o to that of Penfield's two patients,except that it was not the first ncounte with t d of m nt.Dur seizur s.His capaci y for sustaine als of parts of the frontal o the number 584 for at least 15 min ures.The temporal-lobe c scheg th put the mo the anterior ment his attention was diverted by a new topic,the ocampus on the H.M.'s suc ssin remembering a three-digit numbe als produced at most mild material- ific mem Pf the Drachman'amnes d e,p gene al lin left temporal lo oth patients hac conm hin lish that this was ctive evid comes from layed paired compari- Miner.1958).The impar nent was r d clin 1959,Konorski descr ed a metho for testin ife ere for nd Sier attenti top months an the separat d by th t time int ds as or dit ans tha for th and Penfield (1955)hypothesized that neach cas to compare the second one with it Task difficult nin the hip pal regio of the mi or by an 1963 in the lef rate M phere,he e s o a m (thre and Penfiel on the pp mpal rate ta wer .D R in tw nd it was only afte al of the ere assigned to e to p ent as fa The val.All standing hippoca pa ay an ha asks he pa Ppo mpal gyrus,sho sigr ab ero d out with inc ng intr nm o the hi that rem nd c were approaching the and Penfield reported the two cases at the uen Stoddard,and Mohr (1968) using a ad the t He that ,M n of asked M she uld lik to go one sam th e stimulus.With the memory deficit inH.M.became more mal crimination of a tios,bu Clinically,H.M.'smemory disorder appeared identical onds.the sample no longer exerted any control over his Neuron 448 soon as his attention was diverted they were lost. In to that of Penfield’s two patients, except that it was contrast, old memories from his childhood seemed to more severe. Again, there had been no intellectual loss; be intact. in fact, H. M.’s IQ had risen postoperatively, from 104 In fact, the encounter with H. M. was not the first to 117, presumably because he was having far fewer encounter with this kind of memory impairment. During seizures. His capacity for sustained attention was also the early 1950s, Wilder Penfield (Figure 1, left) began to remarkable. Thus, Milner showed that he could retain carry out unilateral removals of parts of the frontal or the number 584 for at least 15 minutes by continuous temporal lobe as a treatment for patients with localized rehearsal, combining and recombining the digits ac￾injury causing seizures. The temporal-lobe removals cording to an elaborate mnemonic scheme, but the mo￾typically included the anterior temporal neocortex to- ment his attention was diverted by a new topic, the gether with the uncus, amygdala, and anterior parahip- whole event was forgotten. pocampal gyrus and hippocampus on the medial aspect H. M.’s success in remembering a three-digit number of the hemisphere. Milner and Penfield found that these for 15 minutes in the absence of distraction was at first removals produced at most mild material-specific mem- sight consistent with Drachman’s view that amnesics ory deficits that varied in kind with the side of the lesion. can hold a simple memorandum indefinitely provided But, unexpectedly, Milner and Penfield encounteredtwo that no interfering activity claims their attention (Drach￾patients with a severe, persistent, and generalized im- man and Arbit, 1966). Yet it was already clear that for pairment of recent memory, following a removal limited H. M. verbal rehearsal played a key role in this holding to the left temporal lobe. Because both patients had process. In contrast, certain simple nonverbal stimuli undergone extensive preoperative testing, it was easy were forgotten by him within less than a minute. The to establish that this was a selective impairment of mem- evidence for this comes from delayed paired compari￾ory, with no accompanying intellectual loss (Penfield son and delayed matching studies. and Milner, 1958). The impairment was manifested clini- In 1959, Konorski described a method for testing cally as a profound anterograde amnesia, such that the memory of single events, which was later adapted for experiences of daily life were forgotten as soon as the work with human subjects by Stepien and Sierpinski focus of attention shifted to a new topic. In addition, one (1960). This technique, called by Milner “delayed paired patient showed a retrograde amnesia covering salient comparison,” consists of presenting two stimuli in suc￾events of the preceding few months and the other cession, separated by a short time interval. The subject showed a retrograde amnesia covering the 4 preceding must then indicate whether the second stimulus is the years. same as or different from the first. This means that sub￾To account for this unexpected memory loss, Milner jects must retain an impression of the first stimulus in and Penfield (1955) hypothesized that in each case there order to compare the second one with it. Task difficulty must have been a pre-existing, but undetected, atrophic may be increased by lengthening the intratrial interval lesion in the hippocampal region of the opposite hemi- or by introducing an intratrial distraction. Prisko (1963; sphere, so that when the surgeon removed the anterior cited by Milner, 1972) used the Konorski method to dem￾hippocampus and parahippocampal gyrus in the left onstrate H. M.’s rapid forgetting of simple perceptual hemisphere, he effectively deprived the patients of me- material. She sampled five different sets of stimuli (three dial temporal-lobe function bilaterally. The reason that visual and two auditory), each set constituting a sepa￾Milner and Penfield focused on the hippocampal region rate task. The stimuli used were clicks, tones, shades was that one patient, P. B., had had his temporal lobec- of red, light flashes, and nonsense patterns. At least five tomy in two stages, and it was only after removal of the values were assigned to each variable, to prevent as far medial structures of the temporal lobe that the memory as possible the use of verbal mediation to bridge the loss was seen. Their hypothesis was confirmed 9 years retention interval. All paired stimuli were easily discrimi￾later, when P. B. died of a pulmonary embolism and the nable at zero intratrial delay. These proved to be ex￾autopsy findings revealed thepresence of long-standing tremely easy tasks for normal subjects, who rarely made extensive right hippocampal atrophy, whereas the rest errors even with a 60-second delay and an interpolated of the right temporal lobe, including the amygdala and distraction. In contrast, H. M. performed all tasks well the parahippocampal gyrus, showed no significant ab- at zero delay, but with increasing intratrial intervals his normality. In contrast, on the operated (left) side, the 22 performance deteriorated sharply, so that at the 60- mm of the hippocampus that remained appeared to be second delay scores were approaching the chance level normal (Penfield and Mathieson, 1974). and were not further impaired by distraction. Milner and Penfield reported these two cases at the Subsequently, Sidman, Stoddard, and Mohr (1968) 1955 meeting of the American Neurological Association confirmed Prisko’s findings, using a delayed matching￾in Chicago, and Scoville read their abstract. He called to-sample technique that allowed the plotting of discrim￾Penfield and said that he thought he had seen a similar ination gradients to show how far the subject’s choice memory disturbance in a patient of his (H. M.) in whom of a matching stimulus deviates from the sample stimu￾he had carried out a bilateral medial temporal-lobe re- lus as the intratrial interval lengthens. In the nonverbal section, also in an attempt to control epileptic seizures. form of their task, H. M. was required to indicate which Penfield asked Milner if she would like to go down to one of eight ellipses matched the sample stimulus. With Hartford, Connecticut to study the patient, and that is zero delay he chose correctly most of the time, showing how the memory deficit in H. M. became more widely a normal discrimination of axis-ratios, but with increas￾known. ing delays his performance deteriorated until, at 32 sec￾Clinically, H. M.’s memory disorder appeared identical onds, the sample no longer exerted any control over his