The hippocampus and space revisited

The hippocampal formation has long been the focus of intense interest among neuroscientists. The discovery by Scoville and Milner (1957) that the mesial temporal lobe, including the hippocampal formation, played a central role in memory function in humans can be said to have started the modern era of research on this brain system. There followed two decades of animal research aimed at creating experimental models of the memory defects observed in humans, including my dissertation research, which met with scant success (Nadel, 1968). Indeed, when John O’Keefe and I started considering the hippocampus and its possible role in spatial mapping several years later, one of o u r greatest challenges was to analyze the extant lesion literature in terms of this theory with the minimum amount of special pleading. There were already several hundred such studies, varying extensively in terms of exact size and regional location of the lesion, the means by which the lesion had been created, the kind of animal used, the nature of the task, the kind of motivation employed, and so on. Yet, it was our feeling in 1976, when we terminated the review of the lesion literature, which was ultimately published in The Hippocumpiis CIS a Cognitive M a p (O’Keefe and Nadel, 1978), that the spatial hypothesis successfully handled the vast preponderance of these lesion studies as well a s what was then known about the physiology of the hippocampal formation. In the years following publication of the book, most published lesion studies were concerned in some way with the spatial map hypothesis; most often, comparisons with rival hypotheses were involved. This was a frustrating period because, although many thought they were testing our ideas, too frequently the major themes we hoped t o stress were misconstrued. In this article I dig back into the book we published in 1978 and reiterate some of the themes that were important to us then, and remain so now. By so doing, 1 hope to bring out some of the reasons why we thought, and continue to think, that space is so special as t o warrant a structure as compelling as the hippocampal formation. I will concentrate o n three major issues. First, I will discuss at some length the fact that our theory was about a ~ p a t i a l memory system, not simply a “spatial” system. Second, I will discuss our assumption that the spatial memory system we allocated to the hippocampus was but one of many spatial systems, and that the role of these various systems can best be understood if one takes into consideration a n animal’s behavior in its natural habitat. Third, I will briefly discuss our view that in the human hippocampus, a t least in the left hemisphere, the mapping system represents something more abstract than physical space. Before turning to these substantive points, however, a brief digression into methods and first principles is in order. Some years before the book was published, O’Keefe and I published a paper (Nadel and O’Keefe, 1974) in which we presented some of the reasons for hypothesizing that the hippocampal system is engaged in cognitive mapping. We also discussed an underlying principle guiding our approach to brain function in general and the hippocampal system in particular-the principle of multilevel analysis and proof. W e asserted that one of the major problems with then-extant models of hippocampal function was that they depended upon data generated within a single domain of inquiry (lesions, physiology, anatomy, etc.). In so doing, they became subject to what we called “hypothesis drift”-as soon as contradictory data were reported, the hypothesis could be easily recast to accommodate the new facts. Because such hypotheses were tied t o only one level of analysis, they could, and in fact did, drift all over the map. The notion that the hippocampus was involved in response inhibition was an excellent example (Nadel et al., 1975). We suggested that a meaningful hypothesis of the function of some brain area should be constrained by data generated from several levels simultaneously, using the method that has come t o be called convergent operations. Thus, we argued that there was little point in deriving a theory of the hippocampus that made great sense in terms of the lesion data, but had nothing to say about physiology and anatomy.