A new way to treat illness: forget about it

Leviathan Press:

If Henry Molaison (HM), the famous epilepsy patient who changed the course of neuroscience, had the new treatment described in this article, he might not have had his medial anterior temporal lobes removed, and he would not have had anterograde amnesia. Epilepsy is a very strange symptom, just like the teenager who recited Edgar Allan Poe's poems in the article, a certain language integration method seems to form a closed loop with epileptic seizures - this also corresponds to the relationship between Hollywood actor Danny Glover and ringtones.

Following this pattern, in addition to the vagus nerve's "chattering" (forgetting-elimination), we can also redesign the path to the disease through artificial intervention. My father is a neurologist, and he had a patient who was tortured by a poem. The patient was named Philip, 12 years old, a student at a famous boarding school in Princeton, New Jersey. He had a task to recite Edgar Allan Poe's poem "The Raven". Before the speech, he had rehearsed no less than dozens of times and could easily recall the whole poem. But when he stood in front of his classmates, something strange happened.

Whenever he recited the poem's famous refrain, "Quoth the Raven 'Nevermore'," the right corner of his mouth would tremble. In front of a group of indifferent teenagers, as the trembling of his mouth continued to intensify, he began to lose control of his body and even had incontinence, until halfway through the recitation, he suddenly convulsed and fell to the ground. It was his first epileptic seizure.

After hearing this story, my father decided to conduct an experiment. On Philip's first visit, he handed the boy a copy of The Raven and asked him to read aloud. As always, whenever Philip read the raven's grim prophecy, he would stutter, clench his teeth, and pull the corners of his mouth to the sides, as if in silent rebuttal.

His father, who had taken the poem away before Philip's seizure and later wrote a note to his teacher so he wouldn't be asked to recite the poem again, explained that Philip's brain had begun to associate certain language patterns with seizures.

A new generation of electronic medicines could make it possible to cure permanent diseases by harnessing neurons to learn new associative rules.

The amazing power of the nervous system lies in its ability to learn, even throughout adulthood. Networks of neurons communicate by detecting new relationships by measuring the speed of electrochemical impulses called spikes. These brief patterns strengthen or weaken connections between cells, forming the physical basis of memory, and the results are mostly beneficial.

As a result, we have developed the ability to link cause and effect, such as a falcon invading its shadows and swooping down on its prey, or a cactus tapping into hidden underground water sources, giving organisms an advantage over predators and competitors.

But sometimes, it seems that neurons work too well. With its extraordinary computing power, the brain has taught us not only language and logic, but also how to get sick.

For example, someone who experiences a random epileptic seizure is 50 times more likely to have a recurrence than someone who has never had one. As with Philip and the Raven, recurrence is more likely to occur when he is exposed to the same stimulus that preceded the first seizure—anxiety, say, or a particular piece of music. The more frequent the seizures, the more powerful and widespread the underlying neural networks may become, leading to more frequent and violent relapses.

(pubmed.ncbi.nlm.nih.gov/18184149/)

Another of my father’s patients, James, is a doctor in his 50s who suffers from spinal arthritis. The disease is so painful that doctors cut the nerves that transmit pain to his lower body. However, years after the surgery, even though his back and legs can no longer send pain signals to his brain, James still feels pain as before. This makes it difficult for him to even put on socks.

A recent study explains why: Like many chronic pain patients, James' original injury activated pain circuits in his brain so frequently and so intensely that those nerves became sensitive to the slightest stimulation, even the lightest touch. In other words, the persistent discomfort formed a "pain memory."

(pubmed.ncbi.nlm.nih.gov/22331213/)

Just like you remember your first kiss, James' brain can still recall the feeling of pain even though his body can no longer feel pain.

Some conditions can also be learned, such as obsessive-compulsive disorder, post-traumatic stress disorder (PTSD), addiction, and even certain digestive diseases that are exacerbated by the coupling of neurons. This commonality has given doctors a sudden insight: if diseases can be learned, can they also be forgotten?

Whenever Danny Glover heard a faint ringing sound, he knew he was having an epileptic seizure. As the sound grew louder, he became increasingly unable to tolerate it. The American actor and director had his first seizure when he was 15, and the condition plagued him for nearly two decades until one day in 1977, when he was 31, he found a way to cope.

As Glover prepared to take the stage at a San Francisco theater for his first major role, he heard the voice again and paced backstage, trying to stop a seizure.

"I won't have an attack. I won't have an attack. I won't have an attack." He kept repeating to himself. He recalled: "Every time I said 'I won't have an attack', I believed that I wouldn't have an attack. Every time I got stronger, the symptoms were getting less and less, and later I could perform on stage normally." When Grof repeated this "self-hypnosis" method for four years, the epileptic seizures suddenly stopped mysteriously. He said that he had never heard that voice again since then.

Practice makes perfect: Danny Glover (stand-up) in his debut in Master Harold ... and the boys in 1982. Glover overcame nearly two decades of epileptic seizures through what he called "self-hypnosis". By the early 1980s, his symptoms had completely disappeared. Chinese audiences are more familiar with him, and he is still associated with many Hollywood movies, such as "Sniper" and "2012". French cartoonist Pierre-Francois Beauchard, who uses the pen name "David B", tells a similar experience in his autobiography "Epileptic". The graphic novel interweaves the physical and mental deterioration of his epileptic brother with his growing obsession with drawing war scenes and monsters, and the fantasy puts him in a trance, allowing him to escape his disease. But his brother, in the end, becomes extremely violent and unrecognizable.

Bishar is victorious. In one scene, confronting his brother who is suffering from an epileptic seizure, he transforms into a dragon, fully armored, cuts the beast to pieces, and declares: “I have conquered the disease that afflicted me.”

What if atrocities could be erased from our collective memory?

Neuroscientists believe that people like Glover and Bishar who have spontaneously recovered from epilepsy may be able to eliminate their pain by exerting some control over the vagus nerve.

© The CutThe vagus nerve is responsible for transmitting information between the brain and organs, and the signals it sends have a calming effect, such as lowering heart rate and blood pressure, or relieving anxiety. Stimulating the vagus nerve can also silence activity in the cerebral cortex, which can smother the source of most epileptic seizures. This brain silencing makes it difficult for neurons to reach certain peaks, reducing the risk of a full-blown seizure.

As part of the autonomic nervous system, the vagus nerve works normally without conscious control. But if you learn the trick, you can activate it at will. Have you ever seen a tired baby rub his eyes before falling asleep? It turns out that simply applying pressure to the eyeballs or massaging the carotid artery under the chin can activate the vagus nerve and calm the nervous system.

We can also manage many of the body's autonomic functions through meditation or mindfulness. For example, some deep-sea divers can maintain oxygen levels in their bodies by slowing their metabolism, yoga masters can lower their heart rates, and some Tibetan monks can significantly increase their body temperature through a breathing exercise called tummo.

(pubmed.ncbi.nlm.nih.gov/8317238/)

Similarly, for patients with epilepsy who cannot be cured by drugs, by observing their brain activity records and capturing signals when they are in a calm state, they can learn to suppress epileptic seizures with their thoughts.

However, this method of will control requires a lot of time and effort to learn, and it is not always successful. Therefore, scientists are working to develop an implant technology that can use electrical pulses to debug neural circuits with potential disease risks. Perhaps one day, this artificial regulator, called "electroceuticals," will accelerate our forgetting process.

Today's electronic drugs only temporarily relieve the disease, interfering with the communication between cells, but the original pathways are not destroyed. When they are removed from the patient's brain or body, the previous symptoms will return. For example, a vagus nerve stimulator is something like a permanent pacemaker, which continuously sends mild shocks to a nerve in the neck through a flexible wire. With the help of a magnetic rod placed on the stimulator, the patient can manually stop or shorten the seizure or even slow the heart rate.

Another popular technique is deep brain stimulation (DBS), which can treat a variety of diseases, such as Parkinson's disease, epilepsy and major depression. This therapy involves implanting needle-like electrodes in the brain and continuously stimulating the surrounding tissue with high-frequency pulses. It is very effective, especially when drugs don't work. For example, in Parkinson's patients, DBS therapy can reduce limb tremors by nearly 90%.

© Psychiatry Advisor However, neuroscientists are only just beginning to understand how this therapy works. In some cases, the electrical pulses appear to raise or lower the threshold of neural activity by quieting or exciting specific brain areas. In other cases, it may reset healthy communication between distant brain structures, which in part use synchronized neural activity at different frequencies to exchange information. These rhythmic activities are called oscillations.

The research suggests that each area of ​​the brain can communicate by matching the oscillations of other areas, much like amateur radio operators tuning in to different channels.

(pubmed.ncbi.nlm.nih.gov/26005114/)

Diseases arise when oscillations disrupt normal cellular activity. For example, neurons in the motor cortex (the center of the brain that coordinates voluntary movement) of a Parkinson's patient become locked into specific oscillations, and when the patient moves, the amplitude of these oscillations increases, resulting in tremors or other movement disorders. DBS breaks this pattern by stimulating a portion of the midbrain's motor network, isolating cells in the motor cortex from the strong oscillations and enabling them to function independently again. However, the technique has not produced lasting effects, perhaps because it stimulates a broad range of neurons at the same time.

(pubmed.ncbi.nlm.nih.gov/25867121/) (www.ncbi.nlm.nih.gov/pmc/articles/PMC2874753/) The comfort of art: This work helped David B to get rid of the troublesome illness that plagued him, and was published in his graphic novel "Epileptics". © David B/Pantheon Books The devices of the future will be more sophisticated. By using neurons to learn the laws of forming new associations, these new generations of electronic drugs have the potential to cure diseases permanently. The most important thing about learning is to master the timing.

For example, suppose neuron A is establishing a connection with target neuron B. If A spikes before B, the connection will be strengthened. But if B spikes first, the connection will be weakened. Neuroscientists suspect that this property, called spike timing dependent plasticity, is a fundamental axiom that neural networks use to encode causal relationships. Artificial stimulation can also redesign disease-causing pathways.

Researchers have begun trying to demonstrate that this is possible: In 2007, for example, researchers at the French National Center for Scientific Research and the University of California, San Diego, manipulated the activity of neurons in the cerebral cortex of a mouse that received input from its whiskers.

(pubmed.ncbi.nlm.nih.gov/17287502/)

Normally, these cells would emit spikes when a whisker is touched. But by electrically stimulating the cells milliseconds before touching the whiskers of mice, and by repeating this action, the scientists were able to suppress the connection between the whiskers and the neurons, so that the cells were less likely to respond to the whisker's movement. The same approach could also be used medically to cure diseases such as chronic pain or post-traumatic stress disorder by weakening overly sensitive neural connections.

Some of the more sophisticated implants not only stimulate the brain but also receive signals. With hundreds of recording electrodes packed into a few cubic millimeters, these devices will sensitively capture the neural signatures of disease, allowing them to more precisely target disease areas. For example, in drug addicts, electronic drugs would detect the rise of desire in the brain and suppress it before it leads to bad behavior. The implant would sniff out the traumatic memory and erase its emotional weight.

(pubmed.ncbi.nlm.nih.gov/17637800/)(pubmed.ncbi.nlm.nih.gov/23407652/) This electrotherapy approach will be reserved for the most difficult patients, for whom traditional interventions have completely failed. But what are the limits of this therapy? Can we erase atrocities from our collective memory? Or wash the guilt out of the hearts of soldiers? Like any medicine, forgetting is both a cure and a poison.

About the author:

Kelly Clancy is a neuroscientist interested in the general principles of biological information processing and is currently a postdoc at the University of Basel and University College London. Previously, she traveled the world as an astronomer and served in the Peace Corps in Turkmenistan. In 2014, she won the Regeneron Prize for Creative Innovation for designing drug-free brain therapies. Her work has been published in publications such as Harper's Magazine, Wired, and The New Yorker. By Kelly Clancy

Translation/Sodium Potassium

Proofreading/Meiji

Original article/nautil.us/issue/103/healthy-communication/how-to-unlearn-a-disease-rp

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