[Feature: The Forefront of Brain Science Research] Satoshi Umeda: The Science of the "Mind" as Seen Through the Functions of the Brain and Body

Psychology, the study of the functions of the mind, is a discipline derived from philosophy when traced back through history. Psychology is said to have started as a "science" in 1879, when Wilhelm Wundt established the world's first "psychology laboratory" in Leipzig. Since then, attempts to explore the mind scientifically have developed, and psychology has been subdivided into multiple fields. Among them, the academic field called "neuropsychology" has achieved significant development as a specialized field that investigates which brain regions' damage causes what kind of mental disorders, targeting cases with brain damage. To give a famous example, patient HM, who suffered damage to the hippocampus located in the temporal lobe, could maintain memories for about a few seconds but showed difficulty in maintaining memories for several minutes. Based on this case report, the concepts of "short-term memory" and "long-term memory" were created.

Independently of the development of neuropsychology as clinical research, measurement technologies for brain activity have also undergone remarkable development. Limiting the discussion to research targeting humans, the measurement technology that initially developed was the "electroencephalogram" (EEG). An EEG is a device that detects weak signals emitted from the neural activity of the brain, using sensors attached to the head to detect signals emitted from the neural activity of the brain parenchyma below the skull. EEG is a technology still widely used today in hospital examinations and research. Attempts to understand the state of the mind using EEG gradually became popular, leading to the development of the academic field of "physiological psychology."

Entering the 1990s, "brain and mind research," which had previously centered on neuropsychology and physiological psychology, changed significantly. The reason lies in the technological innovation of functional MRI (Magnetic Resonance Imaging). MRI is usually a technology that depicts the "structure" of the inside of the body, including the brain. In neuropsychology, MRI is also used to identify damaged areas of the brain. On the other hand, functional MRI technology is a technology that depicts "function" rather than structure. In other words, it is a technology that allows us to see the "state of the mind" as a "state of the brain," such as which parts of the brain are active exactly when reading this text, or where and how the brain is active when feeling anger or sadness. While the previously mentioned EEG has difficulty identifying neural activity down to detailed parts of the brain, it can track activity in millisecond units. While functional MRI can depict detailed parts of the brain, it can only track activity in second units at best. By integrating the results obtained from EEG and functional MRI with the results of neuropsychology, which considers the effects of brain damage, the "brain science of the mind" was rapidly established. Currently, it has also merged with the field of neuroscience targeting animals, leading to the establishment of the field of "cognitive neuroscience."

This development also brought a major impact on psychology itself. Psychology is basically a discipline that targets human behavior, and through numerous experiments, it is a discipline that considers how the mind is constructed. Then, it proposes this as a theory or model, other researchers verify the validity of that idea, and the valid ones remain. Following the development of cognitive neuroscience, this process went beyond the framework of psychology, and theories and models proposed in psychology came to be exposed to verification from the perspective of brain science as well. Currently, even for those studying psychology as software, it has become essential to acquire basic knowledge about the brain, which is the hardware that realizes it.

Cognitive neuroscience focuses on the relationship between the "brain and mind," but this is insufficient for understanding aspects of the mind such as emotions and anxiety. The missing element is the "body." Below, I would like to take up research on emotions, which is my area of expertise, and describe why the science of the body is necessary for the brain science of the mind.

There are several concepts related to emotions, but an especially important concept is the distinction between "emotion" and "feeling." "Emotion" generally refers to a mental state in which a living organism receives a stimulus from the outside (e.g., seeing a bear), some kind of change occurs inside the body (e.g., heart pounding), and that causes the organism to take action (e.g., running away). Emotion is often translated as "jodo" (affect/emotion) in Japanese. Since the mental state associated with it gradually weakens when the external stimulus disappears, emotion can be defined as a transient mental state that induces some kind of action. On the other hand, "feeling" means "subjectively feeling an emotion." The word "kanjo" (emotion/feeling) is often applied to this translation, and the translation "jodo" feels out of place.

Regarding the brain mechanisms of "emotion" (jodo) expressed as behavior, I have the impression that the framework was established by around 2010 with the introduction of functional MRI. However, because "feeling" (kanjo) targets subjectivity, it tended to be excluded from the objects of science until the late 20th century, so the development of research was significantly delayed. It was only after entering this century that this delay was made up for all at once. What on earth was the trigger for that? It was the simultaneous measurement of changes in heart rate, respiration, etc., that are always observed when feeling emotions—that is, changes in autonomic nervous system activity—and changes in brain activity. Through this method, it became possible to clarify what kind of changes occur in which parts of the brain when changes occur in the body. This served as a trigger, and attention was suddenly focused on capturing the moment when subjective feelings arise.

So, where exactly are the brain regions that are active when changes occur in the body? The central region is an area called the "insular cortex." In physiology textbooks and the like, the insular cortex has long been introduced as the "center of pain." This is based on the fact that in cases with damage to the insular cortex, the sensation of pain becomes difficult to occur. However, research from more than 50 years ago also reported results showing that stimulating this area does not cause pain. So, what kind of function does the insular cortex perform? Research using functional MRI has revealed that this area is active not only during pain, but also when feeling an itch, when the heart is beating fast, or when breathing is difficult. Furthermore, it has been shown that the insular cortex is active in the same way not only when one feels pain oneself, but also when seeing a close person in pain. In other words, this area also reacts to "empathy for pain."

Subsequently, research progressed further, and it became clear that activity in the insular cortex increases when the body is not in a stable state (homeostasis). The "body" here includes the state of the autonomic nervous system and vestibular nerve, such as body temperature, sweating, and sense of balance, in addition to the state of internal organs like the heart, lungs, and stomach. In other words, it refers to states expressed subjectively, such as "pounding," "stabbing pain," "flushing," or "dizziness." These sensations are collectively called "interoception." That is, it has become clear that the insular cortex generates "interoception."

This interoception is also active when one subjectively feels emotions. For example, the reason we feel "scared" when there is a loud noise in the dark is because we perceive changes in our physical state: the loud noise occurs, the sympathetic nervous system activity of the autonomic nervous system becomes active, the heart pounds, breathing becomes irregular, and hands sweat. Even if there is a loud noise, if there is no disturbance in the autonomic nervous system, or if the insular cortex does not recognize the disturbance even if it exists, the subjectivity of being "scared" is unlikely to arise.

In this way, it has become clear that understanding the tripartite relationship of "brain-mind-body" is important for elucidating the neural mechanisms of emotion. Interoception also has a deep relationship with feeling "anxiety." In our research, we found that people who easily perceive their heart pounding or difficulty breathing also have a higher tendency to complain of anxiety. Furthermore, it was confirmed that in pathological conditions where the autonomic nervous system shows overactivity in people who originally had no mental problems, anxiety tends to become stronger accordingly. While anxiety tends to be considered a "problem of the mind," what actually causes that state is the state of the body.

These discoveries can also be applied to "preserving emotional functions" in clinical settings. When a brain tumor called a glioma is discovered around the insular cortex, the first choice of neurosurgical treatment is the resection of the area around the tumor. Since the degree of tumor infiltration is not something that can be accurately seen by eye, the actual resection range is often slightly wider in consideration of the prognosis. After resection of the area around the insular cortex, many patients report that they can no longer feel emotions such as anger and sadness that they used to feel normally. This leads to a major impact on daily life. Since the insular cortex is by no means a small area in the brain, if the area that serves as the center of emotion is known in advance, emotional functions can be preserved by sparing that area. However, where the parts related to emotion are is not something that can be immediately known by looking at the brain during surgery.

Therefore, we conducted joint research with a team from the Nagoya University Department of Neurosurgery to clarify this area. Specifically, we used a methodology called awake surgery. In this method, the patient is awakened during surgery, and while weakly stimulating parts of the brain, they are asked to rate presented facial expressions. If a part unrelated to emotion is stimulated, no change occurs in the rating of facial expressions, but if a related part is stimulated, changes occur in the rating of facial expressions, such as judging an angry face as sad. Using this methodology, the center of a person's emotions can be identified with a certain degree of accuracy. Then, the tumor is resected while avoiding that area. By doing this, both the objective of "resecting most of the tumor" and the objective of "preserving emotions" can be met. Based on this concept, research was actually conducted, and the region from the anterior to the middle part of the insular cortex was identified as the center of emotion. *1 *2

The role of the insular cortex in detecting things like heart movements being different from usual is not limited to emotions. Interoception is also related to bringing us "awareness." In our daily lives, there are multiple situations where we remember things we have to do (To Do). Daily life can be said to be full of the execution of plans, such as "I will create document XX when I get to work," "I will go shopping in the evening and buy XX," or "I will take medicine XX after a meal." If it is a sufficiently routinized act like brushing teeth or locking the front door, it can be remembered automatically, but if not, it is not uncommon to fail to remember at the appropriate timing and think "Oh no" later.

In the field of psychology, the memory of actions to be performed in the future, such as plans and appointments, is called "prospective memory," and many studies have been conducted on it. Prospective memory includes two elements: "occurrence recall" and "content recall." Occurrence recall is the element of noticing at the right timing that there is some plan that must be done, and our research has shown that the frontal pole, which is the tip of the frontal lobe, is involved in this awareness *3. On the other hand, content recall is the element of remembering the specific content of the plan, which is, so to speak, "memory power" itself, and central memory mechanisms such as the hippocampus and thalamus are involved.

Up to this point, these are parts that can be clarified through integrated research in psychology and brain science. However, the next question that must be addressed is, "What on earth is awareness generated by?" For example, suppose you leave work holding an envelope that must be dropped in a mailbox. Even if you pass in front of the mailbox you intended to use and the mailbox enters your sight, you won't necessarily notice that you should drop it in. You might walk for a while and then think "Oh no," and think about putting it in the mailbox in front of the station next, but you might fail to remember again in front of the mailbox at the station, notice the envelope in your hand when passing through the ticket gate, and think "Oh no" again. Why can't you remember to drop it in even though the mailbox is in your sight? From a professional perspective, this question can be replaced with the question, "Why couldn't the frontal pole be activated at the appropriate timing?"

What I thought of here is the hypothesis that "interoception is involved in awareness." In other words, by the mailbox entering one's sight, a process that generates "awareness" works in the brain, and the result activates the sympathetic nervous system activity of the autonomic nervous system, making the heart rate slightly faster than usual. Here, a person with sharp interoception senses the change in their own heart rate and generates the awareness of "Oh, that's right." In terms of the process in the brain, this means that neural transmission from the insular cortex to the frontal pole occurs. As a result of conducting an experiment to demonstrate this, it became clear that people who can remember actions they must do at the appropriate timing also have accurate interoception *4. Of course, even for people whose interoception is not sensitive, the possibility of being able to drop it in increases if they continuously pay attention to the fact that they must drop it in. However, there shouldn't be many scenes where one is thinking about that the whole time until dropping it in the mailbox. In technical terms, this is called "mind wandering," but we are thinking about various things in our minds. Even if one is thinking about something else while walking, if we ask what the difference is between a person who can notice dropping the envelope and a person who cannot when the mailbox enters their sight, it is highly likely that it is the difference in the sensitivity of interoception.

As described above, many latent elements are involved in aspects of our minds such as emotions and memory. The range that can be explained in language is only a small part of our consciousness, and what lies behind most activities are unconscious processes. If we intend to thoroughly understand aspects of the mind, we cannot separate the states of the brain and body under consciousness. I feel that merging with necessary fields without being bound by conventional academic domains is essential for breakthroughs in science.