Can the "seal of consciousness" of vegetative people be lifted?

2020-08-28 | Neural Reality Original |

Disorder of consciousness

When I saw Valerie for the first time, she was lying motionless on the hospital bed, staring at the ceiling. When we walked into her ward, she did not respond. I looked at her.Her parents are standing next to her, eyes full of hope and despair. She is so young that she should have a future, but a sudden car accident put the pause button in the lives of everyone in the family.

My colleagues and I came to her hospital bed every day for a week to evaluate her condition. We desperately wanted to detect the smallest signs, no matter how small the reaction-it means she is still alive.I can hear what we say and feel the unreserved love of her parents for her. But every day, we get nothing.

The evaluation of the condition has not been concluded yet, and we still have a glimmer of hope. Although Valerie has lost the ability to move, through advanced neuroimaging technology, we can detect whether Valerie’s specific brain areas can respond to our instructionsReact.

During the days when we analyzed the imaging data, Valerie's parents could only wait in pain. Finally—Valerie's brain showed some slight neural activity, indicating that she can hear and understand us to a certain extentThis seems to be a breakthrough, but what does it mean for her? Can she continue to get better? How does she feel? Can she understand everything we say? Can she finally walk or talk again??

Only the first question led to countless other questions. That day, I decided to devote myself to the research of rehabilitation methods. Even if the challenge is unimaginable, I want to do my best to help patients like Valerie,Even a small improvement is enough for them.

I later started working in the coma science group at the University of Liège in Belgium. Through the study of patients with severe brain injury who have recovered from coma, thanks to the development of advanced resuscitation technology and intensive care treatment, those who have acquired sexualPatients with brain damage can survive even after falling into a coma.

However, they can only maintain a state called "anergy arousal syndrome" in the past called the continuous vegetative state-that is, they are obviously awake, but without any consciousness. Or,If they think they still have some residual consciousness, they are in a kind of "disorders of consciousness, DoC.

Although medical progress has undoubtedly helped save countless lives, it has also created a mysterious dilemma between birth and death. Take anergic awakening syndrome as an example, although patients open their eyes, they will notProduce any meaningful behavior.

In the past 20 years, the development of neuroimaging technology has allowed us to explore the function of the brain in this different state of consciousness. Our laboratory and the University of Cambridge in the United Kingdom have collaborated on a breakthrough study, which involves 54A patient with impaired consciousness.

When they were lying in the brain imager, the researchers asked them to complete two imagination tasks. One was to imagine that they were playing tennis, and the other was to imagine that they were walking around at home. These two imaginations correspond to two respectively.A completely different pattern of brain activity.

Surprisingly, there are five patients who can adjust their brain activities according to their wishes that is, as instructed. This shows that,

Inspired by these findings, the researchers conducted further repetitive behavioral experiments on these five patients, and managed to detect signs of sentiment in three of them. However, the remaining two patients did notExpress any active behavior. This is a large multi-person study that reveals for the first time that a small percentage of patients who are assessed as completely unresponsive actually have some remaining perception and cognition.

This result is shocking and made us realize that some unresponsive patients are more conscious than we thought. Then, if we invent more sensory detection techniques in the next few years, and discover that there are actually more patients, Even the vast majority of patients still have some cognition? What if most of them can feel pain?

Even with the amazing progress created by scientists and clinicians, patients with impaired consciousness can maintain it in recent months or even years, but they still cannot express their feelings and expectations. Their plight has also caused many ethical problems.Challenges. How do we as researchers or nurses face these challenges?

First of all, we need to improve the detection technology most, so that we can more effectively determine which patients are recoverable and which are not. However, we are far from finding this perfect biomarker.

But this raises another problem,

Experiments and results

Unfortunately, disturbance of consciousness is rare, and only six out of 100,000 people will be affected by it. However, because of its chronicity and self-righteous incurable characteristics, patients with consciousness disturbance have become the so-called medical nihilism.Recipients of therapeutic nihilism. This is reflected in the number of scientific papers in recent years-only a few studies have explored how to treat these patients to improve their quality of life or functional recovery.

Medical nihilism is a historical error that needs to be corrected. As a medical group, we must be careful not to give patients' families illusory hope, but also not because of the incurable history, we must not give up hope of conquering some diseases..However, this status quo is showing signs of gradual change, and scientists have begun to challenge the ancient barrier that "permanent barriers of consciousness can never heal".

Recent research shows the potential efficacy of both drug and non-pharmaceutical interventions. For example,

. Nonetheless, these treatments are included

Another potential drug with a mysterious effect is

For example, there is a patient who can only use his eyes to track people walking in the ward, or follow a simple command to squeeze someone’s hand. But 30 minutes after taking Zolpidem, he can respond to instructions without obstacles.Talking, reading magazines.

In other cases, Zolpidem makes people sober, but also causes other troubles: When patients become more and more conscious, they will gradually realize that their cognition is seriously impaired, which makes themBecome extremely depressed. Ethically speaking, deciding whether to use zolpidem on patients is very complicated, and there is no one-size-fits-all answer. However, once zolpidem does induce cognitive improvement, they obviously need additionalMedical monitoring, and frequent reassessment.

-Neural pathway-

It is relatively easier to give a pill to a patient. Even if the results of the administration are mixed, there is no reliable clinical trial. Compared with other physical therapy or more radical treatment methods, clinical treatment is generally more biased towards drug treatment. However,, Because of the lack of a panacea that is universally effective for all patients, we must find other ways to improve other alternative treatments.

One of the methods is transcranial direct current stimulation, tDCS. This is a non-invasive technique that stimulates the brain with a weak current. It has successfully improved the recognition of healthy people and patients with brain injury including those with impaired consciousness.Knowledge function.

I remember an interesting case of treating patients with tDCS a few years ago. It was a 67-year-old woman who was diagnosed with anergic arousal syndrome almost four years ago. When we checked carefully at her bedside,She did not respond at all and showed no signs of consciousness. Except for one of the seven tests, she was able to locate a painful stimulus. But after we implemented tDCS, she was able to respond to some simple commands such asFor three of the four tests, she can open and close her eyes as ordered.

Everyone in our team was extremely surprised because she had never responded to any instructions before. In the next few days, we also analyzed her brain activity and found that she was actually relatively well preservedBrain function. We call this condition "hidden consciousness"-that is, a patient is relatively conscious but cannot be detected by behavioral tests.

In the case of the female patient mentioned above, we guessed that the direct current applied to the prefrontal lobe unlocked the neural pathways of autonomous movement, allowing her to show consciousness. However, from a neurophysiological point of view, we have a positive effect on tDCSThe working mechanism is still poorly understood.

It is gratifying that only a few minutes of stimulation can induce an after-effect for up to several hours. However, if repeated brain stimulation is not performed, this beneficial effect will disappear after the effective time. Be positiveIs that recent research shows that

Compared with other brain stimulation techniques such as repetitive transcranial magnetic stimulation rTMS, which uses a weak magnetic field to regulate neural activity and deep brain stimulation, tDCS is also cheaper and safer, and is used in clinical practiceThe advantage of easy operation.

In addition, like other non-invasive forms of brain stimulation, tDCS also does not require the active participation of patients. It is painless and safe, so it has a promising future. We have performed different times of tDCS stimulation on patients in the past ten years. CollectionThe data show that approximately 30% to 50% of patients with minimally conscious states have achieved clinical improvement after stimulation.

Challenge and Hope

However, a significant obstacle to the clinical application of tDCS is that it requires patients and their families to travel to the hospital or research center to receive treatment. In order to overcome this difficulty, we recently cooperated with a Belgian company to develop a tDCS that can be used at homeEquipment. The family members of the patients follow the operating instructions given by us, and after the correct implementation of brain stimulation, we will observe the clinical improvement effect.

For example, some patients can respond spontaneously with some actions again, while others can respond to some simple commands. These improvements may seem trivial, but for patients and their families, no amount of progress can be significantSignificance. This is especially true when the patient has been in a minimum state of consciousness for months or even years.

The research on the treatment of disorders of consciousness is not only of key clinical significance, it can also help clarify the neural basis of subconsciousness in the physiological state. American neurologist Nicholas Schiff Nicholas Schiff proposed a model to explain why drugs orBrain stimulation therapy can help patients with impaired consciousness.

He believes that in normal cognitive processing, the front area of ​​the brain controls the central nucleus of the thalamus the deep structure of the brain is sensory by regulating the structure of other middle brain regions such as the inner globus pallidus that controls autonomous movement.A relay station for information and movement information. His fronto-parietal-midbrain circuit model is based on this view.

Usually, when the thalamus is activated, it will then activate the frontal and parietal lobe a closely connected cortex that spans the front and more posterior areas of the brain and is responsible for decision-making and movement control. However, in aAfter the severe brain damage that triggers the disturbance of consciousness, those nerve cells that regulate the excitability of the thalamus and the connection between the thalamus and the cortex are lost. As a result, the activity of the thalamus plummets and the activity of the key frontal-parietal connection network is also weakened.

One thing that the most promising brain stimulation techniques have in common is that the parts of their stimulation are related to the above-mentioned key loops. For example, most tDCS tests explicitly target the prefrontal lobe, because this area is responsible for multiple recognitionCognitive functions, such as memory, attention, or action execution. At present, stimulation seems to be the most effective option. Research aimed at other brain regions, such as the more posterior motor cortex or precuneus with selfFunctions such as consciousness are related, most of which are not so successful.

These results indicate that the frontal cortex plays a pivotal role in supporting consciousness, but this view is still open to question. Some researchers support this statement, while others believe that consciousness is caused by specific hot zones in the posterior cortex hotspot controlled.

The latest research also supports this view. For example, when rTMS is applied to the gyri of the corne located between the parietal and temporal lobes, which includes the function of checking spontaneous movement, after 10 courses of treatment, 22 patientsNineteen showed cognitive improvement given that this trial did not design a control group, we should be skeptical of these results.


At present, the specific neural mechanism of consciousness is still to be explored. The work of using tDCS or rTMS to stimulate different brain regions to achieve therapeutic effects is still in progress, and will help to further reveal the mystery of the brain regions that truly support consciousness.

An entirely different treatment method for consciousness disorders also has some prospects. Different transcranial stimulation techniques stimulate the brain through a top-down method-that is, stimulate the cortex to activate the deep brain structures in the descending pathway, such asThalamus; the other technique takes the opposite bottom-up approach—from the central nuclei of the brain to the cortex. The technique called "vagus nerve stimulation" that is still in the laboratory is convenientIs one of them.

Simulation of this nerve through the branch located in the ear is thought to activate many nucleus structures in the brain stem before reaching the thalamus, and then extensively activate the cortical area. However, this intervention technique is only used in a few patients with impaired consciousnessIt has been tested on the above, and further verification is needed before promotion.

Consciousness and its underlying neural mechanisms are still a mysterious problem. Therefore, from a medical or scientific point of view, dealing with patients suffering from consciousness disorders is a huge challenge. Despite the fact that I am aboveWith the exciting discoveries listed, I still deeply doubt that we can find a treatment that can restore all brain functions and help patients with consciousness disorders return to their previous lives.

The extreme brain damage suffered by most patients is simply too serious. Communicating with family members to explain the actual situation is also a constant challenge, because family expectations are always high, and they are tortured by the temptation of illusory hope every day. ButIt is our duty to be as honest as possible, and we need to clarify that even if there is some improvement, it is very small and perishable.

But at the same time, we should not give up. It is very important to improve treatment for those with consciousness disorders that are often forgotten by the academic community. For many years, people have believed that recovery is hopeless. But evidence shows that even after a few years of injury,In rare cases, some patients can still show positive improvement.

We need more effort to help those patients regain the maximum function they can obtain. Help Valerie and patients like her to regain the ability to communicate with “yes/no” for example, use a big moveThumbs to indicate “yes” and closed eyes to indicate “no” It may not sound like a big deal, but her quality of life can be greatly improved as a result-she can tell her caregiver if she feels pain, in bedIs it comfortable to lie down, or does she want to watch a movie.

This field is an art of finding a balance. It is necessary to avoid unrealistic hopes but not to give up hope. To make matters more complicated, finding funds for trials for patients with impaired consciousness is also a problem. Pharmaceutical companies and the pharmaceutical industryAll have no interest in this niche market with no economic benefits. Laboratories and research teams like us must rely on government funding, but the competition for government funding is extremely fierce, and they rarely fund clinical trials. In order to help patients renewTo gain their lost consciousness, we need more creative ideas to pay for the research.

作者:Aurore Thibaut|封面:Leonardo Santamaria

译者:夏明明|审校:Ziming Yuan,Orange Soda



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