Category Archives: Science news

Putting visual information into context

By Nathalie L. Rochefort and Lukas Fischer

The cerebral cortex is the seat of advanced human faculties such as language, long-term planning, and complex thought. Research over the last 60 years has shown that some parts of the cortex have very specific roles, such as vision (visual cortex) or control of our limbs (motor cortex).

While categorizing different parts of the cortex according to their most apparent roles is convenient, it is also an oversimplification. Brain areas are highly interconnected, and studies over the past decade have shown that incoming sensory information is rapidly integrated with other variables associated with a person or an animal’s behavior. Our internal state, such as current goals and motivations, as well as previous experience with a given stimulus shape how sensory information is processed. This can be referred to as the “context” within which a sensory input is perceived. For example, we perceive a small, brightly-colored object differently when we see it in a candy store (where we might assume it is a candy) compared to seeing it in the jungle (where it might be a poisonous animal). In our recent article published in Cell Reports, we investigated the factors that impact the activity of cells in the visual cortex beyond visual inputs as animals learned to locate a reward in a virtual reality environment.

Researchers have known since the 1960s that cells in the primary visual cortex exhibit striking responses to specific features of the visual environment such as bars moving across our visual field or edges of a given orientation. The traditional view of a hierarchical organization of the visual system was that primary visual cortex encodes elementary visual features of our environment, and then forwards this information to higher cortical areas which, in turn, take these individual visual elements and combine them to represent objects and scenes. Our understanding of how an animal’s current behavior influences information processing, however, was limited. Recent studies have started to address this question directly and found that neurons in primary visual cortex show more complex responses than expected. We have set out to use cutting-edge technological advances in systems neuroscience to understand what type of information is processed in the primary visual cortex of awake animals as they learn to find rewards.

A window into the brain, literally

We have combined two recent technologies to record from a large number of individual neurons in primary visual cortex while mice were awake and free to run. An advanced microscopy technique, two-photon calcium imaging, allowed us to visualize the mouse brain and record the activity of hundreds of neurons through a small implanted window.

A key challenge with this technique, however, is that the mouse head has to remain fixed. We, therefore, constructed a virtual reality system in which an animal was placed atop a treadmill, surrounded by computer screens displaying a virtual environment within which they can freely move while their head remains in the same place. The virtual environment consisted of a linear corridor with a black-and-white striped pattern on the wall and a black wall section (visual cue) in which the mouse could trigger a reward (sugar water) by licking a spout. This allowed us to train animals to find rewards at a specific location within the virtual environment while simultaneously recording the activity of neurons in the visual cortex.

More dedicated neurons, more reward

Our first, unexpected, finding was that after learning the task, a large proportion of neurons (~80%) in the primary visual cortex were responding to task-specific elements, with many cells becoming specifically more active when the animal approached the reward area. Interestingly, the number of these “task-responsive” cells strongly correlated with how well the animals performed the task. In other words, the more precisely animals were able to locate the reward location, the more cells we found to be active around that location of the virtual corridor in the visual cortex. This was surprising as neurons in the visual cortex clearly seemed to be as interested in where the animal could get a drop of sugar water, as the visual features of their surroundings. To test the impact that the visual reward cue (black wall section) itself had on the activity, we removed this cue and found that some neurons still responded at the rewarded location. This suggests that these neurons in the visual cortex were no longer only depending on visual information to elicit their responses.

Visual inputs matter, but sometimes motor-related inputs matter more

These results opened up a number of interesting questions about what is driving these responses as it was clearly not only visual inputs. We wanted to understand the factors driving this activity in the visual cortex. Mice could use two strategies to locate the reward when no visual cue was present to indicate the reward point. The first strategy relies on their internal sense of distance based on feedback from the motor systems (motor feedback). In other words, an estimate of how far a mouse has traveled based on how many steps they have taken since the beginning of the corridor. The second strategy would be to rely on an estimate of position based on the way the visual world moves past the animal, known as “optic flow.”

We took advantage of the unique opportunities in experimental design afforded by a virtual reality system to test which information is driving those reward-location specific responses. By creating a mismatch between the animal’s own movement on the treadmill and the visual movement of the external virtual environment, we were able to test whether it is motor feedback or visual flow that determines where the animal thinks it is along the corridor, and, correspondingly, where these neurons representing the reward location become active. The results showed that animals expected the reward location primarily based on motor feedback. This means that there are some neurons in the primary visual cortex that encode information related to the location of a reward, based on an animal’s motor behavior rather than purely visual information.

However, in our final experiment, the importance of visual inputs became clear again: when the visual cue indicating the reward location was put back in, while still maintaining the mismatch between treadmill and virtual movement, the animal’s behavior, as well as the neuronal responses, snapped back to the visual cue, disregarding the number of steps it had taken. This suggests that motor feedback is available to and used by the primary visual cortex, but in a conflict situation, the visual cues indicating a specific location, override other types of information to correctly locate a reward.

Conclusion

These results demonstrate the importance of behavioral context for sensory processing in the brain. The primary visual cortex, a region that was once thought to primarily represent our visual world by detecting elementary visual features such as edges, is also influenced by prior experience, learning, and interactions with our environment. A prominent model proposed to explain sensory cortical function, posits that the cerebral cortex creates a representation of what we expect, based on current sensory inputs and previous experience.

Our results are congruent with this model while emphasizing the large role of contextual factors, such as motor feedback and prior knowledge of a location. Future studies are necessary to determine how different types of inputs to sensory regions of the brain influence the activity of individual neurons and how they shape our perception of the world.

These findings are described in the article entitled The Impact of Visual Cues, Reward, and Motor Feedback on the Representation of Behaviorally Relevant Spatial Locations in Primary Visual Cortex, recently published in the journal Cell ReportsThis work was conducted by Janelle M.P. Pakan from the University of Edinburgh, the Otto-von-Guericke University, and the German Center for Neurodegenerative DiseasesStephen P. Currie and Nathalie L. Rochefort from the University of Edinburgh, and Lukas Fischer from the University of Edinburgh and the Massachusetts Institute of Technology.

This blog originally appeared on the website Science Trends.

Nathalie L. Rochefort has been awarded the 2018 R Jean Banister Prize Lecture. The prize is awarded to early career physiologists in the late stages of a PhD, postdoc or who are in an early faculty position. It was established in 2016 in memory of a former Member of The Physiological Society, (Rachel) Jean Banister who left a legacy to The Society when she passed away in 2013.

Seeing Depth in the Brain – Part II

By Andrew Parker, Oxford University

Stereo vision may be one of the glories of nature, but what happens when it goes wrong? The loss of stereo vision typically occurs in cases where there has been a problem with eye coordination in early childhood. Developmental amblyopia, or lazy eye, can persist into adulthood. If untreated, this often leads to a squint, or a permanent misalignment of the left and right eyes. One eye’s input to the brain weakens and that eye may even lose its ability to excite the visual cortex. If the brain grows up during a critical, developmental period with uncoordinated input from the two eyes, binocular depth perception becomes impossible.

My lab’s work supports a growing tide of opinion that careful binocular training may prove to be the best form of orthoptics for improving the binocular coordination of the eyes. Recent treatment of amblyopia has tended to concentrate on covering the stronger eye with a patch to give the weaker eye more visual experience with the aim of strengthening the weaker eye’s connections to the visual cortex. Now we understand from basic research like ours that there is more to stereoscopic vision than the initial connection of left and right eyes into the primary visual cortex.

Ramon y Cajal

Figure 2: Ramon y Cajal’s secret stereo writing, see Text Box

Secret Stereo Writing. The great Spanish neuroanatomist Ramon y Cajal developed this technique for photographically sending a message in code. The method uses a stereo camera with two lenses and two photographic plates on a tripod at the left. Each lens focuses a slightly different image of the scene in front of the camera. The secret message is on plate B, whereas plate A contains a scrambled pattern of visual contours, which we term visual noise. The message is unreadable in each of the two photographic images taken separately because of the interfering visual noise. Each photograph would be sent with a different courier. When they arrive, viewing the pair of photos with a stereograph device as in Figure 1, the message is revealed because it stands out in stereo depth, distinct from the noisy background. Cajal did not take this seriously enough to write a proper publication on his idea: “my little game…is a puerile invention unworthy of publishing”. He could not guess that this technique would form the basis of a major research tool in modern visual neuroscience.

Our lab is investigating the fundamental structure of stereoscopic vision by recording signals from nerve cells in the brain’s visual cortex. One of the significant technical developments we use is the ability to record from lots of nerve cells simultaneously. Using this technique, I am excited to be starting a new phase of work that aims to identify exactly how the visual features that are imaged into the left eye are matched with similar features present in the right eye.

The neural pathways of the brain first bring this information together in the primary visual cortex. Remarkably there are some 30 additional cortical areas beyond the primary cortex, all in some way concerned with vision and most of them having a topographic map of the 2-D images arriving on the retinas of the eyes. The discovery of these visual areas started with Semir Zeki’s work in the macaque monkey’s visual cortex. Our work follows that line by recording electrical signals from the visual cortex of these animals. To achieve this, we are using brain implants in the macaques very similar to those being trialed for human neurosurgical use (where implants bypass broken nerves in the spinal cord to restore mobility).

turbot

Figure 3: A very odd form of binocular vision in the animal kingdom. The young turbot grows up with one eye on each side of the head like any other fish, but as adulthood is reached one eye migrates anatomically to join the other on the same side of the head. It is doubtful whether the adult turbot also acquires stereo vision. Human evolutionary history has brought our two eyes forward-facing, rather than lateral as in many mammals, enabling stereo vision.

My lab is currently interested in how information passes from one visual cortical area to another.  Nerve cells in the brain communicate with a temporal code, which uses the rate and timing of impulse-like events to signal the presence of different objects in our sensory world. When information passes from one area to another, the signals about depth get rearranged. The signals successively lose features that are unrelated to our perceptual experience and acquire new properties, corresponding closer to perceptual experience. So, these transformations eventually come to shape our perceptual experience.

In this phase of work, we are identifying previously unobserved properties of this transformation from one cortical area to another. We are examining how populations of nerve cells use coordinated signals to allow us to discriminate objects at different depths. We are testing the hypothesis that the variability of neural signals is a fundamental limit on how well the population of nerve cells can transmit reliable information about depth.

To be specific, we are currently following a line of enquiry inspired by theoretical analysis that identifies the shared variability between pairs of neurons (that is, the covariance of neural signals) as a critical limit on sensory discrimination. Pursuing this line is giving us new insights into why the brain has so many different visual areas and how these areas work together.

It is an exciting time. We still need to determine whether our perceptual experiences are in any sense localised to certain regions of the brain or represent the activity in particular groups of neurons. What are the differences between types of neural tissue in their ability to deliver conscious perception?

There are many opportunities created by the newer technologies of multiple, parallel recording of neural signals and the ability to intervene in neural signaling brought by the use of focal electrical stimulation and optogenetics. By tracking signals related to specific perceptual decisions through the myriad of cortical areas, we can begin to answer these questions. The prospect of applying these methods to core problems in the neuroscience of our perceptual experience is something to look forward to in the forthcoming years.

Seeing Depth in the Brain – Part I

By Andrew Parker, Oxford University

The Physiological Society set up the annual, travelling GL Brown Prize Lecture to stimulate an interest in the experimental aspects of physiology. With predecessors such as Colin Blakemore and Semir Zeki, following in their footsteps is a tall order. They are not only at the very top scientifically but also superb communicators.

My lecture series on stereo vision has already taken me around the UK, including London, Cardiff, and Sheffield. I’ll be at the University of Edinburgh on 15 November and Oxford University on 23 November. It’s a nice touch that GL Brown’s career took him around the country too, including Cambridge, Manchester, Mill Hill and central London, before he became Waynflete Professor in my own department in Oxford. The other pleasurable coincidence of giving lectures on stereo vision this year is that there is a 50th anniversary since fundamental discoveries were made about how the brain combines the information from the two eyes to provide us with a sense of depth.

In his 1997 book How the Mind Works Steven Pinker wrote, “Stereo vision is one of the glories of nature and a paradigm of how other parts of the mind might work.” I can’t claim to have written this inspiring sentence myself, but I can at least claim to have chosen stereo vision as my field well before Steven Pinker wrote his sentence.

Stereo vision is, in a nutshell, three-dimensional visual perception. It is the use of two eyes in coordination to give us a sense of depth: a pattern of 3-D relief or 3-D form that emerges out of 2-D images arriving at the left and right eyes. These images are captured by the light-sensitive surface of the eye called the retina. Stereo vision gives us the ability to derive information about how far away objects are, based solely on the relative positions of the object in the two eyes.

Victorian stereograph

Figure 1: “The stereograph as an educator,” illustrating the virtual reality technology of the Victorian era.

The Victorians amused themselves with stereo vision (see Figure 1). Virtual reality is our modern day version of this, but what comes next? The next generation will probably enjoy “augmented reality” rather than virtual reality. With augmented reality, extra computer-generated imagery is projected onto objects in the real world. The aim is to create a perceptual fusion of real objects with virtual imagery. For example, in one prototype I have seen, surgeons perform their operations with virtual imagery (acquired with diagnostic imaging devices) superimposed upon the surgical field in the operating theatre. Needless to say, this places much higher demands on the quality and stability of the virtual imaging systems.

What causes people like Pinker, who are outside the field, to get so excited about stereo vision? Partly it’s just the experience itself. If you’ve been to the 3-D movies or put on a virtual reality headset, you will have the sense of stereoscopic depth. It is vivid and immediate. The other thing that excites Pinker is the way in which the brain is able to create a sense of a third dimension in space out of what are fundamentally two flat images. As a scientific problem, this is fascinating.

We also see parallels between stereo vision and how other important functions of the brain are realised. One straightforward example of that is visual memory. Gaining a sense of stereoscopic depth from two images (left and right) requires matching of visual features from one image to another. Remembering whether or not we have seen something before requires matching of a present image to a memory trace of a previously seen image. Both processes require the nervous system to match visual information from one source to another.

Another aspect that Pinker is highlighting is the way in which the two flat images in stereo are fused to form with a new perceptual quality, binocular depth. A great deal of spatial perception works this way. One obvious example is our ability to use the two ears in combination to form an impression of sound localised in space, based just on the vibrations received by the left and right ear canals.

What is the world like without stereo vision? While you can partly experience this by placing an eyepatch over one eye (try playing a racket sport or carefully making a cup of tea), the difference is most strongly highlighted by the very rare cases when stereo vision appears to have been lost but is then recovered. Susan Barry, professor of neurobiology at Mount Holyoke College, was stereoblind in early life but eventually gained stereo vision with optometric vision therapy.

In a New Yorker article by Oliver Sacks (Stereo Sue, A Neurologist’s Notebook, June 19 2006) Barry describes her newly acquired perception of the world. “Every leaf seemed to stand out in its own little 3-D space. The leaves didn’t just overlap with each other as I used to see them. I could see the SPACE between the leaves. The same is true for twigs on tree, pebbles on the road, stones in a stone wall. Everything has more texture.”

Check back next Wednesday for Part II of Andrew Parker’s blog on stereo vision.

Collaboration: Friend or Foe

This article originally appeared in our magazine, Physiology News.

By Mike Tipton, @ProfMikeTiptonUniversity of Portsmouth

It can be argued that, in the broadest sense, we would not exist without collaboration. It is also easy to argue that our future health, prosperity, and indeed, survival will be dependent on collaboration. However, collaboration is something of a conundrum. Its meaning and usage are so broad as to be almost meaningless, and as a concept it covers a multitude of scenarios, not all of them good. So how do we foster enduring, productive collaboration in science? 

Many people love the idea of collaboration, they pursue it with vigour, offering their services and proclaiming their interest in a project.Others are not keen on collaboration. For most, their view of collaboration largely depends on past experience or worries about future recognition. The problem is that there is a contradiction that runs through “collaboration”, right down to its definitions: a. The action of working with someone to produce something b. Traitorous cooperation with an enemy. Hopefully academic collaboration falls under the former rather than latter definition, but perhaps not always.

Collaboration in nature: lessons for scientists

There is no doubt that collaboration can be a driver for advancement, and even optimal advancement. This is easy to demonstrate in biological terms; for example over a billion years ago one bacteria became host to another, obtaining shelter in return for the production of energy from food and oxygen. Eventually the bacteria merged into a single cell that became the ancestral powerhouses of all multicellular life and the precursors to mitochondria. Today, examples of successful collaboration abound, from the African Oxpecker, and their aquatic equivalent, cleaner fish, to bacteria such as Lactobacillus that inhabit human intestines and help to relieve Irritable Bowel Syndrome, Crohn’s disease and gut dysbiosis. As Darwin said, “in the long history of humankind (and animal kind, too) those who learned to collaborate and improvise most effectively have prevailed.”

What can we learn from the animal kingdom that might help our collaborations with other scientists? The obvious lesson is that those collaborations between organisms that endure are symbiotic rather than parasitic. That is, both collaborators bring something to the relationship and both gain. To coin a cliché, the sum is greater than its constituent parts. Collaborations fail when, in one way or another, they become parasitic. Perhaps we should focus on “symbiosis” rather than “collaboration”?

oxpecker

Figure 1. Collaborators seeing eye to eye: a symbiotic collaboration between the African Oxpecker and the African Cape Buffalo. One feeds, the other has parasites removed.

Scientific collaboration: the benefits

At one level, of course, all science is the product of a collaboration between colleagues within an institution, be they the technicians, students, academics or administrators that enable and conduct research. But what about collaboration across institutions? This is not an insignificant issue; even more so now than previously, successful collaboration is important for the advancement of research areas as well as scientific careers. As science moves unerringly towards complex, multifaceted studies employing advanced and highly specialised techniques, the need to collaborate nationally and internationally increases. This truth is increasingly being reflected in the published literature, where there is a positive relationship between the presence of international collaborating authors on top flight papers and citation impact (Adams & Gurney, 2016).

People are getting the message; as measured by co-authorship on refereed papers, international collaboration grew linearly from 1990-2005, or exponentially if international presentations are assessed (Leydesdorff & Wagner, 2008). In 1981 about 90 % of UK published research output was domestic, by 2014 this figure had fallen to less than 50 %; almost all of the growth in output in the last 30 years was produced by international co-authored collaborations (Adams & Gurney, 2016). In just the last two issues of Experimental Physiology we have published papers from 15 countries, and of the 22 papers published, 13 were collaborations between a total of 34 institutions. Leydesdorff & Wagner (2008) used network analysis to conclude that the growth of international co-authorship can be, at least in part, explained by the organising principle of preferential attachment (“the rich get richer”). Broadening collaboration should therefore be advantageous.

fig2.jpg

Figure 2. Relative increase in international collaborative publications (articles & review indexed in Thomson Reuters Web of Science) since 2000 (Adams & Gurney, 2016). 

The major driver for collaboration is the need to share, be that ideas, equipment, facilities, techniques, resources or data. Without successful collaboration between experts within different fields, some major problems will either not be solved or will take much longer. For example, it is generally agreed that the battle against cancer cannot be won without such collaboration (Savage, 2018). Looking back, without collaboration we would have been less likely to know of the existence of the Higgs Boson or have sequenced the human genome. It is difficult to imagine the big questions of our time, such as understanding the working of the brain, the origin of the universe or the production of clean sustainable energy, being solved without interdisciplinary collaboration. The need for collaboration to provide the diversity of skills and techniques to answer these questions is paramount.  

The UK government is actively encouraging such collaboration through initiatives like the UK Research and Innovation (UKRI) Fellowships Programme. The Industrial Strategy Challenge Fund looks to build collaborations between academics and business. One of the six key areas is “Health and Medicine”. Research England recently invested £67m in 14 collaborative projects to “drive forward world-class university commercialisation across the country”.

Promoting collaboration: opportunities and threats

So, how do we create the conditions that might promote successful symbiotic collaboration within, but even more importantly, across disciplines? We start with an advantage; game theory (e.g. The Prisoners’ Dilemma) research tells us that humans display a systematic bias towards cooperative behaviour in preference to otherwise rational self-interest (Fehr & Fischbacher, 2003). So, we need to foster this altruistic inclination and minimise the threats to collaboration.

Publishing has a role to play in promoting collaboration; since the first issue of the Philosophical Transactions of the Royal Society was disseminated in 1665, potential collaborations have been promoted by the publishing industry reporting what could be done by other people working in the same field. A relatively recent development is the publication of datasets that can be examined and used by others, a new and as yet not fully evolved form of “collaboration”. On the other hand, publication can also be a barrier to collaboration: concerns about recognition of effort, authorship and ownership of ideas or data can introduce anxiety and suspicion. These problems can be minimised by early, open discussion, by scientists, and by journals giving high value to ideas. Following established guidelines for authorship should also help (e.g. International Committee of Medical Journal Editors Guidelines (2017).

Other threats to collaboration come in the form of international politics: BREXIT and access to EU funding, the rise of nationalism, travel bans, language barriers and difficulties in getting work permits. This is a constantly changing canvas within which scientists and leading institutions must lobby and advocate the crucial societal benefits of international collaborative research. Hopefully continued access to international and pan-continental research funding that demands international collaboration will help.  

The role of publishing in prompting collaboration is reinforced by scientific meetings where you meet, learn from and socialise with those working in your field. Having determined from the literature and scientific presentations those who you might work with, it is during social exchanges at meetings that you discover people you want to work with. One potentially negative consequence of subject-specific meetings is that they constrain the technical and academic cross-fertilisation, and consequent collaboration, that might be promoted at more multi-disciplinary meetings.

If we continue to use co-authorship with an individual from another institution as the index of collaboration, I have collaborated with 71 people from 15 countries over three decades (e.g. International Drowning Researchers’ Alliance- idra.world). As far as I can recollect, all of these collaborations, and subsequent close friendships, were forged in the conducive atmosphere of a scientific meeting. It follows that any decline in funding to attend scientific meetings will stifle potentially critical collaborations. It also follows that although, as noted above, it is possible to encourage or require collaboration through targeted funding calls, in the absence of such funding it is very difficult to “administer” long-lasting productive collaborations into existence from nowhere. They have to evolve naturally, through interpersonal contact and understanding of the skill sets and capabilities of different people.

That is not to say that people who do not get on personally cannot collaborate; it is simply that the holistic experience and durability of the collaboration is likely to be diminished. Because, in the end, it is about spending time with those you respect, like, need and can communicate freely with. As in so many other things, Shakespeare had it about right,

Those friends thou hast, and their adoption tried,

Grapple them unto thy soul with hoops of steel

For a scientist, as well as society in general, the benefits of collaboration go far beyond science.

Acknowledgements

I would like to thank Alex Stewart, Sarah Duckering and Joe Costello for their contributions to this article.

 

The First Mars Marathon: Part 3

Martian nutrition: How runners will fuel

Carb-loading for the Red Planet marathon might prove more difficult than simply gorging on a pre-race pasta dinner. Since they will be shivering and burning a lot more calories not only during, but before the race, runners will simply have to eat more on Mars during the pre-race period to fully saturate their muscles with glycogen.

Just getting plates of pasta to Mars will be a major issue. After years in transit, many of the nutrients in any food shipped to Mars will have been lost, and deep-space radiation will have degraded much of a food’s chemical and physical structure. Preparing and shipping food to Mars for the runners to eat requires special methods. Anyone care for high-pressure processed, microwave sterilized, freeze-dried spaghetti and meatballs…anyone?

mars7.png

Use of critical fuels such as carbohydrate and fat will drastically increase on mars due to the extreme cold

Mid-race nutrition is equally important. As stated earlier, the drastically cold temperatures will result in a higher rate of glucose use and glycogen depletion, so the runners will need to fuel more often to keep glucose stores elevated in the face of increased use of these from shivering, coupled with the metabolic demand of running. Marathoners, who rely heavily on their glycogen stores into the later miles of the race will need to ingest glucose during the race at a rate exponentially higher than the recommended 25-60 grams per hour to avoid hitting the dreaded wall around mile 20 of the Red Planet marathon. This drink will likely have to be specially formulated with a higher glucose content.

Authors of a 1998 paper in Experimental Physiology provide evidence that providing a drink containing 15% carbohydrate was able to maintain blood glucose levels better than one containing just 2% during a cycling test to exhaustion (1). For this reason, Martian aid stations will need to occur at regular intervals and provide runners with carbohydrate-rich gels, drinks, or tasty freeze-dried space snacks.

What they’ll wear

Until we evolve into actual Martians, humans won’t get away with running unprotected on the surface of Mars. For now, technology will prove vital to success as runners on this new planet. Newly minted Martian sports scientists and gear technologists will be recruited to design a top of the line marathon-specific spacesuit.

mars8.jpg

Theoretical concept of the Mars runner suit. Source: News.mit.edu

This suit will provide a sealed, pressure-controlled environment, help maintain some warmth and control body temperature, riding a fine line between protection and optimal range of motion. A protective suit is necessary: in the low atmospheric pressure environment of Mars, bodily fluids would boil. This is known as the Armstrong limit of pressure, which Mars sits well below.

Additionally, runners will develop severe impairments in blood pressure maintenance due to the reduced atmospheric pressure. This drastic reduction in blood pressure was demonstrated in a Journal of Physiology study from 2015 (2). Studying astronauts on the International Space Station, researchers noted a reduction in blood pressure of 8-10 mmHg, mainly due to central volume expansion.  The marathon gear will resemble something of a wet suit– a design which is able to solve the low-pressure problem by using super tight wrapping  (instead of gas-pressurization, it uses mechanical counter-pressure) (3). This leaves the body mobile. Wrapping the lower limbs in this counter pressure “fabric” will allow full range of motion at the ankles, knees, and hips,

The suit will require an enclosed helmet with breathing apparatus for runners to get their oxygen which is lacking in the Martian environment and dispense of the large amount of atmospheric as well as metabolically produced CO2. But don’t even think about attempting a snot-rocket.

Additionally, features of the suit crucial to completing our space-race might include an airtight hole in the mask so that runners can ingest their mid-race fluids and gel packs.

One final, and perhaps most vital feature will be the shoes. Just as elite runners have custom shoes designed to their unique gait pattern and foot size, Mars marathoners will need footwear tailored with the same precision and comfort in mind. As it turns out, the painful condition of onycholysis (separation of the finger/toe nail from the nail bed) is not just a problem among ultra-endurance athletes, but astronauts too. Ill fitting gloves combined with the intra-suit pressure can spell disaster (and pain) for anyone carrying out activities in space, and this would surely apply to the feet as well. After 26 miles of running in cramped space-boots, it can only be expected that runners might lose one or more toenails. To prevent this, it will be necessary for runners to have Mars boots fit to their particular foot size, strike, and biomechanics.

Can They Do It?

Just as Opportunity Rover completed its own Red Planet marathon, so too will humans eventually cover 26.2 miles on foot over the dusty red surface of the fourth planet from the Sun.

Will it be fast? Probably not – but let’s hope we break the current standing record of 11 years, 2 months. Evolving a new, skipping gait required for efficient running on Mars will take some time, just as did the adaptation of lower limbs and body structure of Australopithecus to that of the modern Homo erectus, a body ideally formed for endurance running. Tendons and ligaments will have to adjust to the new microgravity environment, and it will take time for muscle fibers to regain their strength and capacity. The deconditioning of the cardiovascular system (due to fewer hemoglobin molecules, reduced ability to both supply and utilize oxygen, and decline in heart and lung function) will take some time to adapt to. Along with the various environmental factors (extreme cold, hypoxia, and dangerous levels of radiation), runners will certainly have a slow marathon debut.

We will eventually design equipment and training protocols that allow us to traverse 26.2 in record times on Mars. Remember, the first marathon run by Pheidippides resulted in his keeling over in death upon arrival. Since then, we have perfected running tactics, advanced our knowledge of performance, and unlocked human physiology such that it is now possible for man to run 26.2 miles at an astonishing 4 minutes and 41 seconds per mile, something once thought impossible.

Perhaps, some day, the elusive 2-hour barrier will be broken, not on a curated and well-paced course in Italy, but near Endeavor crater, some 54.6 million kilometers away.

References:

  1. Galloway et al. The effects of substrate and fluid provision on thermoregulatory, cardiorespiratory, and metabolic responses to prolonged exercise in a cold environment in man. Experimental Physiology. 81 (1998); 419-430
  2. Norsk et al. Fluid shifts, vasodilatation, and ambulatory blood pressure reduction during long duration spaceflight. The Journal of Physiology 593.3 (2015); 573-584
  3. Shrink-wrapping spacesuits. Jennifer Chu, MIT News Office. September 18, 2014. http://news.mit.edu/2014/second-skin-spacesuits-0918

 

The First Mars Marathon: Part 2

By Brady J. Holmer, @B_Holmer

Unlikely or not, it is interesting to ponder the physiological and technical challenges of a Martian marathon. Read our post from last week to learn why runners will be moving in giant leaps. Stride aside, how will the freezing cold, lack of oxygen, calorie requirements, and protective clothing affect the runners?

Cons of the Mars environment:

Temperature: beyond chilly

Race day conditions can be quite unpredictable even on Earth, and Mars will be no exception. Temperatures can vary from a moderate 70˚ F (20˚ C) around noon to an unbearable -195˚ F (125˚ C) at night. For the sake of this thought experiment, let’s assume that race day temperatures hover around the average of -67˚ F (-55˚ C).

At this temperature the blood vessels in many organs and leading to the skin will undergo profound constriction, reducing blood flow to areas where the runners don’t need it (that is, everything but the legs, brain, lungs, and heart). This conserves heat and maintains core body temperature as close to normal as possible.

mars4.png

Average race day temperatures at select endurance races.

Authors of a classic 1998 paper in Experimental Physiology demonstrated that this constriction can occur even at a “mild” temperature of 45˚F (7˚C) for just 90 minutes (1).

Exaggeration of this physiological response in instances of extreme cold (i.e. Mars) would occur due to a condition called non-freezing cold injury (2). Symptoms include damage to vascular tissue and heightened constriction of blood vessels. This means runners will have trouble providing oxygen-rich blood to their working muscles which will be in competition with the core to maintain a survivable temperature. Frostbite on Mars sounds disproportionally painful.

Another main concern of extreme cold exposure will be the detrimental effects of shivering thermogenesis, the body’s involuntary quivering of muscles to produce heat in an attempt to maintain core body temperature. To do this, the body must use fuel sources such as carbohydrate and fat. This also occurs at even relatively “mild” cold temperatures.

A study appearing in a 2005 issue of The Journal of Physiology exposed a group of men to a temperature of 41˚F (5˚C) for just 90 minutes and showed that utilization of glucose and glycogen increased five-fold from normal resting conditions (3). Muscle glycogen, our stored form of carbohydrate, contributed up to 60% of the total increase in heat production during just moderate-level shivering.

Exposure to Mars level cold would exacerbate these effects in runners and lead to a sacrifice of valuable fuel stores in an attempt to stay warm, leaving little for the marathon effort. In a race over 2 hours such as the marathon, fuel partitioning is key, and glycogen stores become important late into the race. Without fuel to provide energy for muscle contractions, performance will inevitably suffer, even if proper nutrition and “carbo-loading” are implemented.

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Solar particle events will lead to a destruction of valuable red blood cells in space.

Oxygen deprivation in the air

Given the vast difference in the composition of the air, breathing on Mars will also be difficult.  The atmosphere of Mars is 95% carbon dioxide (CO2), meaning there is very little oxygen. Normally, CO2 is produced during high intensity exercise such as marathon running, but is counteracted by expiration, preventing accumulation of acidifying ions and the ensuing unpleasant burning feeling in the lungs and legs. In this regard, Mar’s atmospheric gas composition presents an ideal situation for the lung-torching turmoil that all runners fear late into the end miles of a marathon, although now, this will occur from the start. Even the most rigorous altitude training regimen won’t prepare Martian runners for the low-oxygen conditions they will experience. Well-designed spacesuits will need to be implemented to allow runners to inhale a gas composition that resembles one on Earth, while simultaneously helping to expire CO2 at a higher rate than usual.

Wreaking havoc with red blood cells

Let’s not forget about the radiation. Mars’ atmosphere is less dense than the Earth (approximately 100-fold less so), and radiation from the sun is much more potent. Spontaneous and largely unpredictable solar flares that decide to pop up during the marathon will send charged helium nuclei, neutrons, protons, and other dangerous and highly energetic particles coursing through the runner’s bodies. Exposure to one of these solar particle events during the Mars marathon would lead to the destruction of red blood cells (hemolysis) and along with it, the all-important, oxygen carrying hemoglobin molecules, oxidative stress, and damage to muscle fibers.

Runners will likely fall victim to a condition we might call “space anemia”. A study in Physiological Reports from 2017 investigated the response of the circulation to a head down tilt bed rest condition – used to simulate microgravity encountered in space – and found that it resulted in a loss of hemoglobin  (4)! Hemoglobin is necessary to carry oxygen to sites of active muscle during running, and a reduction  is associated with a lower exercise capacity.

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Aerobic capacity and power will both decline after just 15 days in space.

Reduced circulation

Circulatory changes may be further exacerbated by the well-known detrimental effects that microgravity has on aerobic capacity. Indeed, researchers have used a model of sustained bed rest further compounded by low-oxygen space environments such as Mars, to investigate the effects on cardiovascular capacity.

Keramidas et al. demonstrated in a 2017 Experimental Physiology paper that just 10 days in this space-simulating condition impaired whole-body peak oxygen uptake (VO2peak) by 8% with an accompanying reduction in peak power output during an exercise test (5).

Furthermore, in 2018, Salvadego et al demonstrated in The Journal of Physiology that 21 days of hypoxic bed rest led to an 8% reduction in V02peak, a reduction in thigh muscle volume, and impairments in the body’s production of energy (mitochondrial respiration and aerobic metabolism) and an ability to match oxygen supply to demand during leg exercise (6).

These changes lead to a reduction in aerobic performance – and Mars runners will fight against all of these pathological changes as they try and complete the race as they find themselves starved of the ability to get crucial, oxygen rich blood to their working muscles during the race. This means that runners will be less capable of performing at their max capacity on race day.

So far, the prospects are looking quite grim for the runners. Will nutrition or protective suits be their saving grace? Find out on Friday in the final blog of our series.

References

  1. Weller et al. Physiological responses to moderate cold stress in man and the influence of prior prolonged exhaustive exercise. Experimental Physiology. 83 (1998); 679-695
  2. Tipton M.J. Environmental extremes: origins, consequences, and amelioration in humans. Experimental Physiology 101.1 (2016); 1-4
  3. Haman et al. Partitioning oxidative fuels during cold exposure in humans: muscle glycogen becomes dominant as shivering intensifies. The Journal of Physiology 566.1 (2005); 247-256
  4. Trudel et al. Hemolysis during and after 21 days of head-down-tilt bed rest. Physiological Reports. 5.24 (2017)
  5. Keramidas et al. LunHab: interactive effects of a 10-day sustained exposure to hypoxia and bedrest on aerobic exercise capacity in male lowlanders. Experimental Physiology 102.6 (2017); 694-710
  6. Salvadego et al. PlanHab: hypoxia does not worsen the impairment of skeletal muscle oxidative function induced by bed rest alone. The Journal of Physiology 000.00 (2018); 1-15

The First Mars Marathon: Part 1

By Brady J. Holmer, @B_Holmer

Humans have successfully conquered herculean feats of endurance in some of the most unbearable conditions on Earth. Such conquests as the Badwater Ultramarathon, 135 miles (217 km) through Death Valley, where temperatures can reach 130˚ F (54˚ C), or the 100k Antarctic Ice Marathon (average wind-chill -4˚F (-20˚ C)) not only require a certain amount of mental fortitude (some might call it insanity), but also careful consideration of human physiology and its inherent limits. Unpreparedness for such harsh climates can spell disaster; Mother Nature isn’t merciful to those who are ill-prepared. In tests of extreme endurance, environmental conditions, and the body’s response to those conditions, can be the dividing line between successful completion of the race and  a certain meltdown.

It is unlikely that humans will ever lose their aspiration to push the limits of human physiology through feats of endurance. Given humanity’s recent interest in colonizing planets other than our own, it seems likely that our sporting and recreation habits will make their way out into the cosmos.

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Images from http://alpacaengine.com/mars-landscape/ ; https://runningmagazine.ca/elite-qa/eliud-kipchoge-loves-running/ Photo: Nike 2018, Bejo Creative Theme 2018.

Indeed, Tesla CEO and Mars colonization proponent Elon Musk thinks that exploring new planets isn’t just a choice we have, but a necessity, and projects that the first manned trip to Mars will leave no later than the year 2020 (1).  Should we colonize Mars, humans will have stay active to prevent muscular atrophy, deconditioning, and boredom. Eventually, someone will have the crazy idea to try a marathon on the newly colonized Red Planet.

However sci-fi this situation may seem, it is interesting to ask what physiological and technical challenges a Martian marathon would provide. Will the vast climactic differences between Mars’ atmosphere and our own prove insurmountable? Will the elite road runners of our modern time be reduced to hobby joggers in the extreme climate? Or, perhaps even more tantalizing, will this novel atmosphere allow us to finally run a marathon under two hours? Let’s explore the physiology of humankind’s first marathon on Mars.

It may be important to note that the first Mars marathon has been completed, although not by a human. On Tuesday, March 24, 2015, Mars exploration Rover “Opportunity” completed the 26.219-mile (42.195k) journey across the Red Planet’s surface (2). Opportunity’s performance was quite mediocre, finishing in approximately 11 years and 2 months (a speedy pace of 222,000 minutes per mile). Let’s hope humans can improve on the current record.

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The first marathon route completed on Mars. Source: Mars.nasa.gov, Nasa 2015

Fortunately, thanks to Opportunity, we have a perfectly measured course, and the Red Planet marathon will follow the same route, putting the finish tape at the rim of Endeavor crater. On this journey, how will environmental conditions be different, and what adjustments will be required to nutrition and protective clothing? Stay tuned to find out.

The Martian environment

Will the environment on Mars be conducive enough to run, much less perform well in, a marathon, even for the most battle-hardened endurance veterans? Various factors about the climate, both positive and negative, affect physical capacity and physiological response.

Pros: A giant leap for mankind

One benefit, taking nothing else into account, is that runners will be lighter on Mars. Martian gravity is a little less than one third that of the Earth, so a man or woman weighing 154 pounds (70 kilograms) on Earth will weigh a mere 51 pounds (23 kilograms) on Mars. Many of the top-100 world class marathon runners typically weight around 123 pounds (56 kg) – so if we forget about the danger of “floating away” for a moment– this puts Martian runners way below the “elite” weight class.

Weight reduction will dramatically increase V02max (maximum oxygen use, which measures exercise capacity) relative to body weight without any training required! The transition to partial gravity will cause an immediate 67% increase in relative V02max. Compared to changes seen in an Experimental Physiology study in which V02max increased only around 9% after 6 weeks of aerobic exercise training (3), this is quite the shortcut.

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Source: Wikimedia Commons, NASA/JPL/Cornell

 

Another beneficial change upon arrival to Mars will have to do with the biomechanics of running.  Even if we design aerodynamic spacesuits which provide ample range of motion and reduce mass as much as possible, human locomotion will differ substantially; our running will look more like skipping, in fact. Apollo astronauts discovered the benefits of skipping on the Moon. A bouncing gait in the low-gravity conditions on Mars will also be preferred to walking and running since it leads to a threefold reduction in cost of movement. In addition to reducing work, skipping enhances grip control, which will be helpful on Mars’ surface. Covered by in “lunar dust”, it provides little in the way of friction.

Stride rate, typically 150-160 steps per minute for a marathon runner, will dramatically fall on Mars. This is mainly due to the large vertical displacement and increased time spent in the “flight” phase while skipping. Airborne time while running will be 80% longer in duration than on Earth, and stride length approximately 3 times as long. On Earth, the average stride length is 54 and 74 inches (1.3 to 1.8 meters) for men and women, respectively. This means that Martian marathoners will travel around 13.5 to 18.5 FEET (4 to 5.5 meters) per stride. Compare that to Usain Bolt, who has a stride length of about 7 feet (2 m). Talk about a “giant leap for mankind.”

The above changes, resulting in only a decrease in work and slight increase in biomechanical efficiency, may be the only beneficial alterations in running physiology on Mars – and it might look quite funny. Indeed, where gravity gives runners a benefit, the other environmental factors on Mars will all work against running a fast marathon.

Check back next week to learn how the freezing temperatures, and lack of oxygen impact the marathoners, as well as how they’ll fuel up and what they will wear.

References

  1. Elon Musk Has a New Timeline for Humans Living on Mars. June Javelosa. February 19, 2017. https://futurism.com/elon-musk-has-a-new-timeline-for-humans-living-on-mars/
  2. NASA’s Opportunity Mars Rover Finishes Marathon, Clocks in at Just Over 11 years. NASA release 15-049. March 24, 2015. https://www.nasa.gov/press/2015/march/nasas-opportunity-mars-rover-finishes-marathon-clocks-in-at-just-over-11-year
  3. Montero et al. Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training. The Journal of Physiology. 593.20 (2015); 4677-4688