mste

ltip

tem

Mhave dominated the memory literature in recent

years. While it is beyond the scope of this chapterto represent all these approaches (see Schacter and

Tulving, 1994; and a collection of papers in a special

recent issue of Neurobiology of Learning and Memory

by briefly discussing what is meant by the termsystem and then address the nature of memory sys-tems at some length. This will lead to the surprisingproposal that we change the way we think aboutmemory altogether.lecting? If so, how do these relate to one another, if at

all? Questions like these, asked in a variety of ways,terms in the phrase memory system. What examemory? What do we mean by a system? Wectly isll startone of which supports remembering, the other recol- some brush and ask what we mean by each of thebering or recollecting? Are there multiple memories, Before diving into this thicket, we need to clearthat can be accessed in different ways by remem- comes in multiple forms.left many questions open. Is there a single memory and discusses implications of the fact that memoryremembering and recollecting seem different, he speculates about the separate functions they servecomes in different forms, and pointed out that tiated in the brain, and how they interact. It alsoWhile Aristotle clearly recognized that memory memory and ask how they differ, how they are instan-

memory. This chapter considers the different types ofArs Memoria) hardly surprising that there would be many kinds of

man, shares in the faculty of recollection. (Aristotle, needs of complex organisms are similarly diverse, it is

are acquainted with, none, we venture to say, except Since these experiences are many and varied, and the

(as well as man) have memory, but, of all that we enabling organisms to benefit from prior experience.

but also in this, that many also of the other animals These functions all share the common property of

from that of remembering, not only chronologically, serve specific adaptive purposes (cf., Klein et al., 2002).

at recollecting. But the act of recollecting differs Memory is best conceived as a set of functions thatmemory are not identical with those who are quick about memory and its various forms.It has been already stated that those who have a good provide a new perspective on how one migh1.04.1 Introduction (Vol. 82) for a sampling of views; See Chapters 1.02,1.05), I hope to illuminate some recent history and

t think1.04 Multiple Memory SysteL. Nadel, University of Arizona, Tuscon, AZ, USA

2008 Elsevier Ltd. All rights reserved.

1.04.1 Introduction

1.04.2 What Is a System?

1.04.3 What Is a Memory, and a Memory Sy

1.04.4 What Is Memory, Redux

1.04.5 Multiple Knowledge Systems

1.04.5.1 Types of Knowledge Systems

1.04.5.1.1 Knowing what

1.04.5.1.2 Knowing where

1.04.5.1.3 Knowing when

1.04.5.1.4 Knowing who

1.04.5.1.5 Knowing how

1.04.5.1.6 Knowing valence

1.04.5.1.7 Implications of the existence of mu

1.04.6 The Development of Knowledge Sys

1.04.6.1 The Delayed Emergence of Episodic

1.04.6.2 The Impact of Stress

1.04.7 Conclusions

Referencess: A New View

41

42

m? 42

44

45

46

46

46

47

47

47

47

le systems 48

s 48

emory 49

50

51

5141

definition. First, a system is composed of parts, andsecond, these parts interact in some way to form a

42 Multiple Memory Systems: A New Viewwhole whose properties are more than just the sum ofthe separate parts. As important as what the defini-tion includes is what it does not. A system need notmake up a coherent physical entity, and it need notalways act in an interrelated fashion. The parts of asystem can be distant from one another (an extendedfamily for example), and they can sometimes acttogether and sometimes not. What is more, the partsof a system can be made up of similar things or ofquite different things.

Complex biological systems come in a variety offorms, but one thing we can assume they all share isthat they have achieved their present form through aprocess of selection, shaped by phylogeny, epigeneticneeds, and their environmental niche. The brain isamong the most complex of biological systems and isnot one but many systems that must interact effec-tively to sustain life and maximize the potential forprocreation. Memory, in this context, is but one ofmany neurobiological systems, the one that allowsorganisms to benefit from knowledge obtained dur-ing their individual lifetimes. Organisms also benefitfrom knowledge acquired in the course of phylogenyby virtue of the fact that fundamental aspects of theworld we inhabit are built into the structure of thenervous system. Although this knowledge about theworld may emerge over the course of individualdevelopment, it is in no sense learned or remem-bered: It is simply known. Basic facts about thephysical world, such as the laws pertaining to gravity,space, time, and causality, are examples of this kindof knowledge. The associative rules that govern ourunderstanding of how the things we experience relateto each other are another example (See Chapters 1.03,1.06).

1.04.3 What Is a Memory, and aMemory System?

Memory is, by definition, a record created by anindividual as a result of its past experience. Butwhat is the nature of this record, and how long does1.04.2 What Is a System?

A standard definition of system goes something likethis: A system is a group of interacting, interrelated,or interdependent elements forming a complexwhole. There seem to be two critical parts to thisit last? How is it accessed? It has long been understood

that some memories are evanescent while others last along time. A distinction between short-term and long-

term memory has been part of the scholarly discussion

of memory for more than a century, even though theboundaries between these two are not clearly worked

out. In recent years, the notion of workingmemory hasemerged to complicate matters. For some, short-term

memory and working memory (which may or may not

be the same thing) are memory systems, and given thegeneric definition of systems offered above, this seems

indisputably true. However, these are not the systems

of which memory researchers typically speak whenthey speak of multiple memory systems. The notion of

multiple memory systems emerged well after the idea

that memory could exist in different temporal formswas entrenched in the field.

For much of the past century, most memoryresearchers have adopted a particular framework

that viewed memory as reflecting the presence of a

coherent trace in the brain, an engram that could beidentified if only we knew just what we were looking

for. The difficulty inherent in this pursuit was force-fully expressed by Lashley, whose failed search for

the engram led to the contrarian thought that:

I sometimes feel, in reviewing the evidence on the

localization of the memory trace, that the necessary

conclusion is that learning just is not possible. It is

difficult to conceive of a mechanism which can

satisfy the conditions set for it. (Lashley, 1950: 501)

A possible solution to the problem raised byLashleys work was provided by Hebb (1949) in his

connectionist theory of synaptic change, cell assemblyformation, and phase sequence activity. These postu-

lated mechanisms presumed to show how an engram

could be distributed within the brain and how the fullpattern of the memory trace could be activated by

many different paths, or cell assemblies (See Chapters1.33, 1.34, 1.35). His theory showed how a memorytrace could exist, could avoid total disruption when

damage occurred, and could permit what we now call

pattern completion. It seemed, in other words, thatLashley searched in vain because he was looking for

the wrong thing, and that it still made sense to talk

about a fixed memory trace.In order to understand this debate, it is important

to recognize that the term memory was at that time

reserved for what we now call episodic memory (SeeChapters 1.22, 1.23). The term was used to refer tothe recollection, in Aristotles terms, of specific

Multiple Memory Systems: A New View 43events in ones past, such as what happened yester-

day, or the week/month/year before. This usagepersisted at least until the 1960s. Other forms of

knowledge that reflected prior experience were not

labeled as memory per se. Instead, terms such as habitwere used. One result of this usage was the long-

standing resistance to attributing memories to non-human animals (again reflecting Aristotle).

A major shift in terminology resulted from theemergence of neuroscience and attempts to under-

stand the neural bases of learning and memory. Since

the relevant studies were being done in rodentsand various invertebrates, the notion of what consti-

tuted a memory had to be broadened. The term

memory came to be applied to just about any changein the nervous system that resulted from prior experi-

ence, becoming interchangeable with the notion of

plasticity. Given this much broader definition of mem-ory, it was only a matter of time before the idea that

there were qualitatively different kinds of memory

emerged. I have sketched out my understanding ofsome of the historical forces at play here in earlier

papers (Nadel, 1992, 1994), so I will be relativelybrief here.

When the patient HM was first described(Scoville and Milner, 1957), memory was thought of

in the univocal way described above. Milner (1966)

described the deficit created by medial temporalexcision in HM and several other patients as follows:

The pattern of amnesia which emerges from the

clinical observations of the patients with bilateral

hippocampal damage is one in which long-term

memories survive, as does the ability to attend nor-

mally to on-going events. The essential difficulty

appears to be in adding any new information to the

long-term store. (Milner, 1966: 124)

HM could show some learning of motor skills (cf.Corkin, 1968), suggesting to Milner that the pattern

of amnesia demonstrated by these patients is incom-

patible with a unitary-process theory of memory(Milner, 1966: 131). However, this did not lead

immediately to the notion that there were multiple

memory systems, since such motor learning, after all,did not actually involve memory by the definitions of

the time. Instead, the data from amnesia were taken

to support then current models of memory involvingseparate short-term and long-term systems, with a

memory consolidation process responsible for the

transition from one system to another. Milner sug-gested It is possible that in normal learning, thehippocampal region acts to prime activity in corticalareas where storage is taking place (Milner, 1966:130). From this notion the idea that the hippocampuswas critical for what is now called systems consoli-dation emerged, and it has played a central role inthinking about the hippocampal role in memory eversince (see Nadel, 2007, for a brief history and updateof this idea). Although the concept of multiple mem-ory systems is implicit in this notion, it remainedimplicit for some years.

Research attention turned instead to the issue ofwhich brain areas were critical to the amnesic deficit,and the attempt to establish an animal model of thesyndrome observed in HM. The initial failure toreplicate HMs memory deficit with what wereassumed to be comparable lesions in primates(Orbach et al., 1960) left researchers confused. Hadsignificant changes in the function of the relevantstructures emerged during evolution? Did the medialtemporal lobe do something very different in primatesand humans, not to mention rats? These kinds ofquestions were very much in the air in the 1960s.

In a seminal series of papers in the late 1960s,Warrington and Weiskrantz (1968, 1970) showedthat amnesic patients could indeed benefit fromsome forms of prior experience in addition to showingmotor learning. Their early demonstrations includedthe use of fragmented pictures and words amnesicpatients exposed to such materials took less and lesstime to identify the materials with repetition. Theynoted that there are two types of task, motor learn-ing and retention by partial information, which arerelatively well preserved in amnesic subjects, andthey wondered Is there a common factor linkingperformance on these apparently dissimilar tasks?(Warrington and Weiskrantz, 1970: 630). Theypointed out that the presence of spared memorycapacity might allow one to explain the apparentdiscrepancy in the data from the clinic and fromanimal studies, but this would necessitate droppingthe idea that the defect caused by hippocampaldamage was one of impaired memory consolidation.

From a historical perspective, it is intriguing thatboth research programs, in Canada and the UnitedKingdom, had uncovered the fact that in the amnesicsyndrome some forms of learning and memory werespared while others were impaired, but neitherjumped to the idea that there were multiple memorysystems.

This advance came instead from the domain ofanimal research, in particular several programsfocused on the functions of the rat and monkey

Given the expanded view of memory forced upon us

44 Multiple Memory Systems: A New Viewhippocampus. Three publications in 1974 proposed,in rather different ways, that there were multipleforms of memory and that the hippocampus wasonly responsible for one of them. Gaffan (1974) sug-gested that there were two forms of memory, oneinvolving recognition, the other association, and thatthe hippocampal system was only critical for recog-nition. Hirsh (1974) suggested that memory could beeither context bound or context free, and that thehippocampus was critical only for context-boundmemory. Nadel and OKeefe (1974), building on thediscovery of place cells in the hippocampus of the rat(OKeefe and Dostrovsky, 1971), suggested that thehippocampus was critical only for acquiring cogni-tive maps and that the place learning and episodicmemories that depend upon them, whereas otherforms of learning and memory depended on otherbrain circuits.

OKeefe and Nadel (1978, 1979) laid out a com-prehensive theory that rested squarely on the notionthat there are multiple forms of memory.

there are different types of memory . . . localized in

many, possibly most, neural systems. . ..

there is no such thing as the memory area . . . there

are memory areas, each responsible for a different

form of information storage. The hippocampus . . .

both constructs and stores cognitive maps (OKeefe

and Nadel, 1978: 373374).

The authors argued that the hippocampal systemwas concerned with knowing that, while other mem-ory circuits were concerned with knowing how. Thisidea was taken up by Cohen and Squire (1980), whoshowed that amnesics could learn how to mirror readbut could not remember that they had done so.Within a matter of a few years, the notion of multipleforms of memory was accepted in both the animaland human domains, and though there have beenoccasional attempts to argue against this view, theidea seems firmly rooted.

The answer to the question what memory is seems only to complicate matters, because memory ismany things, not one. But how are these many things,these multiple forms of memory, to be distinguishedfrom one another? Do they reflect the operation ofdifferent systems, in the sense described above? Inorder to answer this one question we need to ask, andanswer, several others. Do the different forms ofmemory reflect different kinds of information? Dothey differ in terms of the processes they instantiate?Do they differ in terms of the brain mechanisms andby neuroscientific exploration of memorys biologicalbases, it seems time to rethink the notion of memoryitself. If there are 5, 6, or 10 different kinds of mem-ory, does it make sense to call them all memory? Myanswer is that it does not. Instead, I propose to goback to using the term as it had been used beforerecent developments widened its application. That is,I believe we should use the term memory solely torefer to what happens when an organism recollectsthe past. All else would best be called knowledge(Nadel and Wexler, 1984). As a function of experi-ence we acquire knowledge, which is represented invarious brain systems. Knowledge is used to generateboth memories and behaviors. What we call a mem-ory is constructed from this knowledge as required.The hippocampal system, serving as a contextualbinding device, a creator of cognitive maps, plays acritical role in this construction process.

This way of thinking has its roots in debates morethan 60 years ago between adherents of differentviews of learning and behavior. Following Tolman(1932), we assumed that organisms always act withpurpose, trying out one or another strategy orhypothesis to deal with their current situationstructures they involve? Do these separate learningand memory systems obey different rules of opera-tion? Most researchers would agree that there aredifferent memory systems only if the answer tomost of these questions is yes.

Because of the central role played by the hippo-campal system in thinking about memory, the earlytendency was to talk about two kinds of memory, onedependent upon hippocampal circuits and the othernot. Thus, OKeefe and Nadel (1978, 1979) talkedabout locale and taxon memory, Cohen (1984) andSquire (1987) talked about declarative and proce-dural systems, and others talked about explicit andimplicit systems, to name but a few. There are manycommonalities among these various ways of handlingthe multiplicity of memory, but they all share the fatethat they are too simplistic. Current approaches sug-gest as many as 5 to 10 kinds of memory. As thenumber of putatively separable memory systemsincreases, it becomes important to step back and askthe fundamental questions again. What exactly do wemean by memory? How is prior experience incorpo-rated into current behavior?

1.04.4 What Is Memory, Redux

edge an animal uses to act in the world comes fromprewired circuits. For example, animals do not have

Multiple Memory Systems: A New View 45to learn de novo that stimuli in close temporal conti-guity are more likely to be causally linked to oneanother than stimuli widely separated in time.

By this analysis, we have multiple knowledgesystems, which we use to generate various forms ofbehavior and to construct memories. Much the sameset of questions applies to these multiple knowledgesystems as applies to what have been called multiplememory systems. How do they differ, how do theyinteract, what rules of operation do they obey, howare they instantiated in the brain? If the reader pre-fers, she or he can continue to think about multiplememory systems as they read the words multipleknowledge systems.

One consequence of this proposed shift in termi-nology is that the idea of a brain system devotedpurely to long-term memory no longer makes sense.This idea, stated perhaps most forcefully by Squireand his colleagues with reference to the medial tem-poral lobe (e.g., Squire, 1994), depended on the ideathat damage to this part of the brain affected onlymemory but not short-term processing or perception.This idea has been criticized both in the past (Horel,1978, 1994) and in recent writings (cf. Ranganath andBlumenfeld, 2005; Hannula et al., 2006), and in myview it should now be retired. It makes more sense tothink about all neural systems as both processing andstoring knowledge, with the differences between sys-tems reflecting the nature of the knowledge beingprocessed and stored, and the timescale of thatstorage.

1.04.5 Multiple Knowledge Systems

What kinds of knowledge does an organism need toacquire about its world in order to survive and evenprosper? Bear in mind we are assuming that funda-mental facts about how the world works are built intothe organisms system by phylogeny and do not haveto be relearned by each generation. What does have(cf. OKeefe and Nadel, 1978: chapter 2). We focusedour attention on spatial behavior and spelled out anumber of different hypotheses an animal could useto get around in the world, including place, guidance(or cue), and orientation (or response) hypotheses.Typically, hypotheses require complex interactionsamong different knowledge systems, only some ofwhich reflect learning. That is, some of the knowl-to be learned are those things that cannot have beenacquired in the course of phylogeny. What are they?

Quite a lot it turns out: who your mother, father,sister, or brother are; who, what, and where youshould approach or avoid; what you should eat anddrink, and when; who you should try to copulatewith, and when (and where); how to do various thingssuch as explore, play, fight, hunt, escape predation,find your way home again, and more. A special formof acquired knowledge concerns those accidentalconjunctions that we call events, when actors, actions,and worldly objects come together in combinationsthat could never have been predicted in advance.What sorts of knowledge/memory systems wouldprovide the best way of learning all this and solvingall the problems life confronts us with?

As a first cut, it is useful to note that organismsappear to need knowledge systems concerned withtwo very different kinds of information first is theneed for knowledge accumulated over many similarevents, and second is the need for knowledge aboutunique occurrences, and the limits these might put onthe application of cumulative knowledge (cf., Kleinet al., 2002). Tulvings (1972) discussion of semanticand episodic memory captured this distinction. I havetried to make the case that the term memory shouldbe reserved for recollections of unique episodes, butthere has lately been considerable interest in cumu-lative knowledge, which has been viewed as allowingorganisms to extract reliable information about thestatistical structure of the environment. A significantcomplication in thinking about knowledge systems isthat the systems engaged in processing these twotypes of information are in constant interaction.Indeed, how to think about the relations betweenepisodic and semantic knowledge, and the brainsystems underlying these forms of information, con-stitutes one of the major challenges for the future. Wereturn to this issue later, after addressing in moredetail the question of what kinds of knowledge sys-tems the brain must contain.

Before turning to a discussion of types of knowl-edge systems, it is worth pointing out that thinking interms of knowledge rather than memory forces us toput the function of knowledge acquisition front andcenter. What propels an organism to gather knowl-edge in the first place? This is a question thatbedeviled early psychologists focused on biologicalcategories and drives. The existence of curiosity andexploration were an embarrassment since the mereacquisition of knowledge could not be simplyrelated to any particular biological drive. Within a

informs an organism about the stuff of which exis-

what systems exist within each of the sensory/

46 Multiple Memory Systems: A New Viewtence is made. All else is subservient to this kind ofknowledge, since in the absence of what there is nowhere, when, why, or how. Or, as Kant put it, form inthe absence of content is meaningless. What knowl-edge provides this content, the semantics of existenceone might say.

The category of what knowledge is complex,comprising several different kinds of knowledge,including:framework that emphasizes knowledge, curiosity andexploration become critical. Instead of being rele-gated to sidebar status, these behaviors deservecareful study in their own right. It remains a remark-able fact about modern cognitive neuroscience thatso little attention has been paid to these core func-tions (cf. Avni et al., 2006; Whishaw et al., 2006; fortwo recent exceptions to this neglect).

1.04.5.1 Types of Knowledge Systems

One way to think about knowledge systems is in thefollowing simplistic fashion an organism needsknowledge about what it experiences, where andwhen things happened, who was involved, the valueof the things experienced, and how to act in the futurewhen confronted with similar experiences (SeeChapters 1.21, 1.22, 1.23). One might imagine thatorganisms extract and store knowledge about each ofthese aspects of experience in separate systems, com-bining this knowledge when required to do so by thedemands of a given situation, or an experimenter-defined laboratory task. As we consider each of theseseparately, it becomes clear that things are not assimple as they might seem. To start, these categoriesare not absolutely clear-cut there is overlap betweenthem in some instances, as we see later. Further, somekinds of knowledge are inferred rather than experi-enced. Perhaps the best example concerns why thingshappen. Organisms make inferences about causality,even though these are rarely backed up by directexperience, and these inferences become an importantpart of their knowledge base. Notwithstanding theseproblems, it still seems worthwhile thinking aboutknowledge systems along these lines. In what follows,I briefly discuss each of these kinds of knowledge. Aserious analysis of this approach would require a sub-stantial expansion of this discussion, one that is beyondthe scope of this chapter.

1.04.5.1.1 Knowing what

It is best to start with the kind of knowledge thatperceptual processing streams. These systems con-tain representations of entities in the world and theirproperties, representations that have been shaped bythe experiences an organism has had with these enti-ties in multiple event contexts. Each time an entity isencountered in the world, its what representation isactivated, and as a function of this new experience,the representation altered. These representations areactivated and hence mobilized in the act of memoryretrieval.

1.04.5.1.2 Knowing where

This category is also complex, because animals needto know several things that could be referred to aswhere knowledge. They need to know where theyare at any given moment. They need to know whereimportant things, such as food, water, safety, andconspecifics, are located, both with respect to anenvironmental framework and with respect towhere they are themselves located at any givenmoment. They need to know where events happened.They also need to know how to get from one place toanother (See Chapters 1.20, 1.21, 1.25).

It seems clear that significant neural resources aredevoted to processing and storing where knowledge.Extensive systems seem devoted to representingwhere things are relative to the current location ofthe organism. What is more, this information seemsto be multiply represented, in that it is captured withrespect to several frames of reference. That is, organ-isms simultaneously know where an object is with What happened What entities were involved What properties these entities haveThese three forms of knowledge are quite different inkind, and one might imagine that they are subservedby quite separate underlying neural and cognitivesystems themselves.

Processing and storing information about whathappened is central to memory for events, or epi-sodes, and hence must incorporate the ability tocapture sequence information. Every such sequencewould consist of entities interacting in space and/ortime. The entities themselves must be represented ina fashion that captures their properties, both struc-tural and functional. The ventral visual stream(Ungerleider and Mishkin, 1982) is a well-knownexample of what I am here calling a what system,and indeed this is the name given to it by Ungerleiderand Mishkin. It is reasonable to assume that similar

suggests that the amygdala plays a central role in

Multiple Memory Systems: A New View 47respect to the head, the eyes, the hands, and the body.This is important because action depends upon suchknowledge. In addition to these various ego-centeredspatial systems, there is a system, centered on thehippocampal formation, that represents an organismslocation in absolute, or allocentric, space. This sys-tem makes use of inputs from multiple sources, andincludes elements such as place cells in the hippo-campus (e.g., OKeefe, 1976), head-direction cells inthe thalamus and postsubiculum (e.g., Taube et al.,1990), and the recently discovered grid-cells in theentorhinal cortex (Hafting et al., 2005).

In addition to providing specific informationabout an animals location in space, this system isalso central to knowledge about context, that is, thespatial setting within which events happen (cf., Nadeland Willner, 1980; Nadel et al., 1985). It is this role,we have argued, that makes the hippocampal cogni-tive mapping system central to episodic memory,which by definition incorporates information aboutwhere an event transpired. It is certainly one of themain challenges for the future to discover why andhow spatial mapping and episodic memory utilize thesame circuits (See Chapter 1.33).

1.04.5.1.3 Knowing when

There are at least two kinds of when knowledge thatorganisms might need. First, they might need toknow when, over a long span of time, an eventoccurred. Was it yesterday, last week, last year?This kind of knowledge is integral to episodic mem-ory, and there remain debates about whether animalsother than humans actually represent it. Second,organisms need to know when within a particularevent the various parts of that event occurred. Thismight seem a trivial matter, but if one argues, as weare arguing, that the various parts of an event areprocessed and represented in separable brain regions,then being able to assemble them in appropriatetemporal order, to know when each of them occurredwith respect to the others, is critical. The simplestexample will suffice to make this point: it makes allthe difference whether A comes before or after B,because the attribution of causality depends uponknowing which of these two entities or events camefirst. An organism that gets temporal order wrong isgoing to make the wrong attributions and is not goingto survive very long.

1.04.5.1.4 Knowing who

This is a somewhat simpler category, and one thatmight be of importance only in species with therepresenting value knowledge, but it is by no means

the only structure so engaged. Extensive midbrain

circuits are devoted to assessing and presumably

storing information about the reinforcing value of

various stimuli an organism comes into contact

with. Portions of the cingulate cortex and frontal

cortex also contribute to this system.1.04.5.1.6 Knowing valence

In addition to storing knowledge about the kinds of

entities they confront in the world, organisms repre-

sent the value of these entities, whether they are good

or bad, exciting or frightening, and so on. This kind of

knowledge plays a critical role in determining not

only how an organism deals with such entities in the

future but also how strongly the knowledge itself is

committed to storage. In general, the greater the

valence, the more robust the storage, at least within

most of the brains knowledge systems. As with all

kinds of knowledge, the use of value information is

highly dependent upon the context within which an

organism is acting, including its internal motivational

context. Knowing that something tastes good is much

more useful when one is hungry than when sated, for

example. Considerable evidence in recent decadescapacity to recognize individuals, itself a function of

the sophistication of its what systems. In humans, it

plays a critical role, of course. George is smarter than

Dick leads to a very different conclusion than Dick is

smarter than George, although both statements

employ the same words.

1.04.5.1.5 Knowing how

This is a big category, comprising all the knowledge

referred to as procedural by many authors. There are

some important distinctions to be drawn, however,

between some of these forms of how knowledge.

For example, knowledge of how to carry out some

kind of motor act, such as brushing your teeth

or driving your car or playing squash, is rather

different than knowledge about how to get from

one place to another (e.g., which route to take, not

how to move). It is not within the scope of this

chapter to go into much detail on this category of

knowledge, but current work on the functions of

the caudate nucleus in particular, and the basal gang-

lia in general, are shedding light on how we know

about how.

knowledge systems that depend upon them, show pro-

48 Multiple Memory Systems: A New View1.04.5.1.7 Implications of the existence of

multiple systems

There are many implications of assuming that thebrain is organized into multiple knowledge systems.Consider the fact that the knowledge about an epi-sode in ones life is dispersed within the brain, acrossmultiple systems. What happened, who was involved,where and when it happened these various aspectsof a memory are widely distributed, which meansthat retrieving and reporting an episode memorymust be a constructive act, much as Bartlett (1932)and others have argued. And being constructed,memory for episodes must be open to error in away that engrams were not supposed to be.

Different knowledge systems, utilizing separableneural substrates, could operate by distinct rules.OKeefe and Nadel (1978), for example, proposedthat there were two quite different brain systemsengaged in learning and remembering, which theycalled the locale and taxon systems. The locale sys-tem was associated with the hippocampal formation,and the various taxon systems were associated withneocortical and subcortical structures. It was sug-gested that learning within these two kinds ofsystems reflected different operating principles. Thetaxon systems obeyed standard laws of reinforcementand followed associative principles. Learning withinthe locale system, by contrast, was assumed to pro-ceed independent of reinforcements such as food,water, safety, or access to a mate animals formedcognitive maps whether rewarded or not. Further,OKeefe and Nadel asserted that learning within thelocale system did not follow associative rules.Consistent with these speculations, Hardt andNadel have shown that learning within the localesystem differs from learning within taxon systems inthat the latter reflect the operation of standard asso-ciative phenomena such as overshadowing andblocking, whereas the former does not. Instead,knowledge acquisition in the locale system is auto-matic, such that new information updates previousrepresentations, whether or not reward contingencieshave changed. Behind the assertion that these twolearning systems obey different rules is the assump-tion that the underlying neural architectures in thesystems subserving these two forms of knowledgediffer in critical ways that allow different learningrules to be implemented in each.

In addition to these system-level implications,there are a number of others that reflect the factthat by being separate, knowledge systems can beaffected differentially by all that life has to offer. Inlonged maturation, much of it postnatal. This hassignificant implications for understanding how bothour memory and performance capabilities change dur-ing early life. A prominent example is the hippocampalformation, portions of which undergo substantial post-natal maturation (cf. Nadel and Hupbach, in press).Evidence about the development of the hippocampuswhat follows, I discuss several examples, includingdevelopment, aging, and the reaction of differentsystems to stress. In each case it will be seen thatknowledge systems vary in how they are affected, andthat these variations help us to understand a numberof phenomena of considerable importance.

1.04.6 The Development ofKnowledge Systems

It is reasonable to assume that each neural systemdevelops at its own rate, and that there are differ-ences among neural systems in this regard. To theextent to which a particular form of knowledgedepends upon a specific neural substrate, it is thenlikely that the various knowledge systems have dif-ferent developmental trajectories. The very capacityto know certain things depends upon the develop-ment of the underlying neural system that processesand represents that kind of knowledge. Until thathappens, such knowing should be impossible. It is areasonable further assumption that still-developingsystems are susceptible to alteration, induced eitherby experience or the unfolding of some genetic pro-gram. Such factors are less likely to act on already-developed systems. This means that ways of knowingcan be more or less influenced by early life experi-ence as a function of when they develop.

Neural systems responsible for processing knowl-edge about objects in the world seem largelyfunctional early in life, as must be the case if organ-isms are to respond appropriately to those entitiesand events that are of critical survival value.However, large differences are seen within this cate-gory. Systems responsible for knowing about thesmell or taste of things seem in general to developbefore systems responsible for knowing about thesight or sound of things. The generalization heremight be that systems concerned with knowledgeabout internal states, and stimuli related to thosestates, develop before systems concerned with exter-nal states.

In most mammals, several neural systems, and the

ing from the late maturation of the hippocampus can

Multiple Memory Systems: A New View 49comes from studies of both structure and function. Atpresent, the best evidence comes from studies withrodents, but we now know enough about primatesand humans to state a general case. Across a widerange of species, it appears that the hippocampus firstbecomes functional at about the natural time of wean-ing. Unfortunately, we do not know when this is forhumans, hence we must make guesses based on ana-tomical, physiological, and behavioral data todetermine just when the hippocampus becomes func-tional in humans. Note that it is unlikely that this, orany other, brain structure suddenly becomes func-tional, as if by the flipping of a switch. It is morelikely that hippocampal function emerges piecemeal,taking a considerable time to reach the adult state.

It has been known for several decades that thedentate gyrus of the rat is particularly subject topostnatal development (see Frotscher and Seress,2006, for a recent review). Large numbers of dentategranule cells are created after birth in the rat in aspecial proliferative zone within the hippocampusitself. Initially it was thought that rodents wereunique, and that postnatal maturation of hippocam-pus was either absent or less prominent in primatesand humans. This, however, turns out not to be thecase. Even in these species, the hippocampal systememerges into function after birth. Hippocampal pyr-amidal cells, unlike dentate granule cells, proliferatein the prenatal stage. But, two other critical compo-nents of any developed brain system the integrationof inhibitory neurons and the myelination of fibers lag behind in hippocampus. Seress and his colleaguesconclude that while cells are generally born early,further steps critical to normal function are quiteprolonged.

In rodents, we can use the appearance of explora-tion and place learning as markers of the emergenceof hippocampal function. Data from such studies ingeneral support what was deduced from studies ofstructure namely, that hippocampal function beginsat about 3 weeks of life in the rat. Since the two majorcognitive functions in humans that depend upon thehippocampus are episodic memory and memory forallocentric spatial location, delayed maturationshould be reflected in the late emergence of thesecapacities.

Infants at quite a young age can learn about spaceas it relates to their body or its parts (eyes, hand,head). They can learn to crawl or walk to objects inspace and readily solve simple spatial tasks such asgo right or go to the door and turn left. These kindsof spatial learning do not, however, depend upon ahelp us understand at least part of the syndromeof infantile amnesia (Nadel and Zola-Morgan, 1984;See Chapters 1.15, 2.37). It is a well-established factthat for most individuals, few if any early episodememories survive into adulthood. It is only after 23years of age that significant numbers of episodememories appear to be formed and retained. Overthe years, there has been considerable debate as towhether this syndrome, first discussed at length byFreud, reflects biological maturation or some otherfactors, such as the mismatch between the nonverbalcoding of early memories and the verbal means usedlater in life to retrieve and report memories or theemergence of a sense of self at around 23 years ofage. Arguments against the biological case depend onassertions that the hippocampus develops early inlife, as noted above. These assertions, as we haveseen, rested either on the use of inappropriate tasksor on incorrect interpretations of the nature of con-textual coding and the hippocampal role in it. Nowthat a consensus has emerged to the effect that hip-pocampus is most likely to become functionalfunctioning hippocampus. Instead they dependupon knowledge systems subserved by other, ear-lier-developing, neural systems. The capacity toknow, and use, allocentric space, on the other hand,does depend upon the hippocampus, and data from avariety of studies suggest that this capacity emergesonly between 18 and 24 months of age in humans (cf.Newcombe et al., 1998).

There are several major implications of the post-natal maturation of the hippocampus. The firstconcerns behavior. We assume adult behaviorreflects the presence of both hippocampal and non-hippocampal systems, what they do and how theyinteract. Prior to hippocampal emergence, however,behavior reflects functions and behaviors dependenton brain systems operational at birth. The secondmajor implication concerns development. A develop-ing system is more susceptible to influence than analready developed one. This is presumably why en-vironmental influences exert a particularly strongimpact on the developing hippocampus.

1.04.6.1 The Delayed Emergenceof Episodic Memory

In general, little evidence of episodic memory, asmeasured in standard recall and recognition tests, isobserved until the age of 3 or 4 years. The absence ofepisode memories from the first 2 years of life result-

50 Multiple Memory Systems: A New Viewbetween 18 and 24 months of age in children(Newcombe et al., 2007; Nadel and Hupbach, inpress), we can conclude that a significant part ofinfantile amnesia reflects biological maturation.

Further support for this view comes from the studyof the unique population of developmental amnesics,individuals with damage to the hippocampus caused,typically, by an early anoxic or ischemic event (cf.Vargha-Khadem et al., 1997). These individuals, men-tioned earlier, went unrecognized for quite a whilebecause they did reasonably well in educational set-tings. Only careful testing brought out the fact that theysuffered from quite severe losses in the domain ofepisodic and spatial memory. Developmental amnesicshave general difficulties orienting in space and time,remembering events, finding their way through any butthe most familiar environments, and rememberingwhere they placed objects. However, they are usuallynot impaired in their social and language developmentand score low to average on standard tests of intelli-gence. They have a relative preservation of semanticmemory and often show normal scores on immediateor short-term episodic memory tests, but they areunable to retain episodic information over longer per-iods of time. Studies using structural magneticresonance imaging suggest that the described symp-toms of developmental amnesia are caused by bilateralhippocampal volume reduction of at least 20%30%.

The increased susceptibility to influence followingfrom postnatal development of the hippocampus man-ifests itself in two rather different ways. First,the hippocampus seems to be very sensitive to envi-ronmental perturbations. Careful studies of theneuropsychological impact of early exposure to lead,for example, suggest that impairment of hippocampalfunction contributes to the resulting cognitive deficit(e.g., Finkelstein et al., 1998). Second, genetic condi-tions that influence development in a general way seemto have their greatest impact on late-developing partsof the nervous system (and other organ systems aswell). There is a kind of selection bias inherent here:Genetic conditions that affect structures formed earlyin development might have such devastating effectsthat they are inevitably lethal. Influences on late-devel-oping structures might be prevalent simply becausethey are the only ones that can be survived.

Down syndrome presents such a case. Thiscondition, resulting from an error in very earlyembryonic life, almost always reflects the existenceof an extra copy of chromosome 21 (cf. Nadel, 2003).As a consequence, extra gene product results, and thisin turn leads to a variety of problems in a host of1.04.6.2 The Impact of Stress

Another way in which the existence of multipleknowledge systems matters is that these systems canbe differentially affected by experience. One veryimportant example is offered by how knowledgesystems are affected by arousal and stress. The litera-ture in this area has been confusing, since evidenceexisted that arousal facilitates memory formation(Reisberg and Heuer, 2004), while at the same timeacute stress, which is undoubtedly arousing, has beenshown to impair memory in several studies (Jacksonet al. 2006; Payne et al., 2006). The best way tounderstand this discrepancy is in terms of multipleknowledge systems and how they are differentiallyaffected by stress. Payne et al., for example, showedthat memory for neutral information is impaired bystress at the same time that memory for emotionalinformation is facilitated. This result is best under-stood by assuming that emotional information (valueknowledge) is handled by one system in the brain, theamygdala, while neutral detail, typically of the back-ground context (where knowledge), is handled byanother brain system, the hippocampus. It has beenestablished that within much of the range of physio-logical stress, amygdala function is enhanced whilebiological systems. In almost all cases, these problemsseem to impact the later-developing parts of therelevant system. Thus, in the nervous system, thehippocampus, cerebellum, and prefrontal cortex, allof which mature late, are disproportionately affected.How these effects translate into the mental retarda-tion observed in Down syndrome remains to bedetermined, and the creation of appropriate mousemodels is moving toward that goal. Williams syn-drome might present another such case, as it hasrecently been shown that children with this syn-drome, caused by deletion of a subset of the geneson chromosome 7, have significant abnormalities inhippocampal structure and function (Meyer-Lindenberg et al., 2005).

It seems clear from these various examples thatsome knowledge systems, and in particular thosecritical for what we are here calling memory, developlater than other knowledge systems critical for suchthings as what and how much knowledge. It is worthpointing out that at the other end of the age scale,aging also has an uneven impact on knowledge sys-tems. Evidence suggests that as in development, it isthe hippocampal system, central to episodic memory,that is most at risk (cf. Burke and Barnes, 2006).

recovered memories, are immense (see Jacobs and

behavior involve decision-making at some level,

Multiple Memory Systems: A New View 51creating linkages between previously disconnectedliteratures on memory and choice.

Acknowledgments

Preparation of this chapter was supported by grantsfrom the National Institute of Neurological Disordersand Stroke (NS044107) and the Department ofHealth Services, State of Arizona, HB2354.Nadel, 1998; Payne et al., 2003, for some discussionof these matters; See Chapters 2.14, 2.44).

1.04.7 Conclusions

That there are multiple systems engaged in acquiringand deploying knowledge gained from experienceseems clear. I have argued that it is better to thinkabout these as knowledge systems rather than asmemory systems. This difference is not a meresemantic quibble, since a number of consequencesflow from this change in terminology. However onedoes refer to these systems, the fact that they exist asseparable entities has a variety of implications that Ihave tried to briefly explore in this chapter.

One final implication that I have not exploredconcerns the fact that the existence of multiple, sepa-rate, systems opens up the possibility of competitionbetween systems for control of behavioral output.Within the domain of spatial behavior there is strongevidence that such competition exists between, forexample, strategies that depend upon the egocentricinformation subserved by caudate and other struc-tures and the allocentric information subserved byhippocampus and related structures (cf. Nadel andHardt, 2004). Similar findings have been reportedrecently for a nonspatial task involving probabilisticclassification (Foerde et al., 2006). It remains forfuture research to explicate these competitive rela-tions in greater detail, as they will ultimately turn outto be extremely important in understanding howorganisms deploy optimal knowledge in various cir-cumstances. Looked at in this way, all forms ofhippocampal function is impaired. Thus, the samestress manipulation can simultaneously increaseacquisition of one kind of knowledge while decreas-ing acquisition of another. The implications of thissimple fact for various legal issues, such as the via-bility of eyewitness testimony, and the veracity ofReferences

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Multiple Memory Systems: A New ViewIntroductionWhat Is a System?What Is a Memory, and a Memory System?What Is Memory, ReduxMultiple Knowledge SystemsTypes of Knowledge SystemsKnowing whatKnowing whereKnowing whenKnowing whoKnowing howKnowing valenceImplications of the existence of multiple systems

The Development of Knowledge SystemsThe Delayed Emergence of Episodic MemoryThe Impact of Stress

ConclusionsAcknowledgmentsReferences