Lateralized human hippocampal activity predicts navigation based on sequence or place memory

Abstract

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...

Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys

“…This response was localized to the left hippocampus, whereas the right hippocampus was engaged by navigating based on relative position within the maze. This suggests that the hippocampus in humans may contribute to both egocentric and allocentric spatial processing in a hemisphere-specific manner (53). Although compelling, these observations do not offer insight into whether or not the integrity of hippocampus is necessary for performing both types of spatial processing.…”

“…However, the particular spatial cues used by the monkeys to resolve the task cannot be deduced from our results. In humans, the hippocampus has been shown to be engaged when subjects make a sequence of remembered turns in a virtual starmaze (53). This response was localized to the left hippocampus, whereas the right hippocampus was engaged by navigating based on relative position within the maze.…”

Hippocampal–Dorsolateral Prefrontal Coupling as a Species-Conserved Cognitive Mechanism: A Human Translational Imaging Study

“…Based on these findings, it has been proposed that uncoupling rather than coupling of HC and DLPFC is a signature of successful WM performance (Meyer-Lindenberg et al, 2005). While recruitment of both HC and DLPFC has been reported for imaging studies that examined maze-based navigation (Astur et al, 2005;Iaria et al, 2003;Iglói et al, 2010;Marsh et al, 2010), the role of HC-PFC interactions during maze performance has not been tested previously.…”

Temporal Order Memory Assessed during Spatiotemporal Navigation As a Behavioral Cognitive Marker for Differential Alzheimer's Disease Diagnosis

“…We hypothesized that AD would be best diagnosed by a test assessing spatiotemporal memories acquired through active navigation, because this requires hip-pocampal function (Maguire et al, 1998;Burgess et al, 2002;Igló i et al, 2010).…”

“…Here we use a paradigm consisting in the creation of a nonverbal spatiotemporal memory using the Starmaze navigation task (Rondi-Reig et al, 2006;Igló i et al, 2009Igló i et al, , 2010, which activates the hippocampus in young healthy subjects (Igló i et al, 2010). We tested three age groups of healthy volunteers and FTLD, amnestic MCI (aMCI), and AD patients to disentangle age-and AD pathology-related impairments compared with a battery of other standard neuropsychological tests.…”