The Mysterious Sixth Sense That Helps the Body Understand Itself

The five senses serve to help us understand the external world. A new study sheds light on a sixth sense and its potentially dramatic implications for the body’s development

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A girl suffering from scoliosis. “We’ve showed that the proprioceptive system is responsible for maintaining a straight back,” says Prof. Zelzer.
A girl suffering from scoliosis. “We’ve showed that the proprioceptive system is responsible for maintaining a straight back,” says Prof. Zelzer.Credit: “Diseases of Infancy and Childhood” (1914), F. A. Davis
Asaf Ronel
Asaf Ronel

Pinocchio’s nose grew longer whenever he lied. Our human nose grows longer when the body lies to us about itself. One way to create this phenomenon, which is known as the “Pinocchio illusion,” is to have someone sit on a chair, blindfolded, and ask him to pinch his nose. A small vibrator is applied to the biceps tendon of the arm holding the nose. The vibrations create the illusion that the arm is moving and the joint is straightening itself. Because the blindfolded person is holding his nose with that arm, the brain is convinced that if the arm is moving, this means that the nose is growing longer. Result: The subjects are certain that their nose has changed like that of the famous wooden puppet in the story when it didn’t speak the truth.

The illusion is caused because the vibration affects a small “sensor” in the arm muscle. Such sensors are part of a mechanism, with whose help each person’s sense of body-self is created; this sense is called “proprioception” (perception of self). The five familiar senses serve us to understand the external world, while this “sixth sense,” as it is sometimes referred to, serves us to understand ourselves.

Proprioception has two levels: unconscious and conscious. The unconscious level operates continuously, and carries out the small adjustments that allow us to perform our everyday actions with precision. A striking example of the way the unconscious system works is the well-known knee-jerk reflex. Here, too, the sharp tap just below the kneecap stimulates one of the “sensors” in the leg muscle. The stimulus induces a perception in the brain that the leg is shrinking when it should be remaining in place, so it sends an order to “balance” this by straightening, producing the uncontrolled kicking motion that everyone knows from doctors’ checkups.

To understand what proprioception is at the conscious level, close your eyes and try to understand where your arm is and in what position. The case of Ian Waterman, a 19-year-old from Britain, who in 1971 woke up to find that his body had disappeared, demonstrates the importance of this mechanism for establishing our sense of self. The young man saw his body but was unable to feel or move it. Medical tests showed that he was suffering from a rare syndrome: In the wake of a viral infection in his neck region, his body’s immune system attacked and destroyed the neural fibers that transmit the information about the sense of touch and proprioception from the body to the brain.

About 10 other cases of this syndrome have been recorded since then. Waterman was unique in that he was the first of those affected who taught himself how to walk – solely with the aid of the sense of sight and conscious orders to make his legs move. If he closed his eyes, however, he stumbled.

Waterman’s amazing story is told in Jonathan Cole’s 1995 book “Pride and a Daily Marathon.” The book’s most striking example of the importance of proprioception relates to stages during which Waterman was convinced that his self had disappeared. After losing the basic ability to sense himself and to “feel” the presence of his own body, he had the feeling that he did not exist. The information that Waterman lost, and with it almost his sense of self, arrives via those same neural pathways from sensors that are dispersed throughout the body – in the joints, the tendons and above all in the muscles. The most important sensors (one of which is activated by the Pinocchio illusion, and another by the knee-jerk reflex) are known as muscle spindles.

Prof. Elazar Zelzer, from the molecular genetics department of the Weizmann Institute of Science, Rehovot, is currently studying muscle spindles in an attempt to understand the genetic and molecular mechanisms that inform their activity.

In an article published last month in the scientific journal Nature Communication, Zelzer and his colleagues showed how genes that influence the proprioceptive system are connected to the development of two of the most widespread orthopedic problems in children worldwide: scoliosis (curvature of the spine) and hip dysplasia (in which the hip socket does not completely cover the head of the femur, for which infants are routinely tested for flexibility of the hip joints). A previous study carried out in Zelzer’s laboratory showed also how the system plays a significant role in the process of healing body fractures.

Zelzer is devoting much of his research to subjects with significant medical implications – not least because of the involvement of two physicians in the project, Drs. Ronen Blecher and Eran Assaraf. The two broke off their medical residencies to pursue Phds in Zelzer’s lab. However, to make progress, the group must first decipher the molecular language through which the communication between body and brain takes place. Despite the applied nature of the research, it can be linked to realms including the mind-body connection – a kind of modern version of the pineal gland, which French philosopher René Descartes believed was the seat of the connection between mind and body.

“Yoga practitioners are very well acquainted with the location of the muscle spindles in the body,” Zelzer notes.

Muscle binds

Aristotle stated explicitly that humans have five senses. But as in many realms of knowledge, modern science needed to liberate itself from Aristotelean notions in order to begin to move forward. The 17th-century English physician William Harvey, who played a key role in our understanding of blood circulation, was the first to notice that the muscles that move the fingers are located in the forearm. “Thus we perceive and so feel the fingers to move, but truly we neither perceive nor feel the movement of the muscles, which are in the elbow,” Harvey wrote in a book published in 1628.

Elazar Zelzer. Few labs in the world focus on the role of muscle spindles in the proprioceptive system. His lab is the only one also examining the connection between that system and the skeleton.
Elazar Zelzer. Few labs in the world focus on the role of muscle spindles in the proprioceptive system. His lab is the only one also examining the connection between that system and the skeleton. Credit: Tomer Appelbaum

The term “sixth sense” in reference to the body’s ability to sense itself, was first used by the Scottish physician, scientist and neural system researcher Charles Bell, in an essay from 1826. The muscle spindles themselves were discovered in the mid-19th century. The term “proprioception” was coined in 1906 by the man who is considered the father of neurophysiology, the British physician Charles Scott Sherrington, who won the Nobel Prize in Physiology or Medicine for his work in the field in 1932. As understanding of the sense developed, scientists were divided about whether this self-perception of the body occurs in one place – the brain – or throughout the body.

Today we know it occurs in both: Neural information, which is collected with the aid of the various “sensors” scattered throughout the body, is transmitted to the brain. The information arrives at two separate regions of the brain, along the lines of the division between conscious and unconscious, explains Roy Salomon, who studies the boundaries of human perception in the Gonda Multidisciplinary Brain Research Center at Bar-Ilan University. The unconscious pathways, Dr. Salomon says, connects to the cerebellum, a primordial section of the brain that plays a central part in planning motoric movements and maintaining equilibrium.

The conscious pathway arrives at the central sulcus – a region of the cerebral cortex located exactly between the parietal lobe and the frontal lobe of the brain. Logically, Salomon adds, these neural pathways end at the point that’s located between the region that is responsible for volitional motoric movements and the region that processes the sense of touch.

How is the information collected? There are three different types of sensors in the body that send proprioceptive information: in the joints, in the connections between the tendons and the muscles, and in the muscles themselves. The question of the sensors’ importance has also been a matter of scientific dispute for many years; today, though, it’s thought that the muscle spindles play the central role. For example, one testament to the lack of importance of the sensors in the joints is the ability of people who have undergone hip-replacement surgery to know the position of their shin relative to the hip.

A muscle spindle consists of four different nerve endings that spiral around about a dozen muscle fibers. The small sensor, less than a centimeter long, is wrapped in a spindle-shaped tissue that separates it from the rest of the muscle. The internal structure and the connection to the different neurons allow the spindle to adjust the neural signal it produces to the changes in the length of the muscle. Because of this special structure, when the muscle is motionless, the spindle also “remembers” the position it was in previously.

The number of spindles differs in each muscle, Zelzer explains; all told humans and other mammals each have about 20,000 these tiny sensors. Animals of other orders, he adds, have different mechanisms that serve to create proprioception.

This understanding of the mechanical elements that make possible the body’s perception of itself, was articulated in the first half of the 20th century. Since then, research into proprioception in biology and the humanities, and into muscle spindles in particular, has been neglected. According to Zelzer, this is due to the 1960s revolution in molecular biology, which included the discovery of the structure of DNA.

“Until then, great attention was devoted to the involvement of mechanical signals in biology, with regard to development and functioning,” he explains. “When the molecular revolution began, to a certain extent people were captivated by three examples of molecules – DNA, RNA and proteins – and abandoned the mechanics. Molecular biology became mainstream; those who dealt with mechanics were considered part of the old world.”

The perception that the mechanical signals were important began to coalesce at the end of the 1980s. “Gradually, the fact that there is a very significant mechanical world in addition to the molecular world began to be accepted again. However, for these two worlds to connect, and for the mechanical to receive its due place, it’s necessary to understand the mechanism that is capable of translating the mechanics into the molecular signals of biology,” Zelzer says.

This revolution – deciphering the mechanisms that generate molecular signals – took place in multiple areas of life sciences and neurobiology, he notes. As for the proprioceptive system, however, “even though it was one of the first systems in the body to be characterized, there was no one to create the molecular language for it.” The subject was barely studied in neuroscience, Zelzer adds (and Salomon from Bar-Ilan agrees with him). From the point of view of the body, the professor points out, there are very few laboratories in the world that are studying the role of the muscle spindles in the proprioceptive system. His laboratory is the only one that is also examining the connection between the system and the body’s skeleton.

“We are trying,” he says, “to create the molecular language of this system, and by that means it will be possible to return the system to the center.”

How are the scientists uncovering this molecular language? First, the researchers in Zelzer’s laboratory isolate the spindles. Subsequently, they examine which genes are expressed in them and then try to discover which proteins each gene encodes, and what the proteins do. Their principal method is to inhibit the activity of individual genes and then examine closely the changes that occur when those genes cease to function. As he puts it, “We try to adopt systemic observation – not to focus on the lone tissue but to examine how it interacts with other systems, such as the skeletal one.”

Roy Salomon.
Roy Salomon.Credit: Ilan Assayag

A protein called Piezo2 is a striking example of a molecule that translates a mechanical signal (movement) of the muscle into a molecular signal. The protein, Zelzer relates, is actually a channel that resides on the membrane of the nerve cell that spirals around the muscle fiber. If the muscle’s length changes, the membrane is affected, the channel opens and allows a flow of positive ions (atoms with a positive charge) into the cell. They set off a chain of molecular mechanisms that modify the condition of the neuron.

“Piezo is an example that links the molecular world to the mechanical world,” Zelzer notes.

Bipedal misconception

In their new study, Zelzer et al. showed what happens when a gene like this goes awry. Mice in which the gene was inhibited in the skeleton itself did not develop medical problems. However, when the gene was inhibited in the proprioceptive system only, scoliosis developed at maturation – a spinal misalignment found in about 3 percent of all people, in which the vertebrae in the spinal column curve sideways.

“The conventional assumption in research is that scoliosis is the price we pay for being bipeds,” Zelzer says. “We showed that this is also the case with quadrupeds – and that the proprioceptive system is responsible for maintaining a straight back.”

The second problem from which the mice suffered is known as hip dysplasia, a common condition in 0.1 percent to 0.6 percent of infants; every infant in Israel is checked for it within the framework of the routine checkups in hospitals and the well-baby clinics. To explain the connection between the deformation of a normal hip and proprioception, Zelzer mentions a previous project of his.

As a developmental biologist, he examines how different elements in the skeleton and the muscles develop during pregnancy and natural physical growth. In the earlier study, he relates, he showed that for the joints to develop, the fetus needs to move in the womb, and that the movement encourages joint formation. “The significance of the new research,” he says, “is that not only does there have to be movement, there has to be correct movement.”

If fetuses and children who are developing have problems with the ability to sense their body, their movement is disrupted, and the joints that are involved in those movements are also disrupted. “That is the hypothesis: Not only is movement needed, but a particular movement is needed, so that the joint will develop properly,” Zelzer says.

This hypothesis bears deeper implications for understanding biology and evolution, he adds, and not only in pathological examples – in cases where something goes wrong. What it means is that the structure of the pelvis, a central anatomical organ, is influenced not only by genetics but also by the body’s own movements. If the structure of the pelvis is determined by the movements of animals, it follows that it has plasticity, that it is capable of adjusting itself to changes.

“Let’s say that a mutation occurred in a certain animal that modified its muscle activity, the bone size or the connection of the bone to the muscle,” Zelzer says. “That mutation changes the way the animal walks.” However, because the final form is determined by movement, this means that the pelvis can adjust itself to the change in walking, “and thus preserve its survivability.” Accordingly, in contrast to eye and hair color, which are genetically predetermined, the sixth sense research project presents an example of a system in the body by which activity defines structure.

“Not everything is predetermined; part of the body retains plasticity for changes,” Zelzer sums up.

Another place at which activity and functioning intersect with proprioception is aging. Proprioception is one of the first mechanisms affected by growing old. Because the aging process is frequently accompanied by a deterioration of various cognitive mechanisms in the brain, it is easy to assume that the effects are partly due to the brain’s getting older. But it’s possible that the deterioration of the proprioceptive system, too, is related to the decline in the quality of the signal that arrives from the sensors throughout the body.

Dr. Salomon notes that when the brain feels uncertain about proprioception, it makes us move and in so doing makes the sense more precise. At present, it is impossible to state that this precision mechanism can also help curb the damage to proprioception that comes with age. In order to understand exactly how aging affects the sixth sense, Zelzer adds, it’s necessary also to articulate the specific molecular language of this sense and the changes that come with age. Much research is needed to arrive at reliable conclusions, he says. However, the possible connection between physical activity and the improvement of proprioceptive ability in this sphere, including at advanced ages, is a logical hypothesis about the system that lies on the seam line between body and brain.