Wednesday, June 27, 2012

The Ultimate Brain Quest

Deciphering how human thought works is mind-bendingly difficult, but researchers now know where to start.

Connectome

By Sebastian Seung
Houghton Mifflin Harcourt, 359 pages


[CONNECT1] Thomas Deerinck/NCMIR/Photo Researchers
Nerve cells in the brain. Neurons are supported and protected by smaller, and even more numerous, glial cells.

"Every day we recall the past, perceive the present and imagine the future. How do our brains accomplish these feats? It's safe to say that nobody really knows," Sebastian Seung writes early in Connectome, his exploration of how researchers have at least made a start toward understanding how those feats are accomplished. Mr. Seung, a professor of brain science at the Massachusetts Institute of Technology, is an amiable guide, witty and exceptionally clear in describing complex matters for the general reader.

He begins with the observation that each of us is unique, differing from one another in uncountable ways. These differences arise in part because we have different genes that influence brain development and, accordingly, behavior. Also important are gene-by-environment interactions and gene expression: You might have a genetic predisposition toward alcoholism, but without the right environmental triggers, that gene may never become active. The sequencing of the human genome has provided a map of our 20,000 genes, and we are gradually gaining insights into what these genes do, individually and in combination.

Neuroscientists posit that all of our hopes, desires, beliefs and experiences are encoded in the brain as patterns of neural firings. Just how this happens is not precisely understood, as the author attests, but we have made great strides in understanding how neurons communicate with one another. Progress has also been made in mapping which brain systems control which kinds of operations (my own field of research): One system is responsible for lifting your foot, another senses the pain when you stub your toe; one system helps you to solve arithmetic problems, another enjoys "La Bohème." A new approach to studying brains and individual differences involves making maps of how neurons connect to one another. Following the term genome, these are called connectomes.
 
"Why study connectomes if genomics is already so powerful?" Mr. Seung asks. "The answer is simple: Genes alone cannot explain how your brain got to be the way it is. As you lay nestled in your mother's womb, you already possessed your genome but not yet the memory of your first kiss."

The human brain contains 100 million neurons, and each neuron makes thousands of connections on average. If we assume that each distinct connection pattern gives rise to a distinct brain state—like the effervescent sensation after that first kiss—the number of brain states exceeds the number of known particles in the universe. Your experiences, memories, personality and thoughts are thus encoded in the ways your neurons connect to one another. The next big frontier is mapping those trillions of neural connection patterns to their brain states. By observing a particular network of neurons firing, researchers should know (in theory) whether you are thinking about love or money, beer or burgers.

The associational networks of your brain determine to a large degree how you understand the world and your place in it. When prompted with "red" you might respond "apple," while another person may respond "flame." Your fears and phobias, likes and attractions, were influenced by a lifetime of outcomes and associations. The information thus contained in your connectome is what sets you apart from everyone else, what describes your unique personality. "Information," according to Mr. Seung, "is the new soul."

But before readers can profitably learn about the connections, they need to understand something about neural physiology, neurotransmitters, synapses and neuroanatomy. Mr. Seung is equal to the task: Connectome offers the equivalent of a college course on neuroscience, covering such technical matters as spike trains, cortical layering, ion channels, and the function and structure of axons and dendrites. He also throws in a bit of neurochemistry, assuming no prior knowledge of biology, chemistry or psychology.

Except for the last two chapters, the book is not so much about connectomes as about how to use connectomes to frame neuroscience. We learn about the tools of the neuroscience trade—how they work and why they are important. From there we learn how patterns of neural connections give rise to our perceptions of the world, our reactions to perception and, ultimately, our uniqueness. Although obtaining connectomes for even the simpler brain of the mouse is beyond our technological abilities today, Mr. Seung lays out the technical hurdles and proposes some more attainable near-term goals. But he also makes a passionate case for a decade-long investment of time and energy, comparable to the Human Genome Project, to advance the cause.

Even in the current speculative realm, the connectome is a fascinating, occasionally frustrating, subject. One view is that each connectome or connectivity map will give rise to one and only one brain state and that different connectomes cannot give rise to the same state. Yet the widespread use of pharmaceutical agents such as Prozac and Ritalin suggests otherwise—that knowing the connectome is unlikely to tell us all we need to know about a person's thoughts, feelings, opinions and personality.

The levels of various chemicals in our brains can clearly be altered pharmaceutically. They are also influenced by diet, exercise, stress and normal biological cycles. Even if we know how the neurons are connected and the strength of their synapses, the amount of dopamine, for example, that is available in the brain at any given moment will influence firing patterns. This could cause the same neural network (a group of connected neurons) to give rise to different thoughts or different networks to give rise to similar thoughts.

Despite the fact that we have different brains and different neuronal configurations, when you and I smell a skunk it seems likely that we have equivalent mental states that lead to the same conclusions. Knowing the wiring is a crucial operation in understanding the nature of thought, but it seems not to be enough; we also need to know the precise chemical soup du jour in the brain. And one more additional, crucial step is understanding which types of experiences and environmental events can change the brain's wiring and in what ways.

The last two chapters of Connectome will be catnip for futurists, as Mr. Seung lays out two possible benefits of understanding connectomes: the repair of cryogenically frozen brains and subsequent restoration of consciousness and the uploading of consciousness into computer simulations. In the best (but unlikely) case, either could lead to cognitive immortality. Although the claims are far-fetched, they are beautifully explained and analyzed—as I might have expected from a writer who has produced the best lay book on brain science I've ever read.

Mr. Levitin is a professor of psychology and neuroscience at McGill University in Montreal. His books include This Is Your Brain on Music.

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