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).

About SharpBrains

SHARPBRAINS is an independent think-tank and consulting firm providing services at the frontier of applied neuroscience, health, leadership and innovation.
SHARPBRAINS es un think-tank y consultoría independiente proporcionando servicios para la neurociencia aplicada, salud, liderazgo e innovación.

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