Your Inputs are Lying: The Neurobiological Side of Nausea

    At one point or another, we have all experienced the terrible sensation of nausea. Whether you are traveling by car, boat, or plane, motion sickness can be both uncomfortable and incapacitating. So why is it that we get nauseous? Surely such a strong response must have an evolutionary purpose. In this paper I will explore the neurological aspect of the nausea reaction, suggesting that nausea stems from the misalignment of inputs. I propose that motion sickness is caused not by motion, but rather by the sensation of motion with the perception of immobility. Finally, I will use the framework we have developed to explain possible treatments of this failed adaptive process.

Sensory Input & The Picture In The Head
    Before we directly approach nausea, it is important to discuss the role of sensory input. We rely upon our senses to help us navigate our surroundings. In this manner, our sensory input is like an input stream for a computer; it is a set of incoming data that is used to make decisions. So how do we use this data stream? We rely on our senses to understand our surroundings, such that we can create [what we believe to be] an accurate picture in the head. In the example of sight, our retinas take snapshots of color and our brain stitches them together into a comprehensible landscape. When we "see" something, it is actually the aggregation of numerous tasks. First our retinas must identify certain wavelengths of point source light. Then, our retinas send action potentials to our brain, which weaves these electrical signals together into a focused image. Finally, our brain must remember the "camera settings" (where we are looking, etc) and temporarily store them for rapid access. This pathway provides us with a visual input stream. This visual stream is then merged with further input streams to provide a detailed understanding of our surroundings. Specifically, we gather motion information from the proprioceptors of our deep tissues and also from the balance center in the inner ear (3). By merging sensory information with motion information, we are able to form spatial awareness. This spatial awareness represents a 3-dimensional representation of what we believe to be the world around us. This construct is the "picture in the head." It may not actually represent what is occurring, but it is our best guess as to our surroundings.
    By assembling a picture in the head, we can approximate our spatial position relative to where we have been and where we are going. On the evolutionary level, this construct allows us to discern and consider potential threats and targets, as well as judge distances. Imagine we see a lion and can hear it roar. We can identify the lion's approximate distance and then make a survival choice based on this information. Whether we should run, hide, or fight depends on correctly assessing our surroundings in our constructed view of reality. As we begin to run, we update our mental picture using information from our senses and balance center. In other words, we take in input streams, construct a spatial model of our surroundings, consider our options based on this constructed notion of the world around us, and then act upon it.
     As mentioned, our constructed reality is continually adjusted and updated as we move through an environment (3). This continuously updated reality allows us to lean forward as we start to run up a hill, or to anticipate an impact when we are falling. In this sense, the nervous system is acting like an empirical scientist. It is acting with an expected outcome, seeing what happens, and modifying expectations based on the difference between expected and observed outcomes. For example, when you step onto a boat, your nervous system becomes aware of the movement of the boat. You sense the rocking motion and your body calibrates its posture accordingly. It course-corrects your position so that you do not fall over. However, like all systems, the system of processing sensory input into a spatial awareness construct is susceptible to glitches. Perhaps such a glitch is at the heart of the nausea reaction.

What Causes Nausea
    Now that we have outlined the sensory input stream and its relationship to the picture in the head, we can attempt to apply it to our understanding of this terrible sensation known as nausea. As we all know, nausea is the feeling of stomach uneasiness. Specifically, the Chemoreceptor Trigger Zone (CTZ) in the medulla is signaling to the Vomiting Center. The Vomiting Center induces nausea by signaling the stomach via the Vagus nerve (5). This signal cascade results in the sensation of stomach instability, which registers in the iFunction as nausea and discomfort. Although this condition is a frequent side effect of various medications and procedures, we will be most concerned with motion sickness.
    In attempting to understand the cause of motion sickness, we shall return to the metaphor of our sensory information as an incoming computer data stream. Assume that this data stream might be corrupted. Imagine that the incoming data contains a virus or faulty information upon which the user might make a devastating choice. Surely we would want a way to identify potential threats to the system, so as to alert the user that the incoming data has been corrupted. Rather than using virus scan software, our bodies employ corollary discharge signals. These signals constantly report activity of one part of the nervous system to other parts of the system. In other words, internal feedback runs both vertically and horizontally; we are continuously [and unknowingly] processing information about the state of various components of our nervous system. This occurs without our conscious involvement; the iFunction is not directly involved in processing these corollary discharge signals. Rather, it occurs as a background program.
    So how do these corollary discharge signals function like the virus scan software? They check for alignment of various sectors of the nervous system. Theoretically, all input streams should be in agreement. If the balance-detecting center of the ear reports that we are falling but the eyes report no change, our body senses a misalignment. The misalignment registers as an incongruity of input-a corruption of the data stream. The incoming sensory input appears to be compromised, so there must be something wrong with what we are perceiving. As a result, the best course of action would be to shut down the computer until we can identify the problem. Correspondingly, our body triggers the nausea response. First, our body gets tired. We become weak and lethargic. If our sensory input is compromised, it is essential that we not go running around making [potentially] devastating decisions on faulty information. In this sense, perhaps nausea is actually a protective mechanism (3). If the feeling persists, we may even vomit. This is also an evolutionarily logical mechanism. The misalignment of sensory input may be due to ingestion of a toxin, hence removal of the stomach contents may eliminate the threat (4). We vomit because our body has identified a potential danger; our body has decided to shut down and "re-boot" the system. Hence, vomiting may also be a protective measure.
    Consider the example of carsickness. The rider perceives a steady environment  [the inside of the car]. However, they sense motion as they go around the curve. If we sense acceleration to the right, why would the seatback not be moving? Similarly, in the case of a boat we sense the upward and downward movement of the waves. Once again, our immediate surroundings, [the deck/rigging], are immobile. Our nervous system detects a misalignment of inputs and triggers the nausea mechanism. In both times, it is not the actual motion that causes motion sickness. Rather, motion sickness appears to be caused by a misalignment of the input streams. Perhaps our discussion of the nausea mechanism can inform us as to possible treatment methodologies.

Combating Nausea
    Now that we have outlined the process of the nausea reaction, perhaps we can identify potential treatments for this terrible feeling. Most resources encourage sufferers to hydrate, minimize food intake, breath slowly, and look at the horizon when possible (2,3,5). Additionally, driving the car [rather than being a passenger], and sitting in the front seat have been known to help. However, these options are not always feasible, and are certainly not universally successful.
Perhaps it is possible that further treatment could be aimed at the neurological aspect of this condition. Let us first consider the role of the iFunction. Recall that much of the nausea reaction is going on without the iFunction knowing the details. Specifically, the iFunction only gets hints of the results of this process. But why is it that we have evolved to not be aware of the constant checking of our sensory input? Perhaps we run this check in the background because it would otherwise be exhausting. Imagine how useless a virus scan program would be if it ran continuously in the middle of your monitor. Rather, you just want it to run in the background; you don't want to waste energy concentrating on it. Similarly, our iFunction is largely detached from the nausea reaction. This suggests that the iFunction is not a viable target for treatment. Anecdotally, I would even go so far as to suggest that iFunction involvement makes nausea worse; consciously trying not to get motion sick only makes it worse. Perhaps we can find a different mechanism for potential treatment.
    Rather than targeting the iFunction, maybe we could target the unconscious "background" behavior; we could inhibit the alignment check. In the computer example, this would be akin to turning off the virus scan software. For this discussion, let us return to the metaphor of the nervous system acting as an empirical scientist. Specifically, I asserted that the nervous system is acting with an expectation, seeing what happens, and then modifying expectations based on outcomes. We need to inhibit this empirical process. How could we suppress the feedback loop and corresponding course-correction? Perhaps if we suppressed the corollary discharge signals in general we could accomplish this goal. In other words, if we could "turn down the volume" on the feedback, we might not perceive the misalignment of various facets of the system. In this sense, a nervous system depressant might help. By suppressing nervous system stimulation, a depressant might also suppress the detection of misalignment. Of course, this also bears the risk of further disorientation. The success of such a treatment would likely depend on its interaction with specific parts of the nervous system.
    Consider the example of alcohol. Alcohol is a nervous system depressant that slows functional processes (6). For this reason, it may also slow the misalignment check that causes the nausea reaction. While I cannot advocate you consume alcohol prior to getting on a boat or going in a car, it seems that [at least in theory] this might help decrease the nausea reaction. By inhibiting the alignment check, one would theoretically inhibit the motion sickness response. In actuality, most resources strongly discourage alcohol consumption for anyone prone to seasickness, as it has the potential to make you "feel dizzy anytime you or the boat moves, especially with overindulgence" (1).
    While alcohol may not be the most effective option, antiemetics do indeed exhibit similar inhibitory behavior. Consider the example of Phenergan, the antiemetic used by NASA to prevent astronaut motion sickness in flight. Phenergan works by inhibiting incoming signals to the Vomiting Center of the brain. Specifically, it appears to reduce the efficacy of incoming signals from the balance center in the inner ear (2). In this sense, Phenergan is able to reduce the misalignment of incoming sensory information and thereby inhibits the normal nausea response. By "turning down the volume" of the feedback signals, Phenergan is able to minimize the nausea response. Unlike alcohol, this medication is able to target a specific pathway in the nervous system. Hence, by inhibiting one of the input streams, this medication eases the misalignment that causes nausea. For this reason, any treatment that could successfully inhibit the input stream may decrease the nausea mechanism.

    Nausea appears to be a failed adaptive process. Our nervous system triggers this uncomfortable sensation when it detects a misalignment of input signals. Although this is an evolutionarily logical reaction, it has become a nightmarish mechanism for travelers. By disassembling this response, we are able to see that it is not the actual motion that causes motion sickness. Rather, it is the incongruity of what we see and what we feel. By suppressing our sensations or our perceptions, we might be able to avoid this unfortunate response. Until future research offers new solutions, travelers will be forced to stand guard with an airsickness bag.

Side Note: Thus far, treatments appear to be focused on altering the motion sensation. Medications like Phenergan do not alter visual input, but rather impede information coming from the balance center. It is important to remember that motion sickness comes from the misalignment of what we see and what we feel. Hence, treatment could theoretically target not only sensation but also sight. Although initially no mechanism comes to mind, perhaps future research will explore this potential treatment avenue.
 

Sources

(1) http://www.marinemedical.com/articles/seasick.htm

(2) http://www.netdoctor.co.uk/medicines/100002055.html

(3) http://www.medicinenet.com/motion_sickness/article.htm

(4) http://www.aidsmeds.com/articles/Nausea_7486.shtml

(5) http://www.biobands.com/generalnausea.htm

(6) http://www.intox.com/physiology.asp

Class notes, Neurobiology (Prof Grobstein), Spring 2010