Neurobehavioral Analysis

A Brief Note

The content of this website focuses on research and analysis—from a macro (broad/bird's-eye) perspective—regarding behavior as the ultimate manifestation of neurological and physiological functions. Central to this approach is the importance of methodologies for the objective and quantitative measurement and analysis of behavior, which represents the organism's ultimate, integrated function. This initiative is grounded in the belief that such research can contribute to preclinical medical studies, including the evaluation of drug efficacy and safety. We launched the "Neurobehavioral Analysis Links" website as a platform, hoping that the expansion of these research perspectives would create individual "links" that eventually evolve into a comprehensive network.

1. Perspective of  this website

The content of this website is a macroscopic (bird's-eye view) analysis of behavior as a manifestation of neural and physical functions. Here, we emphasize the importance of a methodology for objectively and quantitatively measuring and analyzing the integrated function of the living body, which is behavior. We hope that the spread of such research perspectives will form a circle (Link) and eventually form a network (Links), and have launched a website called "Neurobehavioral Analysis Links".

From the above perspective, the scope of the website covers basic research on neuropsychiatric diseases using laboratory animals and preclinical research as its application. Basic research includes the manifestation and measurement of disease syndrome, and elucidation of the mechanisms that lead to the manifestation of syndrome. On the other hand, preclinical research is more practical and includes the development of methods at the laboratory animal level and the acquisition/analysis of data on the therapeutic effects or safety of drugs, cells, etc. in the laboratory animals. Here, we consider it important to conduct research based on or in accordance with the spirit of Good Laboratory Practice (GLP), which can be legally guaranteed, with the goal of ensuring the reliability of data in clinical settings related to human diseases.

2. Neurobehavioral analysis research

2.1. Perspective of neurobehavioral analysis research

When humans are born, they first cry, suck milk, move, and sleep. Then, they respond to various stimuli, laugh, make sounds, which become words, interact with their parents, siblings, and other family members, play with toys, and expand their diverse behavioral repertoire from the family to society. From this flow, we can see that behavior begins with a response to internal sensory stimuli, and eventually includes a response to external sensory stimuli. The basis of such reactions is physiological reflexes (responses) that are inherent to living organisms, and behavioral spontaneous reactions (behaviors). Furthermore, based on these two, the former becomes a conditioned reflex (response), and the latter is a learned behavior called an operant conditioned response (behavior). These are then intricately intertwined and integrated. All of these are determined, first of all, by the morphological and physical characteristics of the human body in the external environment, and biological factors such as physiological functions, biochemical functions, molecular biological functions, and genetic bases are greatly involved in these constraints.

The behavioral aspect that is the subject of this study is the most integrated biological function throughout a person's life. It can also be said to be the final output, including various physiological processes of the organism. Behind healthy behavior, the normal functioning of the brain and nervous system is a prerequisite. In reality, these are not always normal, and various neuropsychiatric disorders exist. Even if we are not diagnosed with a disease, our brains are extremely fragile, and our behavior does not always maintain a high Quality of Life (QOL) or Well Being (WB). Therefore, scientific understanding of human behavior and appropriate control of one's own behavior are one of the most important issues in our lives, both for the diagnosis and establishment of treatment for neuropsychiatric disorders, and for maintaining a high QOL or WB.

Understanding behavior based on the above background and elucidating the neural mechanisms of the brain behind it are themes of neuroscience, and one of these is the perspective of neurobehavioral analysis research. Just as economics is divided into Micro Economy and Macro Economy, neuroscience can be divided into Micro Neuroscience, which focuses on neurons, cell activity, molecular biological events, and genetic analysis, and Macro Neuroscience, which studies behavior as an integrated system of the living body. This website will freely describe neurobehavioral analysis research mainly from the latter perspective, Macro Neuroscience.

2.2. The behavior as alpha (A) and omega (Z)

Our greatest interest is our own familiar behavior and the behavior of others. Even if we intend to turn our eyes to the far reaches of the universe or to the history of the distant past, we cannot deny that our interest is still human behavior. Furthermore, society, economy, politics, and even religion, and history, can be said to be the result of the accumulation of people's behaviors in the presence of insurmountable environmental conditions.

Of course, the world as a physical environment is vast and infinite, and a world far beyond the scope of our perception exists. However, only a very limited and minute part of this has a direct impact on humans and determines human behavior. It can be said that the results of human adaptive or maladaptive behavior in this limited environment have shaped human life, society, culture, civilization, and history. Based on this background, if we consider the world as a human-centered microcosm, we can also imagine a perspective in which everything in this world begins with human behavior, has human behavior as its goal, and ultimately ends with that behavior.

Our own behavior includes movements of the limbs and trunk, walking, exercise, language, thinking, and goal-directed execution actions. The conscious and introspective sensations felt during such behaviors can also be said to be factors deeply involved in behavior. Only a small portion of these behavioral flows can be objectively grasped by oneself, and the majority of the rest exists in a vast expanse that goes beyond one's own awareness or consciousness. In all of these aspects, the brain plays a major role as a physical structure, and various bodily organs and tissues are also involved. There, morphological physiological events, biochemical events, cellular events, molecular biological events, genetic events, and other events are intricately and intricately intertwined. These events are conveniently divided by the researcher as the research progresses. However, the living body itself exists as a single integrated system, regardless of such divisions. In this large stream of biological functions, there is behavior as a part that is clearly visible to us. In this sense, as mentioned above, we have been conducting neurobehavioral analysis research for many years, thinking that we can imagine a perspective in which behavior begins, behavior becomes the target or goal of research, and behavior ends.

2.3. Preclinical medical research from the perspective of neurobehavioral analysis

The author majored in psychology at university. After completing the graduate studies, the author received guidance from Dr. Tomoji Yanagida (1930-2016), a world-renowned researcher in drug dependence (addiction), not only in drug dependence studies, pharmacology, and psychopharmacology, but also on how to conduct research and how to write papers. Since then, the author has been cooperating with many excellent instructors and colleagues, and have continued the neurobehavioral analysis research and preclinical research for many years.

The content of  the author's research was to conduct preclinical research on neuropsychiatric disorders from the perspective of neurobehavioral analysis. In this basic research, the aythor has used mice, rats, common marmosets, cynomolgus monkeys, and rhesus monkeys as experimental animals. In each individual study, The author tried to make full use of the characteristics of each experimental animal. This meant taking into account the advantages and disadvantages of each experimental animal from the perspective of each research purpose, and not sticking to a specific experimental animal and forcing the research to continue. Looking back, this is not usually an easy thing to do, and the author believes that it was possible in part because the author was affiliated with a research institute whose purpose was to develop experimental animals.

In addition, when conducting basic research using experimental animals, the author kept the following two points in mind. The first was the reality that patients and medical doctors encounter in clinical medical settings, and the second was the reality that pharmaceutical companies that are developing drugs to treat diseases encounter. For each of these, the author used important feedback for the conduct of research to the extent that the author understood it. In basic research in preclinical medicine, the author has believed that research cannot be continued without being conscious of the critical gaze from the two perspectives mentioned above.

2.4. Neuropsychiatric diseases from the perspective of neurobehavioral analysis

In the case of the treatment of many neuropsychiatric diseases, the author believes that the first step is to diagnose syndrome as behavioral disorders. Syndrome includes symptoms and signs. Symptoms are aspects based on the patient's own subjective complaints, such as headaches and nausea, that the patient reports to the doctor, and are called subjective "symptoms." On the other hand, signs are the patient's physical condition and behavioral variations that are recognized as a result of the doctor's objective examination of the patient, separate from the symptoms. Both have been considered to be extremely important starting aspects in clinical diagnosis and in neurobehavioral analysis research.

In the treatment of neuropsychiatric diseases, once a diagnosis of syndrome is confirmed, treatment such as psychotherapy and medication is started. Therefore, the degree of behavioral remission of the patient's disease or the reduction of syndrome will be the immediate goal of the treatment. For example, in the case of Parkinson's disease, a neurological disorder, the patients or their family notice the abnormality in their motor function and the resulting inconvenience in daily life, and seeks a doctor's diagnosis. Once the diagnosis is confirmed, treatment such as medication begins, and the effectiveness of the treatment becomes an important issue. In this sense, treatment begins with behavior, and the behavior is the goal.

2.5. Does everything begin and end with behavior?

Above, the author has mentioned examples of treatments that "begin and end with behavior" but is this the case for everything? For example, in the case of Parkinson's disease, even if it is diagnosed based on syndrome, degeneration or loss has already progressed in the dopamine nerves of the nigrostriatal system of the basal ganglia in the brain of the patient, and this can sometimes be diagnosed at an early stage by brain imaging analysis such as Positron Emission Tomography (PET) or Single Photon Emission Tomography (SPECT). In addition, familial Parkinson's disease is known to develop due to gene mutations in α-synuclein, parkin, LRRK2, etc., and genetic testing may be able to predict the possibility of developing the disease. Furthermore, another neurodegenerative disease, Huntington's disease, is known to develop due to a gene mutation located on the fourth chromosome. In other words, it is known that the gene huntingtin may miscode a protein, causing neurological disorders at a certain age. In addition, there are many cases in which cerebrovascular diseases and brain tumors in the field of neurosurgery are found through brain imaging tests such as medical checkups, without the patient having any subjective symptoms. In light of the above, it is natural to point out that neuropsychiatric diseases, like physical diseases, do not all begin and end with behavior. For the diagnosis, treatment, and elucidation of the mechanism of neuropsychiatric diseases, research on genetic, molecular biological, cellular, biochemical, morphological, physiological, and pathological phenomena is important, as with other physical disorders. In fact, basic research on neuropsychiatric diseases has been conducted in this way. However, this website simply aims to emphasize the importance of using objective, quantitative, and precise measurement methods for the behavior of the organism as an integrated system.

Based on the above, in preclinical research at the in vivo level using laboratory animals, the author first tried to accurately focus on a specific aspect of the syndrome of neuropsychiatric diseases. Therefore, the author has conducted research in a style focussing to measure behavioral aspects of syndrome objectively and quantitatively. Looking back, the author believes that this research style was influenced by the education in the psychometrics and the experimental analysis of behavior at university (see Operant Behavior in Neuroscience ). After that, the author was given the opportunity to broaden its horizons little by little at several research institutions, based on this base. As a result, the author was able to expand its specialty to basic research and preclinical research on neuropsychiatric diseases using various laboratory animals.

Postscript: Touching on the world of "starting with cells and ending with cells"

When the author continues research based on behavioral science for many years, the author reaches the point of view that everything starts and ends with behavior. However, on the other hand, the author wanted to break away from such a fixed idea, so the author also learned pathology by self-study. The author had always thought that studying physiology was also important for someone who majored in psychology, but the author felt that studying pathology was easier for outsiders to absorb knowledge. The reason for this is that in physiology, you only learn about the body's systems under normal conditions, but in pathology, by studying the body's systems that are broken, you can also learn about the normal system at the same time, and the author felt that this was a factor that made it easier to learn. Of course, there is a question of what level you should study both physiology and pathology, and in the author's case, it was at a very elementary level.

The above is based on the author's past experience of studying neurobehavioral science.

Based on the above basic flow of thought, this website has been constructed with the table of contents below regarding the research that the author has conducted to date.