1 E. Tulving, Episodic Memory: from Mind to Brain, Annual Review of

Psychology 53 (2002): 1-25.

MEMORY AND THE BRAIN

Morris Moscovitch

Introduction

Memory is central to our lives, from the mundane and trivial, such asknowing where we put things down, to the social, such as rememberingwho we've met and under what circumstances, to the deeply personal,such as reliving significant experiences that define us. It provides us witha sense of who we are and where we belong physically, socially, andhistorically. It also orients us toward the future. By providing us with asense of time past and what transpired, memory allows us to anticipatethe future and plan for it. For these reasons, there are investigators whobelieve that this type of personal memory, tied as it is to a sense of aconscious self, is a uniquely human attribute, which Tulving1 callsautonoetic consciousness. This latter is specific to humans. Rudiments ofit, however, may exist in non-human species, even insofar as to allow theindividual to reflect on the past and perhaps relive past experiences,though tests have not yet been designed to allow us to questionnon-humans about this aspect of their mental life. What suggests thathumans and non-humans may have certain types of memory in commonis not just our observation of animals whose behaviours resemble ourown, but the knowledge, gained through research, that humans andnon-humans have in common brain mechanisms associated withmemory. By studying memory from the view of brain function we maygain an appreciation not only of the mechanisms that make memorypossible, but also of its variety. As we will learn, memory is not unitary,but multifaceted, consisting of many types, each mediated by differentbrain structures, concerned with different content, and with its own modeof operation. Though inter-related, the memory functions mediated bythese different structures can nonetheless be dissociated one from theother so that some types of memory remain preserved while others areimpaired. By studying neuropsychological disorders following braindamage we can learn how memory is organized not just at a brain level,but also at a psychological level and gain some insight into thoseprocesses that make the mental life of each individual unique.

2 Morris Moscovitch

2

H. J. Markowitsch, Neuropsychology of Memory: System, Organic, and PsychicDisorders, and Functional Imaging Correlates, in A. Yamadori, R. Kawashima. T.Fujii, and K. Suzuki, Frontiers of Human Memory (Sendai, Japan: TohokuUniversity Press, 2002), 305-315; M.D. Kopelman. Disorders of Memory, Brain 125(2002): 2152-2190.

Neuropsychological investigations of memory and the brain beganwith the study of amnesia and will serve as the topic of this essay.Though insights into the neuropsychology of memory have been gainedfrom recent investigations which use neuroimaging techniques that allowone to view the brain as it performs its memory functions, it is still thedisorders of memory following brain damage that provide a better senseof the impact that memory loss has on the individual, and exactly whichaspects of memory can operate independently of one another. I will,however, refer to some neuroimaging studies briefly as the occasiondemands.

The term amnesia, as a description of a clinical disorder, refers to aloss of memory for personal experiences, public events, or information,despite otherwise normal cognitive function. The cause of amnesia canbe either primarily organic, resulting from neurological conditions such asstroke, tumor, infection, anoxia, and degenerative disorders such asAlzheimer's disease, which affect brain structures implicated in memory;or it can be primarily functional or psychogenic, resulting from sometraumatic psychological experience. Although psychogenic disorders arefascinating and provide insights into the relation between emotion andmemory,2 my attention will focus exclusively on organic amnesia. Thefollowing questions will be addressed: What are the characteristics ofamnesia? What structures are involved in forming memories (and whosedamage causes amnesia) and what function does each serve in theprocess? Does amnesia affect recent and remote memories equally, and,by implication, are memory structures involved only in memory formationand shortly thereafter, or are they also implicated in retention andretrieval over long intervals? Are all types of memory impaired in amnesiaor is amnesia selective, affecting only some types of memory and notothers? Finally, what implications does research on amnesia have forresearch and theory on normal memory?

Characteristics of organic amnesia

The following are the typical symptoms of organic amnesia: oldmemories and the sense of self or identity are preserved but the ability toacquire new memories is severely impaired. Though capturing an

Memory and the Brain 3

3

S. S. Korsakoff, Etudes mdico psychologique sur une forme du maladie de la

mmoire,. Revue Philosophique (1899) 28: 501-30. Translated and republished byM. Victor and P. I. Yakovlev, Neurology 5 (1955): 394-406.

4

P. Rozin, The Psychobiological Approach to Human Memory, in R. Rozenzweigand E . L. Bennett, eds., Neural Mechanisms of Learning and Memory(Cambridge, MA: MIT Press, 1976).

5

W. B. Scoville and B. Milner, Loss of Recent Memory after BilateralHippocampal Lesions, Journal of Neurology, Neurosurgery, and Psychiatry 20(1957): 11-21.

essential truth about organic amnesia, this statement needs to bequalified in important ways in the light of new research.

The scientific investigation of organic amnesia effectively began withKorsakoff's 18893 description of its symptoms in people with organic braindisorders at the turn of the century, during what Rozin called the "GoldenAge of Memory Research."4 Likewise, it can be said that the modern eraof neuropsychological research on memory and amnesia was ushered inby Scoville and Milner's5 publication of a single case: H. M., a man in histwenties, who became amnesic after his medial temporal lobes wereneuro-surgically removed bilaterally to control epilepsy which was notresponsive to drug treatment. Some aspects of the memory disorderKorsakoff described are peculiar to a kind of amnesia that now bears hisname (amnesia related to vitaminCthiamineCdeficiency typicallyassociated with alcoholism), while others are common to all forms ofamnesia, including the one suffered by H.M. The symptoms are bestdescribed by contrasting impaired abilities with preserved ones. They areas follows:

(1) Memory is impaired for various types of material, which is whythe amnesia is often referred to as global, though as we shall see not allmemories are affected equally. Perception, intelligence, and othercognitive functions are relatively preserved. Thus, amnesic people canappear normal in conversation and in solving problems as long as theydo not have to refer to events in the recent past. They can play chess,solve cross-word and jigsaw puzzles, comprehend complex instructions,and reason logically. This impression is corroborated by their normalperformance on standard tests of intelligence; on the other hand, they areimpaired on standard tests of memory.

4 Morris Moscovitch

6

A. Baddeley, "Working Memory: Looking Back and Looking Forward," NatureReviews: Neuroscience 4 (2003): 829-839.

7 B. Kolb, I. Q. Whishaw, Fundamentals of Human Neuropscyhology,

4th edition (New York: W. H. Freeman, 1996). See also L. R. Squire and P.Alvarez, Retrograde Amnesia and Memory Consolidation: A NeurobiologicalPerspective, Current Opinion in Neurobiology 5 (1995): 169-77.

(2) The memory function that is impaired is only long-term orsecondary memory, that memory which lasts long after the informationhas been received and registered, such as remembering what happenedyesterday or even a few minutes ago; what is not impaired is short-termor primary memory which is used to hold information briefly in mind, suchas a telephone number or address that one heard for the first time a fewseconds ago. Unaffected also is working memory,6 which is used tooperate on the information held in mind, such as remembering a short listof groceries and re-ordering them according to produce and cannedgoods. As an example, amnesic people have a normal digit span, whichrefers to the number of digits one can repeat immediately in sequence,typically 7 + or 2 (short-term memory), and even to a normal backwarddigit span in which the digits must be recalled in reverse order (workingmemory). They are impaired, however, at retaining and recalling even asub-span list of words after a short interval that is filled with distractingactivity, even if given ample opportunity to rehearse the materialbeforehand. The reason for this is that they lack the neural mechanismsfor storing and retaining information in long-term memory. In a moreordinary life example, amnesic people can remember sentences wellenough to respond to them, but cannot follow a conversation to the end ifreference is made to utterances that occurred at the beginning. The samedissociation between long-and-short-term memory holds for all material,including words, stories, complex visual patterns, faces, melodies, andsome aesthetic stimuli.7

(3) Long-term memory loss in amnesia is most noticeable for eventsand information acquired after the onset of the disorder and into thefuture as well as in the period immediately preceding it, but not forinformation acquired long before that. That is, the individual will have ananterograde amnesia that extends into the future but a retrogradeamnesia limited to the time preceding the onset of the disorder. Thus,amnesic people have difficulty remembering what they learned orexperienced since the onset of the disorder, even their current addressand neighbourhood if they had moved to a new place, but they can

Memory and the Brain 5

8

B. Milner, Amnesia Following Operation on the Temporal Lobe, in C. W. M.Whitty and O. L. Zangwill, eds., Amnesia. (London: Butterworth, 1966).

9

R. Ribot, Diseases of Memory (New York: Appleton, 1882).

10D. L. Schacter and R.L. Buckner, Priming and the Brain, Neuron 20 (1998),

185-195.

remember their old home and neighbourhood, and some old experiencesand events.8 However, as we will see, retention of some types of oldmemories, may be more selective and not as well-preserved as had oncebeen believed, whereas other types follow the general rule. This rule,first espoused by Ribot (1882)9 holds that the old memories are retainedbetter than new ones and are more resilient in the face of brain damage(see below).

(4) A distinction is made in amnesia between memories that arerecollected consciously or explicitly and those that are retrieved implicitlywithout conscious awareness. Anterograde long-term memory loss inamnesia applies only to information that can be recollected consciously,i.e., to explicit memory. Acquisition, retention, and recovery of memorywithout awareness is normal. For example, having studied a set of wordsor pictures, amnesic patients perform poorly when their memory is testedexplicitly for recognition (e.g., which of the following items do yourecognize as having been presented to you?) or recall (e.g., tell me theitems you had studied). However, their memory for studied items, isnormal if they are tested implicitly by seeing how performance is alteredby the study experience without making any explicit reference to thestudy episode. Thus, though they cannot recall or recognize the itemsthey studied, amnesic people will perceive them more quickly andaccurately than items they did not study, or complete them better whenthey are degraded, such as by filling in the missing letters in a word orcompleting the lines in a picture. Performance on these implicit tests ofmemory by amnesics indicates that information about the studied items isheld in memory though they are not aware of that.10 My personalexperience in learning to type illustrates the dissociation between implicitand explicit memory. I learned to type by trial and error instead of takinglessons. When I began taking lessons, I noticed that although my typinghad improved a great deal, clearly indicating that I had learned where

6 Morris Moscovitch

11

For reviews see J. P. Aggleton and M. W. Brown, Episodic Memory, Amnesia,

specific keys were, I nevertheless discovered that I could not explicitlyrecount where each (or for that matter any) key was. My implicit memoryof the location of the keys, demonstrated by my typing skills, was good,but my explicit memory of them was very poor.

These characteristics will serve as the foundation for later discussionof empirical and theoretical investigations of amnesia, normal memory,and brain function. Indeed, research on amnesia, fascinating in its ownright, has had a powerful impact on memory research and theory,especially since the landmark discovery of Scoville and Milner. Thisresearch can be divided into two interacting streams: a functional neuro-anatomical one, concerned with identifying the neuro-anatomicalsubstrates of memory and determining their precise function; and a(neuro)psychological one, concerned with the implication that amnesiahas for understanding normal memory at a functional level. Each will nowbe dealt with in turn.

Neuroanatomy of amnesia

Amnesia is caused by bilateral damage to structures in the limbicsystem and to the adjacent cortex in the medial temporal lobes. Theseregions, though inter-related, form two subsystems, one centered on thehippocampus and the other on the peri-rhinal cortex which is adjacent tothe hippocampus. Each of them connects to separate regions in thethalamus or diencephelon, a mid-line structure beneath the cortex.

The hippocampal formation, in the medial temporal lobes, is themost prominent of the memory structures. It consists of the hippocampusproper with its various subfields and regions, plus the dentate gyrus andthe subiculum. Communication between the hippocampus and neocortexoccurs through a series of relays. The hippocampus is connected directlyto the entorhinal cortex which in turn is connected to theparahippocampal gyrus and peri-rhinal cortex which respectively projectbi-directionally, primarily to the temporal and parietal lobes of theneocortex. There are also projections from the hippo-campus andperi-rhinal cortex via the fornix and anterior cingulate to the mammillarybodies and the dorsomedial nucleus of the thalamus, which are in thediencephalon. The loop of medial temporal and diencephalic structuresconstitutes the limbic system. The hippocampus is thus ideally situated tocollate information about the cognitive (neocortex) as well as theemotional (limbic) state of the organism and bind that information into amemory trace that codes for all aspects of a consciously-experiencedevent.11

Memory and the Brain 7

and the Hippocampal-anterior Thalamic Axis, Behavioral and Brain Sciences 22(1999): 425-89. N. J. Cohen and H. Eichenbaum, Memory, Amnesia and theHippocampal System (Cambridge, MA: MIT Press, 1993). N. J. Cohen and H.Eichenbaum, The Hippocampus and Mechanisms of Declarative Mmemory,Behavioural Brain Research 103 (1999): 123-33. J. O'Keefe, and L. Nadel, TheHippocampus as a Cognitive Map (Oxford: Oxford University Press, 1978).

12

M. D. Kopelman, N. Stanhope and D. Kingsley, Retrograde Amnesia inPatients with Diencephalic, Temporal Lobe, or Frontal Lesions, Neuropsychologia37 (1999): 939-58. See also D. M. Freed, S. Corkin and N. J. Cohen, Forgettingin H.M: A Second Look, Neuropsychologia 25 (1987): 461-72.

Functions of the neuroanatomical substrates of memory

There is considerable debate about the role that each of the componentsof the memory system have and how they interact with one another.Korsakoff's amnesia is associated with damage to the diencephalon,whereas amnesia caused by anoxia, encephalitis, and somedegenerative disorders such as Alzheimer's Disease are associated mostoften with medial temporal lobe damage. Although close inspectionreveals differences in memory loss among the various conditions, somehave not been substantiated reliably and others could not be attributedwith certainty to differences associated with diencephalic and medialtemporal lobe damage, as opposed to damage to other structures thatoften accompanies the various disorders. For example, it had beenproposed that the medial temporal lobes were necessary forconsolidation and retention of new information whereas the diencephalonwas needed only to register and encode new material. Investigatorsclaimed that people with amnesia caused by damage to the diencephelonhad difficulty acquiring information, but once acquired, they retained itnormally. Source investigators claim that people with medial temporaldamage, showed abnormally rapid forgetting, though other investigatorsfound no difference in forgetting rates between amnesic groups, or evenbetween them and controls.12

However, there is, general agreement that people with Korsakoff's,but not medial temporal, amnesia showed a number of memory deficits inaddition to loss of memory for the content of an experienced event.These included confabulation in which the person provides patently falseand often contradictory information without being aware that he or she is

8 Morris Moscovitch

13M.Moscovitch. Confabulation, in D.L. Schacter, ed., Memory Distortion: How

Mind, Brains, and Societies Reconstruct the Past (Cambridge, MA: HarvardUniversity Press, 1995) pp. 228-251; A.Gilboa and M. Moscovitch, The CognitiveNeuroscience of Confabulation: A Review and Model, in A. Baddeley, B. Wilsonand M. Kopelman, eds., Handbook of Memory Disorders, 2nd edition (Chichester,U.K.: John Wiley and Sons, 2002).

14

M. Moscovitch and G. Winocur, The Neuropsychology of Memory and Aging,in F. I. M. Craik, and T. A. Salthouse , eds., The Handbook of Aging and Cognition.(Hillsdale, NJ: Erlbaum, 1992) 315-372. M. Moscovitch and G. Winocur, TheFrontal Cortex and Working with Memory, in D.T. Stuss and R. T. Knight, eds., TheFrontal Lobes (Oxford: Oxford University Press, 2002).

15

Ibid.

16

Ibid., also P. C. Fletcher and R. N. A. Henson Frontal Lobes and HumanMemory: Insights from Functional Neuroimaging, Brain 124 (2001): 849-881.

17

For reviews see J. P. Aggleton and M. W. Brown, Episodic Memory, Amnesia,and the Hippocampal-anterior thalamic axis, Behavioral and Brain Sciences 22(1999): 425-89. N. J. Cohen and H. Eichenbaum, Memory, Amnesia and theHippocampal System. (Cambridge, MA: MIT Press, 1993). H. Eichenbaum, TheHippocampus and Mechanisms of Declarative Memory, Behavioural Brain

doing so, a kind of "honest lying".13 They also have poor memory for thesource and the temporal order of events, susceptibility to interference,and poor meta-memory (knowledge about memory).14 These deficits, allof which involve strategic aspects of memory, were shown to be relatedmore to dysfunction of the frontal lobes of the brain that oftenaccompanies Korsakoff's amnesia, than to diencepahlic damage per se.15

These studies indicated that there is a need to consider the contributionof additional structures, such as the frontal lobes, to help organizememories and to monitor and verify them. Recent functionalneuroimaging studies of memory in normal people have confirmed theimportance of frontal contributions to memory by showing that thesestructures are active whenever memory is being used.16

Influenced by research on animal models of memory, investigatorsfocused on differences among the structures in the medial temporal lobeitself, and its projections to the diencephalon.17 Memory for single items is

Memory and the Brain 9

Research 103 (1999), 123-33. J. O'Keefe and L. Nadel, The Hippocampus as aCognitive Map (Oxford: Oxford University Press, 1978).

18

N. J. Cohen and H. Eichenbaum, Memory, Amnesia and the Hippo-campalSystem (Cambridge, MA: MIT Press, 1993). H. Eichenbaum, The hippocampusand mechanisms of declarative memory, Behavioural Brain Research 103(1999):123-33. H. Eichenbaum and N. J. Cohen, From Conditioning to ConsciousRecollection: Memory Sstems of the Brain. (Oxford: Oxford University Press, 2001).

19

D. Moscovitch and M. P. McAndrews, Material-specific Deficits inRemembering in Patients with Unilateral Temporal Lobe Epilepsy and Excisions,Neuropsychologia 40 (2002): 1335-1342; A. P. Yonelinas The Nature ofRecollection and Familiarity: A Review of 30 Years of Research, Journal ofMemory and Language 46 (2002): 441B517; A. P. Yonelinas, N. E. A. Kroll, J. R.Quamme, M. M. Lazzara, M. J. Sauve, K. F. Widaman, and R. T. Knight Effectsof Extensive Temporal Lobe Damage or Mild Hypoxia on Recollection andFamiliarity, Nature Neuroscience 5 (2002): 1236B1241.

20

Yonelinas, Review, 2002.

dependent on the peri-rhinal system whereas memory for relationalinformation, i.e. the items and the relations among them, whether it beamong spatial elements, among objects, or among words,18 is dependenton the hippocampal system. The lesion evidence in humans is roughlyconsistent with these proposals based on animal models wheredissociations of function are observed along the lines predicted by themodels.19 Recognition memory for single items, and the sense offamiliarity that accompanies that recognition, is disrupted followingperi-rhinal system lesions but is spared in people with hippocampalsystem lesions that do not encroach on the peri-rhinal system. On theother hand, memory of contextually-rich information, such as that whichaccompanies recall and recollection of an experienced event (relationalinformation), rather than a single item, is disrupted following hippocampalsystem lesions but not peri-rhinal system lesions.20

Because amnesic people with circumscribed lesions are rare,investigators have turned to neuroimaging studies in normal people totest the hypothesis that different aspects of memory are mediated bydifferent regions of the medial temporal lobe. In general, the evidencehas been supportive of the hypotheses that have been advanced here,with greater activation in the right hippocampus on tests of relational

10 Morris Moscovitch

21

E. A. Maguire, N. Burgess, J. G. Donnett, R. S. J. Frackowiack, C. D. Frith, andJ. O'Keefe, Knowing Where and Getting There: A Human Navigation Network,Science 280 (1998): 921-924; N. Burgess, E. A. Maguire, J. OKeefe The HumanHhippocampus and Spatial and Episodic Memory, Neuron 35 (2002): 625-641.

22

K. Henke, B. Weber, S. Kneife, H. G. Wieser, and A. Buck, The HippocampusAssociates Information in Memory, Proceedings of the National Academy ofSciences of the United States of America 96: 5884-5889.

23 N. Burgess, E. A. Maguire, and J. OKeefe, The Human Hippocampus and

Spatial and Episodic Memory, Neuron 35 (2002): 625-641; A. M. Owen, B. Milner,M. Petrides, and A. C. Evans. A Specific Role for the Right Parahippocampal Gyrusin the Retrieval of Object-location: A Positron Emission Tomography Study, Journalof Cognitive Neuroscience 8 (1996): 588- 602; J. P. Aggleton, D. McMackin, K.Carpenter, J. Hornak, N. Kapur, S. Halpin, C. M Wiles, H. Kamel, P. Brennan, S.Carton, and D. Gaffan, Differential Cognitive Eeffects of Colloid Cysts in the ThirdVentricle that Spare or Compromise the Fornix, Brain 123 (2000): 800-815; L. L.Eldridge, B. J. Knowlton, C. S. Furmanski, S. Y. Bookheimer, and S. A. Engel,Remembering Episodes: A Selective Role for the Hippocampus during Retrieval,Nature Neuroscience 3 (2002): 1149-1152.

memory for spatial21 and non-spatial information22 and for recollection,23

and in the region of the peri-rhinal cortex on tests of object andobject-location memory and familiarity.

Whatever the final verdict is regarding the role of the various regionsof the medial temporal lobe and diencephalon, the evidence indicatesthat the type, extent, and severity of anterograde amnesia is a function ofthe size, side, and location of the lesion. This rule applies as well to thedeficits indicative of retrograde amnesia.

Retrograde amnesia and memory consolidation: where and when arememories stored?

Whereas studies of anterograde amnesia tell us about memoryacquisition, studies of retrograde amnesia provide clues about the timecourse involved in consolidating long-term memories and thephysiological processes and neural substrates which contribute toconsolidation and storage. Until recently, it was widely believed thatretrograde amnesia associated with medial temporal and diencephalicdamage was short-lasting and temporally-graded, such that memory losswas more severe for information acquired near the time of amnesia onset

Memory and the Brain 11

24

L. Nadel, A. Samsonovich, L. Ryan, and M. Moscovitch, Multiple Trace Theoryof Human Memory: Computational, Neuroimaging, and Neuro-psychological results,Hippocampus 10 (2000): 352-368. A. Gilboa, G. Winocur, C. L. Grady, S. J.Hevenor, and M. Moscovitch, Remembering Our Past: Functional Nneuroanatomyof Recollection of Recent and Very Remote Personal Events, Cerebral Cortex 14(2004): 1214-1225. L. Nadel, A. Samsonovich, L. Ryan, and M. Moscovitch,Multiple Trace Theory of Human Memory: Computational, Neuroimaging, andNeuropsychological Results, Hippocampus 10 (2000): 352-368.

25

E. K. Warrington and H. I. Sanders, The Fate of Old Memories, The QuarterlyJournal of Experimental Psychology 23 (1971): 432-42. M. Kinsbourne and F.Wood, Short-term Memory Processes and the Amnesic Syndrome, in D. Deutsch,and A .J. Deutsch, eds., Short-term Memory. (New York: Academic Press, 1975).

26

T. Fujii, M. Moscovitch and L. Nadel, Consolidation, Retrograde Amnesia, andthe Temporal Lobe, in F. Boller, and J. Grafman, eds., The Handbook ofNeuropsychology, Vol. 4. (L. S. Cermak, section ed.), (Amsterdam: Elsevier, 2000);Also, M. Moscovitch, R. Westmacott, A. Gilboa, D. R. Addis, R. S. Rosenbaum, etal, Hippocampal Complex Contribution to Retention and Retrieval of Recent andRemote Episodic and Semantic Memories: Evidence from Behavioral andNeuroimaging Studies of Healthy and Brain-damaged People, in N. Ohta, C. M.

than for that which was acquired long before. Accordingly, the medialtemporal lobes, particularly the hippo-campus, and possibly thediencephalon, were considered to be temporary memory structures,needed only for memory retention and retrieval until memories wereconsolidated in the neocortex and other structures where they were thenpermanently stored and from where they could be retrieved directly.

Nadel and Moscovitch and others24 identified a number of problemswith the prevailing view. Though the duration of retrograde amnesiasometimes is short, it is more often the case that large medial temporal(or diencephalic) lesions will result in retrograde amnesia for details ofautobiographical events. This may extend for decades, or even a lifetime,far longer than it would be biologically plausible for the consolidationprocess to last. These ideas are consistent with earlier observationsmade by Warrington and Sanders, and Kinsbourne and Wood. 25

However, retrograde amnesia for public events and personalities, is lessextensive and often is temporally graded; this is truer still of semanticmemory which includes knowledge of new vocabulary and facts about theworld and ourselves (e.g. our address, the names of our friends, our job),what some have called personal semantics to distinguish these fromautobiographical episodes.26 The distinction between temporally

12 Morris Moscovitch

MacLeod, and B. Uttl, eds., Dynamic Cognitive Processes (Tokyo: Springer-Verlag, 2005), 333-380.

27

E. Teng, and L. R. Squire, Memory for Places Learned Long Ago is Intact afterHippocampal Damage, Science 400 (1999): 675-77. See also R. S. Rosenbaum,S. Priselac, S. Kohler, S. E. Black, F. Gao, L. Nadel, and M. Moscovitch, RemoteSpatial Memory in an Amnesic Person with Extensive Bilateral HippocampalLesions, Nature Neuroscience 3 (2000): 1044-1048.

28

F. Vargha-Khadem, D. G. Gadian, K. E. Watkins, A. Conneley, W. VanPaesschen, and M. Mishkin, Differential Effects of Early Hippocampal Pathology onEpisodic and Semantic Memory, Science 277: 376-380.

extensive and temporally-limited retrograde amnesia also applies tospatial memory. Schematic cognitive maps of old neighbourhoods thatare adequate for navigation are retained but they lack topographicaldetails and local environmental features, such as the appearance andlocation of particular homes, that would allow the person to have detailedcognitive maps of their locale. 27

Based on this evidence, Nadel and Moscovitch concluded, contraryto the traditional consolidation model, that the function of the medialtemporal system is not temporally limited but that it is needed torepresent even old memories, whether autobiographical or spatial, in rich,multifaceted detail, for as long as the memory exists. Neocorticalstructures, on the other hand, are sufficient to form domain-specific andsemantic representations based on regularities extracted from repeatedexperiences with words, objects, people, environments, and even ofautobiographical episodes that one recollects repeatedly, creating a gistof each episode. The medial temporal lobe system may aid in the initialformation of these neocortical representations, but once formed they canexist on their own. Recent evidence from studies of children whosehippocampus was damaged at birth or shortly thereafter supports thisview. Vargha-Khadem et al28 found that the children acquired sufficientgeneral knowledge (semantic memories) to complete high school eventhough their memory for autobiographical episodes was impaired.Corroborating evidence is also provided by neuroimaging studies ofrecent and remote autobiographical and semantic memory. Thesestudies found that the hippocampus is activated equally during retrieval ofrecent and remote autobiographical memories, but not during retrieval of

Memory and the Brain 13

29 L. Ryan, L. Nadel, K. Keil, K. Putnam, D. Schnyer, T. Trouard, and M.

Moscovitch, The Hippocampal Complex and Retrieval of Recent and Very RemoteAutobiographical Memories: Evidence from Functional Magnetic ResonanceImaging in Neurologically Intact People, Hippocampus, 2001, 11, 707-714; A.Gilboa, G. Winocur, C. L. Grady, S. J. Hevenor and M. Moscovitch, RememberingOur Past: Functional Neuroanatomy of Recollection of Recent and Very RemotePersonal Events, Cerebral Cortex 14 (2004): 1214-1225. F. Haist, J. BowdenGore, and H. Mao, Consolidation of Human Memory over Decades Revealed byFunctional Magnetic Resonance Imaging, Nature Neuroscience, 4 (2001): 1139-1145. L. Nadel, and M. Moscovitch, Memory Consolidation, Retrograde Amnesiaand the Hippocampal Complex, Current Opinion in Neurobiology 7 (1997):217-227. M. Moscovitch, Recovered Consciousness: A Hypothesis concerningModularity and Episodic Memory, Journal of Clinical and ExperimentalNeuropsychology 17 (1995): 276-291.

memory for public events or personal semantics; see Maguire forautobiographical event memory, and Haist et al for famous faces. 29

To account for this evidence, in 1977 Nadel and Moscovitchproposed a Multiple Trace Theory (MTT) according to which a memorytrace of an episode consists of a bound ensemble of neocortical andhippocampal/medial temporal lobe (and possibly diencephalic) neuronswhich represent a memory of the consciously-experienced event.Formation and consolidation of these traces, or cohesion, is relativelyrapid, lasting on the order of seconds or at most days. Each time an oldmemory is retrieved, a new hippocampally-mediated trace is created sothat old memories are represented by more or stronger traces than arenew ones, and therefore are less susceptible to disruption from braindamage than more recent ones. With respect to autobiographicalepisodes, the extent and severity of retrograde amnesia and perhaps theslope of the gradient are related to the amount and location of damage tothe extended hippocampal complex in the neocortical temporal lobes.Remote memories for the gist of events, and for personal and publicsemantics, are not similarly dependent on the continuing function of thehippocampal complex.

Proponents of the standard consolidation model, however, arguethat severe and temporally-extensive retrograde amnesia is observedonly when the lesion extends beyond the hippocampus to includeneocortical structures where remote memories, both auto-biographicaland semantic, are represented. It remains to be determined what specificcontributions the different regions of the medial temporal lobes anddiencephalon make, and how they act in concert with the neocortex and

14 Morris Moscovitch

30

P. Rozin, The Psychobiological Approach to Human Memory, in R. Rozenzweigand E. L. Bennett, eds., Neural Mechanisms of Learning and Memory (Cambridge,MA: MIT Press, 1976).

31

E. Tulving, Elements of Episodic Memory (Oxford: Clarendon Press, 1983). M.Kinsbourne and F. Wood, Short-term Memory Processes and the AmnesicSyndrome, in D. Deutsch and A. J. Deutsch, eds., Short-term Memory (New York:Academic Press, 1975).

32

A. Baddeley, Working Memory (Oxford: Oxford University Press, 1986); andBaddeley, 2003, see footnote 6.

other brain areas to form and retain both detailed, contextually-richrepresentations and context- independent knowledge.

Amnesia and neuropsychological theories of normal memory: whichtypes of memory are affected?

Research on amnesia and other memory disorders has influencedtheories of normal memory at least since the end of the nineteenthcentury but at no time has this been more apparent than in the lastquarter of the twentieth century.30 Because amnesia is selective, affectingsome memories and not others, research on amnesia has been used topromote the view that memory is not unitary, but rather consists ofdissociable components, each governed by its own principles andmediated by different structures.For example, evidence showing that retrograde amnesia affects detailedautobiographical memory more than semantic memory supports to theidea that episodic and semantic memory are functionally andneurologically distinct.31

One of the characteristics of amnesia is that it affects long-term orsecondary memory more than short-term or primary memory. Thisobservation was one of the crucial pieces of evidence used in the 1960sand early 1970s to argue for a functional separation of memory into atleast these two major components. The idea has since become almostuniversally accepted and opened the field to investigation of thefunctional differences between the two major components, todevelopment of the concept of working memory,32 and to identification ofthe mechanisms supporting working and primary memory in the frontaland posterior neocortex.

Memory and the Brain 15

33L.S. Cermak, ed., Human Memory and Amnesia. (Hillsdale, NJ: Erlbaum, 1982);

N. J. Cohen and H. Eichenbaum. Memory, Amnesia and the Hippocampal System(Cambridge, MA: MIT Press, 1993); B. Kolb, and I. Q. Whishaw, Fundamentals ofHuman Neuropscyhology 4th edition (W. H. Freeman: New York, 1996); M.Moscovitch, E. Vriezen, and Y. Goshen-Gottstein, Implicit Tests of Memory inPatients with Focal Lesions or Degenerative Brain Disorders, in F. Boller and H.Spinnler, eds., The Handbook of Neuropsychology, Vol. 8. (Amsterdam: ElsevierPress, 1993), 133-173; D. L. Schacter, and R. L. Buckner, Priming and the Brain,Neuron 20 (1998), 185-195; L. R. Squire, and S. M. Zola, Episodic Memory,Semantic Memory, and Amnesia, Hippocampus 8 (1998): 205-211.

Beginning in the late 1960s, research on animal models and humansindicated that the formation and retention of some types of long-termmemory are spared in amnesia, but there is continuing debate on howbest to characterize them. It is generally accepted that only consciousrecollection is affected by amnesia. Memory retrieval without awarenessseems to be intact. For example, it was noted that people with bilateralmedial temporal-lobe lesions, such as the patient H.M., could learn andretain motor skills for months or years, though he had no memory of thelearning episode minutes after it was over. The same was true ofperceptual skills involved in reading mirror-reversed words or inidentifying degraded or fragmented pictures and words. That more thanjust a skill was involved became apparent when patients could completeor identify items to which they had been exposed more accurately andmore quickly than new items, which suggests that they stored informationpeculiar to that item even though at a conscious level they could notrecall or recognize that they had studied it. At the same time, similarphenomena were reported in normal people for material they could notconsciously recollect, which suggests that the dissociation betweenmemory with and without awareness was not peculiar to amnesia but wasindicative of something fundamental about the organization of memory.33

These observations not only had a major impact on our understanding ofnormal memory, but were also instrumental in re-vitalizing research onunconscious processes in cognition and emotion, an area of investigationthat had been abjured by mainstream experimental psychology for almosta century.

A number of terms have been used to refer to memory with andwithout awareness, including declarative and non-declarative (orprocedural) memory, direct and indirect memory, memory and habit,controlled and automatic memory. I prefer the terms explicit and implicitmemory because they are descriptively accurate, refer to the types oftests used to assess memory, and are close to theoretically neutral as tothe processes and mechanisms involved. In the last twenty years,research on normal people and on people with amnesia has identified a

16 Morris Moscovitch

34

M. Moscovitch, Memory and Working with Memory: A Component ProcessModel Based on Modules and Central Systems, Journal of Cognitive Neuroscience4 (1992): 257-267; C. L. Wiggs, and A. Martin, Properties and Mechanisms ofPerceptual Priming, Current Opinion in Neurobiology 8 (1998): 227-233.

number of characteristics of implicit memory. The structures implicated inamnesia, the medial temporal lobes and diencephalon, are not neededfor normal implicit memory. Instead, performance is mediated by a varietyof structures, depending on the type of implicit memory that is beingtested. Like explicit memory, implicit memory is not unitary and consistsof a variety of different subtypes. Although a detailed description of allthem is not possible, three types of which we know a great deal havebeen identified: perceptual implicit memory or priming, conceptual implicitmemory, and procedural memory.

On tests of perceptual implicit memory, the test stimulus resemblesthe studied target perceptually (e.g., a perceptually de-graded version ofit, or even an identical repetition of it) whereas on tests of conceptualimplicit memory, the test stimulus resembles the target semantically (e.g.,having studied the word "horse", the participant may be asked to make asemantic decision to the word during tests, or asked to produce it inresponse to the word "animal".) Performance is measured by speed oraccuracy of the response to the test stimulus, without explicit reference tothe studied items, and the implicit nature of the test is corroborated if theperson is not aware that the response or test item refers to a studiedstimulus. Increases in accuracy or decreases in response latency to oldstudied items as compared to new ones are indicative of implicit memoryfor the studied items.

Research on perceptual implicit memory suggests that performanceis mediated by the same perceptual modules or representation systemsof the posterior neocortex that are involved in perceiving the stimuli.These modules are modified by the act of processing some givenmaterial, leaving behind a record of that process. As a result, processingis faster and more accurate when the system is re-exposed to thatmaterial as compared to new material.34 The modules are domainspecific, in that separate ones exist for objects, faces, words, andpossibly places. They are also pre-semantic in that they do not representthe meaning of the item but only its structure. Thus, performance onperceptual implicit tests is sensitive to changes in perceptual or structuralaspects of the stimulus but not to changes in semantic aspects.

The opposite holds for performance on conceptual implicit tests,which is mediated by conceptual systems in the lateral temporal lobe and

Memory and the Brain 17

35

For reviews on implicit memory see Moscovitch, Dobbins L. Schacter, Vriezenand Goshen Gottstein, Schacter and Buckner. M. Moscovitch, E. Vriezen, and Y.Goshen-Gottstein, Implicit Tests of Memory in Patients with Focal Lesions orDegenerative Brain Disorders, in F. Boller and H. Spinnler, eds., The Handbook ofNeuropsychology, Vol. 8 (Amsterdam: Elsevier Press, 1993), 133-173.

36

M. Moscovitch, E. Vriezen, and Y. Goshen-Gottstein, Implicit Tests of Memoryin Patients with Focal Lesions or Degenerative Brain Disorder, in F. Boller and H.Spinnler, eds., The Handbook of Neuropsychology Vol. 8. (Amsterdam: ElsevierPress, 1993), 133-173.

inferior frontal cortex.35 As with perceptual modules, improvement inperformance results from modifications in the conceptual systemsthemselves.

Tests of procedural implicit memory involve learning rules, motorsequences, conditioned responses, and subjective probabilities ofstimulus-response associations without explicit memory for any of them.The structures that have been identified as crucial for procedural learningare the cerebellum for classical conditioning, and the basal ganglia, whichare subcortical structures concerned, in part, with motor function. There issome indication of pre-frontal involvement if learning rules or motorsequences involves strategic, sequential, or inhibitory components.36

Changes in these structures during execution of procedures underlies thechanges in performance observed on implicit tests of procedural memory.

In studying implicit memory, great care must be taken to insure thatperformance on tests of memory that are ostensibly implicit are notcontaminated by explicit components, such as might occur when askingparticipants to identify degraded stimuli they had studied earlier. It is forthis reason that studies of amnesic patients are so useful. Because theirexplicit memory is so poor, equivalent performance between amnesic andnormal people on an implicit test is taken as evidence that the test inquestion was not contaminated by explicit memory.

Amnesia and beyond: a neuropsychological, component process modelof memory

Studies of memory in amnesia have indicated that memory is notunitary but rather consists of a variety of different forms, each mediatedby different component processes which in turn are subserved bydifferent neural mechanisms. Because neither short-term or workingmemory, nor implicit memory is impaired in amnesia, we might conclude

18 Morris Moscovitch

37

M. Moscovitch, Recovered Consciousness: A Hypothesis concerningModularity and Episodic Memory, Journal of Clinical and ExperimentalNeuropsychology 17 (1995): 276-291. M. Moscovitch, Memory and Working withMemory: A Component Process Model Based on Modules and Central Systems,Journal of Cognitive Neuroscience 4 (1992): 257-267.

that these types of memory are not dependent on the medial temporallobes and diencephalic structures which are damaged in amnesia. Thesestructures, however, are necessary for conscious recollection oflong-term, episodic memories. It has been proposed that any informationthat is consciously experienced is picked up obligatorily and automaticallyby the hippo-campus and related structures in the medial temporal lobesand diencephalon. However, these structures bind into a memory tracethose neural elements in the neocortex and elsewhere that mediate theconscious experience of an event. The episodic memory trace thusconsists of an ensemble of hippocampal and neocortical neurons. Thehippocampal component of the trace acts as an index or file entrypointing to the neural elements in the neocortex, which represent both thecontent of the event and the conscious experience of it. "Consciousness"is therefore part of the memory trace. Retrieval occurs when an externalor internally generated cue triggers the hippocampal index, which in turnactivates the entire neocortical ensemble associated with it. In this way,we recover not only the content of an event but the consciousness thataccompanied our experience of it. In short, when we recover episodicmemories, we recover conscious experiences.37

According to this model, both encoding and retrieval ofconsciously-apprehended information via the hippocampus and relatedstructures is obligatory and automatic, yet we know from experience andfrom experimental investigation that we have a measure of control overwhat we encode and what we retrieve from memory. Moreover, ifencoding is automatic and obligatory, the information cannot beorganized, yet memory appears to have some temporal and thematicorganization. How can we reconcile this model of memory with what weknow about how memory works? One solution is that other structures,particularly those in the frontal lobes, control the information delivered tothe medial temporal and diencephalic system to encode, initiate andguide retrieval, monitor, and help interpret and organize the informationthat is retrieved. By operating on the medial temporal and diencephalicsystem, the frontal lobes act as working-with-memory structures thatcontrol the more reflexive medial temporal and diencepahlic system andconfer a measure of intelligence and direction to it. Such a

Memory and the Brain 19

38

M. Moscovitch, Memory and Working with Memory: A Component ProcessModel Based on Modules and Central Systems, Journal of Cognitive Neuroscience4 (1992): 257-267. M. Moscovitch and G. Winocur. The Frontal Cortex and Workingwith Memory, in D.T. Stuss and R.T. Knight, eds., The Frontal Lobes. (Oxford:Oxford University Press, 2002).

39

See Fletcher and Henson, footnote 16.

40

See Winocur and Moscovitch, footnotes 14, 24, 30, 44.

complementary system is needed if memory is to serve functions otherthan mere retention and retrieval of past experiences.38

As invaluable as studies of amnesia have been to our understandingof memory, in order to have a full appreciation of how memory worksthose studies need to be supplemented by investigations of memory inpeople with other types of disorders, particularly those implicating thefrontal lobes. The realization that the frontal lobes play a crucial role inmemory was slow in coming, but once it did, there was a burgeoning ofresearch on the frontal lobes, fueled by developments in functionalneuroimaging, that rivaled, and in recent years surpassed, research onthe medial temporal lobes. As a result, investigators have identified anumber of crucial regions of the pre-frontal cortex that are implicated inencoding, retrieval, monitoring and verification, and have begun mappingtheir interaction with the medial temporal lobes and posterior neocortex.Though the precise function of each region is still uncertain and beingdebated vigorously,39 it is becoming increasingly clear that memory relieson a network of structures, of which the medial temporal lobes and pre-frontal cortex are important parts.40 The interaction among thesestructures accounts for the formation, retention, and retrieval of durablememories which can be used flexibly in the service of ones goals andaspirations, and which con-tribute to ones sense of a personal past andfuture, and possibly ones identity.