Connectome: A New Way To Think About What Makes You You

Surfing the web is a fine way to augment what I've already read. Here's another Connectome web article. I'm all for Sebastian Seung's vision. It makes perfect sense to me.


March 22, 2012

by Maria Popova

“You are more than your genes. You are your connectome.”

The nature vs. nurture debate pitted the hard and social sciences against each other for decades, if not centuries, stirred by a central concern with consciousness, what it means to be human, what makes a person, and, perhaps most interestingly to us egocentric beings, what constitutes character and personality. In Connectome: How the Brain’s Wiring Makes Us Who We Are, MIT Professor of Computational Neuroscience Sebastian Seung proposes a new model for understanding the totality of selfhood, one based the emerging science of connectomics — a kind of neuroscience of the future that seeks to map and understand the brain much like genomics has mapped the genome.

A “connectome” denotes the sum total of connections between the neurons in a nervous system and, like “genome,” implies completeness. It’s a complex fingerprint of identity, revealing the differences between brains and, inversely, the specificity of our own uniqueness. Seung proposes a simple theory: We are different because our connectomes differ from one another. With that lens, he argues, any kind of personality change — from educating yourself to developing better habits — is a matter of rewiring your connectome.

That capacity is precisely what makes the connectome intriguing and infinitely promising — unlike the genome, which is fixed from the moment of conception, the connetome changes throughout life. Seung explains:

Neuroscientists have already identified the basic kinds of change. Neurons adjust, or “reweight,” their connections by strengthening or weakening them. Neurons reconnect by creating and eliminating synapses, and they rewire by growing and retracting branches. Finally, entirely new neurons are created and existing ones eliminated through regeneration.We don’t know exactly how life events — your parents’ divorce, your fabulous year abroad — change your connectome. But there is good evidence that all four R’s — reweighting, reconnection, rewiring, and regeneration — are affected by your experiences. At the same time, the four R’s are also guided by genes. Minds are indeed influenced by genes, especially when the brain is ‘wiring’ itself up during infancy and childhood.*

[…]
The connectome theory of mental differences is compatible with the genetic theory, but it is far richer and more complex because it includes the effects of living in the world. The connectome theory is also less deterministic. There is reason to believe that we shape our own connectomes by the actions we take, even by the things we think. Brain wiring may make us who we are, but we play an important role in wiring up our brains.”

Harnessing the power of those four R’s, Seung believes, is the most important goal of neuroscience — but, given your connectome is 100 billion times larger than your genome and has a million times more connections than your genome has letters, it’s a daunting task. Still, new technologies and new directions of scientific curiosity are bringing us closer to understanding this microcosm of meticulously structured chaos.

Map of the C. elegans nervous system, or 'connectome,' borrowing from the language of genomics
DNA is a long chain-like molecule composed of nucleotides connoted by the letters A, C, G, and T, and your genome is the entire sequence of nucleotides in your DNA. Similarly, your connectome is the totality of connections between the neurons in your nervous system.

At the heart of Seung’s vision is a new way of thinking about human personality, a fascinating and controversial subject we’ve previously explored. He proposes an apt metaphor, underpinning which is a desire not only to find and understand our connectomes, but also to develop methods for changing and optimizing them:

In the nineteenth century, the American psychologist William James wrote eloquently of the stream of consciousness, the continuous flow of thoughts through the mind. But James failed to note that every stream has a bed. Without this groove in the earth, the water would not know in which direction of the flow. Since the connectome defines the pathways along which neural activity can flow, we might regard it as the streambed of consciousness.

          The metaphor is a powerful one. Over a long period of time, in the same way that the water of the stream slowly shapes the bed, neural activity changes the connectome. The two notions of the self — as both the fast-moving, ever-changing stream, and the more stable but slowly transforming streambed** — are thus inextricably linked. This book is about the self as the streambed, the self in the connectome — the self that has been neglected for too long.”

In elaborating on this dichotomy of the self, Seung echoes Daniel Kahneman’s notion of the experiencing self vs. the remembering self: One self changes rapidly from moment to moment, becoming angry and then cheering up, thinking about the meaning of life and then the household chores, watching the leaves fall outside and then the football game on television. This self is the one intertwined with consciousness. Its protean nature derives from the rapidly changing patterns of neural activity in the brain.

The other self is much more stable. It retains memories from childhood over an entire lifetime. Its nature — what we think of as personality — is largely constant, a fact that comforts family and friends. The properties of this self are expressed while you are conscious, but they continue to exist during unconscious states like sleep. This self, like the connectome, changes only slowly over time. This is the self invoked by the idea that you are your connectome.”

Of Magic Bullets and the Connectome

An 1822 illustration of Der Freischütz depicting the opening scene with Max and Kilian

I wrapped Sebastian Seung's Connectome yesterday, It's a wonderfully comprehensive, yet easy to grasp tour-de-force dissertation on neuroscience, biology, and more.

His chapter on psychopharmacology, Changing, has several interesting tidbits which I will reprise here.

 I found out the oft-used drug term "magic bullet" comes from a 1940 Warner Bros. film, Dr. Ehrlich's Magic Bullet, the title perhaps in turn inspired by a plot device in Carl Maria Von Weber's opera Der Freishutz. In this opera Max sells his soul to the devil for seven magic bullets which are guaranteed to hit their mark. Dr. Paul Erlich first imagined, and then discovered chemicals that killed bacteria, but spared other cells, like a magic bullet that flew unerringly to its target. This has been the ideal for medical treatments ever since --  the "magic bullet" that hits its target and avoids "side effects."

Historically, most psychoactive drugs have been discovered by chance, as "side effects" themselves. The first antipsychotic, chlorpromazine (Thorazine), started out as a chemical die for the textile industry. In 1891 Dr. Erlich discovered that some of the chemicals in the same phenothiazine class could be used to treat malaria. After giving the drug to psychiatric patients as a sedative, doctors came to realize that it specifically reduced symptoms of psychosis. By the end of the fifties chlorpromazine had swept through the psychiatric hospitals of the world.

1940 Theatrical Poster

Then iproniazid, originally developed for tuberculosis, was found to have an antidepressant side effect. Imipramine was developed as a "me-too" drug in the footsteps of Thorazine. It failed as an antipsychotic, but seemed to relieve depression. Thus began the use of the tri-cyclic antidepressants.

After these accidental discoveries, attempts were made to develop an actual "rational" drug discovery, based on a modern understanding of biology and neuroscience.

According to well-known theories dating from the sixties, certain disorders are caused by surplus or deficiencies of neurotransmitters levels. So came the development of fluxotine (Prozac) and the other "me-too" SSRIs, said to be the only real psychopharmacolical advances since the "Golden Age" of the fifties.

But there is a problem with the neurotransmitter theory. Fluxotine affects serotonin levels immediately, yet it lifts mood only after several weeks. What could account for this long delay?

According to one speculation, the serotonin boost causes other changes in the brain over the longer term. Perhaps it's these changes that relieve depression, but what exactly could they be? Neuroscientists have looked for effects of fluxotine of the four "Rs" (reconnection, rewiring, regeneration, and reweighting), and found that it increases the creation of new synapses, branches, and neurons in the hippocampus. Moreover as Mr. Seung mentioned in his discussion of rewiring, fluxotine restores ocular dominance plasticity in adults, possibly by stimulating cortical rewiring. This doesn't prove that the drug's antidepressant effects are caused by connectome change, but it has opened the minds of neuroscientists to the idea.

It's time to practice the four Rs -- reconnect, rewire, reweight, and regenerate.