Lynn Nadel

The Hippocampus as a Cognitive Map

Table of Contents: Chapter 1 - Remembrance of places past: a history of theories of space / Chapter 2 - Spatial behaviour / Chapter 3 - Anatomy / Chapter 4 - Physiology / Chapter 5 - Introduction to the lesion review / Chapter 6 - Exploration / Chapter 7 - Discrimination and maze learning / Chapter 8 - Aversively motivated behaviour / Chapter 9 - Operants: the limited role of the locale system / Chapter 10 - Reactions to reward change / Chapter 11 - Maintenance behaviours / Chapter 12 - Stimulation studies / Chapter 13 - Long-term memory / Chapter 14 - An extension of the theory to humans / Chapter 15 - The amnesic syndrome

Memory consolidation, retrograde amnesia and the hippocampal complex

Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subjects lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re‐experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra‐hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time‐limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory.

The cognitive neuroscience of remote episodic, semantic and spatial memory

The processes and mechanisms implicated in retention and retrieval of memories as they age is an enduring problem in cognitive neuroscience. Research from lesion and functional neuroimaging studies on remote episodic, semantic and spatial memory in humans is crucial for evaluating three theories of hippocampal and/or medial temporal lobe-neocortical interaction in memory retention and retrieval: cognitive map theory, standard consolidation theory and multiple trace theory. Each theory makes different predictions regarding first, the severity and extent of retrograde amnesia following lesions to some or all of the structures mentioned; second, the extent of activation of these structures to retrieval of memory across time; and third, the type of memory being retrieved. Each of these theories has strengths and weaknesses, and there are various unresolved issues. We propose a unified account based on multiple trace theory. This theory states that the hippocampus is needed for re-experiencing detailed episodic and spatial memories no matter how old they are, and that it contributes to the formation and assimilation of semantic memories and schematic spatial maps.

Spatial memory deficits in patients with lesions to the right hippocampus and to the right parahippocampal cortex.

Spatial memory tasks, performance of which is known to be sensitive to hippocampal lesions in the rat, or to medial temporal lesions in the human, were administered in order to investigate the effects of selective damage to medial temporal lobe structures of the human brain. The patients had undergone thermo-coagulation with a single electrode along the amygdalo-hippocampal axis in an attempt to alleviate their epilepsy. With this surgical technique, lesions to single medial temporal lobe structures can be carried out. The locations of the lesions were assessed by means of digital high-resolution magnetic resonance imaging and software allowing a 3-D reconstruction of the brain. A break in the collateral sulcus, dividing it into the anterior collateral sulcus and the posterior collateral sulcus is reported. This division may correspond to the end of the entorhinal/perirhinal cortex and the start of the parahippocampal cortex. The results confirmed the role of the right hippocampus in visuo-spatial memory tasks (object location, Rey-Osterrieth Figure with and without delay) and the left for verbal memory tasks (Rey Auditory Verbal Learning Task with delay). However, patients with lesions either to the right or to the left hippocampus were unimpaired on several memory tasks, including a spatial one, with a 30 min delay, designed to be analogous to the Morris water maze. Patients with lesions to the right parahippocampal cortex were impaired on this task with a 30 min delay, suggesting that the parahippocampal cortex itself may play an important role in spatial memory.

The Neuropsychology of Down Syndrome: Evidence for Hippocampal Dysfunction

This study tested prefrontal and hippocampal functions in a sample of 28 school-aged (M = 14.7 years, SD = 2.7) individuals with Down syndrome (DS) compared with 28 (M = 4.9 years, SD = .75) typically developing children individually matched on mental age (MA). Both neuropsychological domains were tested with multiple behavioral measures. Benchmark measures of verbal and spatial function demonstrated that this DS sample was similar to others in the literature. The main finding was a significant Group x Domain interaction effect indicating differential hippocampal dysfunction in the group with DS. However, there was a moderate partial correlation (r = .54, controlling for chronological age) between hippocampal and prefrontal composite scores in the DS group, and both composites contributed unique variance to the prediction of MA and adaptive behavior in that group. In sum, these results indicate a particular weakness in hippocampal functions in DS in the context of overall cognitive dysfunction. It is interesting that these results are similar to what has been found in a mouse model of DS. Such a model will make it easier to understand the neurobiological mechanisms that lead to the development of hippocampal dysfunction in DS.

Précis of O'Keefe & Nadel's The hippocampus as a cognitive map

Theories of spatial cognition are derived from many sources. Psychologists are concerned with determining the features of the mind which, in combination with external inputs, produce our spatialized experience. A review of philosophical and other approaches has convinced us that the brain must come equipped to impose a three-dimensional Euclidean framework on experience – our analysis suggests that object re-identification may require such a framework. We identify this absolute, nonegocentric, spatial framework with a specific neural system centered in the hippocampus. A consideration of the kinds of behaviours in which such a spatial mapping system would be important is followed by an analysis of the anatomy and physiology of this system, with special emphasis on the place-coded neurons recorded in the hippocampus of freely moving rats. A tentative physiological model for the hippocampal cognitive map is proposed. A review of lesion studies, in tasks as diverse as discrimination learning, avoidance, and extinction, shows that the cognitive map notion can adequately explain much of the data. The model is extended to humans by the assumption that spatial maps are built in one hemisphere, semantic maps in the other. The latter provide a semantic deep structure within which discourse comprehension and production can be achieved. Evidence from the study of amnesic patients, briefly reviewed, is consistent with this extension.

Multiple Trace Theory of Human Memory: Computational, Neuroimaging, and Neuropsychological Results

Hippocampal‐neocortical interactions in memory have typically been characterized within the “standard model” of memory consolidation. In this view, memory storage initially requires hippocampal linking of dispersed neocortical storage sites, but over time this need dissipates, and the hippocampal component is rendered unnecessary. This change in function over time is held to account for the retorgrade amnesia (RA) gradients often seen in patients with hippocampal damage. Recent evidence, however, calls this standard model into question, and we have recently proposed a new approach, the “multiple memory trace” (MMT) theory. In this view, hippocampal ensembles are always involved in storage and retrieval of episodic information, but semantic (gist) information can be established in neocortex, and will survive damage to the hippocampal system if enough time has elapsed. This approach accounts more readily for the very long RA gradients often observed in amnesia. We report the results of analytic and connectionist simulations that demonstrate the feasibility of MMT. We also report a neuroimaging study showing that retrieval of very remote (25‐year‐old) memories elicits as much activation in hippocampus as retrieval of quite recent memories. Finally, we report new data from the study of patients with temporal lobe damage, using more sensitive measures than previously the case, showing that deficits in both episodic and spatial detail can bed observed even for very remote memories. Overall, these findings indicate that the standard model of memory consolidation, which views the hippocampus as having only a temporary role in memory, is wrong. Instead, the data support the view that for episodic and spatial detail the hippocampal system is always necessary. Hippocampus 10:352–368, 2000

Long-axis specialization of the human hippocampus

Investigation of the hippocampus has historically focused on computations within the trisynaptic circuit. However, discovery of important anatomical and functional variability along its long axis has inspired recent proposals of long-axis functional specialization in both the animal and human literatures. Here, we review and evaluate these proposals. We suggest that various long-axis specializations arise out of differences between the anterior (aHPC) and posterior hippocampus (pHPC) in large-scale network connectivity, the organization of entorhinal grid cells, and subfield compositions that bias the aHPC and pHPC towards pattern completion and separation, respectively. The latter two differences give rise to a property, reflected in the expression of multiple other functional specializations, of coarse, global representations in anterior hippocampus and fine-grained, local representations in posterior hippocampus.

Fornix lesions selectively abolish place learning in the rat.

Abstract Rats with lesions in the fornix, a major afferent/efferent pathway of the hippocampus, failed on a water-finding task when place learning was required but succeeded in the same task when cue learning was required. These data, in conjunction with earlier physiological findings, indicate that the hippocampus functions as a cognitive mapping system.