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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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