《认知神经科学》课程教学资源（参考文献）[Squire, L. R.（1992）] Memory and the hippocampus_a synthesis from findings with rats, monkeys, and humans

62is-23 Memory and the Hippocampus:A Synthesis From Findings With Rats,Monkeys,and Humans Larry R.Squire This article c na h largely in a ampus and th dif t fu s The hipp us (t r with plicit and trasteditha hipp ampus6ilsasndhabt,inptcoodno sent a whole memory In recent years a co sus has been developing about the the medial temporal lobe was responsible for H.M.'s amnesia roleofther was not knowr ior in a selective way:Howe consi rable unc ans and nonhuman primates,the term hipp could e ion that the hi h brings to a hig ory in humans and nonhuman primates. dem nteg x1966 mnesia foll urgical rem d of the media obe bila ststhat,in ad on to the hippocampus proper dial tem al lobe (es dam ntal principle that m mory could be ory systen ere wa ond.the idea is developed that the the hippocan and underly Miler,97),precisely what da amage withir tant kind of ere memory ot simila tion that the i ith hin la-Mo an,Frank commentsoneaicerYeiong mpa function weref de the hi 2161 195

Psychological Review 1992, Vol. 99, No. 2,195-231 In the public domain Memory and the Hippocampus: A Synthesis From Findings With Rats, Monkeys, and Humans Larry R. Squire Veterans Affairs Medical Center, San Diego, California and University of California, San Diego This article considers the role of the hippocampus in memory function. A central thesis is that work with rats, monkeys, and humans—which has sometimes seemed to proceed independently in 3 separate literatures—is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented, which proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippo￾campus is needed temporarily to bind together distributed sites in neocortex that together repre￾sent a whole memory. In recent years a consensus has been developing about the role of the mammalian hippocampal formation in learning and memory. The idea that the hippocampus is important for mem￾ory is not in itself new. What is new is that this idea is now supported by direct and compelling evidence for each of the three species that has been important to this work: rats, mon￾keys, and humans. In addition, there have been major gains in understanding exactly how the hippocampal formation is in￾volved in memory. Not too many years ago, when the topic of memory and hippocampus was discussed in the context of research on hu￾mans and nonhuman primates, the term hippocampus could be used only tentatively. Elegant neuropsychological studies of the noted amnesic patient H. M. (Scoville & Milner, 1957) had demonstrated convincingly that memory depends on the integ￾rity of the medial temporal lobe (Milner, 1966). H. M. devel￾oped severe amnesia following surgical removal of the medial temporal lobe bilaterally in an attempt to relieve severe epi￾lepsy. Continuing study of H. M. (Corkin, 1984; Milner, 1972) established the fundamental principle that memory could be dissociated from other intellectual functions. However, the me￾dial temporal lobe is a large region that includes the hippocam￾pus, amygdala, and adjacent cortical areas. Although there was reason to believe that the posterior aspect of the lesion was especially critical, that is, the hippocampus and underlying cortex (Scoville & Milner, 1957), precisely what damage within This research was supported by the Medical Research Service of the Department of Veterans Affairs, National Institute of Mental Health Grant MH24600, the Office of Naval Research, and the McKnight Foundation. I thank Stephen Kosslyn, Stuart Zola-Morgan, Frank Haist, and Gail Musen for their helpful comments on earlier versions of this article. Correspondence concerning this article should be addressed to Larry R. Squire, Veterans Affairs Medical Center, 3350 La Jolla Vil￾lage Drive, San Diego, California 92161. the medial temporal lobe was responsible for H. M.'s amnesia was not known. In the rat, which has been the most commonly used experi￾mental animal for neurobehavioral studies, it was clear that the hippocampus proper was important for some function, be￾cause lesions placed within the hippocampus disrupted behav￾ior in a selective way. However, until recently there has been considerable uncertainty about which tasks are the appropriate ones for detecting behavioral deficits and about how to inter￾pret the deficits. The purpose of this article is threefold. First, recent evidence is summarized, which brings to a high level of certainty the conclusion that the hippocampus itself is important for mem￾ory in humans and nonhuman primates. Indeed, there is now good correspondence among the findings for all the commonly studied mammalian species. Furthermore, the recent evidence suggests that, in addition to the hippocampus proper, certain adjacent and anatomically related cortical structures in the me￾dial temporal lobe (especially entorhinal, perirhinal, and para￾hippocampal cortex) also participate in memory functions. The components of the medial temporal lobe memory system can now be identified in broad outline. Second, the idea is developed that the role of the hippocam￾pus (and related cortex) is narrower than once believed. The hippocampus is essential for a specific but important kind of memory—here termed declarative memory (other similar terms include explicit and relational memory). The first sugges￾tion that the hippocampus is involved in only one kind of mem￾ory was developed by Hirsh (1974) on the basis of studies of rodents with hippocampal lesions. Subsequently, other hypothe￾ses about hippocampal function were also presented that con￾tained the idea that only a particular kind of memory is depen￾dent on the hippocampus (Gaffan, 1974; O'Keefe & Nadel, 1978; Olton, Becker, & Handelmann, 1979). Eventually, consid￾erable evidence for the idea that only one kind of memory is 195

196 LARRY R.SQUIRE 1982)e othe ely amnesic (Cohen,1984 Squire Indeed,in the absence of the hippo mpus.sev nitive function were rene dly evaluated and his m pairment was d ented.The only cognitive deficit that was the tion of R.B's brain after his deathn revealed a d that the role fthe hinr in memo is time limited.Amne patients.includ campal dal extent of the hippocar asonably b SRk然2S uire,Haist,& of retro cas thus showed that to th hippocampusi ent to cause and cl mesia in the monkey (2 gan Squi 199% rage is only t rary Memory is gradually reo pp learn ng M ris initial bl duces selective neuronal loss in the ed later,bilateral CAl damage and f the Medial foun e that the at and mor ey pro ing e ntial for ncxDerimcnta memory The strongly supported b and studies of the effects of selective lesions in rats. 89 Memory-Impaired Patients The ding rats are dise ussed more fully in a later s ovided val Additional confir ation for the idea that the human hippo 1987) have been thosc where the amnesia occurs against a back Robninneiomicalinomatioanvingpgticas pocampus was developed tha permits visualization of the hir rofound forgetful pocamp det nes a)and o Until re 89).con campus were demonstr ated in 4 pati en with circu be at neur path patients being studied.S case studies attribu the mbria. damage sizel.In contrast,the area of the e temp et al1985;Victor.Ang call.6 damage in patients with a selective m nory disorde and othe truct matter on firme ound.Patient B.became the severity of H.M.s memory impairment resulted from dam 97 at the age earuyo-Morg.quire. age be structu

196 LARRY R. SQUIRE affected by hippocampal damage accumulated in demonstra￾tions of entirely intact learning and memory abilities in patients who were otherwise severely amnesic (Cohen, 1984; Squire, 1982). The important implication was that memory is not a single entity. Indeed, in the absence of the hippocampus, sev￾eral other kinds of learning can still be accomplished, includ￾ing the learning of skills and habits, simple conditioning, and the phenomenon of priming. Third, the idea is developed that the role of the hippocampus in memory is time limited. Amnesic patients, including pa￾tients with confirmed hippocampal damage, have difficulty recalling the recent past but can recall remote events as well as normal subjects (MacKinnon & Squire, 1989; Squire, Haist, & Shimamura, 1989). Recently, the significance of this observa￾tion has been illuminated by a prospective study of retrograde amnesia in the monkey (Zola-Morgan & Squire, 1990c). The findings indicate that the role of the hippocampal formation in memory storage is only temporary. Memory is gradually reor￾ganized as time passes after learning. Memory is initially de￾pendent on the hippocampus formation, but its role diminishes as a more permanent memory is gradually established else￾where, probably in neocortex. Identification of the Components of the Medial Temporal Lobe Memory System Information about which structures and connections are im￾portant for memory (and that when damaged produce amnesia) comes from three sources: studies of neurological patients with circumscribed memory impairment, systematic experimental work with an animal model of human amnesia in the monkey, and studies of the effects of selective lesions in rats. Memory-Impaired Patients Cognitive studies of memory impairment have provided valu￾able information about the organization of memory functions (Baddeley, 1982; Cermak, 1982; Milner, 1972; Schacter, 1985; Squire, 1986; Weiskrantz, 1987). The most informative cases have been those where the amnesia occurs against a back￾ground of normal intellectual function and intact immediate memory. The hallmark of the disorder is profound forgetful￾ness for new material (anterograde amnesia) and some loss of previously acquired information (retrograde amnesia). Until re￾cently, comparatively little was known about what neuropatho￾logical changes in the medial temporal lobe had occurred in the patients being studied. Several single-case studies attributed memory impairment to hippocampal damage (Cummings, Tomiyasu, Read, & Benson, 1984; DeJong, Itabashi, & Olson, 1968; Duyckaerts et al., 1985; Victor, Angevine, Mancall, & Fisher, 1961), but the assessment of memory functions ia these cases was often informal or incomplete. In addition, the dam￾age was often not restricted to the hippocampus but extended into the amygdala, the parahippocampal gyrus, and other structures. The findings from a carefully studied single case have placed the matter on firmer ground. Patient R. B. became amnesic in 1978 at the age of 52 as the result of an ischemic event that occurred following open-heart surgery (Zola-Morgan, Squire, & Amaral, 1986). Ischemia (ISC) refers to a condition during which the blood supply to the brain is insufficient. In R. B.'s case, a tear occurred in the atrium of the heart. R. B. survived for 5 years after the ischemic event, during which time his cog￾nitive functions were repeatedly evaluated and his memory im￾pairment was documented. The only cognitive deficit that was noted was moderately severe memory impairment. Examina￾tion of R. B.'s brain after his death in 1983 revealed a lesion in the CA1 region of the hippocampus (Zola-Morgan et al., 1986, Figure 1). The lesion was bilateral and extended the full rostro￾caudal extent of the hippocampus. There was some other minor pathology, but the only finding that could reasonably be associated with the amnesia was hippocampal damage. This case thus showed that damage limited to the hippocampus is sufficient to cause easily detectable and clinically significant memory impairment. Recently, another case has been reported of memory impairment associated with a bilateral lesion of the hippocampus (Victor & Agamanolis, 1990). The CA1 region of the hippocampus is especially vulnerable to ischemic damage. Thus, global ischemia in the rat also pro￾duces selective neuronal loss in the CA1 region together with memory impairment (Auer, Jensen, & Whishaw, 1989; Davis & Volpe, 1990). Also, as discussed later, bilateral CA1 damage and memory impairment can be found after global ischemia in the monkey (Zola-Morgan & Squire, 1990a; Zola-Morgan et al., in press). The findings from R. B., and the observed effects of global ischemia in the rat and monkey, provide compelling evi￾dence that the hippocampus proper is essential for mammalian memory. The same conclusion is now strongly supported by findings of memory impairment in rats following surgical dam￾age limited to the hippocampus when appropriate tasks are used (Barnes, 1988; Eichenbaum, Mathews, & Cohen, 1989; Olton et al., 1979; Sutherland & Rudy, 1989). The findings with rats are discussed more fully in a later section. Additional confirmation for the idea that the human hippo￾campus is important for memory has come from recent im￾provements in magnetic resonance (MR) imaging, which make it possible to obtain anatomical information in living patients (Figure 1). A high-resolution protocol for imaging human hip￾pocampus was developed that permits visualization of the hip￾pocampal formation in considerable detail (Press, Amaral, & Squire, 1989). Using this protocol, abnormalities in the hippo￾campus were demonstrated in 4 patients with circumscribed memory impairment (Squire, Amaral, & Press, 1990). Specifi￾cally, in the patients, the region of the hippocampus (defined as the fimbria, dentate gyrus, hippocampus proper, and subicu￾lum) appeared markedly shrunken and atrophic (57% of normal size). In contrast, the area of the temporal lobe excluding the hippocampal region was normal. Thus, the MR technique has been able to provide direct visual evidence of hippocampal damage in patients with a selective memory disorder. One important finding was that neither patient R. B. nor the 4 other amnesic patients studied with MR imaging were as severely memory impaired as the well-studied surgical patient H. M. (Scoville & Milner, 1957). This observation suggests that the severity of H. M.'s memory impairment resulted from dam￾age to medial temporal lobe structures other than or in addi￾tion to the region of the hippocampus itself. Recently, it has

MEMORY AND THE HIPPOCAMPUS 19 pane righ (Fron ganiz ead8pomtnmnainthtteatdeawuwiagnaninal man amnes I the monkev s the subicular complex Memory Impairment in Nonhuman Primate order to reach the hippo f th ampal gyrus.This more estricted lesion has b to mimic the surgical er to the hippocampus and+to the Monkeys t ol-Moran 198 ola-Morga squ 1086.7E o failed by hu Saunders,&Malamut.9:Squire&Zola-Morgan,9 for onofeasy object discriminations,eight-pairc era of r lays tested up to0s(Zoa-Morgan&Squire,199b).It is useful the sia in the ed frequently in earl on the an t pairs to be learned together,are among the tasks sensi d the sequence ially imp rtant in und ding patient H.M.s am (10 to 20 trials for normal monkeys).Concur ent discrimina esia.A lesion of the hippocampal formation isordinarily pro tion tasks are ones in which pairs of objects are pre

MEMORY AND THE HIPPOCAMPUS RR 197 Figure 1. Top left panel: Section through the hippocampus of a normal subject. Top right panel: Section through the hippocampus of amnesic patient R. B. showing damage to the CA1 region. Bottom left panel: Magnetic resonance scan of a normal subject (resolution = .625 mm). Several anatomical features of the hippocampal formation can be distinguished. Bottom right panel: Magnetic resonance scan of amnesic patient W H. using the same protocol. The hippocampal formation is markedly reduced in size. The calibration bars to the right represent 5 cm in 1-cm increments. (From "Memory: Organization of Brain Systems and Cognition" by L. R. Squire, S. Zola-Morgan, C. B. Cave, F. Haist, B. Musen, and W Suzuki, 1990, Cold Spring Harbor Symposium on Quantitative Biology, 55, p. 1012. Copyright 1990 by Cold Spring Harbor Laboratory. Reprinted by permission.) become possible to confirm this idea directly using an animal model of human amnesia in the monkey. Memory Impairment in Nonhuman Primates In 1978, it was reported that a large medial temporal lobe lesion in monkeys, which was intended to mimic the surgical lesion sustained by patient H. M., caused severe memory im￾pairment (Mishkin, 1978). The lesion included the amygdala, the hippocampus (including the dentate gyrus and subiculum), and surrounding cortical regions (the H+A + lesion, Figure 2). Although more work was needed before the impairment was well understood (Mahut & Moss, 1984; Mishkin, Spiegler, Saunders, & Malamut, 1982; Squire & Zola-Morgan, 1983; for recent reviews, see Squire & Zola-Morgan, 1991; Zola-Morgan & Squire, 1990b), Mishkin's 1978 publication was the first in a new era of research on the anatomy of memory, and in this sense it signaled the successful development of an animal model of human amnesia in the nonhuman primate (Table 1). The H+A + lesion was used frequently in early work on the ani￾mal model of human amnesia. However, the effects of more limited lesions involving the hippocampal formation were also of interest, primarily because of the early suggestion (Scoville & Milner, 1957) that damage to the hippocampal region might be especially important in understanding patient H. M.'s am￾nesia. A lesion of the hippocampal formation is ordinarily pro￾duced by a direct surgical approach through the ventral surface of the brain that damages the hippocampus proper, the dentate gyrus, the subicular complex, together with the underlying cor￾tex that is necessarily removed in order to reach the hippocam￾pus, that is, the posterior entorhinal cortex and much of the parahippocampal gyrus. This more restricted lesion has been termed H+ , where H refers to the hippocampus and + to the underlying cortex (see Figure 2). Monkeys with the FT lesion are impaired on a variety of memory tasks (Mahut, Moss, & Zola-Morgan, 1981; Moss, Ma￾hut, & Zola-Morgan, 1981; Zola-Morgan & Squire, 1986; Zola￾Morgan, Squire, & Amaral, 1989a) that are also failed by hu￾man amnesic patients (Squire, Zola-Morgan, & Chen, 1988; see Table 2). The tasks used to demonstrate memory impairment include retention of easy object discriminations, eight-pair con￾current discrimination learning, and delayed response with de￾lays tested up to 30 s (Zola-Morgan & Squire, 1990b). It is useful to emphasize that simple object-discrimination tasks and con￾current object-discrimination tasks, which require several ob￾ject pairs to be learned together, are among the tasks sensitive to FT" lesions. Simple object-discrimination tasks are ones that present to the animal two easily distinguishable objects. A choice of the correct object is rewarded, and the sequence is repeated until animals choose the rewarded object consistently (10 to 20 trials for normal monkeys). Concurrent discrimina￾tion tasks are ones in which different pairs of objects are pre-

198 LARRY R.SQUIRE 鸿 TEO CBL PONS ng the com e in the perirhi ndicated all ofth cal In the fis ddle d N rk:New fs ht 1990 b by pe Memory S em"by I R.So nd S.Z 253.. 1380.Copyrieht 1991 by the steny the rewarded pair (several hundred n succeeding trial. Monkeys and lea eF in98 when the delay between presenta Mishkin valier,1984: ire Zola-Mo 1990).The s cores of both normal and operate d animals ar tain skill-ba orhabit-basda Mala (Mahut.Zola-MoanMoss 198 ce ofth a-Morg Squire,198 )The 1986Z01a Morga Squire,&Amaral,】 a than when mor The most widely used task sensitive has shkin,978).Also,the magnitude of the deficit,that s,the dif d by normal an nd test ng are done pos

198 A LARRY R. SQUIRE B UNIMOOAL AND POLYMOOAL ASSOCIATION AREAS (Frontal, temporal, and parietal lobes) Figure 2. Panel A: A ventral view of the left hemisphere of a monkey brain showing the components of the large H*A+ lesion that first established an animal model of human amnesia. H = hippocampus, A = amygdala; and + refers to the adjacent cortex underlying each structure [periamygdaloid cortex, perirhinal cortex, entorhinal cortex, and parahippocampal cortex]. The view shows the amygdala [square-shaped black-and-white plaid], the hippocampus [black], and the underlying cortical regions typically included in surgical ablations of these structures. Large dots = perirhinal cortex; horizontal lines = periamygdaloid cortex; diagonal lines = entorhinal cortex; fine dots = parahippocampal cortex. Panel B: A schematic view of the structures of the medial temporal lobe important for declarative memory. The entorhinal cortex is the major source of inputs to the hippocampus. Approximately two thirds of the input to entorhinal cortex originate in the perirhinal and parahippocampal cortices. The entorhinal cortex also receives other direct projections from orbital frontal cortex, cingulate cortex, insular cortex, and superior temporal gyrus. As indicated, all of these projections are reciprocal. In the figure, the area designated hippocampus includes dentate gyrus, the cell field of the hippocampus proper, and the subicular complex, sts = superior tem￾poral sulcus; amis = anterior middle temporal sulcus; pmts = posterior middle temporal sulcus; ios = inferior occipital sulcus; CBL = cerebellum; OLF = olfactory bulb; OC = optic chiasm. (Panel A: From "Neuropsychological Investigations of Memory and Amnesia: Findings From Humans and Nonhuman Primates," p. 442, by S. Zola-Morgan and L. R. Squire, 1990, in A. Diamond, The Development and Neural Bases of Higher Cognitive Functions, New York: New York Academy of Sciences. Copyright 1990 by the New York Academy of Sciences. Reprinted by permission. Panel B: From "The Medial Temporal Lobe Memory System" by L. R. Squire and S. Zola-Morgan, 199\, Science 253, p. 1380. Copyright 1991 by the American Association for the Advancement of Science. Reprinted by permission.) sented successively (e.g., eight pairs of objects, five times each during 40 daily trials). Training continues until animals choose consistently the rewarded object of each pair (several hundred trials for normal monkeys). In contrast to these tasks, the learn￾ing of pattern discrimination tasks and learning of the 24-hr concurrent discrimination task (Malamut, Saunders, & Mish￾kin, 1984) are not affected by even larger removals within the medial temporal lobe (for discussions of this difference, see Mishkin, Malamut, & Bachevalier, 1984; Squire & Zola-Mor￾gan, 1983). The point is that monkeys with H+ lesions can suc￾ceed at certain skill-based or habit-based tasks (Mishkin, Mala￾mut, & Bachevalier, 1984; Zola-Morgan & Squire, 1984). The significance of this finding is developed later in the article. The most widely used task sensitive to H1 " lesions has been delayed nonmatching to sample. This task requires an animal to remember a single visual object across a delay (up to 10 min) and then to demonstrate recognition of the object at the end of the delay. Recognition is tested by presenting the animal with a two-choice test (the original object and a new one) and reward￾ing a choice of the new object. New pairs of objects are used on each succeeding trial. Monkeys with № lesions are impaired on delayed nonmatch￾ing to sample (Figure 3), as well as on the other tasks mentioned earlier. Performance is good when the delay between presenta￾tion of the sample object and the choice is short and it becomes poorer as the delay increases (Overman, Ormsby, & Mishkin, 1990). The scores of both normal and operated animals are lower when monkeys are trained and tested postoperatively (Mahut, Zola-Morgan, & Moss, 1982; Zola-Morgan & Squire, 1986; Zola-Morgan, Squire, & Amaral, 1989a) than when mon￾keys are first trained preoperatively and then tested postopera￾tively (Mishkin, 1978). Also, the magnitude of the deficit, that is, the difference between the scores obtained by normal and operated animals, appears numerically larger when training and testing are done postoperatively, as compared with preoper￾atively. However, signal-detection analysis suggests that the defi-

MEMORY AND THE HIPPOCAMPUS 199 Table 1 That Have Been Produced in Monkeys With Reference Selective of memory(decarative) skil-basme n:278eS9t18 diate memory is spared zola-M d L ad Am Diam of Sciences Adapted by permission. cisntheemocodiosaeaaaiCRnonl193817T86 etheen of the task and the abilitytoemere medial temporal together as the performance ceiling is approached.The tures are important for n mory func ions can be obt ed by ups of animais.For xamp in studies of monkeys with 、skills that oud assist in t s a dela ether the n emory imp ess sever medial temn al lohe el.Clo Amaral.Zola-Morgan.&Squire.199:Zola motorskills(Salmon,Zola-Morgan,&Squire,197),andit facil Morgan et al,in press).Ischemia was produced by 15-mi Table 2 Performance of Amnesic Patients and Monkeys With HA Lesions on the Same Tasks Amnesic patients Monkeys with H+A*lesions Te对 + Reference Delayed nonmatching to sample Mishkin,197:Zola-Morgan g.garconcurTentdiscrimination Squire et al.,1988:Oscar-Berman + Zola-Morgan&Squire,1985 omcmtmo Motor skill learning la-Morgar 8nrmtisgnindicatsnoimpair of the s for fullerd ons of

MEMORY AND THE HIPPOCAMPUS 199 Table 1 Characteristics of Human Amnesia That Have Been Produced in Monkeys With Large Bilateral Medial Temporal Lobe Removals Characteristic Reference Selective loss of one kind of memory (declarative) Sparing of skill-based memory Severity of memory impairment dependent on locus and extent of damage Immediate memory is spared Memory is impaired when the number of stimuli exceeds immediate memory capacity Distraction exacerbates the memory impairment Memory impairment is modality general Memory impairment can be enduring Malamut, Saunders, & Mishkin, 1984; Zola￾Morgan & Squire, 1984, 1985 Malamut etal, 1984; Zola-Morgan & Squire, 1984 Mishkin, 1978; Zola-Morgan & Squire, 1985,1986 Mishkin, 1978; Overman, Ormsby, & Mishkin, 1990; Zola-Morgan & Squire, 1985 Zola-Morgan & Squire, 1985 Zola-Morgan & Squire, 1985 Murray & Mishkin, 1984 Zola-Morgan & Squire, 1985 Note. References are to representative studies and are not exhaustive. From "Neuropsychological Investi￾gations of Memory and Amnesia: Findings From Humans and Nonhuman Primates" (p. 438) by S. Zola-Morgan and L. R. Squire, 1990, in A. Diamond, The Development and Neural Bases of Higher Cognitive Functions, New York: New York Academy of Sciences. Copyright 1990 by the New \fork Academy of Sciences. Adapted by permission. cits in these two conditions are equivalent (Ringo, 1988). Preop￾erative training improves postoperative performance of both normal and operated animals and brings their scores closer together as the performance ceiling is approached. The benefit of preoperative training for postoperative performance is proba￾bly due to postoperative savings of some preoperatively ac￾quired information about the rules of the task as well as postop￾erative retention of certain skills that could assist in the task of remembering a new sample object across a delay (e.g., attention and immobility). Some of this information probably survives medial temporal lobe surgery, as has been shown directly for motor skills (Salmon, Zola-Morgan, & Squire, 1987), and it facil￾itates the relearning of the task and the ability to remember new objects across a delay. Useful information about which medial temporal lobe struc￾tures are important for memory functions can be obtained by comparing the severity of memory impairment in different groups of animals. For example, in studies of monkeys with ischemic damage to the hippocampus, one can ask whether a detectable memory impairment is produced in the monkey and whether the memory impairment, if detectable, is less severe or more severe than the impairment associated with the H4 " lesion (Rempel, Glower, Amaral, Zola-Morgan, & Squire, 1991; Zola￾Morgan et al., in press). Ischemia was produced by 15-min Table 2 Performance of Amnesic Patients and Monkeys With H+A* Lesions on the Same Tasks Amnesic patients Test Reference Monkeys with H+A + lesions Reference Delayed nonmatching to sample + Retention of object + discrimination 8-pair concurrent discrimination + Object reward association + 24-hr concurrent discrimination + Motor skill learning - Pattern discrimination + Squire, Zola-Morgan, & Chen, 1988; + Oscar-Herman & Bonner, 1985 Squire, Zola-Morgan, & Chen, 1988 + Squire et al., 1988; Oscar-Berman & + Bonner, 1985 Squire et al., 1988 + Squire etal., 1988 Pursuit rotor task; Brooks & - Baddeley, 1976 Predicted outcome; not yet tested - Mishkin, 1978; Zola-Morgan & Squire, 1985 Zola-Morgan & Squire, 1985 Zola-Morgan & Squire, 1985 Phillips & Mishkin, 1984 Malamut, Saunders, & Mishkin, 1984 Lifesaver task; Zola-Morgan & Squire, 1984 Zola-Morgan & Squire, 1984 Note. References are to representative studies and are not exhaustive. Plus sign indicates impairment; minus sign indicates no impairment. Monkeys may approach the 24-hr concurrent-discrimination task and the pattern-discrimination task differently than humans approach these two tasks. Humans try simply to memorize which stimulus is correct and which is incorrect (i.e., using declarative memory). Monkeys gradually learn incrementally, perhaps by gradually strengthening associations or by "tuning in" relevant dimensions of the stimuli (for fuller discussion, see Zola-Morgan & Squire, 1984). From "Neuropsychological Investigations of Memory and Amnesia: Findings From Humans and Nonhuman Primates" (p. 446) by S. Zola-Morgan and L. R. Squire, 1990, in A. Diamond, The Development and Neural Bases of Higher Cognitive Functions, New York: New York Academy of Sciences. Copyright 1990 by the New \fork Academy of Sciences. Adapted by permission