The hippocampus is crucial for both spatial navigation and episodic memory, suggesting that it provides a common function to both. Here we adapt a spatial paradigm, developed for rodents, for use with functional MRI in humans to show that activation of the right hippocampus predicts the use of an allocentric spatial representation, and activation of the left hippocampus predicts the use of a sequential egocentric representation. Both representations can be identified in hippocampal activity before their effect on behavior at subsequent choice-points. Our results suggest that, rather than providing a single common function, the two hippocampi provide complementary representations for navigation, concerning places on the right and temporal sequences on the left, both of which likely contribute to different aspects of episodic memory.T he hippocampus plays a crucial role in both spatial navigation and episodic memory (1-6). However, the nature of the fundamental hippocampal process or representation that might underlie both functions remains the subject of intense speculation, including suggestions that it is best characterized as associative (7), sequential (8), flexible relational (2), allocentric (1, 5, 9), or spatial contextual (4, 5). Similar speculation surrounds the nature of any lateralization of these representations (1, 5, 10), and whether the firing of hippocampal neurons in freely moving rodents reflects allocentric position, spatial context, or sequential position along a route (5, 11, 12). Here we show that the hippocampus predicts and supports navigation via sequential representations in the left hippocampus and allocentric spatial representations in the right hippocampus. These complementary lateralized representations suggest an explanation for the multiple hippocampal contributions to different aspects of spatial and episodic memory.Within spatial memory a distinction has been made between "allocentric" (world-centered) and "egocentric" (body-centered) representations, with allocentric (or place-learning) and simple egocentric (stimulus response-like) navigation shown to depend on the hippocampus and dorsal striatum, respectively, in rodents (5, 13). recently demonstrated that an additional sequential egocentric representation depends on the rodent hippocampus. The human hippocampus has likewise been associated with allocentric representations of location, allowing accurate navigation from new starting locations (15) based on the configuration of environmental cues (16, 17) or recognition of locations from a new viewpoint (18,19). Similarly, navigation via a fixed route (15, 17) or relative to a single landmark (16), consistent with simple egocentric representations, has been associated with the dorsal striatum. However, to our knowledge, the neural bases of the sequential egocentric representation have not yet been identified in humans, and could provide a link between spatial navigation and episodic memory.Here we adapt the Starmaze task developed for mice (14,20) to investigate the neural base...

At least two main cognitive strategies can be used to solve a complex navigation task: the allocentric or map-based strategy and the sequential egocentric or route-based strategy. The sequential egocentric strategy differs from a succession of independent simple egocentric responses as it requires a sequential ordering of events, possibly sharing functional similarity with episodic memory in this regard. To question the possible simultaneous encoding of sequential egocentric and allocentric strategies, we developed a paradigm in which these two strategies are spontaneously used or imposed. Our results evidenced that sequential egocentric strategy can be spontaneously acquired at the onset of the training as well as allocentric strategy. Allocentric and sequential egocentric strategies could be used together within a trial, and bidirectional shifts (between trials) were spontaneously performed during the training period by 30% of the participants. Regardless of the strategy used spontaneously during the training, all participants could execute immediate shifts to the opposite non previously used strategy when this strategy was imposed. Altogether, our findings suggest that subjects acquire different types of spatial knowledge in parallel, namely knowledge permitting allocentric navigation as well as knowledge permitting sequential egocentric navigation.