In 1900, the Second International Congress on Mathematics in Paris was dominated by David Hilbert, a near-celebrity mathematician. In his much anticipated speech, which opened the conference and (at least metaphorically) the century, Hilbert set out a series of outstanding problems and proposed that solving them would serve as the strategic plan for future mathematics. Although he presented ten problems in this speech, he soon added thirteen more to complete the set that the world now knows as Hilbert’s problems.

I know of no other area where a single individual so dominated an entire field for more than a century. (Some of Hilbert’s problems are still unsolved.) The epitaph on his tombstone in Gottingen, Germany, is taken from yet another of his speeches:

Wir mussen wissen

Wir warden wissen

This translates as:
We must know
We will know

The inscription is an apparent retort to the famous Latin maxim, Ingoramus et Ignorabimus: We do not know; we cannot know. Ironically, by the time Hilbert died, Kurt Gödel had proved the ancient Romans right, and Hilbert’s hopes to place mathematics on an unassailable foundation were never to be realized.

But Hilbert was right about one thing. His famous Paris speech began with a call to arms:

“Who among us would not be happy to lift the veil behind which is hidden the future; to gaze at the coming developments of our science and at the secrets of its development in the centuries to come.”

Who indeed. But instead of going on, as one might have expected, to predict what might await his field in the future, he presented this future as a great unknown circumscribed by twenty-three crucial problems. It was great insight to wonder about the future in terms of questions, not results.

Unlike Hilbert, I don’t believe that some number of questions can define the limit of a field, as if once we answered them, we could call it quits. Numbering the unknown is, in my opinion, generally a bad idea—although one that mathematicians may be excused for being unable to resist.

I suggest instead we take a careful look at what we think we know about the brain and what questions that knowledge generates. In spite of thousands of papers and over two thousand books, according to Amazon, published on the brain and nervous system from scientists around the world in just the past decade, the amount we don’t know has grown, not diminished. That’s how science is supposed to work, so this is a sign of health.

Let’s take an example, one among hundreds or even thousands. A decade ago, deep brain stimulation was used to treat the movement problems associated with  Parkinson’s disease. Who would have thought then that it would also be useful for schizophrenia? Now we have to ask ourselves, how is a disease we always considered primarily motor (tremors, muscle stiffness, disturbed gait) related to a disease we considered primarily cognitive and perceptual (voices, hallucinations, emotional disturbances)? Why do treatments for Parkinson’s relieve motor deficits but often have the curious side effect of causing patients to become inveterate gamblers? These questions are fundamental to our thinking about how the nervous system is organized.

Many other examples could be taken from current neuroscience research, and there are more that no one knows about yet—the unknown unknowns. More generally, we might think about how to make sure that these unknowns have their day in the light and that they are not passed over by entrenched dogma that results from too high a regard for our accrued knowledge. In many cases in the history of science, knowledge, or apparent knowledge, has inhibited progress for years, if not decades.

Neuroscientists often divide the brain into two major systems—the sensory and the motor, that is perception and behavior. There are many other ways to organize the brain, which we never tire of listing in textbooks, but sensory and motor is one of the most fundamental and in some ways the most philosophical as well. I suggest that this habit colors the way we think about the brain in often unconscious ways that may also be quite limiting. How might this entrenched thinking be problematic?

Aristotle named the five senses possessed by animals. That was 2000 years ago, and most people still think we have five senses, sight, hearing, touch, smell, and taste, as most textbooks report. But this simple list doesn’t begin to cover our sensory abilities. Even “touch” barely suffices to describe the range of skin sensations, from itch to temperature to various sorts of pain (sharp, dull, throbbing) in addition to the sensations we actually call touch. Completely missing from Aristotle’s list are proprioception (knowing the position of your joints and muscles) and the vestibular sense (where your head is and how it is moving).

Leaving out these last two, body position and inertia, is particularly interesting because they are closely related to the other side of the nervous system, the motor system. This system includes all those parts of the brain that are involved in running your muscles and skeleton and that allow you to move through the world. Despite many neurological diseases that affect the motor system and some important research, it has never gotten quite the attention that the sensory systems have. I can see no good reason for this omission beyond pure bias. Donald G MacKay, a noted psychologist at UCLA, evaluated the nature of this bias among neuroscientists:

“…action was functionally, temporally and evaluatively subordinate to perception; functionally subordinate because they [referring to current neuroscientists] considered perception the sole means by which knowledge was acquired (empiricism); temporally subordinate because they considered perception a necessary precursor for action; and evaluatively subordinate because they viewed the contemplative life as superior to a life of action (labor).”

Let’s face it, perception does sound much more enticing. Sensations—the aesthetics of the visual arts, the ethereal beauty of music, the intoxication of exotic perfumes, the appreciation of gourmet food or fine wines—bring the pleasures of the world into our consciousness. Comparatively, the motor system sounds so vocational, involved in getting from here to there, not falling over, and putting food into your mouth. Thus the last century of neuroscience has been marked by an emphasis on sensory systems and the implicit notion that understanding sensory systems would lead us to understand the most complex workings of the brain.

Have we been striding confidently down the wrong path?

A new generation of neuroscientists working on the motor system are going so far as to claim that the brain is primarily a motor organ—that the senses are secondary, simply providing information that permits you to move toward food and sex and away from danger. Did the brain begin as a motor organ and then add sensory abilities for greater efficiency? The distinction is important because it alters almost entirely the way we should think about the brain.

Let’s take this perspective, as a thought experiment, and see where it leads us. Imagine that the first thing a network of electrically active cells connected together (a primitive brain or nerve net) might do would be to regulate some sort of rhythmic repetitive movement. Peristalsis comes to mind as one possibility. Worms still use this method for locomotion, and it persists in the movements of our gut and digestive system. Undulating movements might be another primitive type of patterned motor activity that eventually becomes swimming and then walking (both largely repetitive and rhythmic movements). When you think about it, there are many such patterns: breathing, chewing, swallowing, blinking—even talking, which is all too often repetitive if not rhythmic.

Evolution is nothing if not conservative, so if the brain started out as a series of microcircuits for controlling simple repetitive patterns of behavior, maybe this is still the fundamental organization. Perhaps if we look carefully, we will see remnants of these primitive circuits being used for “newer” brain functions like sensory processing, emotional control, decision making, even learning and memory.

Pushing the envelope a little further, even consciousness might have a motor component. After all, isn’t a hallmark of human consciousness our language ability? And what is language if not a complex motor behavior involving breathing, laryngeal control, and rapid, precise movements of the tongue and lips? Andre Breton, the poet and de facto leader of the surrealist movement, stated that the speed of speech is faster than thought. Once we get past all the obvious jokes about speaking without thinking, we realize that indeed we do not think through each statement as we speak, but that our motor mouths race far ahead of our thinking apparatus.

What is the future of neuroscience? Taking a cue from Hilbert, I suggest we consider where the next crucial questions will come from in brain science. What don’t we know that we don’t even know we don’t know? Me, I would put my wager on the motor system as a fertile place to dig around in the next century.

Stuart Firestein is Chair of the Department of Biological Sciences at Columbia University and the author of Ignorance: How It Drives Science.

photo by Reigh LeBlanc