When I first started reading comic books there were many superheroes that interested me. Naturally the list included Batman, Iron Man, Daredevil, Captain America, Thor, Nova, the Flash, the Black Panther, the Phantom, and lots more.

What I enjoyed best of all were team ups where you got more heroes per page. Classics like the Fantastic Four, the Justice League, the Justice Society, and the Defenders as well as the Inhumans, the Invaders, and the Legion of Superheroes. The group to top the list for me, though, has always been “The Avengers”. They are “Earth’s Mightiest Heroes” after all.

The Avengers are also the Earth’s super group of scientists. Back in the 1963 debut story (penned by Stan-the-man-Lee, of course) “The Coming of the Avengers!”, the original line-up included Iron Man, Ant-Man, Wasp, Thor, and the Hulk. This was arguably the most well-educated superhero group ever, well, assembled.

The scientists in that group included Dr. Bruce Banner (atomic physicist, the Hulk), Tony Stark (Iron Man, who may or may not have a PhD but has 2 master’s degrees in engineering from MIT), Dr. Hank Pym (sub-atomic physicist, Ant-Man), Janet van Dyne (not sure about her training, but she knew her way around the lab as the first Wasp), and Dr. Donald Blake (physician and surgeon, Thor).

That’s a line-up of heavy hitters of science that even one of my superheroes of science, Sir Francis Bacon, could be proud of. This remains even when it’s admitted that while rampaging around as the Hulk, we don’t usually get many insights about the Higgs-Boson and Thor isn’t typically trying to help treat injuries. Despite that, I am going to go ahead and assign the original Avengers line-up an A+ in scientists, if not always for science itself.

The 2012 Avengers movie re-envisions the origin and uses a plot that’s a lot closer to the excellent Marvel “Ultimates” story lines. In the spirit of recreating and reinvisioning story lines, in this post I want to concentrate on turning the lens of science on good ole’ Shellhead.

Iron Man is one of those few superheroes representing a more “realistic” take on what might be possible. As I wrote in “Inventing Iron Man—The Possibility of a Human Machine”, his origin story has some very plausible bits to it. This makes him seem more accessible as a character. But it’s accessing the mind of the Golden Avenger—connecting the Iron Man exoskeleton to Tony Stark’s brain—that is the main focus here.

Malleable Maps in Iron Man’s Mind

Starting in utero, a calibration of the motor and sensory inputs to and from your body parts began. This process has continued in your brain throughout your life. This results in a loose “mapping” of neurons that goes on in the somatosensory and motor parts of your brain. As a result you have multiple representations of your body in your brain. This gives rise to our sense of self, body “image”, and body “schema”.

These representations have been refined and tuned throughout your life along with your changing body size and the experiences you’ve had. Except in the case of tragic accidents where a limb may have been lost or amputated, your body has always been there with you 24/7. Your body is you and it’s there all the time.

It turns out that tool use can alter these representations. But tools that we use aren’t part of our body and aren’t with us all the time. At least not physically. But are they with us in our brains? We use tools only when we need them (we always need our bodies). It turns out that the sensory maps of our bodies in our brains can be reshaped to include parts of the way we use tools.

This kind of melding with the tool is termed “embodiment” and reflects the plasticity your nervous system experiences to keep you as a fully functional you. This process is heavily influenced by the sensation of moving the tools and the visual input that you get from seeing yourself using the tools.

The main premise of my Iron Man book is that for Tony Stark’s exoskeleton to work as we see it work in comics, graphic novels and movies it would need to be connected directly to the brain and spinal cord of the user. It would need to be the most fantastic brain machine interface ever created.

My view of Iron Man is very similar to the version that Warren Ellis created in the Marvel Iron Man “Extremis” story arc. Warren advanced the concept of an embedded interface between the nervous system and a highly modular armor. In broad strokes, this is really the only way it could work. But if such an ultimate brain machine interface existed could such a “tool” be incorporated into the cortical representation of a real human brain?

Extending your reach beyond your grasp…

French and Italian scientists headed up by Lucilla Cardinali, confirmed brain plasticity from tool use in a really simple but clever study back in 2009. They developed a long hand-held “grabber” like those used to clean up trash from parks and streets without the user having to bend over.

In this experiment the researchers asked participants to practice using the grabber to pick up and move things around on a table. They measured reaching and grasping movments before and after using the grabber. Surprisingly, practice using the grabber changed later arm movements performed even when the grabber wasn’t used!

There were changes in pointing movements and in how long participants perceived their arms to be. They thought their arms were longer, likely because the tool allowed them to reach further. From a functional perspective within the brain, their arms were longer since they could reach further with the grabber.

This plasticity is related to changing those body maps in the brain as a result of using a tool. Tools give us different abilities, like reaching further in this example, and this change in function pushes the plastic changes in the brain. The strength and length of that plasticity is not completely certain.

Could the changes become durable enough to become real memories for a new representation or map? We know that limb amputation can lead to changes in the maps. It leads to emptying some territory in those maps and taking over of territory by brain cells for other regions. The opposite perspective, that is, what happens when you add something to a map that is already complete, isn’t well understood.

Enter the alien arm…

Primate research using neural prosthetics controlled by the brain show very strong changes that occur after only a few weeks. These “prosthetic motor memories” are in features of long-term memories. So it seems that the brain can incorporate foreign parts into this schema.

This idea of incorporating foreign parts into the body was shown in 1998 by Matthew Botvinick and Jonathan Cohen at Carnegie Melon in Pittsburgh. They conducted what is now known as the “rubber hand illusion”.

Using a life-sized rubber arm as an “alien limb”, these scientists hid the left arm of each participant behind a blinding screen. Participants then focused their vision on this “alien limb”. Using small paintbrushes, the experimenters then simultaneously stroked the alien hand (fully in view) and the real hand (hidden out of view behind the screen). After 10 minutes of this conditioning, participants were asked a number of questions about the experience.

Some of the answers were astounding. They suggested an illusion which provided touch sensation on the alien limb and not the real hand. That is, they seemed to feel the touch of the viewed brush as if the rubber hand had actually sensed the touch. One participant said that “I found myself looking at the dummy hand thinking it was actually my own.” This powerful illusion has now been employed in many other experiments with similarly striking results.

A Swedish scientific team headed by Henrik Ehrsson extended the “rubber hand illusion” to upper limb amputees. Using procedures similar to the initial experiment above, they created a sensation of embodiment that a rubber hand was actually a real hand attached to the stump where the amputated limb used to be.

Although this illusion works well in able- bodied persons, the researchers weren’t sure if it could still work after amputation. Strong illusions were actually found in one third of the amputees. Interestingly, the illusions were more powerful when the tests were done soonest after amputation.

The illusion was so powerful that in some cases suddenly plunging a syringe into the rubber hand produced physiological responses of anxiety (changes in skin conductance) that would occur if the hand was part of their body! Clearly a process of “embodiment” was occurring. This group has recently done something that provides a bit of an answer to something I have been puzzling over since I wrote “Inventing Iron Man”.

Paul’s puzzle…

Here it is: I don’t really understand where the Iron Man suit of armor could be represented in the somatosensory and motor cortices of Tony Stark. Above we discussed how we can reshape our body schema with practice using tools and in response to trauma like limb amputation. But those approaches all make use of neuronal territory that exists and is reshaped or was lost and is reused. What about something completely new like a whole new body? That’s what is meant to be shown in the Figure below.

Figure 1: Extended use of a neuroprosthetic (like the Iron Man exoskeleton) will lead to plasticity in the brain maps of the body. Changes in brain activity shift when a monkey learns a reaching task (A). The human motor body map (where would the Iron Man suit of armor fit? (B)). How the Iron Man suit of armor might be incorporated into the normal body map (C). All panels from “Inventing Iron Man: The Possibility of a Human Machine” Johns Hopkins University Press, 2011 E. Paul Zehr ©). A courtesy Sedwick (2009); panel B modified from Penfield and Rasmussen (1950); panel C courtesy Patrick J. Lynch.

And it’s an experiment from Ehrsson’s group that helps us get to the answer. Instead of jumping directly to the idea of a whole new body, they asked instead: “Could it be possible that, in the not-so-distant future, we will be able to reshape the human body so as to have extra limbs? A third arm helping us out with the weekly shopping in the local grocery store, or an extra artificial limb assisting a paralysed person?” These questions are certainly on par with considering the question of embodying the Iron Man exoskeleton.

To see if you can really trick your brain into thinking you have an extra arm they used a variation of the “rubber hand illusion”. And it includes a very bold placement of a 3rd limb—the rubber arm—right beside the person’s actual arm. So it’s right out there in full view. They then did the basic procedure of brushing the real fingers and those of the rubber hand. All while participants looked on.

Of course, the rubber hand illusion worked again. This elegant experiment included all kinds of control conditions and even some physiological measures like galvanic skin response that all showed the fake arm could even be “threatened” by danger (this time by cutting with a knife). The upshot was that those in the study felt like they had a second right hand!

The concluding paragraph of this paper reads as follows: “Thus, under certain circumstances, healthy humans can experience somatic sensations that seem to violate the human body plan.” This real-life research work is the closest thing I’ve found that possesses the answer to whether there is enough neuroplasticity to adapt to a full Iron Man exoskeleton. The answer is a tentative yes!

On Machine, (Hu)man, and Mind

A prosthetic limb or exoskeleton that is meant to be incorporated into the user’s body schema needs to include sensors and feedback. For example, sensors on the digits of the Iron Man suit could be used to activate brain areas that normally get that sensation from the real fingers! The idea is that over time the sensation from the artificial sensor would become integrated into the perceptions of the person such that they are “one with the body”. Embodiment.

This means that an Iron Man suit of armor should have sensors on the fingers, hands, toes, etc. that would normally be activated on Tony Stark’s body. Using this approach, Tony would embody Iron Man like he declared by saying “the suit of Iron Man and I are one” in Iron Man 2.

Since the lines between science and science fiction are pretty labile, it’s likely not a surprise that real experimental work shows this to be very useful. In 2010, Aaron Suminski, Nicholas Hatsopoulos, and colleagues at the University of Chicago used a “sleeve” placed over a monkey’s arm to help learn how to move a cursor on a computer screen driven by recording activity in motor cortex.

Including sensation from the robotic limb improved the ability to learn the brain-machine interface commands. The scientists at the University of Chicago allowed the monkeys to use visual and somatosensory feedback together and learned how to control the cursor much faster and more accurately than without those sensations.

Back in 2011, my “Inventing Iron Man” book had only been out for a few months when I was asked to comment on a paper just about to appear in “Nature”. A research team at the Duke University Center for Neuroengineering headed by Miguel Nicolelis, a pioneer and leader in the area of brain machine interface, trained two monkeys using brain activity to control and move a virtual hand.

The critical piece in this experiment—and a requirement for functional training with the fictional Iron Man exoskeleton—was that electrical activation in the sensory and motor parts of the brains were used. Motor signals were used to drive the controller and then feedback was given directly into the brain by stimulating the sensory cortex when the monkeys made accurate movements. This huge advance actually provides patterns of electrical stimulation to the brain that mimic sensory inputs in movement.

This is really asking what happens when you take tool use—where the Iron Man suit of armor is the tool—to the extreme? What would happen in the brain if the tool is a representation of the body? What would happen to the body maps if we increase the representation of the body in the brain without first taking something away?

Would the neural plasticity associated with this affect the connection between your brain and your real body? How strong would the plasticity—the remapping—be and would you forget how to use your own real body if you used it too much? There remain a lot of questions. And a lot of work needs to be done. To borrow a bit of physics/engineering/mathematics jargon, some “non-trivial” problems remain.

Some trivia about non-trivial problems…

A major non-trivial problem has to do with the “form and function” relationships in biology. The cool thing about most of the body is that you can tell a lot about physiology (how it works) from the anatomy (how it looks). Function comes from form.

In your cardiovascular system you’ve got a big muscular pump in the form of the heart that receives and pushes blood all around the body. Taking a good look at the heart along with all the piping coming in and out, allows a reasonable estimate of what it does and how blood flows in the body.

In the case of the human nervous system, you have a big brain containing about 100 billion neurons. Those 100 billion neurons might have on average ~5000 connections from other neurons. That could produce about 100 trillion connections. A pretty big number. Far bigger than the estimated number of galaxies in the universe estimated to be between 200 to 500 billion. Overall this is a huge number of connections to consider.

This is part of what allows the nervous system to present with a much broader scope. Not because the anatomy is impenetrable or that much more complicated within different areas of the brain. It is certainly complex, but the general features of the connections from those 100 billion neurons form into tracts and bands of connections within the brain that can be reasonably identified (mostly).

The real non-trivial problem comes from the fact that the function—the behaviour—of the brain cannot be directly predicted from anatomy. Enter those 100 trillion connections. The key thing is that the network activity in the brain emerges from the activity of whatever synaptic connections are active at any given time. It is a constantly shifting landscape of network activity.

For a simple approximation of this complexity, imagine sitting in a ship that is rising and falling on the swells of the Mediterranean. Boats all around you rise and fall such that at any given moment you see different boats. Those boats all represent active connections between neurons that are expressed when you can see them and silenced when you cannot. To complete the metaphor, multiply by many trillions.

The real answers to these questions lie ahead. While we await those answers and work towards their solutions, let’s close with one of my favourite neuroscience quotes. The South African zoologist Lyall Watson (1939-2008) wrote: “If the brain were so simple we could easily understand it, we would be so simple we couldn’t.”

Luckily for us and the advance of knowledge there are many scientists who keep trying to illuminate the function of the human brain. In true “Avengers” fashion, the lack of simplicity is offset by the vigor and rigor of their efforts. I look forward to future developments. Developments, possibly inspired by fiction, but created for a new reality in neurorehabilitation (see Figure below).

Figure 2: Summary of the goals of brain- machine interface technology and research. These range from simple applications to control computer cursors all the way to linking up a human to an Iron Man exoskeletal interface. (From “Inventing Iron Man: The Possibility of a Human Machine” Johns Hopkins University Press, 2011 E. Paul Zehr ©)