On August 24, 2016, a 25-year-old man in a vegetative state woke up for the first time through specialized ultrasound brain stimulation in the Medical Department of University of California, Los Angeles (UCLA) in the United States (US). Simple movements and basic conversation were possible on the third day of brain stimulation as a result of stimulation of the thalamus that invokes arousal in the sleep-wake cycle. This shows potential for the recovery of vegetative patients. The specific symptoms of vegetative state or the possibilities of regaining consciousness are not well-known to the public. The Sungkyun Times (SKT) investigates vegetative state through the analysis of the definition, death or recovery, and the specialized ultrasonic technology for a new life.
What Is Vegetative State?
Definition of Vegetative State
Vegetative state is the condition in which only vegetative functions including ingestion, absorption, respiration, excretion, and blood circulation are active, while the function of animals, including motion, sensory operation, and the mind is inactive. Vegetative state stems from the damage of the cerebral cortex due to accidents or diseases. Damage to the cerebrum induces loss in functions of memory, recognition, and judgement, meaning that patients in a vegetative state are unconscious and unresponsive to external stimuli. As vegetative functions are still operating, however, spontaneous breathing, heartbeats, and gastrointestinal motility (the passing of food through the mouth, down the throat and into the digestive tracts) function normally, meaning that a patient can maintain life without life-sustaining equipment as far as nutrients are supplied in this state.
Vegetative State vs Brain Death
Vegetative state is often confused with brain death since their symptoms seem similar, but they are completely different. The criterion to distinguish these two states is the damaged area of the brain, especially whether the brainstem is damaged or not. A vegetative state is caused by a partial impairment of the cerebrum excluding the brainstem, while brain death is caused by an impairment of nearly all parts of the brain, including the brainstem.
The primary function of the brainstem is to maintain an autonomic operation of the body, but since the brainstem is undamaged in a vegetative state, patients can still sustain their life spontaneously. Brain-dead patients are incapable of spontaneous respiration or even unconscious movements, implying that all body functions stop except for the heartbeat. Brain-dead patients, therefore, require artificial respirators, and unavoidably draw their last breaths from cardiac arrest in usually two weeks, or a month at most. This is different from a vegetative state in that vegetative patients at least have a possibility of recovering consciousness. Maintaining autonomic operation means that the brainstem keeps the human body awake. Vegetative patients are in a state of “arousal” but do not have “recognition” ability. It means that while patients are awake since the sleep-wake cycle still operates, they are unable to understand, remember, and make decisions. Considering that brain-dead patients are not even awake, brain death is a loss of both arousal and recognition functions.
|blog.naver.com/ The criterion to distinguish these two states is the damaged area of the brain, especially whether the brainstem is damaged or not.|
Death or Recovery?
Euthanasia and Death with Dignity
In 2009, the Korean Medical Association, the Korean Academy of Medical Sciences, and the Korean Hospital Association announced the “Guideline to Withdrawal of a Life-sustaining Therapy.” Patients in persistent vegetative state (PVS), who have been vegetative for over six months, were included as the candidates of suspension of medical care for life prolongation. This announcement raised controversies on whether the inclusion of vegetative state should be accepted. An incident relevant to this dispute is the “Grandma Kim” case, which occurred on the same year. Kim fell into a vegetative state while undergoing a biopsy at Severance Hospital, and received life-sustaining treatment for about a year. It was a treatment just for maintenance, not an improvement of the state. Kim’s family asked for the withdrawal of life-sustaining therapy saying that Kim did not want to prolong her life by relying on artificial equipment, but the hospital refused. The family members then filed a lawsuit and the Supreme Court reached a verdict to admit the intent for death with dignity. It was the first court case in Korea that accepted the right to choose death. The right to choose death has been discussed actively after this case. A 2014 survey conducted by the Korea Institute for Health and Social Affairs showed terminal patients’ perspectives on euthanasia and death with dignity. When asked what they wanted most in the last moments of their lives, 33% of terminal patients chose pain alleviation, and 20% chose not laying a burden on their families. On the subject of preferred place of death, 39.5% chose their homes more than a hospital, contrary to actual results. 37.3% said they want to make decision on life prolongation on their own, and 58% agreed on death with dignity. The Korean government proposed systems such as advance directives and do-not-resuscitate (DNR) in respect to the intent for death with dignity, but the systems have been rarely implemented. The Well-dying Act, which passed the National Assembly this January and is expected to come into effect starting from 2018, is the most controversial legislation. It legislates the right to withdraw life-sustaining therapy and receive hospice and palliative care, which helps patients alleviate the pain of incurable diseases. Vegetative patients, however, were excluded from the range of terminal patients, because they still have a probability of awakening. Disputes on whether vegetative state is terminal or not are on-going and have not yet reached a conclusion. Controversies are a result of unclear standards of unnecessary and excessive life-sustaining treatment. Whether life prolongation is really “futile” or not should be considered more carefully to thoroughly respect the will of the dying. Since vegetative state is on the borderline of incurableness, cautious deliberation on the possibility of recovery is demanded.
Possibility of Recovery
Since the brainstem still functions in a vegetative state, maintenance of life also means the possibility of recovery. Joseph Fins, the chief director of Medical Ethics at Weill Cornell Medical College, made a statement in July, 2016 that 68% of brain- damaged patients, including those in vegetative state, can wake up, especially after the first three to six months, and 21% can recover enough to carry out simple activities. Families of patients suffering from cognitive impairment due to brain damage, however, are sometimes asked for a decision to withdraw life- sustaining equipment or to agree with organ donations. Fins noted that almost two-thirds of deaths in brain-damaged patients are caused by a suspension of life prolonging treatments, rather than injuries. About 40% of minimally-conscious vegetative patients are misdiagnosed as permanently unable to regain consciousness, which stems from the hasty assumption that minimally-conscious state (MCS) is almost the same as death. Although it is true that patients in PVS have a low probability of regaining consciousness, MCS can still be a sign of recovery. An experiment in 2010 conducted by the University of Cambridge in England and the University of Liege in Belgium proved that the brain of a vegetative patient is awake, suggesting the possibility of consciousness.
|indaily.kr/ This image shows brain networks in two vegetative patients (left and middle), but oneof whom imagined playing tennis (middle), and a healthy adult (right).|
An experiment concluded that four out of 23 vegetative patients were conscious. Researchers ordered the test subjects to imagine two scenes, playing tennis or walking down the street. When researchers examined their functional Magnetic Resonance Imaging (fMRI) and electroencephalographs (EEG), the brains of the subjects worked in the same manner as healthy brains. The motor cortex was activated in the first scene, and the area controlling the part of spatial recognition was activated in the second scene. Researchers then asked questions and ordered subjects to imagine the first scene when the answer is “yes” and the second scene when the answer is “no.” Subjects answered correctly on simple questions, which opens the room for conversation with vegetative patients.
There are some cases of waking vegetative patients up by stimulating the brain, and a representative case was a surgery using a technology called “deep brain electrical stimulation (DBS),” conducted by the Cleveland Clinical Trial Center and a research team of Weill Cornell Medical College. DBS is a technology that transplants electrodes into the brain and stimulates it with electrical pulses. It works by inserting electric chips into a brain through craniotomy, a surgery in which a bone _ap is temporarily removed from the skull, and connecting micro chips with external equipment like computers. A 38-year- old vegetative patient who was in MCS for six years recovered consciousness after 48 hours of electrode transplant, and managed simple daily activities.
Ultrasound Brain Stimulation, New Life to Vegetative Patients
Concept of Transcranial Focused Ultrasound Stimulation (tFUS)
Transcranial Focused Ultrasound Stimulation (tFUS) is a newly developed brain-stimulating technology that uses specialized ultrasonic waves. “Transcranial” means “across or through the brain,” which stands for the characteristic of FUS that ultrasonic waves go through the brain without craniotomy. It is advanced in the aspect of safety and efficiency, compared to current technologies like electrode insertion and transcranial magnetic stimulation (TMS). Transcranial FUS is safe in that it invokes stimulation without any harm to the body, as it does not require surgeries to remove skull bones like electrode insertion. This technique is therefore “noninvasive.” The efficiency of tFUS can be explained by comparing it to that of TMS, which also does not require a craniotomy. The greatest advantage of tFUS is that it can control the range and intensity of ultrasound delicately in specific parts of the brain. It uses small ultrasonic devices to make the range and intensity of ultrasonic waves narrower and lower, enabling brain stimulation without touching peripheral nerves. TMS, on the contrary, can cause brain damage as its range and intensity of stimulation are wider and higher. It is also easier to develop wearable devices with tFUS because it does not need big and heavy equipment.
Present State of Application
The application of tFUS substantiated the exercise-inducing possibility of animals. In 2013, Harvard University succeeded in an experiment that examines the thought of a person through brain waves using tFUS, and then moves a rat’s tail after stimulating a rat’s brain with tFUS. When a person thinks of a certain motion, brain waves show the activation of the motor cortex, and a rat moves its tail after receiving the message through tFUS. It is a brain to brain interface (BBI), which means that human and rat brains can interact through tFUS. Interface is an interaction between a “speaker” and a “receiver.” In this experiment, the human brain is the speaker and the rat’s brain is the receiver. BBI process is comprised of brain to computer interface (BCI) and computer to brain interface (CBI). BCI is the process in which the brain waves of a speaker are converted into digital signals that electronic devices can understand, while CBI is the process in which digital signals are restored into brain waves that the receiver can understand. In other words, the rat could move its tail because it processed the information that the person transmitted, and tFUS technology worked as a medium for BBI.
|extremetech.com/ BBI is comprised of brain to computer interface (BCI) and computer to brain interface (CBI).|
Prospect and Significance
Scientists are still working on BBI to apply tFUS on humans, beyond animals. If BBI can be applied on human body, it would be a new opening for vegetative patients to recover consciousness by stimulating their nerves. Medical communities are studying on ways to produce imaginary senses through tFUS. When researchers stimulated areas of the subjects’ brains related to hands using ultrasonic waves, they felt nine types of senses, including coldness, heaviness, and numbness. The medical field, including Korea, is making a high-resolution brain activity map that shows the brain activation aspect at the moment of subjects’ feeling senses. The brain activity map specifies structural and functional networks of synapses. The plan is to connect the navigator of the brain activity map on the computer with specific parts of the brain of vegetative patients, and produce intended imaginary feelings. Since tFUS can be applied on accurate areas, the brain activity map can further help stimulation with minimized error range. The significance of tFUS is that it produces intended senses by controlling brain nerves without direct contact with the human body. The current plan is to stimulate the senses on the whole body, rather than just the hand. Popularization of this technology is anticipated as an innovative method for consciousness recovery of vegetative patients and as treatment for nerve disorders.
It is true that it is difficult for patients in PVS to regain consciousness, but there are still some hopes for awakening since vegetative state meets the basic requirements for life maintenance. Vegetative patients can wake up after a number of weeks, months, or even years. Specialized ultrasonic technology has recently been developed, which enables far safer and more efficient treatment and suggests brighter future for vegetative patients. Generalization of tFUS would open up a new chapter for the medical field to cure brain diseases.
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