Everyone will have bad memories that will never be forgotten. Those memories are usually faded and forgotten, but some memories continue to haunt me. In my case, I was infected with norovirus because of the raw oysters I ate a long time ago and suffered for more than a week.
There are memories that are more difficult and lasting than avoiding the same food absolutely with the memory of suffering from food. Patients with posttraumatic stress disorder (PTSD) suffer for the rest of their lives because they cannot erase the memories after experiencing really difficult stress and shock. Emotionally difficult memories not only come back from time to time, but also stimulate emotional and physical reactions to the extent that they interfere with daily life.
In some ways, the phenomenon of PTSD feels like a warning about the human desire to dream of cognitive augmentation and improve memory. This is because the human brain learns desired information with difficulty and easily forgets it, but unwanted bad experiences remain for a long time. Why does our brain keep the memories we want to forget for a long time regardless of our will?
The reason why negative memory information such as fear and stress does not disappear like PTSD is because the memory control mechanism called ‘memory extinction’ works abnormally. Memories have various characteristics such as creation, transformation, and extinction, and the same is true of fear memories. Researchers have chosen a method of reproducing the creation and change of fear memories in experimental animals in order to understand in detail the ever-changing characteristics of memory. A behavioral measurement technique called fear conditioning is one of the most widely used.
Fear conditioning is the simultaneous processing of neutral external environments or stimuli that do not cause a fear reaction in mice (e.g., a specific place or meaningless sound) and a powerful electrical stimulus that causes the mouse to feel fear because it is very painful. conditioning)’. After fear conditioning, mice produce an extreme fear response when a neutral stimulus is given even without electrical stimulation, which is expressed as a non-moving freezing behavior.
This is the same as when a mouse encounters a predator, such as a cat, fox, or hawk, it also shows a stop action according to the feeling of extreme fear. This conditioning is so powerful that fear memories can be created instantly and maintained for weeks to months, which is quite a long-lasting fear memory, given that laboratory mice have a lifespan of about one to two years. The memories produced by fear conditioning can be viewed as one of the simplest forms of PTSD.
Memories caused by fear conditioning are also easily found in humans. For example, if your most comfortable bedroom is infested with cockroaches, that room will no longer be a comfortable place, but will become the scariest room in the world. In addition, even if you go to a room with wallpaper, structure, lighting, and smell similar to the room where cockroaches were infested, you may feel rejected because of your old memories.
Now, let’s repeatedly expose the mice to the (no longer neutral) environment and stimuli used for fear conditioning, but without the painful electrical stimulation. Then a new ‘learning’ takes place. The mice now learn that the environment or stimulus used for conditioning is independent of the electrical stimulation of pain they have experienced in the past.
Humans, too, can feel safe in a space once they have been completely free of cockroaches and made sure for a few days or weeks that the room is safe and free of bugs. Then we call the horror memory of the bedroom ‘disappeared’ or ‘forgotten’. As such, since the loss of the original fear memory comes from learning ‘newly’ that the fear-evoking factor and the stimuli irrelevant to the fear are no longer ‘associated’, the loss of memory is the result of new learning, interfering with the existing memory. It can be seen that new memories are formed.
Evidence that fear memories seem to disappear as they are interrupted by new memories can be seen in other phenomena as well. Even after the fear memory acquired through fear conditioning has been extinguished, fear may be recovered if the mouse is exposed to a new, neutral environment that has nothing to do with fear.
This is called regeneration of fear memory, and the reason why this phenomenon is observed is also because existing fear memory information competes with new suppressive memory information that ‘suppresses’ it. So, when the mouse’s fear suppressive memory is exposed to a completely different new stimulus or environment, it is suppressed by other memory information, so that the original fear memory appears to be revived.
In this way, humans and other animals compete with each other for various memory information and exist in the brain, and can selectively pull out desired information as needed. This type of memory competition seems to be advantageous in storing and processing various information. .
The ‘non-disappearing fear memory’ experienced by PTSD patients is a problem with the new learning of inhibitory memory that enables the disappearance of these fear memories. In order to erase the memories that made it difficult for you, you cannot learn anew that the stimulus is no longer painful or disturbing. This abnormally working memory processing mechanism also interferes with the formation of various types of fear memories.
According to a study using fMRI (10.1523/JNEUROSCI.4287-13.2014) on soldiers who participated in the Iraq War by Professor Israel Liberzon’s research team at the University of Michigan, veterans diagnosed with PTSD, unlike normal veterans, had a past history. The physical fear response to the new dangerous environment unrelated to the fear memory was low, and the new fear memory related to it was not well formed.
Generally, when we encounter new threatening environments and stimuli that are different from the existing one, we create new fear memories. Since the new fear memory contains information different from the existing fear memory, even when similar emotional responses such as ‘threat’ and ‘fear’ are stimulated, we can distinguish and remember all the various information that causes fear. This would have worked evolutionarily in favor of survival by enabling animals to cope with various threats. However, when there is a problem with the mechanism that processes memories in various ways, such as PTSD, the fear memory becomes fixed and it is difficult to cope with various situations.
So what factors cause PTSD? One of the main clues is extreme ‘stress’. Stress can interfere with memory loss even in normal people, as in those with PTSD. A research team led by Professor Elizabeth Phelps of New York University created conditioned fear memories by showing neutral pictures unrelated to pain or fear while giving weak electrical stimulation to the wrists of 127 normal people.
At this time, it was found that those who received mild stress by dipping their hands and arms in ice water significantly lowered the degree of extinction when inducing the disappearance of the generated fear memories, and eventually, the fear memories were maintained higher than the control group (
One of the many brain regions that ‘learn’ memory loss is the prefrontal cortex. Factors that inhibit memory loss, such as stress, or the formation of ‘inhibitory memories’ of fear memories can cause deterioration of the function of the prefrontal cortex. It can be interpreted that excessive stress caused by extreme fear and pain affects the functions of various memory-related brain regions, including the prefrontal cortex, and adversely affects normal learning and memory processes.
The molecular mechanism responsible for the flexibility of memory can also be inferred through the case of realizing the phenomenon of non-disappearance of memory in normal laboratory animals. Researches in various directions are being conducted, but one example is a study published in 2008 by Professor Anthony G Phillips’ research team at the University of British Columbia, Canada (doi.org/10.1038/sj.npp.1301642).
They found that α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor, one of the membrane proteins that plays a major role in signal transduction between excitatory neurons in normal mice, is endocytosed. ), the formation of fear memories by fear conditioning was normal, but only the disappearance of fear memories was selectively reduced.
Endocytosis of AMPA receptors has a function of mediating long-term depression (LTD), in which synaptic transmission between neurons is reduced for a long time, and other studies have also reported errors in AMPA receptor endocylation and It has been reported that if there is a problem with long-term synaptic degradation caused by other molecular changes, there is a problem with the formation of new memories that replace the memories that have already been formed.
Therefore, in PTSD patients, certain molecular mechanisms that regulate plastic changes in signal transmission between nerve cells were abnormally changed by stress, etc., and this seems to act as a major factor in preventing the formation of new memories that are different from existing memories.
However, finding the cause of abnormal memory formation and disappearance such as PTSD only in the brain seems to have limitations. Professor Karl Deisseroth’s research team at Stanford University published a study in the journal Nature in March of this year that provides a new perspective on the origin of ’emotion’ that we have taken for granted.
In general, it was believed that the external environment and stimuli that arouse fear are transmitted to the brain through the sensory nervous system, and the brain generates emotional signals in areas related to emotions and transmits them to the body through the autonomic nervous system. So, negative emotions such as fear are felt in the brain and eventually transmitted to the body, leading to an increase in heart rate and changes in muscle/vascular/skin tissue.
However, the Diceros research team has evidence that anxiety and fear responses have an emotional signal system that is transmitted from the body to the brain in addition to the signal system that is unilaterally transmitted from the brain to the body, and that body-brain interaction occurs and negative emotions are expressed. was presented (doi.org/10.1038/s41586-023-05748-8).
The research team artificially induced cardiac tachycardia and heart rate to rapidly increase in mice, similar to a stressed situation, through optogenetics technology. Tachycardia could increase anxiety and fear responses in mice.
Artificial cardiac tachycardia induction using optogenetic technology and subsequent increase in anxiety behavior. Provided by Nature
This suggests the possibility that heart rate changes induced by external stress, etc., can be combined with emotion-related activities in the brain to be finally expressed as anxiety and fear responses. The researchers proposed the posterior insular cortex as the brain region that mediates these body-brain interactions.
Because, it was found that the activity of the postinsular cortex greatly increased when cardiac tachycardia was induced under a threatening environment, and on the contrary, optogenetic suppression of the activity of the postinsular cortex significantly relieved anxious behaviors caused by the threatening environment and artificial tachycardia. Because.
Therefore, in the future, in order to understand memory-related disorders such as PTSD, we will have to dig into the learning and memory-related mechanisms in the brain in detail, and at the same time pay attention to various memory control mechanisms by brain-body interaction.
It is not yet known whether the reason why negative memories are difficult to erase is because these brain-body interactions work complexly or whether these similar but different brain-body interactions are involved in all types of memories.
But as we continue to dig into these new facets of learning and memory, we believe we will gain a deeper understanding of why certain memories stick more firmly in our heads than others.
※Introduction of the author
Hyungjoo Park. He works in the Neurovascular Unit Research Group at the Korea Brain Research Institute and is an adjunct professor in the Department of Brain and Cognitive Sciences at the Daegu Gyeongbuk Institute of Science and Technology (DGIST). He is currently researching the molecular mechanisms of interactions between cells that control learning and memory using a mouse model, and is also working on a book introducing interesting research results on memory formation and change in the brain to the general public.
