Prologue: Just Follow the MusicAs the first violin arpeggios emerged from the marble walls of the ample hall and capriciously ventured down the stairs from the second floor to the main entrance of the deserted medical school building, I could not help but feel disoriented by the total absurdity of the situation. After all, no medical student would be prepared to find himself listening to a concerto in the middle of the night while taking a quick break from one of the busiest hospital emergency rooms in the world. Yet, my initial uneasiness was soon replaced by music that breathed a whole new life, full of hope and adventure, into a soggy tropical summer evening. Perhaps that is why, even though those arpeggios seduced my brain nearly a quarter of a century ago, I can still vividly recall how the stunning beauty of the melody, not the otherwise meaningless individual notes, composed an earnest collective plea that beckoned me to follow the siren music. I swiftly bounded up the stairs and mutely walked through a thin corridor to find myself standing at the entrance to the auditorium where the "Vorspiel," the overture of Wagner's Parsifal, was remorselessly playing. Unable to resist, I followed the music and entered the auditorium.
How disappointing it felt, then, when I realized that, except for an elderly, well-dressed gentleman who was busily working, apparently trying to fix a worn-out faulty projector that had mangled one too many of his slides over the years, the auditorium, with all its chandeliers blazing, was completely empty. Built in the late 1920s, each of the classroom auditoriums at the University of Sv£o Paulo medical school was a model of elegant economy. At the front, a tidy, boxlike stage demarcated the space from which professors lectured. A heavy wood table, a sturdy chair, and a long, well-worn sliding blackboard completed the humble teacher's domain. The student seating was stacked into steep, straight rows, allowing backbenchers inhabiting the last rowincluding meto live well beyond the catedraticos' authoritative stare during the unending lectures.
By now, the old manhis close-cropped white hair matching his pristine lab coatwas startled by the sound as I opened the door to the lecture hall. Yet he turned to me to reveal his effortless Mediterranean smile. Without giving up his struggle with the projector, he waved his left hand almost as if we had known each other for years. On the lecturer's desk I saw, to my dismay, the evidence that clearly incriminated that unsuspicious gentleman with that night's musical recital: a turntable, two expensive-looking loudspeakers, and the covers of a few records by the Berlin Philharmonic.
"Come in. Welcome. We have wine and cheese. I am having some difficulties with the projector tonight, but we will be ready to start in a moment. By the way, my name is Professor César Timo-Iaria. I am the teacher of this course."
He had barely finished the sentence when a loud metallic pinging resounded from the slide projector and light spilled onto the lecture hall's screen. Without waiting for my reply, he swiftly changed position to stand behind the projector, looking very much like a battle-proofed admiral on his ship's bridge. After dimming the chandeliers and waiting for the second track of the record to start playing, he began clicking through his slides with a joy that I had only seen and experienced as a child while playing soccer in the narrow streets of my old neighborhood. Sitting there alone in the dark, lullabied by Tannhv§user's singing, which echoed around the entire auditorium while images wholly unrelated to the typical medical curriculum were glancing off the screen, I felt both provoked and enticed like in no other lecture I had attended before in my life.
"But what course are you teaching?" I asked.
"Introduction to Physiology," Professor Timo-Iaria replied, without looking at me.
Just to be sure, I looked at the screen again. Like all medical students, I had taken the mandatory introduction to physiology course a few years earlier and, as far as I could tell, none of the images I was seeing matched what I had been taught then.
"How come?" I insisted.
"How come what, son?" he rebutted, still not looking at me.
"How could this be 'introduction to physiology'? Your slides, they are all about, I mean, you are showing only . . ."
"Yes?" He looked amused by my discomfort, as if he had seen this happen many times before. "Go ahead. Tell me what is so surprising to you."
The music, the images, an old man lecturing in the middle of the night in a vast and empty auditorium. Nothing made any sense. Half-perplexed and mildly irritated, I finally let him have it.
"Stars, galaxies, those are the images you are showing. Look, now there is a radio telescope on the screen. What is this? How could this be an introduction to physiology?"
"Well, this was the beginning. It all started there, from the big bang to brains in just about fifteen billion years. Quite a voyage, wasn't it? I will explain what I mean."
Through an endless visual parade of mindless shining spiral galaxies, budding star clusters, playful nebulas, rebellious comets, and exploding supernovas, all tendered by music that seemed to have been composed by universal gods, I watched Dr. Timo-Iaria's slide-by-slide depiction of the epic that led to the emergence of the human mind. Planets were formed. Most remained bare, lifeless lands. But on at least one, an interesting experiment led to the emergence, a few billion years ago, of the biochemical and genetic mechanisms for sustaining and replicating life. And life blossomed, struggled to survive, and, always full of hope and aspirations, started to evolve through many utterly unpredictable and tenuous roads.
Next, I saw images of the first hominid couples walking, side by side, millions of years ago in the middle of an African night in what today is Ethiopia's Afar Desert. And then, at the very moment when Wagner's Tannhv§user was at last granted freedom from the Venusberg by rejecting immortality for the simple reward of experiencing what it is to be human, I shared the instant in which those early ancestors first looked at the infinite bright sky above them, full of awe and fear, while a raging electrical storm crisscrossed their brains searching for answers to the questions that still torment us today. I realized that by looking timidly but curiously to the sky, those first men and women launched a long and noble relay race that since has united us all in the search for the fundamental explanations of our existence, our consciousness, and the meaning of all that surrounds us. The symbolic birth of science could not have been better chronicled. Clearly, the seasoned admiral on the bridge knew very well how to steer his ship.
The dying notes of Tannhv§user's "Pilgrim's Chorus" announced the final slide, which, after being projected on the screen, lingered there as both of us remained in solemn silence. The slide showed a side view of a human brain. After a couple of minutes, Dr. Timo-Iaria turned on the lights, came down from his station by the projector, and walked calmly toward the auditorium door. Before leaving the room, he turned as if to say good-bye. Instead, he said: "This is the first lecture of the introduction to human physiology course. But I forgot to mention that I also teach an advanced course on neurophysiology. The first class is tomorrow night. I strongly advise you to take that class, too."
Stunned by what I had just experienced, I could only think of asking, "And what do I need to do to enroll in that course?"
Smiling again as he exited through the hall, Dr. Timo-Iaria dispensed his very first piece of advice to the lifelong student he had by now so effortlessly recruited.
"Just follow the music."
For the past twenty-five years, I have often remembered Dr. Timo-Iaria's unshakable belief that music and the scientific method represent two of the most astounding by-products to emerge from the endless toils and torments of the human mind. That may explain why I decided to dedicate my whole career to listening to a different type of music, the kind of symphonies composed by vast ensembles of brain cells.
Technically speaking, I am a systems neurophysiologist. At least this is the way most of my neuroscience colleagues would define the type of work that my students and I carry out in my laboratory at the Center for Neuroengineering at Duke University, in Durham, North Carolina. In general terms, systems neurophysiologists spend their lives investigating the physiological principles that underlie the operation of the large variety of neural circuits formed by nerve fibers that emanate from the hundreds of billions of cells that inhabit our brains. Such intricate brain networks, which dwarf by many orders of magnitude the complexity and connectivity of any electrical, computational, or machine grid ever assembled by humans, allow each individual brain cell, known as a neuron, to establish direct contact and communicate with hundreds or even thousands of its peers. By virtue of their particular morphology, neurons are highly specialized in receiving and transmitting minute electrochemical messages through their cellular contacts, called synapses, which they use to communicate with other neurons. It is through these immensely interconnected and highly dynamic cellular networks, which are known rather prosaically as neural circuits, that the brain goes about its main business: the production of a multitude of specialized behaviors that collectively define what we usually, and proudly, refer to as "human nature."
By harnessing massive waves of millivolt electrical discharges, these microscopic neural grids truly provide for every act of thinking, creation, destruction, discovery, cover-up, communication, conquest, seduction, surrender, love, hate, happiness, sadness, solidarity, selfishness, introspection, and elation ever perpetrated by every one of us, and our ancestors, throughout humanity's whole existence. Had the word miracle not been appropriated by another area of human enterprise, I believe society should grant neuroscientists exclusive rights to use it when reporting the wonders that brain circuits can generate on a routine basis.
For most systems neurophysiologists, like me, the ultimate quest is to decipher the physiological mechanisms that allow these bursts of neurobiological electricity to give birth to the vast repertoire of human action and behavior. In seeking that holy grail, however, much of neuroscience over the past two hundred years has been embroiled in settling the hotly contested dispute over what specific regions of the brain serve a particular function or behavior. At one extreme, radical localizationists, who are the legitimate but often unclaimed heirs of Franz Gall, the father of phrenology, still firmly believe that distinct brain functions are generated by highly specialized and spatially segregated areas of the nervous system. In the other corner, a smaller but fast-growing crowd, whom I call the distributionists, professes that rather than relying solely on unique specialization, the human brain calls on populations of multitasking neurons, distributed across multiple locations, to achieve every one of its goals. In defending this position, we distributionists propose that the brain seems to utilize a physiological mechanism that is somewhat equivalent to an election, a neuronal vote in which large populations of cells located in many different regions of the brain contribute, albeit each in small and different amounts, to the generation of a final behavioral product.
Over the past two centuries, both the localizationist and the distributionist camps have elected the cortexthe most superficial component of the brain, lying just beneath the bone layer of the skullas the main neuronal battlefield for their never-ending dispute. The origins of this battle can be traced to the days when phrenologists claimed to be able to recognize key personality traits of an individual simply by palpating the scalp in search of skull bumps that reflected the disproportional enlargement of particular areas of the cortex that, according to their doctrine, generated attributes such as affection, pride, arrogance, vanity, and ambition. According to this doctrine, each human emotion and behavior was generated by a particular cortical territory.
Although Gall and his pseudoscience were discredited in due time, this general framework survived and morphed into one of the key dogmas of twentieth-century neuroscience. About one hundred years ago, a glorious series of experiments by the first generation of full-time brain researchers, led by the genial Spaniard Santiago Ramón y Cajal, demonstrated that, as in all other organs, an individual cell, the neuron, constitutes the brain's fundamental anatomical unit. Almost by default, the single neuron was also quickly anointed as the fundamental functional unit of the central nervous system. The ascension of the single neuron doctrine, combined with a dazzling 1861 report by Pierre Paul Broca, the French physician who observed that a localized lesion of the left frontal lobe could lead to a profound loss of speech and paralysis of the right half of a patient's body, temporarily put the distributionist camp in disarray. But just as the distributionists were becoming isolated, Sir Charles Sherrington came to their rescue. Sherrington argued that even one of the brain's simplest functions, the spinal cord arch reflex, depended on the collaboration of many neurons and distinct neural circuits to work properly.
In the last decade, although no decisive blow has yet been delivered, the distributionists have gained the high ground in the battle over the brain's soul. Discoveries emanating from neuroscience laboratories around the world are overturning the localizationists' model. Among these collective efforts, research conducted in my lab at Duke University over the last two decades has helped to show categorically that a single neuron can no longer be viewed as the fundamental functional unit of the brain; instead, connected populations of neurons are responsible for the symphonies of thought composed by brains. Today, we can record the music produced by these neural ensembles and even replay a small fraction of it in the form of concrete and voluntary motor behaviors. By listening to just a few hundred neuronsan infinitesimally small sample of the billions of neurons in the brainwe are already beginning to replicate the process by which complex thoughts become instantaneous body actions.
What principles guide the composition and conduction of these neural symphonies? After more than two decades delving into the workings of neural circuits, I have found myself looking for those principles both outside the brain, beyond the boundaries that have constrained our biological evolution out of humble beginnings in stardust, as well as deep inside the central nervous system, trying to identify and give voice to the brain's own point of view. Here I propose that, like the universe that fascinates us so much, the human brain is a relativistic sculptor; a skillful modeler that fuses neuronal space and time into an organic continuum responsible for creating all that we see and feel as reality, including our very sense of being. In the following chapters, I will propose that, in the next decades, by combining such a relativistic view of the brain with our growing technological ability to listen and decode even larger and more complex neural symphonies, neuroscience will eventually push human reach way beyond the current constraints imposed by our fragile primate bodies and sense of self.
I can imagine this world with some confidence because of the work conducted by my lab to teach monkeys to utilize a revolutionary neurophysiological paradigm, which we named brain-machine interfaces (BMIs). Using such BMIs, we were able to demonstrate that monkeys could learn to control voluntarily the movements of extraneous artificial devices, such as robotic arms and legs, located either close to or very far from them, using only their raw electrical brain activity. This unleashes a vast array of possibilities for the brain and the body that could, in the long run, completely change the way we go about our lives.
To test the different versions of our BMIs, we took advantage of a new experimental approach to read directly and simultaneously the electrical signals produced by hundreds of neurons that belong to a neural circuit. This technology was initially developed as a way to test the distributionists' viewpoint: that populations of single neurons, communicating with one another across different brain regions, are required to generate any brain function. But once we discovered how to listen to some motor neural symphonies played by the brain, we decided to push further: to record, decode, and transmitall the way to the other side of the worldthe motor thoughts of a primate cortex. We then translated these thoughts into digital commands to generate humanlike motion in machines that were never designed to acquire such unique human traits. It was at that moment that our BMIs stumbled on a way to liberate the brain from the constraints imposed by the body and made it capable of using virtual, electronic, and mechanical tools to control the physical world. Just by thinking. This book tells the story of those experiments and how they have changed our understanding of brain function.
For the vast majority of people alive today, the full impact of our research with BMIs will be felt primarily in the medical arena. Unraveling the brain's intricate workings by building advanced BMIs will lead to the development of amazing new therapies and cures for those afflicted by devastating neurological disorders. Such patients will be allowed to regain mobility and the sense and feeling in an otherwise lame body through a variety of neuroprosthetics, devices the size of a modern heart pacemaker that harvest healthy brain electrical activity to coordinate the contractions of a silk-thin wearable robot, a vest as delicate as a second skin but as protective as a beetle's exoskeletona suit capable of supporting a paralyzed person's weight and making formerly immobile bodies roam, run, and once again exult in exploring the world freely.
Yet, BMI applications promise to reach way beyond the borders of medicine. I believe future generations will be in a position to enact deeds and experience sensations that few today can imagine, let alone verbalize. BMIs may transform the way we interact with the tools we fabricate and how we communicate with one another and with remote environments and worlds. To grasp what this future world may look like, you first need to picture how the execution of a few of our daily routines will change radically when our brain's electrical activity acquires the means to roam freely around the world pretty much like radio waves sail above us today. For a moment, imagine living in a world where people use their computers, drive their cars, and communicate with one another simply by thinking. No need for cumbersome keyboards or hydraulic steering wheels. No point in relying on body movements or spoken language to express one's intentions to act upon the world.
In this new brain-centered world, such newly acquired neurophysiological abilities will seamlessly and effortlessly extend our motor, perceptual, and cognitive skills to the point that human thoughts can be efficiently and flawlessly translated into the motor commands needed to produce either the minute manipulations of a nanotool or the complex maneuvers of a sophisticated industrial robot. In that future, back at your beach house, sitting in your favorite chair facing your favorite ocean, you may one day effortlessly chat with any of a multitude of people anywhere in the world over the Internet without typing or uttering a single word. No muscle contraction involved. Just by thinking.
If that is not enticing enough, how about experiencing all the sensations aroused by touching the surface of a different planet, millions of miles away, without leaving your living room? Or even better, how would you feel if you could access your ancestral memory bank and readily download the thoughts of one of your forefathers and create, through his most intimate impressions and vivid memories, an encounter you both would have never shared otherwise? That is just a glimpse of what living in a world beyond the boundaries imposed upon the brain by the body may bring to our species.
Such wonders will soon no longer be the stuff of science fiction. This world is starting to take shape before our very eyes, right here and right now. And to become immersed in it, as Dr. Timo-Iaria would say, all you have to do is just follow the music that begins playing on the very next page.
Excerpted from Beyond Boundaries by Miguel Nicolelis
Copyright 2011 by Miguel Nicolelis
Published in 2011 by Henry Holt and Company
All rights reserved. This work is protected under copyright laws and reproduction is strictly prohibited. Permission to reproduce the material in any manner or medium must be secured from the Publisher.