In future organoid studies, the combination of tissue engineering techniques and organoids for organoid co-culture

---

At present, the application of BCIs in patients with DoCs is a promising direction, but there are still many problems to be solved
.

The basis of BCIs for patients with DoCs is to detect the brain's response to external stimuli, and the application of the audiovisual multimodal P300 is promising
.

Currently, complex paradigms require a lot of time to train and it is difficult to enforce uniform clinical standards, which hinders their clinical promotion and application
.

Going forward, a simplified paradigm for BCIs will facilitate the operation of most clinicians and reduce training and testing time
.

Through BCIs, misdiagnosis of patients with DoCs can be reduced and new rehabilitation techniques can be used to provide personalized diagnosis and treatment plans for patients with DoCs
.

From the discovery of the self-organization phenomenon of sponge cells, organoid research has experienced decades of development from concept to application
.

Gradually mature culture systems and advanced analytical techniques have enhanced the application of organoids in biomedicine
.

Although the problems in organoid research remain to be resolved, their potential value for future biomedical research is undeniable
.

In future organoid research, tissue engineering techniques are combined with organoid co-culture and multi-organoid co-culture.

---

Original link: https://doi.
org/10.
1007/s12264-022-00920-y

Corresponding authors: He Jianghong (left), Yang Yi (middle); first author: He Qiheng (right)

(Source: He Jianghong Team of Beijing Tiantan Hospital Affiliated to Capital Medical University)

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End of this article