Consciousness disorder
When I first saw Valerie, she was lying motionless in the hospital bed, staring at the ceiling. She didn't respond when we walked into her ward. I looked at her parents standing next to her, and my eyes were full of expectation and despair. She was so young that she should have a future, but a sudden car accident put the life of all the family on hold.
my colleagues and I came to her bedside every day for a week to assess her condition. We desperately want to detect the slightest sign, no matter how small the reaction is. All this means that she is still alive, can hear what we say, and can feel the unreserved love of her parents. But every day, we get nothing.
The assessment of the disease is still inconclusive, and we still have a glimmer of hope. Although Valerie lost her mobility, through advanced neuroimaging technology, we can detect whether certain brain regions of Valerie can respond to our instructions.
during the days when we analyzed the imaging data, Valerie's parents could only wait in pain. Finally? Valerie's brain showed a little nervous activity, indicating that she could hear and understand our instructions to some extent. This seems to be a breakthrough, but what does it mean for her? Can she keep getting better? How does she feel? Can she understand everything we say? Can she finally walk or talk again?
just the first question leads to countless other questions. That day, I decided to devote myself to the research of rehabilitation methods. Even in the face of unimaginable challenges, I want to do my best to help patients like Valerie, even if there is only a slight improvement for them.
I later started working in the coma science group of the University of Liege in Belgium. By studying patients with severe brain injury who wake up from coma, we try to relate the activity of neurons to the degree of consciousness (or unconsciousness). Thanks to the development of advanced resuscitation technology and intensive care treatment, occasionally, patients with acquired brain injury can survive even after falling into coma.
however, they can only remain in a kind of? Non-reactive awakening syndrome? The state of (formerly called persistent vegetative state)? That is to say, they are obviously awake, but they have no consciousness. Or, if you think they still have some residual consciousness, they are in a kind of? Minimum state of consciousness? . These conditions are collectively referred to as disorders of consciousness (DoC).
Although medical progress has undoubtedly helped save countless lives, it has also created a mysterious dilemma between life and death. Take unresponsive arousal syndrome as an example. Although patients open their eyes, they will not have any meaningful behavior. Patients in the lowest conscious state have almost completely lost their ability to live, but they can follow and stare at a moving object, move their feet according to simple instructions, or pinch other people's hands.
in the past 2 years, the development of neuroimaging technology has enabled 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 conducted a breakthrough research, which involved 54 patients with consciousness disorder.
while they were lying in the brain imager, the researchers asked them to complete two imaginary tasks. One is to imagine yourself playing tennis, and the other is to imagine yourself walking around the house. These two kinds of imagination correspond to two completely different brain activity patterns respectively.
Surprisingly, five patients can adjust their brain activities according to their wishes (that is, according to the instructions), which shows that they can understand and follow the instructions of the researchers even if they can't express any conscious signs in bed.
inspired by these findings, the researchers further conducted repetitive behavioral experiments on these five patients, and managed to detect conscious symptoms from three of them. However, the remaining two patients did not express any active behavior. This is a large-scale multi-person study, which reveals for the first time that a small number of patients who have been assessed as completely unresponsive actually have some residual perception and cognition.
This result is shocking and makes us realize that some unresponsive patients are more conscious than we thought. So, what if we invent more perceptual detection techniques in the next few years and find that 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 consciousness disorder can last for several months or even years, but they still can't express their feelings and expectations. Their plight has also caused many ethical challenges. How do we face these challenges as researchers or nurses?
first of all, we need to improve the detection technology, so that we can more effectively decide which patients can recover and which ones can't. However, we are still far from finding this perfect biomarker.
But this brings up another difficult problem, that is, what should be done for those patients who unfortunately may have to maintain their consciousness disorder for a long time. We certainly can't abandon them. This is why my colleagues and I have worked hard to develop effective treatment strategies.
experiments and achievements
fortunately, consciousness disorder is rare, and only six out of 1, people will be affected by it. However, because of its chronic and self-righteous incurable characteristics, patients with mental disorders have become the recipients of the so-called 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 mistake that needs to be corrected. As a medical group, we must be careful not to give false hope to patients' families, but we must not give up hope for the conquest of some diseases because of the incurable history. However, this situation shows signs of gradual change, and scientists have begun to challenge it? Persistent disturbance of consciousness can never be recovered? The ancient boundary.
Recent studies have demonstrated the potential efficacy of both drug and non-drug interventions. For example, amantadine? A nerve stimulator used to control Parkinson's symptoms? It seems to have a slight effect on accelerating the recovery of patients with consciousness disorder.
in addition, deep brain stimulation? Implanting electrodes in the brain to reconnect nerve axons and stimulate nerve activity? Can improve behavior, including making a person who was in the lowest consciousness regain the ability to name things and chew food. Nevertheless, these treatments all contain risks and potential serious side effects. Especially deep brain stimulation, after all, it is invasive.
another potential drug with mysterious effect is zolpidem. It is usually used to promote sleep, but in rare cases (5%? 7% probability), it can really wake the patient from the unconscious state.
For example, a patient can only follow people walking in the ward with his eyes, or squeeze others' hands according to simple orders. But after taking zolpidem for 3 minutes, he can respond to instructions, speak and read magazines without any obstacles. Unfortunately, this effect can only last for a few hours, and then the patient will return to the lowest state of consciousness. You can imagine how difficult it is for his wife to understand what happened and accept that her husband only has a few hours of waking time every day or week.
In other cases, zolpidem not only makes people awake, but also causes other troubles: as patients become more conscious, they will gradually realize that their cognition is seriously damaged, which makes them extremely depressed. Ethically speaking, it is very complicated to decide whether to use zolpidem on patients or not, and there is no universal answer. However, once zolpidem does induce cognitive improvement, they obviously need additional medical monitoring and frequent re-evaluation.
- neural pathway -
It is relatively easier to give patients a pill. Even if the consequences of 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 generally effective for all patients, we must find another way and improve other alternative treatments.
one method 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 cognitive function of healthy people and patients with brain injury (including patients with consciousness disorder).
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 unresponsive arousal syndrome almost four years ago. When we carefully examined her bedside, she didn't respond at all and didn't show any signs of consciousness. In addition to one of the seven tests, she was able to locate a pain stimulus. But after we implemented tDCS, she was able to respond to some simple instructions (for example, in three of the four tests, she could open and close her eyes as ordered).
everyone in our team was very 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 actually had relatively well-preserved brain function. We call this situation? Concealed consciousness? That is, a patient is relatively conscious, but can not be detected by behavioral tests.
In the case of the above-mentioned female patient, we suspect that the direct current applied to the frontal lobe unlocks the neural pathway of voluntary movement, thus making her show consciousness. However, from the perspective of neurophysiology, we still know little about the working mechanism of tDCS. The most likely guess is that tDCS increases the excitability of nerve cells, improves their activity intensity and communication ability (in other words, it starts a process of nerve remodeling, which is the basis of learning and memory. )
It is gratifying that only a few minutes of stimulation can induce after-effects for several hours. But without repeated brain stimulation, this beneficial effect disappears after effective time. On the positive side, recent studies show that if the patient is engaged in an activity task at the same time of stimulation, the synaptic connections related to this activity will be strengthened by tDCS. This may be beneficial to the recovery of specific activities.
compared with other brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation, tDCS has the advantages of being cheaper, safer and easier to operate in clinical practice.
In addition, like other non-invasive forms of brain stimulation, tDCS does not need the active participation of patients, and it is painless and safe, so it has a bright future. We have stimulated patients with tDCS for different times in the past ten years. The collected data show that about 3% to 5% patients with the lowest consciousness state have achieved clinical improvement after stimulation.
challenges and hopes
however, a significant obstacle to the clinical application of tDCS is that it requires patients and their families to go to and from hospitals or research centers in person for treatment. In order to overcome this difficulty, we recently cooperated with a Belgian company to develop a tDCS instrument that can be used at home. After the patients' families followed our instructions and correctly implemented brain stimulation, we will observe the clinical improvement effect.
For example, some patients can spontaneously respond to some actions again, while others can reply to some simple commands. These improvements may seem insignificant, but for patients and their families, even the smallest progress is of great significance. This is especially true when the patient has been in the lowest state of consciousness for several months or even years.
The research on the treatment of consciousness disorder is not only of critical clinical significance, but also helps to clarify the neural basis of consciousness in physiological state. Nicholas Schiff, an American neurologist, put forward a model to explain why drugs or brain stimulation therapy can help patients with consciousness disorder.
He thinks that in normal cognitive processing, the anterior region of the brain controls the central nucleus of thalamus (the deep structure of the brain, which is the relay station of sensory information and motor information) by regulating the structures of other middle brain regions (such as the medial globus pallidus, which controls voluntary movement). His frontal parietal lobe? The midbrain loop model is based on this view.
Usually, when the thalamus is activated, it will then activate the frontal parietal lobe (a closely related cortex spanning the front and back brain regions, which is responsible for decision-making and motor control). However, after a serious brain injury that usually triggers the disturbance of consciousness, the nerve cells that regulate the excitability of thalamus and the connection between thalamus and cortex are lost. As a result, the activity level of thalamus plummeted, and the activity of the key frontal and parietal lobe connection network also weakened.
The most potential brain stimulation technologies have the same feature that the parts they stimulate are all related to the above-mentioned key loop. For example, most tDCS experiments explicitly target the prefrontal lobe, because this area is responsible for a variety of cognitive functions, such as memory, attention, or motor execution. At present, the stimulus part seems to be the most effective choice. Most studies aimed at other brain regions, such as the motor cortex or the anterior cuneiform lobe (related to self-awareness and other functions), were not so successful.
These results show that the frontal cortex plays an important role in supporting consciousness, but this view remains to be discussed. Some researchers support this statement, while others believe that consciousness is controlled by a specific hotspot further back into the cortex.
The latest research also supports this view. For example, when rTMS was applied to the angular gyrus (located between the parietal lobe and the temporal lobe, which includes the function of checking spontaneous movement), after 1 courses of treatment, 19 of 22 patients showed cognitive improvement (since this experiment did not design a control group, we should be skeptical about these results).
- thalamus -
At present, the specific neural mechanism of consciousness remains to be explored. The work of stimulating different brain regions with tDCS or rTMS to achieve therapeutic effect is still going on, which is conducive to further uncovering the mystery of the brain region that really supports consciousness.
Another completely different treatment for consciousness disorder also has some prospects. Different transcranial stimulation techniques stimulate the brain through top-down methods? That is to stimulate the cortex to activate the deep brain structures in the descending pathway, such as the thalamus; The other technology, on the other hand, takes a bottom-up approach? From the central nuclei of the brain to the cortex. What is still in the laboratory? Vagal nerve stimulation? (vagus nerve stimulation) technology is its.