A Pirate’s Life is NOT for Me: A Deep Dive into Motion Sickness

Posted by megkirch on December 20, 2018 in genetics, Pharmacology, Sensory Systems, Uncategorized | 1 Comment

A few months ago, I spent three and a half anxious hours on a rickety motorboat on western Tanzania’s Lake Tanganyika. The cause of my anxiety was not the fact that we were floating over the second deepest freshwater lake in the world in a boat that had already begun to take in some water and whose exposed motor was protected by nothing more than a pair of recycled jeans (see below picture). No, the primary source of my anxiety was that at any moment my motion sickness would kick in, and I would be stuck on that boat for hours feeling deathly ill.

 

Blessedly, thanks to the miracle of Dramamine combined with a particularly (and intentionally) engrossing conversation with a friend and fellow passenger who shared my anxiety, I made it back to land physically and psychologically sound. But my fear had not been unfounded; I’ve suffered from motion sickness for as long as I can remember, and I have a particularly harried history with boats. As we rocked and rolled with the waves on the lake that felt more like an ocean, I further distracted myself from my physical disorientation with a series of questions: Why did my body have such a negative reaction to floating on water in addition to winding roads, reading in cars, etc? Why was I so impacted by the waves while many of my fellow passengers seemed to be genuinely enjoying themselves? And how was a little pill of Dramamine able to keep my sickness at bay? To find out, we’ll have to take a winding road from the inner ear deep into the brain – I’d recommend taking the front seat.  

 

Vestibu-what?

 

Any investigation into motion sickness requires an appreciation of the vestibular system – our brain’s mechanism for perceiving motion and balance. Like all sensory systems in the brain, peripheral structure(s) with specialized neurons are necessary for receiving information from the environment – in this case, relating to motion and balance – and transducing it into electrical signals that can be sent along to the brain. The visual system has the retina, the auditory system has the cochlea, and the vestibular system has the coolest sounding of them all – the vestibular labyrinth – which resides in the inner ear. The labyrinth consists of multiple distinct organs, each involved in processing different types of motion. For instance, the semicircular canals are responsible for the perception of rotational motion, while the otolith organs (the utricle and saccule) respond to linear and gravitational acceleration.

 

While there have now been many studies illustrating the importance of the vestibular system for the experience of motion sickness, there is one that I find particularly amusing. 50 years ago, 22 individuals – 12 healthy, and 10 with defective vestibular labyrinths – were put on a ship for 18 hours from Nova Scotia to a little island in the north Atlantic called St. Pierre…for research. Due to the inevitably severe weather that they encountered on their sea voyage, all 12 healthy individuals became seasick. Remarkably, of the 10 labyrinth-defective individuals, not a single one became seasick despite feeling similarly anxious to the healthy individuals [1].

Thus, the vestibular labyrinth appears to be an important ingredient for motion sickness. But the vestibular system is constantly active as we move through our day-to-day lives; what causes it to go awry?

 

Your senses (and predictions) in conflict

It was originally intuited that motion sickness occurs when different sensory signals are in conflict with each other. For instance, as much as I’ve tried, I can’t read while riding in a car. The original “sensory conflict” theory posited that this was because reading a book in a moving vehicle would eliminate any visual signals indicating that I’m moving (i.e., moving landscape out of the car window), while my vestibular system would still be telling me that I am, in fact, moving.

Although conflicts among sensory signals can certainly play a role in motion sickness, they on their own are insufficient to fully explain the phenomenon. For instance, if the sensory signals themselves induce motion sickness, why is it that people who often get carsick while riding in cars don’t feel sick if they’re the one driving? Enter sensory conflict theory 2.0, which emphasizes not so much the conflict among sensory signals as the conflict between predicted and actual sensory signals [3].

 

An important aspect of cognition in general is that the brain does not passively take in and perfectly replay sensory information to enable perception. Instead, it is constantly making predictions from and about its sensory input, and then makes adjustments once that input actually comes in. On the plus side, this enables the brain to work quickly and efficiently (read more about your “lying brain” in this previous NeuWrite post). But on the downside, these predictions can sometimes yield big errors that have major consequences. For instance, as a passenger in a car, you have no control over the motion of the vehicle. So on winding roads, when your body is constantly turning and accelerating and engaging your vestibular system, your brain has no way of predicting those turns and accelerations before they happen. Consequently, the arriving vestibular signals are constantly in conflict with your brain’s predictions, and (if you’re like me) your body suffers the consequences. In contrast, if you’re the one driving, your car is essentially an extension of your own body; your movements (turning the wheel, pressing on the brakes or gas) govern the vehicle’s (and therefore, your) motion. The motor signals that your brain sends to your body to turn the wheel, press the brakes etc. also come with a warning – “head’s up, we’re about to swerve right!”! Your brain can make an accurate prediction of your movement, and brain and body are both happy.

Precisely how and where your brain computes those predictions and compares them against your actual sensory experience is not completely known. However, the cerebellum and the brainstem seem to be key players. So-called “sensory conflict neurons” in each of these areas distinguish between predicted vs. actual vestibular sensory input by responding to passive (unintended) but not intentional head movements [4]. For instance, imagine you’re sitting in a swivel chair; these neurons in your brain would become active if someone sneaks up behind you and swivels you around, but not if you made the identical swivel motion by your own volition. Thus, activity of these neurons indicates a conflict between incoming sensory signals (a change in your rotational acceleration due to the swivel of your swivel chair) and prediction signals (expectation of remaining stationary).

But where do those prediction signals come from? Once again, the cerebellum is a major suspect. However, if that were the case (and if the sensory conflict hypothesis is correct), one would expect people without cerebellums to never experience motion sickness, but this isn’t always the case [5]. Overall, there is still a lot of work to be done to figure out exactly how motion sickness arises in the brain.

 

Where does the sickness come in?

As many of us know all too well, motion sickness manifests as much more than just a thought of “hmm, something about the sensory input I’m getting is weird”. Somehow, the conflict in the brain gets transformed into physical discomfort…nausea, and sometimes even vomiting. So how, and why, does that happen?

Although there are still a lot of unanswered questions, various nuclei (clusters of neurons) in the brainstem appear to be involved. Not only is the brainstem the first destination in the brain of vestibular sensory signals coming from the vestibular labyrinth, but it is also communicates with the autonomic nervous system which regulates many bodily functions. For instance, there are particular brainstem nuclei containing neurons that connect with motor neurons in the spinal cord which are in turn responsible for diaphragm and abdominal muscle contractions that happen during vomiting [6]. One brainstem nucleus, called the parabrachial nucleus, is particularly notable because it not only responds to vomiting-inducing stimuli, but also outputs to the brain’s limbic system. Since the limbic system is involved in emotional and behavioral responses, this pathway through the parabrachial nucleus is thought to mediate the sensation of nausea [6].

Why our brains decide to cope with motion sickness through nausea with or without vomiting is utterly perplexing. There’s no clear reason why motion sickness is remotely evolutionarily advantageous, and yet it is experienced by a significant proportion of our species and a number of other species as well [7]. It has been proposed that motion sickness is an unfortunate byproduct of an evolutionarily advantageous adaptation to expel any ingested substance that causes the vestibular system to go out of whack (a symptom of some toxins) [7]. But this is just a theory, and the etiological purpose of motion sickness remains largely mysterious.

Thankfully, the “sickness” aspect of motion sickness can be treated! Dramamine (or “dimenhydrinate” by its chemical name) is the most common medication against motion sickness. It is an antihistamine, meaning that it blocks particular histamine receptors. You may have heard of antihistamines in the context of allergy medications, and yes, we’re talking about similar things. Histamines are compounds involved in immune responses, but they can also act as neurotransmitters in the nervous system. Although the mechanism of Dramamine isn’t fully known, its action in blocking histamine receptors in some of the brainstem nuclei alluded to above may allow it to effectively block the pathways leading to nausea and/or vomiting [8].

 

Why me?!

As a child, I was always jealous of my brother who could comfortably read in the car during road trips without any fear of the physical symptoms described above. Why was I so unlucky?

I’m apparently not alone; approximately one in three individuals are especially prone to motion sickness (and it’s particularly common in women), though just about anyone is susceptible under the most extreme of circumstances. Individual differences in motion sickness susceptibility have been observed since the earliest days of motion sickness research, but modern genetic tools are finally allowing us to ask what particular genes are involved. Moreover, understanding the normal functions of the genes associated with motion sickness may tell us more about how it arises in the brain.

A recent study utilizing the 23andMe database identified a number of small genetic variations that were more prevalent in people reporting susceptibility to car sickness. Unsurprisingly, many of these variations impact genes normally involved in balance or the development of the ears (home to the vestibular labyrinth!) or eyes. Interestingly, some of the other genetic variations identified are associated with blood sugar regulation and hypoxia (oxygen deficiency), but direct links with motion sickness are not yet clear [9].

All in all, motion sickness is a terribly uncomfortable and inconvenient condition, but from a neuroscientist’s perspective, it’s really quite fascinating. There is still much to be learned about how the brain combines and compares sensory signals with sensorimotor predictions and precisely how the negative symptoms of motion sickness are produced. So the next time I am a backseat passenger on a windy road or being thrown around on a boat, I will attempt to distract myself from the inevitable nausea by contemplating what we know and don’t yet know about the neurobiology of my physical and psychological state. Maybe it will help you, too? But honestly, just take some Dramamine.

 

References:

[1] Kennedy RS, Graybiel A, McDonough RC, Beckwith FD (1968). Symptomatology under storm conditions in the North Atlantic in control subjects and in persons with bilateral labyrinthine defects. Acta Otolaryngol, 66(6):533–40. doi:10.3109/00016486809126317

[2] Bertolini G, & Straumann D (2016) Moving in a Moving World: A Review on Vestibular Motion Sickness. Front. Neurol. 7:14. doi: 10.3389/fneur.2016.00014

[3] Oman CM. Motion sickness: a synthesis and evaluation of the sensory conflict theory. Can J Physiol Pharmacol. 1990;68:294–303.

[4] Oman CM, & Cullen KE (2014). Brainstem processing of vestibular sensory exafference: implications for motion sickness etiology. Experimental brain research, 232(8), 2483-92.

[5] Uno A, Takeda N, Kitahara T, Sakata Y, Yamatodani A, Kubo T (2000) Effects of vestibular cerebellum lesion on motion sickness in rats. Acta Otolaryngol (Stockh.) 120:386–389

[6] Yates BJ, Catanzaro MF, Miller DJ, & McCall AA (2014). Integration of vestibular and emetic gastrointestinal signals that produce nausea and vomiting: potential contributions to motion sickness. Experimental brain research, 232(8), 2455-69.

[7] Treisman M (1977). Motion sickness: an evolutionary hypothesis. Science, 197(4302), 493. https://doi.org/10.1126/science.301659

[8] Zhang L, Wang J, Qi R, Pan L, Li M & Cai Y (2016), Motion Sickness: Current Knowledge and Recent Advance. CNS Neurosci Ther, 22: 15-24. doi:10.1111/cns.12468

[9] Hromatka BS, Tung JT, Kiefer AK, Do CB, Hinds DA, & Eriksson N (2015). Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis, Human Molecular Genetics, 24 (9), 2700–2708. https://doi.org/10.1093/hmg/ddv028

 

Images:

Featured image/gif:  https://giphy.com/gifs/archiecomics-episode-3-archie-comics-the-show-3oEdvaWfB09qNbyzZK

Lake Tanganyika: personal photograph

Vestibular labyrinth: from Wikipedia Commons

Schematic: from [2]

Jaws gif: https://giphy.com/gifs/jaws-seasickness-nVXI64uSa3XMI