Review
Associative memory and the medial temporal lobes

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Associative recognition and recall depend on structures in the medial temporal lobes (MTLs). There is disagreement about whether associative memory is functionally heterogeneous, whether it is functionally distinct from intra-item associative memory and how the MTLs contribute to this kind of memory. Despite an increase in research on associative memory, work has lacked a theoretical framework to guide design and interpretation of studies. One view provides a useful framework by postulating that associative memories differ in the degree to which their informational components converge in MTL structures that create familiarity-supporting or recollection-supporting memory representations. Using this framework, we consider psychological, lesion and functional imaging evidence, highlighting how informational convergence in the brain underlies the associative nature of both memory and perception.

Introduction

Declarative memory comprises memory for personal experiences (episodic memory) and for facts and concepts (semantic memory). Declarative memory is essentially associative, linking together component parts (e.g. words and objects) either directly or via spatial, temporal or other kinds of relationships. These components are represented by neural activity in different parts of the neocortex that project to the medial temporal lobes (MTLs) where they are integrated to create associative memories. At retrieval, one component can cue recall of other components, which reactivates part or all of a ‘memory’. Therefore, recall is inherently associative. Alternatively, previously encoded episodic or semantic information can be recognized. According to the dual-process model 1, 2, recognition memory is mediated by recollection and familiarity. Recollection is cued recall of associated information within a recognition situation; familiarity involves no recall and occurs when exposure to information leads to a ‘feeling’ of memory.

Some researchers believe that familiarity occurs only for item memories and not for inter-item associations (e.g. Ref. [3]). However, others believe that familiarity also occurs for inter-item associations (e.g. Ref. [4]). Items (e.g. cars) comprise components (e.g. lights and windows) that are bound together in such a way that they are, typically, consciously perceived and remembered as single entities. Therefore, item memories are also associative. New items (e.g. unknown words or faces) can be created at encoding through a process of unitization or intra-item association, which binds components together, often using an established spatial framework (e.g. the layout of a face). This creates a representation that is usually perceived and remembered as one entity. However, there are no objective criteria for identifying whether unitization has occurred. The occurrence of unitization needs to be identified by markers other than the presence of familiarity. When two items are encoded together without an obvious ‘object-creating’ framework, it is difficult to prove that a new item has been created when the result does not ‘feel’ unequivocally like an entity. Intuitively, the speed with which new item memories are formed should depend on how easily components fit into a pre-existing template (e.g. a face framework). However, identification of such templates is subjective and, therefore, there might be disagreements. Progress is possible provided that associations that are agreed to be unitized carry measurable costs (e.g. greater difficulty in perceiving and recognizing components) that are not shared by equally well-learned associations that are agreed to be non-unitized.

Despite these difficulties, investigation is needed into whether the functional and neural bases of intra-item associative memory and non-unitized inter-item associative memory differ. Furthermore, inter-item associative memories have distinct characteristics that might have functionally and neurally different bases. Thus, within-domain associative memories are not perceived and remembered as one entity. They form between the same or very similar kinds of items (e.g. two faces; a door and a window) that are likely to be represented by activity in closely adjacent and interacting neocortical neurons. The items in these memories feel like they ‘go together’, but they do not form a single entity. Between-domain associative memories are also not perceived and remembered as one entity. They form between different kinds of items that might come from distinct sensory modalities (e.g. face–voice) or link items spatially, temporally or via another kind of relationship (e.g. A angered B). These items and relationships are likely to be represented by patterned activity in relatively distant and weakly connected neocortical neurons. This processed information feeds into the MTLs where it is integrated to create associative memories and possibly perceptual representations.

Declarative memory comprises intra-item, within-domain and between-domain associations that are bound into memory in the MTLs (Figure 1). How well each of these kinds of associative memories supports familiarity and recollection should be fully explored using appropriate memory-testing procedures (Box 1, Box 2). Current views on how the MTLs support the processes that underlie these associations are discussed below, after which psychological, lesion and functional neuroimaging evidence that discriminates between these views are considered in turn.

Section snippets

The role of the MTLs in associative memory

One view that implies neurofunctional differences among intra-item, within-domain and between-domain memories states that different MTL structures mediate within-domain and between-domain memory in qualitatively distinct ways [4]. This domain dichotomy (DD) view proposes that the perirhinal cortex has a key role in mediating recognition memory for unitized associations and for non-unitized, within-domain associations (e.g. face–face associations) (Figure 2). The perirhinal cortex supports

Psychological evidence from normal subjects

The views described above make different predictions about how well recognition of within- and between-domain associations is supported by familiarity. There is evidence that recognition for rapidly acquired intra-item associations is well supported by familiarity (e.g. Ref. [3]). Most research on within-domain associations has focused on learning to associate unrelated pairs of words. Initially, this research suggested that there was little, if any, familiarity for rapidly learned

Human and animal lesion evidence

The DD view predicts that selective hippocampal lesions will disrupt recognition of between-domain associations but only mildly disrupt within-domain and intra-item associative recognition. The extent of the recognition deficit should be a function of how well familiarity memory can support recognition. The patient YR, who had relatively selective hippocampal lesions, showed the pattern of recognition that is predicted by this view. YR's item familiarity was normal [12] and her performance on

Functional imaging studies in humans

If the MTLs create (encode) and reactivate (retrieve) associative memory representations, encoding leading to subsequent memory should involve the same MTL sites as retrieval, unless the MTL itself produces memory feelings [33] or the information that is encoded and remembered is not the same. Several studies have shown that encoding that leads to item familiarity activates the perirhinal cortex (e.g. Refs 34, 35) and that familiarity itself deactivates this region (e.g. Refs 36, 37, 38), but

Concluding comments

Currently, psychological, lesion and functional imaging evidence is broadly consistent with the DD view, but no studies have directly contrasted the predictions of the different views. A central set of issues concerns whether within-domain associations support associative familiarity more than between-domain associations do, and how much this is influenced by encoding instructions and retrieval test formats. How much familiarity for different kinds of unitized and non-unitized association is

Acknowledgements

We thank Christine Denby for her contributions to the preparation of Figure 1 and Wael El-Deredy, Donna Lloyd, Ellen Poliakoff and Dimitris Tsivilis for their helpful comments on the revised draft.

References (80)

  • S.A. Bunge

    Prefrontal and hippocampal contributions to visual associative recognition: interactions between cognitive control and episodic retrieval

    Brain Cogn.

    (2004)
  • R. Sperling

    Putting names to faces: successful encoding of associative memories activates the anterior hippocampal formation

    Neuroimage

    (2003)
  • R. Vandenberghe

    Blood flow in human anterior temporal cortex decreases with stimulus familiarity

    Neuroimage

    (1995)
  • J.Z. Xiang et al.

    Differential neuronal encoding of novelty, familiarity and recency in regions of the anterior temporal lobe

    Neuropharmacology

    (1998)
  • M.D. Rugg et al.

    Human recognition memory: a cognitive neuroscience perspective

    Trends Cogn. Sci.

    (2003)
  • U. Rutishauser

    Single-trial learning of novel stimuli by individual neurons of the human hippocampus–amygdala complex

    Neuron

    (2006)
  • P.A. Gooding

    A meta-analysis of indirect memory tests for novel material in organic amnesics

    Neuropsychologia

    (2000)
  • G. Mandler

    Recognizing: the judgment of previous occurrence

    Psychol. Rev.

    (1980)
  • A.P Yonelinas

    Recognition memory of faces: when familiarity supports associative recognition judgments

    Psychon. Bull. Rev.

    (1999)
  • A.R. Mayes

    Associative recognition in a patient with selective hippocampal lesions and relatively normal item recognition

    Hippocampus

    (2004)
  • K.A. Norman et al.

    Modeling hippocampal and neocortical contributions to recognition memory: a complementary-learning-systems approach

    Psychol. Rev.

    (2003)
  • L.R. Squire

    The medial temporal lobe

    Annu. Rev. Neurosci.

    (2004)
  • A.P. Yonelinas

    Recognition memory ROCs for item and associative information: the contribution of recollection and familiarity

    Mem. Cognit.

    (1997)
  • W.E. Hockley et al.

    Familiarity and recollection in item and associative recognition

    Mem. Cognit.

    (1999)
  • Quamme et al. (2007) Effect of unitization on associative recognition in amnesia. Hippocampus. DOI: 10.1002/hipo.20257...
  • J.S. Holdstock

    Under what conditions is recognition spared relative to recall after selective hippocampal damage in humans?

    Hippocampus

    (2002)
  • A.R. Mayes

    Relative sparing of item recognition memory in a patient with adult-onset damage limited to the hippocampus

    Hippocampus

    (2002)
  • P.J. Brasted

    Role of the hippocampal system in associative learning beyond the spatial domain

    Brain

    (2003)
  • J.K. Parkinson

    A selective mnemonic role for the hippocampus in monkeys: memory for the location of objects

    J. Neurosci.

    (1988)
  • D. Gaffan

    Effects of fornix transection upon associative memory in monkeys: role of the hippocampus in learned action

    Q. J. Exp. Psychol. B

    (1984)
  • E.A. Murray

    Neural substrates of visual stimulus–stimulus association in rhesus monkeys

    J. Neurosci.

    (1993)
  • F. Vargha-Khadem

    Differential effects of early hippocampal pathology on episodic and semantic memory

    Science

    (1997)
  • E. Düzel

    Brain activity evidence for recognition without recollection after early hippocampal damage

    Proc. Natl. Acad. Sci. U.S.A.

    (2001)
  • E.J. Barbeau

    Preserved visual recognition memory in an amnesic patient with hippocampal lesions

    Hippocampus

    (2005)
  • K. Henke

    Memory lost and regained following bilateral hippocampal damage

    J. Cogn. Neurosci.

    (1999)
  • J.S. Holdstock

    Item recognition is less impaired than recall and associative recognition in a patient with selective hippocampal damage

    Hippocampus

    (2005)
  • K.S. Giovanello

    Disproportionate deficit in associative recognition relative to item recognition in global amnesia

    Cogn. Affect. Behav. Neurosci.

    (2003)
  • J.P. Aggleton

    Differential cognitive effects of colloid cysts in the third ventricle that spare or compromise the fornix

    Brain

    (2000)
  • G. Weniger

    Impaired associative memory in temporal lobe epilepsy subjects after lesions of hippocampus, parahippocampal gyrus, and amygdala

    Hippocampus

    (2004)
  • C.E. Stark et al.

    Hippocampal damage equally impairs memory for single items and memory for conjunctions

    Hippocampus

    (2003)
  • Cited by (0)

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