Interoception is the sense least known to science. The five classic senses (sight, hearing, smell, taste, and touch) help us perceive the external world. However, when discussing these five senses, we forget that we can perceive our body from the inside. Some examples of interoceptive sensations are pain, thirst, hunger, nausea, or itching (Chen, et al., 2021). Studying in-depth neuroscience of interoception will provide answers to pending questions and its functions.
Interoception not only refers to our sensations but encompasses all the processes by which an organism perceives, interprets, integrates, and modulates the sensory signals within us (Chen, et al., 2021).
Therefore, interoception is more complex than the sensation from our viscera. It also includes the emotional and cognitive activation that this sensation produces and changes to regulate internal bodily processes (Berntson & Khalsa, 2021).
In its most recent version, the term interoception refers to the interpretation and integration made of by the internal and external stimulation of the organism. This also includes associated cognitive and emotional processes so that a global internal representation of the organism is produced, including conscious and unconscious aspects (Berntson & Khalsa, 2021).
Historical Evolution of the Concept of Interoception
About 150 years ago, neurophysiological studies provided results on how physiological parameters determine the normal internal state of the individual. Tests were performed (such as a blood test or a measurement of muscle tension). Thus, possible to determine whether the “internal state” in that parameter was within the expected normal range or if there was any alteration.
Around the 1950s, this field was studied from a more dynamic point of view. A lot of attention was not paid to the parameters outside the norm. Attention was paid to how the body achieves balance, or how to achieve homeostasis.
The evolution of the scope of study changes, therefore, according to the following diagram:
Determination of the normal values (19th century) → Search for homeostasis (20th century) → Integration of interoceptive processes with the rest of the body (21st century)
Pending Questions about the Concept of Interoception
However, further investigation on the interoception concept is needed.
Let’s look at some of these questions that continue to intrigue researchers and that we will try to answer in this entry:
What are the exact neural circuits of interoception and their interaction dynamics with the rest of the components of the central and peripheral nervous system?
How are these interoceptive sensations related to the rest of the basic physiological processes (for example, the heartbeat, the secretion of gastric juices, hearing, or sweating)?
How do neurological and psychiatric disorders (both central and peripheral) affect interoceptive networks? Conversely, how do interoceptive processes modulate the course of diseases and disorders associated with them (behaviors, lack of sleep, etc.)?
How can interoceptive sensations be measured objectively and using numerical values? What technologies are available to make these measurements and to modulate the proprioceptive experience?
To answer these questions, it is convenient to take into account the difficulties posed by the study of interoception.
Explanations about the Concept of Interoception
First of all, the terms“integrating” or “perceiving” are thought of as a unidirectional relationship. That is, the information goes from the sensory receptor organs to the central nervous system. However, the communication between organs and the central nervous system is complex. The relationship between the two is bidirectional. Furthermore, it integrates simultaneously with other organs and brain areas. It is not even a single round-trip processing. Each stage of processing, each interconnection between the organs and the brain, undergoes modulations along the way. Communication between them can be processed back and forth numerous times.
Therefore, a complex network is formed between the brain and the organs, which can only be analyzed by advanced computing systems (such as supercomputers or artificial intelligence systems). Therefore, it is not surprising that this concept of integration has gained strength with this century’s technological advancements.
A second difficulty is the distinction between exteroceptive (coming from the outside) or interoceptive (from internal organs) sensory organs. In general, our sense organs are located on the border between the inner and outer world. Therefore, either of them is susceptible to influences from both. For example, vision is considered an exteroceptive system. However, we can visually perceive many things that come from within us. Another example is the retinal detachment that gives us the sensation of seeing lightning that is produced by internal traction of the retina.
In the same way, the sensation of hunger (mediated by the vagus nerve) is considered an interoceptive stimulus, but it may be enhanced by an external odor. It is not easy to determine whether a sensation comes from the external or internal world. On most occasions, we will have to say that interoception or exteroception is rather a matter of degree (more or less external sensation, or more or less internal sensation).
What Causes Interoception?
The alterations of the internal environment that the interoceptive sensory organs capture can be of three types:
-Biochemical signals: inorganic atoms and molecules, organic molecules and small peptides.
-Mechanical forces that cause traction or compression of cells.
-Thermal and electromagnetic signals, which can be emitted with different wavelengths and energy levels.
Types of Interoceptors
Interoceptors capture molecules and energies that are transduced into electrical signals. They allow the release of hormones or send any other type of signals that the brain is capable of detecting, integrating, or interpreting.
Interoceptors can be chemoreceptors (which react to chemicals), humoral receptors (which detect changes in the composition of blood or lymph, such as hormones), mechanoreceptors (which detect the presence of force or pressure on them), and nociceptors (which free nerve endings that transmit the sensation of pain).
However, very little is still known about the types and characteristics of interoceptors. Only a few of them are known. Surely in the coming years, many more will be discovered and we will know more about those that have already been identified.
Location of interoceptors
Interoceptors can be found in the nervous system, but also other non-neural systems, such as the circulatory or lymphatic system.
Many classical neuroendocrine systems have some of their processing within the nervous system while terminating in a non-neural organ (e.g., a gland). Other interoceptors, such as mechanoreceptors or thermoreceptors, are always found within neural processing. Although they capture sensations, such as pressure or heat, come from other internal organs or the external environment.
Depth of interoceptive processing
Proprioceptive information sometimes does not require further deep processing. A reflex arc is produced that causes a behavior without cortical mediation. Other times, however, higher-order processing occurs in which perception, cognition, and affect intervene. Thus creating a sensation of consciousness.
It has been seen that, in humans, the insula (brain structure located in the Sylvino fissure, which integrates information from many regions and is involved in emotional processing, decision-making, and attention) is activated when attention is paid to interoceptive sensations. For this reason, it is believed that this region acts as a key interoceptive center to integrate interoceptive sensations whether they come from stimuli from outside or inside the body.
Ascending pathways of interoception
There are two ascending peripheral neural pathways (also called afferents) that process interoceptive information to the central nervous system. Each of them uses different types of peripheral sensory ganglia.
The first pathway is the cranial-vagal pathway. It passes through the nodose or jugular ganglia, and projects to the nucleus of the solitary tract (column of gray matter located in the medulla oblongata). The nerve impulses that travel through this pathway are often called “parasympathetic afferents.” This pathway is thought to primarily carry information that comes from mechanoreceptors and chemoreceptors.
The second pathway uses the spinal cord, and its ganglia project information to the brain through the spinal cord. Nerve impulses from this pathway are called “sympathetic afferents” and are believed to carry information related to pain, tissue injury, and temperature.
Information from both pathways is then processed in subcortical structures (medial nucleus of the solitary tract, parabranchial nucleus, and ventromedial nucleus of the thalamus). From here, they project to higher brain structures (the hypothalamus, insula, anterior cingulate cortex, and somatosensory cortex). It is believed that these latter brain areas are where the integration and interpretation of this information occurs.
Finally, the insula is strongly connected to several paralimbic brain regions (anterior cingulate cortex and orbitofrontal cortex), which could help connect interoceptive experiences with emotional and cognitive processing.
Regulation of Interoception
The central nervous system can generate signals that allow modulating or regulating interoceptive signals. The neurons responsible for this function are called “central regulators of interoception.” These regulatory neurons cause increases or decreases in the response intensity of interoceptive, emotional, and exteroceptive signals.
Signals from regulatory neurons can also be transmitted to peripheral organs through non-neural pathways (venous and lymphatic pathways) and descending neural pathways (cranial-vagal and spinal pathways).
In the case of non-neural pathways, the final effectors (that is, the place where the different pathways arrive) interact directly with the substances that have arrived through the body’s humors (blood or lymph). On the other hand, in neural pathways, the end effectors create a synapse with the non-neural cells of the internal organ.
In both afferent (from the organ to the central nervous system) and efferent (from the central nervous system to the organ) impulses, both pathways (neural and non-neural) can interact with each other so that impulses from one pathway can influence the other.
Functions in the Regulation of Interoception
The function of central interoceptive neurons is to send signals and transmit them to target internal organs. Its effects can be measured through observable changes in the target internal organs (where the information arrives) and it is impossible (with current scientific and technical means) to directly measure its action.
Even so, several techniques allow us to understand a little better how these interoceptive pathways work. When using neuroanatomical techniques, transmission pathways of interoceptive information are strongly branched and interconnected with the rest of the neural networks. This complexity extends throughout the entire path, from its origin to its termination in the cerebral cortex. However, there is still much to know about how neural and non-neural pathways connect the brain with the periphery and how they interact with each other and with the rest of the nervous transmission networks.
It has been seen that all these branches converge and diverge at different points. However, it remains unknown what happens at the synaptic or cellular level in all these processes. With current techniques, you can see the large branches of each path, but when these are very far apart it is difficult to trace precisely where each branch goes. This fact means that many of these connections are unknown for now.
Studies on the Functioning of Interoceptors
Until a few years ago there were only a few studies that used evoked potentials, vasectomized animals, and humans with neuronal lesions. However, the use of functional magnetic resonance imaging in humans has shown that there is a large network of connections between the brain and the viscera. The insula appears to be the place with the greatest convergence of interconnections.
Activation of the insula (and the centers that connect to it) correlates with a wide variety of interoceptive functions that influence visual perception, mental timing, emotion, empathy, language, music perception, and self-awareness. However, many things remain to be known, such as what specific types of neurons are involved in each of these functions, how the interpretation of these sensations is carried out, how they are integrated with other sources of information, or how interoceptive information is regulated.
Importance of Interoceptors
Having optimal sensitivity, interpretation, integration, and regulation of the body’s signals (whether these processes reach the level of consciousness or not) is very important to perform basic physiological functions. These include breathing, eating, fluid intake, urination, or maintaining body temperature. These functions of interoceptors are also necessary for other physiological experiences, such as emotions, adaptive behaviors, or motivation.
All of these processes can also help generate physiological patterns and complex behaviors, which are based on exteroceptive and interoceptive information and can help us better cope with stressful situations.
Variables that Measure Interoceptive Activity
In animals, interoceptive activity can be known down to the level of functioning of a single neuron. It is also possible to know neuronal activity using neurophysiological techniques or in vivo tests of neuronal functioning. Finally, it is also possible to measure the functioning of entire organs or the behavior of animals.
On the contrary, in humans, research has many more limitations and the studies are usually correlational. In these cases, heartbeats, skin conductance responses, subjects’ self-report responses, or assessments of the subject’s level of consciousness can be measured. Body regulation techniques can also be used, such as variations in blood pressure or the triggering of baroreflexes (reflexes that are triggered to compensate for variations in blood pressure).
Diseases and Disorders in Interoception
In recent years it has been proven that dysfunctions in interoception are part of many behavioral, psychiatric, and neurological disorders. For example, alterations in the structure, functional activity, and connectivity of the interoceptive neural network have been seen in migraines and many other types of chronic pain. Also substance abuse disorders, such as alcoholism, anxiety, depression, affective disorders, post-traumatic stress disorder, obsessive-compulsive disorder, autism spectrum disorders, eating disorders, somatic disorders, cerebral infarctions, and neurodegenerative diseases.
In some neurodevelopmental and psychiatric disorders, such as schizophrenia, attention deficit hyperactivity disorder, autism spectrum disorders, depression, or anxiety disorders, alterations are observed in the brain networks in which interoceptive information is integrated. These networks also process emotions and cognitive processes. The symptoms of these patients also suggest the existence of damage to the functioning of the interoceptive system.
For example, patients with autism spectrum disorders show problems in emotional processing, and alterations are observed in the connectivity of the insula. All of these alterations suggest that there may be alterations in interoceptive processing and when observing these patients it is found that many have an increase in sensitivity to painful stimulation and a greater number of gastrointestinal symptoms.
Alcohol addiction and other substance abuse can also cause changes in interoceptive processing, such that the stress response is increased and emotional processing is altered. Both alterations are also accompanied by a large number of central and peripheral symptoms that are related to interoceptive stimulation, such as alteration of the normal functioning of the intestine or the abnormal feeling of hunger. All of these symptoms are in turn related to the processing of the vagus nerve, which, as we have seen, is closely related to the interoceptive system.
In the same way, irritable bowel syndrome is characterized by the presence of high visceral sensitivity and an alteration in the functioning of the insula. Obesity shows alterations in the functioning of the intestine, and again alterations are observed in the connectivity of the insula and the brain regions with which it connects.
Manipulations on the Interoceptive System
The complex interoceptive processing network (both bottom-up and top-down) provides many intervention possibilities in which to modify interoceptive functioning and its associated disorders.
Three groups of interventions have been proposed: behavioral, neuronal stimulation, and pharmacological.
There are behavioral techniques that are the least invasive and the safest. For instance, meditation and cognitive behavioral therapy. These techniques typically employ exteroceptive stimulation, such as sounds, images, somatic sensations, or cognitive activities. They trigger changes in brain functioning and cause effects on descending interoceptive networks. However, the limitations of these techniques include the scarcity of well-defined therapeutic objectives, their low effectiveness, and the time required to cause changes.
However, the power of the above techniques should not be underestimated. Although they are slower in achieving their objectives, obtaining long-term profits is safer and probably more stable.
The specialist in Tibetan Buddhism Bruce Allan Wallace said, that the only means that human beings have to know their mind is their mind. The mind can be educated through the practice of meditation. When attention is not trained, the mind tends to wander, become agitated, or act more erratically. Conversely, if the mind is used to exploring and experimenting with consciousness, less desirable cognitive states can be replaced by greater emotional stability and greater liveliness in our perceptions (Brandmeyer, Delorme, & Wahbeh, 2019).
Interventions on the Interoceptive System
Therefore, both meditation and cognitive-behavioral therapy help process interoceptive information and integrate with the rest of the sensations and cognitive processes.
On the other hand, neural stimulation techniques include transcranial magnetic stimulation, direct current magnetic stimulation, deep brain stimulation, vagus nerve stimulation, and transcutaneous electrical stimulation of peripheral nerves. If clear objectives are established where to perform the stimulation, the side effects are usually small.
However, in most interoceptive disorders these points cannot be identified, nor are there treatments that have scientifically validated their effectiveness. Additionally, in some of these treatments (such as deep magnetic stimulation or vagus nerve stimulation), neurosurgery must be performed.
Pharmacological interventions, such as blocking ghrelin (a digestive system hormone that regulates appetite and contributes to intestinal homeostasis) or its receptors, are promising. There are no studies that have demonstrated their effectiveness. In the future, pharmacological techniques that act on both the brain and peripheral organs may be used. However, there is still much to know about the effectiveness of these treatments and their possible adverse side effects.
Key Ideas of the Interoceptive System
Interoception is the least known system in current neuroscience. This system not only addresses the processing of interoceptive sensations (from bottom to top, and from top to bottom), but their interaction with other sensations, the interpretation made of these sensations, and the regulation mechanisms.
There are two main routes of transmission of interoceptive information: the cranial-vagal route, which processes information from the mechanoreceptors and chemoreceptors, and the dorsal spinal route, which transmits information about pain, tissue injuries, and temperature.
Interoceptive information connects, through the insula, to numerous parts of the cerebral cortex related to the control of attention, emotions, and motivation.
Meditation and behavior modification techniques have some limitations. However, they are the ones that can provide the most stable long-term changes. Neuronal stimulation or the use of drugs, may also be useful in some patients, but more research is needed.
Berntson, G., & Khalsa, S. (2021). Neural Circuits of Interoception. Trends in Neuroscience, 44(1), 17-28.
Brandmeyer, T., Delorme, A., & Wahbeh, H. (2019). The neuroscience of meditation: classification, phenomenology, correlates, and mechanisms. Progress in Brain Research, 244, 1-29.
Chen, W., Schoesser, D., Arensdorf, A., Simmons, J., Cui, C., Valentino, R., . . . Langegin, H. (2021). The Emerging Science of Interoception: Sensing, Integrating, Interpreting, and Regulating Signals within the Self. Trends in Neuroscience, 44(1), 3-16.