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To Be (Your Connectome), or Not to Be (Your Genome)

NO ROAD, NO trail can pen­e­trate this for­est. The long and del­i­cate branch­es of its trees lie every­where, chok­ing space with their exu­ber­ant growth. No sun­beam can fly a path tor­tu­ous enough to nav­i­gate the nar­row spaces between these entan­gled branch­es. All the trees of this dark for­est grew from 100 bil­lion seeds plant­ed togeth­er. And, all in one day, every tree is des­tined to die.

This for­est is majes­tic, but also com­ic and even trag­ic. It is all of these things. Indeed, some­times I think it is every­thing. Every nov­el and every sym­pho­ny, every cru­el mur­der and every act of mer­cy, every love affair and every quar­rel, every joke and every sor­row — all these things come from the for­est.

You may be sur­prised to hear that it fits in a con­tain­er less than one foot in diam­e­ter. And that there are sev­en bil­lion on this earth. You hap­pen to be the care­tak­er of one, the for­est that lives inside your skull. The trees of which I speak are those spe­cial cells called neu­rons. The mis­sion of neu­ro­science is to explore their enchant­ed branch­es — to tame the jun­gle of the mind.

Neu­ro­sci­en­tists have eaves­dropped on its sounds, the elec­tri­cal sig­nals inside the brain. They have revealed its fan­tas­tic shapes with metic­u­lous draw­ings and pho­tos of neu­rons. But from just a few scat­tered trees, can we hope to com­pre­hend the total­i­ty of the for­est?

In the sev­en­teenth cen­tu­ry, the French philoso­pher and math­e­mati­cian Blaise Pas­cal wrote about the vast­ness of the uni­verse:
Let man con­tem­plate Nature entire in her full and lofty majesty; let him put far from his sight the low­ly objects that sur­round him; let him regard that blaz­ing light, placed like an eter­nal lamp to illu­mi­nate the world; let the earth appear to him but a point with­in the vast cir­cuit which that star describes; and let him mar­vel that this immense cir­cum­fer­ence is itself but a speck from the view­point of the stars that move in the fir­ma­ment.

Shocked and hum­bled by these thoughts, he con­fessed that he was ter­ri­fied by “the eter­nal silence of these infi­nite spaces.” Pas­cal med­i­tat­ed upon out­er space, but we need only turn our thoughts inward to feel his dread. Inside every one of our skulls lies an organ so vast in its com­plex­i­ty that it might as well be infi­nite.

As a neu­ro­sci­en­tist myself, I have come to know first­hand Pascal’s feel­ing of dread. I have also expe­ri­enced embar­rass­ment. Some­times I speak to the pub­lic about the state of our field. After one such talk, I was pum­meled with ques­tions. What caus­es depres­sion and schiz­o­phre­nia? What is spe­cial about the brain of an Ein­stein or a Beethoven? How can my child learn to read bet­ter? As I failed to give sat­is­fy­ing answers, I could see faces fall. In my shame I final­ly apol­o­gized to the audi­ence. “I’m sor­ry,” I said. “You thought I’m a pro­fes­sor because I know the answers. Actu­al­ly I’m a pro­fes­sor because I know how much I don’t know.”

Study­ing an object as com­plex as the brain may seem almost futile. The brain’s bil­lions of neu­rons resem­ble trees of many species and come in many fan­tas­tic shapes. Only the most deter­mined explor­ers can hope to cap­ture a glimpse of this forest’s inte­ri­or, and even they see lit­tle, and see it poor­ly. It’s no won­der that the brain remains an enig­ma. My audi­ence was curi­ous about brains that mal­func­tion or excel, but even the hum­drum lacks expla­na­tion. 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.

Daunt­ed by the brain’s com­plex­i­ty, many neu­ro­sci­en­tists have cho­sen to study ani­mals with dras­ti­cal­ly few­er neu­rons than humans. The worm shown in Fig­ure 2 lacks what we’d call a brain. Its neu­rons are scat­tered through­out its body rather than cen­tral­ized in a sin­gle organ. Togeth­er they form a ner­vous sys­tem con­tain­ing a mere 300 neu­rons. That sounds man­age­able. I’ll wager that even Pas­cal, with his depres­sive ten­den­cies, would not have dread­ed the for­est of C. ele­gans. (That’s the sci­en­tif­ic name for the one-mil­lime­ter-long worm.)

Every neu­ron in this worm has been giv­en a unique name and has a char­ac­ter­is­tic loca­tion and shape. Worms are like pre­ci­sion machines mass-pro­duced in a fac­to­ry: Each one has a ner­vous sys­tem built from the same set of parts, and the parts are always arranged in the same way.

What’s more, this stan­dard­ized ner­vous sys­tem has been mapped com­plete­ly. The result  is some­thing like the flight maps we see in the back pages of air­line mag­a­zines. The four-let­ter name of each neu­ron is like the three-let­ter code for each of the world’s air­ports. The lines rep­re­sent con­nec­tions between neu­rons, just as lines on a flight map rep­re­sent routes between cities. We say that two neu­rons are “con­nect­ed” if there is a small junc­tion, called a synapse, at a point where the neu­rons touch. Through the synapse one neu­ron sends mes­sages to the oth­er.

Engi­neers know that a radio is con­struct­ed by wiring togeth­er elec­tron­ic com­po­nents like resis­tors, capac­i­tors, and tran­sis­tors. A ner­vous sys­tem is like­wise an assem­bly of neu­rons, “wired” togeth­er by their slen­der branch­es. That’s why the map shown in Fig­ure 3 was orig­i­nal­ly called a wiring dia­gram. More recent­ly, a new term has been intro­duced — con­nec­tome. This word invokes not elec­tri­cal engi­neer­ing but the field of genomics. You have prob­a­bly heard that DNA is a long mol­e­cule resem­bling a chain. The indi­vid­ual links of the chain are small mol­e­cules called nucleotides, which come in four types denot­ed by the let­ters A, C, G, and T. Your genome is the entire sequence of nucleotides in your DNA, or equiv­a­lent­ly a long string of let­ters drawn from this four-let­ter alpha­bet.

In the same way, a con­nec­tome is the total­i­ty of con­nec­tions between the neu­rons in a ner­vous sys­tem. The term, like genome, implies com­plete­ness. A con­nec­tome is not one con­nec­tion, or even many. It is all of them. In prin­ci­ple, your brain could also be sum­ma­rized by a dia­gram that is like the worm’s, though much more com­plex. Would your con­nec­tome reveal any­thing inter­est­ing about you?

The first thing it would reveal is that you are unique. You know this, of course, but it has been sur­pris­ing­ly dif­fi­cult to pin­point where, pre­cise­ly, your unique­ness resides. Your con­nec­tome and mine are very dif­fer­ent. They are not stan­dard­ized like those of worms. That’s con­sis­tent with the idea that every human is unique in a way that a worm is not (no offense intend­ed to worms!).

Dif­fer­ences fas­ci­nate us. When we ask how the brain works, what most­ly inter­ests us is why the brains of peo­ple work so dif­fer­ent­ly. Why can’t I be more out­go­ing, like my extro­vert­ed friend? Why does my son find read­ing more dif­fi­cult than his class­mates do? Why is my teenage cousin start­ing to hear imag­i­nary voic­es? Why is my moth­er los­ing her mem­o­ry? Why can’t my spouse (or I) be more com­pas­sion­ate and under­stand­ing?

This book pro­pos­es a sim­ple the­o­ry: Minds diff er because con­nec­tomes dif­fer. The the­o­ry is implic­it in news­pa­per head­lines like “Autis­tic Brains Are Wired Dif­fer­ent­ly.” Per­son­al­i­ty and IQ might also be explained by con­nec­tomes. Per­haps even your mem­o­ries, the most idio­syn­crat­ic aspect of your per­son­al iden­ti­ty, could be encod­ed in your con­nec­tome.

Although this the­o­ry has been around a long time, neu­ro­sci­en­tists still don’t know whether it’s true. But clear­ly the impli­ca­tions are enor­mous. If it’s true, then cur­ing men­tal dis­or­ders is ulti­mate­ly about repair­ing con­nec­tomes. In fact, any kind of per­son­al change — edu­cat­ing your­self, drink­ing less, sav­ing your mar­riage — is about chang­ing your con­nec­tome.

Sebas­t­ian Seung is Pro­fes­sor of Com­pu­ta­tion­al Neu­ro­science and Physics at the Mass­a­chu­setts Insti­tute of Tech­nol­o­gy, where he is cur­rent­ly invent­ing tech­nolo­gies for map­ping con­nec­tions between the brain’s neu­rons, and inves­ti­gat­ing the hypoth­e­sis that we are all unique because we are “wired dif­fer­ent­ly.” This arti­cle is an excerpt from his new book Con­nec­tome: How the Brain’s Wiring Makes Us Who We Are (Houghton Mif­flin Har­court; Feb­ru­ary 2012).

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Categories: Cognitive Neuroscience, Education & Lifelong Learning, Health & Wellness

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As seen in The New York Times, The Wall Street Journal, BBC News, CNN, Reuters,  SharpBrains is an independent market research firm tracking how brain science can improve our health and our lives.

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