What is the experience of "soul out of the body"?

 The state of dissociation is often described as a feeling of separation from reality or the experience of "soul out of the body". This state of altered consciousness is commonly seen in people who have developed mental illness due to destructive trauma or abuse. A class of narcotic drugs and seizures can also evoke this state. The basis of the free nervous system has always been a mystery. However, Vesuna et al. published a paper in Nature, describing the local brain rhythm behind this state. The results of their research will have a profound impact on neuroscience.

　　 The author first used widefield calcium imaging to record neuronal activity in the whole brain of mice. They studied how a series of sedative, anesthetic or hallucinogenic drugs can change these brain rhythms, including three drugs that can cause freeing-ketamine, phencyclidine (PCP) and dizozepine (MK801).

　　Research found that only free drugs caused strong oscillations in neuronal activity in the brain area called retrosplenial cortex. This brain area is critical for various cognitive functions, including episodic memory and navigation capabilities. The frequency of oscillation is very low, about 1-3 Hz. In contrast, non-free drugs such as the anesthetic propofol and the hallucinogen lysergic acid diethylamide (replica hermes) did not cause this rhythmic activity in the cortex after compression.

　　 Vesuna et al. used two-photon imaging, a high-resolution technique, to analyze active cells in more detail. The analysis found that the oscillation only occurred in the cells of the fifth layer of the post-compression cortex. The author subsequently recorded neuronal activity in multiple brain regions. In general, the cortex and other parts of the cortex have a functional connection with neuronal activity in the post-compression cortex; however, ketamine cuts this connection, allowing many of these brain areas to no longer communicate with the post-compression cortex.

　　 Next, the researchers wanted to know whether the cortical rhythm would lead to freeing after the pressure was induced. The fifth layer of cells in the mouse post-compression cortex they used was modified to express two ion channel proteins that are sensitive to light. The first is the light-sensitive channel-2, which can cause neuronal excitement under blue light irradiation. The second is eNpHR3.0, which can silence neurons under yellow light. The researchers irradiated these cells with blue and yellow light in turn, artificially inducing a 2 Hz rhythm, producing a free state behavior similar to that caused by ketamine. (Figure a below) For example, the mice did not jump or back up when threatened, nor did they try to escape in the tail suspension experiment; but they responded normally to the pain caused by the hot plate. They feel intact, but are slow to respond to threats, suggesting a dissociation from their surroundings.

Induce free state. a. Optogenetics technology can regulate neuronal activity under light irradiation. Vesuna et al. regulated a single layer of neurons in the cerebral cortex of mice. The research team used blue light to stimulate neuronal activity, and then used yellow light to inhibit this activity, resulting in low-frequency neuronal oscillations, similar to those seen in mice receiving ketamine. Such oscillations can cause behaviors with free characteristics. b. The authors show that the corresponding brain area (called the deep posteromedial cortex) of patients with epilepsy will have the same oscillations before the seizure. Electrical stimulation of this brain area will trigger the same vibration and free experience. These two experiments show that in different species, low-frequency oscillations in a small brain area can cause dissociation.

　　 Subsequently, the author deleted the two genes encoding ion channel proteins in the post-compression cortex. The first gene encodes a channel activated by the neurotransmitter glutamate molecule. The second gene encodes a hyperpolarized activated cyclic nucleotide gated 1 (HCN1) channel-this channel is activated by cations and is sometimes called a "pacemaker" because it allows the heart and neurons to produce rhythmic activity ". Vesuna et al. found that in mice lacking any of the aforementioned genes, the rhythm induced by ketamine was reduced. However, ketamine only needs HCN1 channel to cause free-like behavior.

　　 Do these results also apply to humans? Vesuna and colleagues recorded electrical activity in multiple brain regions of an epilepsy patient who had previously implanted electrodes in the brain to track the location of the epilepsy. The patient was free before the seizure. The authors found that this dissociation is related to the 3 Hz rhythm that occurs in the deep posteromedial cortex-this human brain area corresponds to the mouse postcompression cortex brain area. The research team performed electrical stimulation on the deep posteromedial cortex during a brain imaging process. As a result, the patient reappeared free (Hermes Birkin 35cm for sale).

　　 It is too early to draw a decisive conclusion from an individual. However, the work of Vesuna and colleagues provides convincing evidence that low-frequency rhythms in the deep posteromedial cortex are the evolutionary conservative mechanism behind the dissociation of different species.

Most of the success of Vesuna and colleagues' research depends on the reversible release of ketamine. In sub-anaesthetic doses, this miraculous drug can cause dissociation, help relieve pain (analgesia), and have antidepressant and suicide prevention effects. At this dose, electroencephalogram (EEG, which detects neuronal activity on the surface of the brain) shows that ketamine can suppress 8-12 Hz oscillations over a large area. At higher doses that can induce unconsciousness, EEG shows that the frontal lobe of the human brain has a rhythm that switches between low frequency (1-4 Hz) and high frequency (27-40 Hz). Considering that this change occurs in most areas of the brain surface, the study found that only a small depth of cells can specifically induce freeing is particularly shocking. To our knowledge, ketamine has never previously reported the oscillations described by Vesuna et al. This is probably because the surface EEG recording cannot detect the local rhythms generated in the deep cortex.

The rapid development of 　　 technology has brought more and more sophisticated instruments that can precisely control neural circuits with high time resolution. The work of Vesuna and colleagues highlights how these advances can help researchers explore the nature of consciousness. They are also changing the discipline of anesthesiology-allowing researchers to better understand how anesthesia makes people unconscious, how these mechanisms overlap with natural sleep, and how humans regain consciousness after anesthesia. Research on consciousness and anesthesia also overlap, because anesthesia is an effective and reliable way to induce reversible changes in consciousness. Understanding the neural mechanisms of these changes may lead to the development of new technologies to regulate consciousness and suppress pain while avoiding the adverse effects of existing drugs, including changes in heart rate and blood pressure, respiratory arrest, delirium, and nausea.

　　The complex state of dissociation can only be fully described by humans, because only humans can report their feelings. For example, to prove that the free and analgesic effects of ketamine are independent of each other, it must be studied in humans. In the future, research on the use of free drugs in humans will continue to attract attention-such as revealing the connection (if any) between the brain rhythm reported by Vesuna et al. and the various useful effects of ketamine. Such studies should also include drugs that can weaken the free-induced effects of ketamine, such as benzodiazepine and lamotrigine. To further understand how ketamine changes brain rhythm and related behavioral states, it is also expected to develop treatments for patients with chronic pain, depression, and even free diseases.

　　 However, these studies are very difficult to do, because the study of deep cortical rhythms can only be carried out on people with electrodes implanted in the skull. For ethical reasons, only people who need implanted electrodes for treatment can participate in this type of research. We are deeply grateful to them for giving us the opportunity to better understand the inner workings of the human brain.