Immune Neuromodulation: The Impact on Behavior and Cognition

A few centuries ago, most philosophers believed that the mind was a matter of the supernatural world and not related to the body. Descartes had doubts about everything except the mind and held onto the belief that he truly exists because he can think. Some, like George Berkeley, even went as far as to radically reject the material world. They argued that our perception of the external world is an illusion created by the mind, which stems from the central soul. Modern neuroscientists, however, deny the duality between the brain and mind and demonstrate that the mind originates from brain activity. However, brain activity is influenced by external and internal signals that shape our moods, feelings, and behaviors.

The brain is located in a dark box and receives external signals through various pathways.

We are sometimes faced with negative moods, emotions, and even behaviors without knowing the reasons behind them. We often assume that these emotions or unusual behaviors stem from acute or chronic depression. It has been well-recognized that the modern lifestyle contributes to negative moods and depression. We are constantly bombarded with terrible news through the media and social networks about war, famine, terrorist attacks, and climate disasters. They are the main source of anxiety in humans. However, sometimes we experience negative emotions without any apparent reason.

We know that the brain is the origin of our behaviors, emotions, thoughts, will, judgments, and, briefly, mind. However, recent discoveries reveal that, although the brain plays a crucial role in integrating signals to generate the mind and consciousness, it cannot do so without both external and internal signals.

The central nervous system (CNS) receives multiple signals through afferent nerves and chemical compounds from sensory receptors or other sources. The signals are integrated and adapted with previous signals that are saved to form the most accurate perception of the body and the surrounding environment. The brain, based on these perceptions, provides feedback to respond to stimuli and maintain the internal environment of the body. With this approach, the brain automatically regulates electrolytes, pH, blood pressure, respiration, and heart rate through these perceptions.

CNS is evolved to prioritize survival and reproduction as its main mission, rather than perceiving the reality of the outside world. Therefore, it sometimes makes incorrect perceptions in favor of fulfilling its mission.

Body systems are internal signals that have a hidden impact on brain functions.

Some internal signals received by the CNS are more secret than others and they mysteriously influence the brain. Since we do not have a direct understanding of the perception of these signals, we may attribute their effects on the mind to other causes. For instance, the signals received by gut microbiota through the nervous system or chemical molecules affect the CNS and have an influence on moods, emotions, thoughts, and even decisions and behaviors. Alterations in the population of microbes can influence our desires and behaviors, such as cravings for certain foods or the motivation to exercise. These microbes also affect the immune system, which is responsible for finding and destroying pathogens, as well as repairing and compensating for tissue damage.

Some recent studies have found that immune response dysfunction affects cognitive functions and personality. In a pioneering study, it was found that alterations in immune function in response to pathogens can lead to antisocial behavior through the immune cytokine, IFN-γ. This cytokine is released in response to bacterial or viral infections. The blood-brain barrier is a symbol of the separation between the mind and body systems because it strictly controls the transfer of chemical compounds, hormones, and cells. However, this study revealed that the brain interacts directly with the immune system and its related cytokines through the meningeal lymphatic system. The study suggests a co-evolutionary link between social behavior and an anti-pathogen immune response driven by IFN-γ signaling.

Immune system: A new sense

We know that the immune system acts as a protective mechanism, detecting and relaying information about external and internal disturbances to the brain. This information is transmitted through peptides and immune cells, primarily microglia. The interactions between molecules derived from immune cells, such as cytokines, and neural circuits form a neuroimmune connectome, which is still not fully understood. Once the connectome is mapped, it is expected to provide a better understanding of the anatomical and functional organization of this type of perception and its impact on neurological diseases.

New studies challenge the traditional belief claiming that both the brain and the immune system operate separately and suggest that their interaction should be reevaluated. The immune input into the brain, known as immune neuromodulation, can have a significant impact on behavior and brain function. In sickness, feeling weak, sleepy, and having a decreased appetite can be attributed to an overactive immune response in the brain. Conversely, an impaired or dysfunctional immune system can lead to abnormal consequences and impact brain function.

In brief, mind and behavior are influenced by our immune system beyond what we think. It was thought for a long time that the brain and immune system work in isolation. However, modern science shows a direct interaction between these two systems, and the immune response triggered by pathogens can directly modulate mood and behaviors.