Is­rael Rosen­field and Ed­ward Ziff

The New York Review of Books - - Contents - Is­rael Rosen­field and Ed­ward Ziff

Pa­tient H.M.: A Story of Mem­ory, Mad­ness, and Fam­ily Se­crets by Luke Dit­trich.

Ran­dom House,

440 pp., $28.00; $20.00 (paper)

On Septem­ber 1, 1953, Wil­liam Scov­ille, a neu­ro­sur­geon at Hartford Hospi­tal in Con­necti­cut, op­er­ated on a twen­ty­seven-year-old man named Henry Gus­tav Mo­lai­son, who suf­fered from se­vere epilepsy. Scov­ille re­moved two pieces of tis­sue—the left and right sides of the hip­pocam­pus—from Mo­lai­son’s brain. The hip­pocam­pus, lo­cated near the cen­ter of the brain, forms a part of the lim­bic sys­tem that di­rects many bod­ily func­tions, and Scov­ille thought that epilep­tic seizures could be con­trolled by ex­cis­ing much of it. The re­sult, how­ever, as the jour­nal­ist Philip Hilts wrote in Mem­ory’s Ghost (1995), was that

from H. M.’s mo­ment in surgery on­ward, ev­ery con­ver­sa­tion for him was with­out pre­de­ces­sors, each face vague and new. Names no longer rose to the sur­face, nei­ther his­to­ries nor en­dear­ing mo­ments came any­more. Re­as­sur­ances of wel­come had to be sought ev­ery mo­ment from ev­ery look in ev­ery pair of eyes.

H. M., as he came to be known in the med­i­cal lit­er­a­ture (his real name was not dis­closed un­til his death in 2008), could no longer re­mem­ber any­thing he did. He could not re­mem­ber what he had eaten for break­fast, lunch, or sup­per, nor could he find his way around the hospi­tal. He failed to rec­og­nize hospi­tal staff and physi­cians whom he had met only min­utes ear­lier, re­mem­ber­ing only Scov­ille, whom he had known since child­hood. Ev­ery time he met a sci­en­tist from MIT who was study­ing him reg­u­larly, she had to in­tro­duce her­self again. He could not even rec­og­nize him­self in re­cent photos, think­ing that the face in the im­age was some “old guy.” Yet he was able to carry on a con­ver­sa­tion for as long as his at­ten­tion was not di­verted.

H.M.’s con­di­tion sug­gested that the hip­pocam­pus was es­sen­tial for the con­ver­sion of short-term mem­o­ries to longterm mem­o­ries, and he be­came the most widely cited ex­am­ple in stud­ies of the dis­tinc­tion be­tween them. Eric Kan­del, James Schwartz, and Thomas Jes­sell drew on his case in 2000:

Brain trauma in hu­mans can pro­duce par­tic­u­larly pro­found am­ne­sia for events that oc­cur within a few hours or, at most, days be­fore the trauma. In such cases older mem­o­ries re­main rel­a­tively undis­turbed. . . . Stud­ies of mem­ory re­ten­tion and dis­rup­tion of mem­ory have sup­ported a com­monly used model of mem­ory stor­age by stages. In­put to the brain is pro­cessed into short-term work­ing mem­ory be­fore it is trans­formed through one or more stages into a more per­ma­nent long-term store.1 Pa­tient H.M., by Scov­ille’s grand­son, Luke Dit­trich, is a mem­oir of his grand­fa­ther and H. M. Much of the book de­scribes, with jus­ti­fied quiet in­dig­na­tion, the fail­ures of the neu­ro­sur­gi­cal pro­ce­dures that were widely prac­ticed by Scov­ille and other neu­ro­sur­geons in the past cen­tury.

The pro­ce­dures that Dit­trich de­scribes have a long his­tory. In the late nine­teenth cen­tury, for ex­am­ple, Dr. Got­tlieb Bur­ck­hardt, a Swiss psy­chi­a­trist, “per­formed the first mod­ern neu­ro­sur­gi­cal at­tacks on men­tal ill­ness.” Bur­ck­hardt had no ex­pe­ri­ence or train­ing as a neu­ro­sur­geon, but one of the first pa­tients he se­lected for his ex­per­i­ments was a “‘dis­turbed, un­ap­proach­able, noisy, fight­ing’. . . fifty-oneyear-old, ‘par­tic­u­larly vi­cious woman,’ who’d been in­sti­tu­tion­al­ized for six­teen years.” Af­ter five op­er­a­tions, over the course of which he re­moved eigh­teen grams of her brain, Bur­ck­hardt noted that his pa­tient had be­come “more tractable.” As Dit­trich writes, “Her pre­vi­ous in­tel­li­gence, he added, ‘did not re­turn.’” Bur­ck­hardt con­cluded that his pa­tient “has changed from a dan­ger­ous and ex­cited de­mented per­son to a quiet de­mented one.” Psy­chosurgery be­came in­creas­ingly pop­u­lar in the 1940s, and in 1949, Egas Moniz re­ceived the No­bel Prize for in­vent­ing the pro­ce­dure called lo­bot­omy, in which the neu­ral con­nec­tions to the pre­frontal lobe are sev­ered. Dit­trich writes:

The No­bel Com­mit­tee had en­dowed psy­chosurgery with a patina of no­bil­ity, demon­strat­ing that fu­ture break­throughs in the field might pay great pro­fes­sional, ther­a­peu­tic, and sci­en­tific dividends. For am­bi­tious tin­ker­ers like my grand­fa­ther, the lure was ir­re­sistible.

He gives a fas­ci­nat­ing portrait of Scov­ille, who sought pro­fes­sional ad­vance­ment through his ex­per­i­men­tal op­er­a­tion on H. M., de­scrib­ing him as “a rest­less ex­plorer in the oper­at­ing room, never sat­is­fied with ex­ist­ing tech­niques or meth­ods, even the ones he had in­vented.” What emerges from Dit­trich’s ac­count is a pro­found sense of the ig­no­rance, the ar­ro­gance, and the pas­sion that drove his grand­fa­ther and other neu­ro­sur­geons to per­form op­er­a­tions that of­ten left their pa­tients de­mented. They had a drive to in­no­vate—to pur­sue new, un­tried, ex­per­i­men­tal pro­ce­dures with un­pre­dictable con­se­quences—and were un­trou­bled by their harm­ful out­comes.

Dit­trich shows how H. M.’s case pointed the way to a better un­der­stand­ing of some of the more puz­zling as­pects of how our brains func­tion and the na­ture of our con­scious be­hav­ior. Af­ter surgery, he notes, H.M. was in­sen­si­tive to plea­sure and pain. When sub­jected to in­creas­ing lev­els of heat from a do­lorime­ter, which causes con­sid­er­able pain in nor­mal sub­jects, “Henry sat calmly,... even as his skin be­gan to burn and turn red.” He lost “a ca­pac­ity for de­sire”: “in the six decades be­tween his op­er­a­tion and his death he never had a girl­friend, or a boyfriend, never had sex, never even mas­tur­bated.” H.M.’s in­sen­si­tiv­ity and his in­dif­fer­ence to plea­sure and pain seem crit­i­cal to an un­der­stand­ing of his loss of mem­ory. For all of our mem­o­ries are sub­jec­tive. Your mem­o­ries are in re­la­tion to you, your friend’s mem­o­ries are in re­la­tion to him or to her, and so on. The loss of plea­sure and pain is a loss of sub­jec­tiv­ity, of an abil­ity to re­late to ob­jects, to per­sons, and to one­self— an abil­ity H. M. lost when Dit­trich’s grand­fa­ther re­moved his hip­pocam­pus. Dit­trich’s book con­cludes with an in­ter­view with Suzanne Corkin, a pro­fes­sor of psy­chol­ogy at MIT. For al­most fifty years she stud­ied H.M., and she and her men­tor, Brenda Mil­ner, wrote a num­ber of im­por­tant pa­pers about the hip­pocam­pus’s func­tion in es­tab­lish­ing long-term mem­o­ries. They showed that H.M. could no longer form mem­o­ries of space or time or ac­quire gen­eral knowl­edge of the world, but he could learn new mo­tor skills. Their work was the ba­sis of the un­der­stand­ing of mem­ory and hip­pocam­pal func­tion since the 1960s. When Dit­trich in­ter­viewed Corkin in 2015, he asked what she was go­ing to do with her notes on H. M.:

Dit­trich: Are you aim­ing to give his files to an archive?

Corkin: Not his files, but I’m giv­ing his mem­o­ra­bilia to my depart­ment. And they will be on dis­play on the third floor. . . .

Dit­trich: Right. And what’s go­ing to hap­pen to the files them­selves?

She paused for sev­eral sec­onds.

Corkin: Shred­ded.

Dit­trich: Shred­ded? Why would they be shred­ded?

Corkin: No­body’s gonna look at them.

Dit­trich: Re­ally? I can’t imag­ine shred­ding the files of the most im­por­tant re­search sub­ject in his­tory. Why did you do that?

Corkin: Well, you can’t just take one test on one day and draw con­clu­sions about it .

Many read­ers will be shocked by the rev­e­la­tion that Corkin’s notes were shred­ded. (Whether they were re­mains a mat­ter of con­tro­versy; in 2016 MIT re­sponded to Dit­trich with an open let­ter claim­ing that noth­ing was ac­tu­ally de­stroyed, and Dit­trich then posted on­line a record­ing of his in­ter­view with Corkin telling him the ma­te­rial was gone.) Yet even had they sur­vived, they would not have re­vealed much of the deeper sig­nif­i­cance of H. M.’s case, which has be­come ev­i­dent only through new neu­ro­bi­o­log­i­cal re­search.

Re­cent stud­ies of how the brain or­ga­nizes space and reg­u­lates how one makes sense of one’s en­vi­ron­ment have shown that the hip­pocam­pus is con­cerned with much more than con­vert­ing short-term mem­o­ries into long-term mem­o­ries. For ex­am­ple, H.M.’s sen­sa­tions, thoughts, and per­cep­tions af­ter the op­er­a­tion had no con­ti­nu­ity at all. “Ev­ery day is alone in it­self,” Corkin quotes him as say­ing. Sum­ma­riz­ing H. M.’s in­ter­view tran­scripts, Corkin writes:

The most com­pelling mo­ments were al­ways the rare ones when Henry would try to ex­plain what it was like to be him.... He never quite suc­ceeded, since his am­ne­sia wouldn’t let him hold on to the ideas long enough to get them out. He’d seem on the verge of a break­through, of a de­fin­i­tive state­ment, and then his train of thought would de­rail, and he’d start all over again.

Th­ese and other ob­ser­va­tions of sci­en­tists who stud­ied H.M. are con­sis­tent with the more re­cent find­ing that, in the words of the neu­ro­sci­en­tists Marc W. Howard and Howard Eichen­baum, “one of the func­tions of the hip­pocam­pus is to en­able the learn­ing of re­la­tion­ships be­tween dif­fer­ent stim­uli ex­pe­ri­enced in the en­vi­ron­ment.” The work of Eichen­baum and oth­ers has

be­gun to give us not only a new view of the func­tion of the hip­pocam­pus, but a new un­der­stand­ing of the na­ture of mem­ory. It is be­com­ing in­creas­ingly clear that hu­man and an­i­mal mem­ory de­pend on the abil­ity of the hip­pocam­pus to es­tab­lish re­la­tions be­tween an in­di­vid­ual and his or her sur­round­ings. Stud­ies by brain sci­en­tists in­clud­ing Eichen­baum and John O’Keefe have shown that the hip­pocam­pus is made up of cells with dif­fer­ent kinds of func­tions. Most im­por­tant are “place” cells, dis­cov­ered by O’Keefe in re­search that won him the No­bel Prize, which re­spond to an an­i­mal’s lo­ca­tion in space by caus­ing elec­tri­cal dis­charges called ac­tion po­ten­tials, cre­at­ing men­tal maps of an an­i­mal’s en­vi­ron­ment. Th­ese maps are at var­i­ous scales, like maps of an en­tire city as op­posed to maps of in­di­vid­ual streets. “Place cells,” wrote Howard and Eichen­baum in 2015, “are ap­par­ently not cod­ing for a place per se but a spa­tial re­la­tion­ship rel­a­tive to a land­mark, or set of land­marks.”

There is con­sid­er­able ev­i­dence that the ac­tiv­i­ties of hip­pocam­pal neu­rons also help es­tab­lish our re­la­tion­ships to many other types of en­vi­ron­men­tal and in­ter­nal stim­uli, such as sounds, odors, pain, plea­sure, and fear. Howard and Eichen­baum pro­posed that “the spa­tial map in the hip­pocam­pus is a spe­cial case of a more gen­eral func­tion in rep­re­sent­ing re­la­tion­ships . . . in­clud­ing both spa­tial and non-spa­tial [stim­uli].” In each case, the neu­rons are able to con­vey a re­la­tion­ship to our con­scious­ness. The hip­pocam­pus also or­ga­nizes tem­po­ral stim­uli (in­clud­ing when an event took place) and se­quen­tial stim­uli (in­di­cat­ing the order of a series of events). The hip­pocam­pus re­ceives and in­te­grates many other va­ri­eties of in­for­ma­tion to cre­ate mul­ti­sen­sory re­la­tions, which is what mem­ory is all about.2

But in what sense are re­la­tion­ships of this kind in­volved in re­mem­ber­ing other sorts of in­for­ma­tion that ap­par­ently have noth­ing to do with spe­cific events or our en­vi­ron­ment, such as ran­dom lists of words and num­bers? Con­sider, for ex­am­ple, Alexan­der Luria’s de­scrip­tion in his book The Mind of a Mnemonist (1968) of a pa­tient, S, who could

re­call ta­bles of num­bers writ­ten on a black­board. S. would study the ma­te­rial on the board, close his eyes, open them again for a mo­ment . . . and . . . re­pro­duce one series from the board.

How is this abil­ity to re­call ran­dom words and num­bers, even years later, re­lated to what sci­en­tists have recently sug­gested is the func­tion of the hip­pocam­pus, which is ap­par­ently es­sen­tial to our ca­pac­ity to re­mem­ber? Luria de­scribes how the mnemonist re­mem­bers. He never re­calls ar­bi­trary lists of words or num­bers with­out first es­tab­lish­ing a set­ting—a re­la­tion—in which he heard the lists:

Ex­per­i­ments in­di­cated that [the mnemonist] had no dif­fi­culty re­pro­duc­ing any lengthy series of words what­ever, even though th­ese had orig­i­nally been pre­sented to him a week, a month, or a year, or even many years ear­lier. . . . Dur­ing th­ese test ses­sions S. would sit with his eyes closed, pause, then com­ment: . . . You were sit­ting at the ta­ble and I in the rock­ing chair... You were wear­ing a gray suit and you looked at me like this . . . Now, then, I can see you say­ing . . .

In other words, the mnemonist ac­cesses (i.e., re­calls) what ap­pear to be im­printed words only by re­call­ing the set­ting in which they were first “im­printed” in his mem­ory. Once he re­calls that set­ting, S. has a tech­nique that al­lows him to mem­o­rize ar­bi­trary lists of num­bers, words, or both. The mnemonist, Luria notes, when given a long series of words to mem­o­rize, would

find some way of dis­tribut­ing th­ese im­ages of his in a men­tal row or se­quence. Most of­ten (and this habit per­sisted through­out his life), he would “dis­trib­ute” them along some road­way or street he vi­su­al­ized in his mind. Some­times this was a street in his home town, which would also in­clude the yard at­tached to the house he had lived in as a child and which he re­called vividly. On the other hand, he

might also se­lect a street in Moscow. Fre­quently he would take a men­tal walk along that street . . . and slowly make his way down, “dis­tribut­ing” his im­ages [evoked by the words] at houses, gates, and store win­dows.

There is no ex­am­ple in Luria’s book sug­gest­ing that the mnemonist can re­call with­out es­tab­lish­ing a set­ting. We would sug­gest that all rec­ol­lec­tions de­pend on a set­ting that the in­di­vid­ual may or may not be aware of.

This mnemonic tech­nique has been known since the an­cient Greeks. Cicero tells us that an aris­to­crat named Sco­pas was giv­ing a ban­quet, at which the poet Si­monides chanted a poem in honor of his host that in­cluded “a pas­sage in praise of Cas­tor and Pol­lux.”3 Sub­se­quently a note was brought to Si­monides that two young men were wait­ing for him out­side, but when he went to greet them he did not find them. Mean­while the ban­quet hall col­lapsed dur­ing his ab­sence, killing all of the guests. The corpses were badly man­gled and could not be iden­ti­fied. Si­monides re­mem­bered the place where each of the guests was sit­ting and was there­fore able to iden­tify them. Si­monides is gen­er­ally known as the in­ven­tor of the art of mem­ory. Most re­mark­able is that the art he in­vented op­er­ates not un­like the way the hip­pocam­pus cre­ates hu­man and an­i­mal mem­ory by means of cells that map lo­ca­tion in space, or cre­ate tem­po­ral mark­ers, or en­code se­quences of events. Es­sen­tial to the brain’s cre­ation of mem­o­ries is that all of our mem­o­ries are sub­jec­tive—they are cre­ated from the point of view of the in­di­vid­ual who is re­mem­ber­ing. We have a sense of self be­cause we have a pre­ex­ist­ing sense of our body that con­tains that self. The ba­sis of our sub­jec­tiv­ity is our “body im­age,” a co­her­ent, highly dy­namic (it is con­stantly chang­ing with our move­ments), three-di­men­sional rep­re­sen­ta­tion of the body in the brain. This body im­age is an ab­strac­tion the brain cre­ates from our move­ments and from the sen­sory re­sponses elicited by those move­ments—us­ing one’s left hand to pick up an ap­ple, for ex­am­ple. “The co­her­ence of con­scious­ness through time and space is again re­lated to the ex­pe­ri­ence of the body by way of the body im­age,” John Searle wrote in th­ese pages in 1995. “With­out mem­ory there is no co­her­ent con­scious­ness.”4

Since our sub­jec­tiv­ity de­pends on our body im­age, if our body im­age is al­tered for neu­ro­log­i­cal rea­sons, so too are our rec­ol­lec­tions. Af­ter he badly in­jured his leg on a moun­tain in Nor­way, Oliver Sacks de­scribed what is known as the “alien limb” phe­nom­e­non in his book A Leg to Stand On (1984):

The leg had van­ished, tak­ing its “place” with it. Thus there seemed no pos­si­bil­ity of re­cov­er­ing it.... Could mem­ory help, where look­ing for­ward could not? No! The leg had van­ished, tak­ing its “past” away with it! I could no longer re­mem­ber hav­ing a leg. I could no longer re­mem­ber how I had ever walked and climbed.

Since the nine­teenth cen­tury it has been known that the brain cre­ates “maps” of the body in the cor­tex. There is a cor­ti­cal map of sen­sa­tions (a sen­sory map) and a cor­ti­cal map of move­ment (a mo­tor map). In the sen­sory cor­ti­cal map (also known as the sen­sory ho­muncu­lus), the re­gion in the brain that is ac­ti­vated, for ex­am­ple, by touch­ing the hand, fingers, and arm— the cor­ti­cal area that “rep­re­sents” the sen­sa­tions cre­ated by a cot­ton swab moved from the tip of the fingers to the arm—is ad­ja­cent to the rep­re­sen­ta­tion of the face.

A coun­ter­part of the alien limb is the “phantom” limb—a limb per­ceived by an am­putee who feels as if an arm or leg that was lost in surgery is still at­tached to the body. The phantom limb might be ex­tremely painful. When points re­mote from the am­pu­ta­tion line are touched, such as the am­putee’s face, he or she para­dox­i­cally feels a phantom limb. Re­mark­ably, mem­o­ries re­lated to the orig­i­nal limb may be linked to the phantom limb. The sub­ject may even per­ceive that the phantom limb is wear­ing a wed­ding ring or jew­elry; when the weather turns hu­mid, the phantom limb may ex­pe­ri­ence arthritic pain. The pa­tient’s phantom limb is not only a rec­ol­lec­tion of the lost arm or leg, but one that in­cludes the pa­tient’s ex­pe­ri­ences re­lated to that limb.

O r take the case of a man whose mem­o­ries are trans­formed when he be­comes blind, as the the­olo­gian John Hull de­scribes in his book Touch­ing the Rock (1990). Hull be­came in­creas­ingly blind be­tween the ages of twenty and forty. When he lost his sight, he noted, “the pro­por­tion of peo­ple with no faces in­creased. . . . I have fairly clear pic­tures of many peo­ple whom I have not met again dur­ing th­ese three years, but the pic­tures of the peo­ple I meet ev­ery day are be­com­ing blurred. Why should this be?” Hull an­swers his own ques­tion:

In the case of peo­ple I meet ev­ery day my re­la­tion­ship has con­tin­ued be­yond loss of sight, so my thoughts about th­ese peo­ple are full of the lat­est de­vel­op­ments in our re­la­tion­ships. Th­ese have partly con­verted the portrait, which has thus be­come less im­por­tant. In the case of some­body I know quite well but have not seen for sev­eral years, noth­ing has hap­pened to take the place of the portrait, and when I think of those peo­ple, it is the portrait which comes to mind.

Hull goes on to say that he was deeply dis­tressed that he was los­ing the vis­ual por­traits of his wife and chil­dren. Hull’s mem­o­ries (as is true of all of our mem­o­ries) were con­tin­u­ously be­ing “up­dated.” He could still vi­su­al­ize peo­ple he had known be­fore he be­came blind and had not been in con­tact with since. But now that he was liv­ing in a world with­out any new im­ages, his mem­o­ries of peo­ple with whom he was reg­u­larly in touch were be­ing up­dated into a non­vi­sual form—the sounds of their voices and the sen­sa­tions of touch­ing their hands and faces. When one be­comes blind, the con­ti­nu­ity of vis­ual mem­ory is lost.

When mem­o­ries are first formed, they are “short-term” and un­sta­ble. But with time, the phys­i­cal rep­re­sen­ta­tion of the mem­ory in the brain formed by the synap­tic junc­tions be­tween neu­rons be­comes more sta­ble. This process is called con­sol­i­da­tion. The sta­bi­lized mem­o­ries then be­come “long-term” mem­o­ries. H. M.’s brain was un­able to cre­ate long-term mem­o­ries. Re­cent neu­ro­phys­i­o­log­i­cal stud­ies have shown that even long-term mem­o­ries are very dy­namic and that each time the brain tries to ac­ti­vate a “mem­ory trace”—the phys­i­cal rep­re­sen­ta­tion of the mem­ory in the brain, also called the “en­gram”—the na­ture of that trace changes. In other words, mem­o­ries are al­tered ev­ery time the brain re­calls them. This al­ter­ation of an ex­ist­ing mem­ory is called re­con­sol­i­da­tion. Be­cause the mem­ory trace changes, you can never re­mem­ber the same thing twice in ex­actly the same way.

The process of re­con­sol­i­da­tion, sci­en­tists have shown, changes the mem­ory—that is, the way the mem­ory is rep­re­sented at the synap­tic junc­tion is al­tered. The recog­ni­tion of the mal­leabil­ity of mem­ory is noth­ing new. What is new is the ob­ser­va­tion that the con­nec­tions be­tween neu­rons that many sci­en­tists be­lieve have a cen­tral part in gen­er­at­ing mem­o­ries change when­ever the brain seeks to re­cover the in­for­ma­tion they rep­re­sent. Th­ese changes may be the rea­son we can gen­er­al­ize. Over time, some mem­o­ries are as­sim­i­lated into cat­e­go­riza­tions or gen­er­al­iza­tions. When we re­call tak­ing the sub­way, we do not nec­es­sar­ily re­call each trip separately but rather tak­ing the sub­way in gen­eral; and such rec­ol­lec­tion may in­clude an im­age of the sub­way. The brain sim­pli­fies our un­der­stand­ing of our en­vi­ron­ment and our re­la­tion­ship to it. Mem­ory may ap­pear to be a re­pro­duc­tion of im­ages, sounds, and even thoughts that can be stored in the brain in a man­ner anal­o­gous to the way in­for­ma­tion can be stored on a CD, but it is be­com­ing in­creas­ingly ev­i­dent that this is too limited an un­der­stand­ing. Rather, as Eichen­baum, O’Keefe, and oth­ers have shown, mem­ory is the estab­lish­ment by the hip­pocam­pus of com­plex re­la­tions among a va­ri­ety of sen­sory stim­uli from the point of view of the in­di­vid­ual who is re­mem­ber­ing. Thus when Scov­ille re­moved H. M.’s hip­pocam­pus, H. M. lost more than an abil­ity to con­vert short-term mem­o­ries to long-term mem­o­ries; he lost the abil­ity to es­tab­lish such re­la­tions.

Yet sci­en­tists still don’t un­der­stand the ways that changes in the synap­tic junc­tions be­tween neu­rons, or changes in the neu­rons them­selves, are re­lated to our mem­o­ries, thoughts, and ac­tions. In­deed, neu­ro­bi­ol­ogy has yet to de­fine the phys­i­cal na­ture of the long-last­ing changes in neu­ronal con­nec­tions that are cre­ated as mem­o­ries are formed. Even a sim­ple mem­ory must in­volve vast num­bers of such changes. Ad­vanced tech­niques for imag­ing brain ac­tiv­ity, such as FMRI, re­veal which brain regions are ac­ti­vated when a mem­ory is re­called, but the res­o­lu­tion is far too low to study in­di­vid­ual neu­rons, let alone in­di­vid­ual synapses. As Luke Dit­trich has so aptly shown, much of what we know about mem­ory to­day still comes from study­ing the ir­repara­ble harm done to H. M.

Col­lage by Eric Edel­man

The Soviet neu­ropsy­ch­ogist Alexan­der Luria, author of The Mind of a Mnemonist (1968), with pa­tients; 1960s

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