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

2022/03/07

Psychology, the study of the functions of the mind, is historically a discipline derived from philosophy. It is said that psychology got its start as a "science" in 1879, when Wilhelm Wundt established the world's first "psychology laboratory" in Leipzig. Since then, attempts to scientifically explore the mind have evolved, and psychology has been subdivided into multiple fields. Among these, the academic field known as "neuropsychology" has undergone significant development as a specialized field that investigates which brain regions cause which mental disorders by studying cases with brain damage. To give a famous example, patient HM, who suffered damage to the hippocampus located in the temporal lobe, was able to retain memories for a few seconds but had difficulty retaining memories for several minutes. This case report became the basis for the concepts of "short-term memory" and "long-term memory."

Independently of the development of neuropsychology as clinical research, brain activity measurement technology has also undergone remarkable development. Limiting the discussion to research on 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, it detects signals emitted from the neural activity of the brain parenchyma below the skull. EEG is a technology that is 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 dramatically. 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 right now while reading this text, or how and where the brain is active when feeling anger or sadness. While the aforementioned EEG makes it difficult to identify neural activity in detailed parts of the brain, it can track activity in milliseconds. While functional MRI can depict detailed parts of the brain, it can only track activity in seconds. It became possible to integrate the results obtained from EEG and functional MRI with the results of neuropsychology, which considers the effects of brain damage, and 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 has also had 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 structured. Then, it proposes this as a theory or model, other researchers verify the validity of that idea, and the valid ones remain. With the development of cognitive neuroscience, this process has gone beyond the framework of psychology, and theories and models proposed in psychology have come to be exposed to verification from the perspective of brain science. Today, 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 an organism receives a stimulus from the outside (e.g., seeing a bear), some change occurs inside the body (e.g., heart pounding), and this 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 an external stimulus gradually weakens when the 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 Japanese word "kanjo" (emotion/feeling) is often applied to this translation, and the translation "jodo" feels out of place.

Research on the brain mechanisms of "emotion" (jodo) expressed as behavior seems to have had its framework 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 the turn of this century that this delay was made up for all at once. What exactly was the trigger? It was the simultaneous measurement of changes in autonomic nervous activity, such as changes in heart rate and respiration that are always observed when feeling emotions, and changes in brain activity. This method made it possible to clarify what kind of changes occur in which parts of the brain when changes occur in the body. This triggered a sudden surge of attention toward capturing the moment when subjective emotions 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 less likely 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 itchy, when the heart is beating fast, and when breathing is difficult. Furthermore, it has been shown that the insular cortex is active 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, further research progressed, 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 nerves and vestibular nerves, such as body temperature, sweating, and sense of balance, in addition to the state of internal organs such as the heart, lungs, and gastrointestinal tract. 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 activates the sympathetic nervous activity of the autonomic nervous system, 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 are more likely to be aware of their heart pounding or difficulty breathing also tend to report higher levels of anxiety. Furthermore, it was confirmed that even in patients who originally had no mental problems but developed conditions where the autonomic nervous system shows overactivity, anxiety tends to increase accordingly. While anxiety is often thought of as a "problem of the mind," it is actually the state of the body that triggers that state.

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 for neurosurgical treatment is resection of the area around the tumor. Since the degree of tumor infiltration cannot be accurately seen with the naked 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 part that serves as the center of emotion is known in advance, emotional function can be preserved by sparing that part. 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 the neurosurgery team at Nagoya University 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, it is possible to identify a person's emotional center with a certain degree of accuracy. Then, the tumor is removed while avoiding that area. By doing this, both the goal of "removing most of the tumor" and the goal of "preserving emotion" can be met. Based on this concept, research was actually conducted, and it was discovered that the region from the anterior to the middle part of the insular cortex is the center of emotion. *1 *2

The role of the insular cortex in detecting things like heart movement 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 "creating document XX when I get to work," "going shopping in the evening to buy XX," or "taking 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, memory for 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: "noticing the intention" and "recalling the content." Noticing the intention is the element of noticing in a timely manner that there is a plan that needs to be done, and our research has shown that the front part of the frontal lobe, called the frontal pole, is involved in this awareness *3. On the other hand, recalling the content is the element of remembering the specific details of the plan, which is "memory" itself, and involves central memory mechanisms such as the hippocampus and thalamus.

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 exactly generates awareness?" 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 field of vision, you won't necessarily notice that you should mail it. You might walk for a while and then think "Oh no," and then think about putting it in the mailbox in front of the station, but fail to remember again in front of that mailbox, and only notice the envelope in your hand when passing through the ticket gate, thinking "Oh no" again. Why can't you remember to mail it even though the mailbox is in sight? From a professional perspective, this question can be replaced with the question, "Why was the frontal pole not activated at the appropriate timing?"

What I thought of here was the hypothesis that "interoception is involved in awareness." In other words, when the mailbox enters the field of vision, a process that generates "awareness" works in the brain, and the result activates the sympathetic nervous 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, "Oh, that's right." In terms of processes in the brain, this means that neural transmission occurs from the insular cortex to the frontal pole. As a result of experiments to demonstrate this, it became clear that people who can remember actions they need to 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 mail it increases if they continuously pay attention to the fact that they must mail it. However, there are surely not many scenes where one is thinking about that the whole time until mailing it. 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 mailing 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 are 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.