Generalization of cognitive maps across space and time.

Prominent theories posit that associative memory structures, known as cognitive maps, support flexible generalization of knowledge across cognitive domains. Here, we evince a representational account of cognitive map flexibility by quantifying how spatial knowledge formed one day was used predictively in a temporal sequence task 24 hours later, biasing both behavior and neural response. Participants learned novel object locations in distinct virtual environments. After learning, hippocampus and ventromedial prefrontal cortex (vmPFC) represented a cognitive map, wherein neural patterns became more similar for same-environment objects and more discriminable for different-environment objects. Twenty-four hours later, participants rated their preference for objects from spatial learning; objects were presented in sequential triplets from either the same or different environments. We found that preference response times were slower when participants transitioned between same- and different-environment triplets. Furthermore, hippocampal spatial map coherence tracked behavioral slowing at the implicit sequence transitions. At transitions, predictive reinstatement of virtual environments decreased in anterior parahippocampal cortex. In the absence of such predictive reinstatement after sequence transitions, hippocampus and vmPFC responses increased, accompanied by hippocampal-vmPFC functional decoupling that predicted individuals' behavioral slowing after a transition. Collectively, these findings reveal how expectations derived from spatial experience generalize to support temporal prediction.

Memory Reactivation during Learning Simultaneously Promotes Dentate Gyrus/CA2,3 Pattern Differentiation and CA1 Memory Integration.

Events that overlap with previous experience may trigger reactivation of existing memories. However, such reactivation may have different representational consequences within the hippocampal circuit. Computational theories of hippocampal function suggest that dentate gyrus and CA2,3 (DG/CA2,3) are biased to differentiate highly similar memories, whereas CA1 may integrate related events by representing them with overlapping neural codes. Here, we tested whether the formation of differentiated or integrated representations in hippocampal subfields depends on the strength of memory reactivation during learning. Human participants of both sexes learned associations (AB pairs, either face-shape or scene-shape), and then underwent fMRI scanning while they encoded overlapping associations (BC shape-object pairs). Both before and after learning, participants were also scanned while viewing indirectly related elements of the overlapping memories (A and C images) in isolation. We used multivariate pattern analyses to measure reactivation of initial pair memories (A items) during overlapping pair (BC) learning, as well as learning-related representational change for indirectly related memory elements in hippocampal subfields. When prior memories were strongly reactivated during overlapping pair encoding, DG/CA2,3 and subiculum representations for indirectly related images (A and C) became less similar, consistent with pattern differentiation. Simultaneously, memory reactivation during new learning promoted integration in CA1, where representations for indirectly related memory elements became more similar after learning. Furthermore, memory reactivation and subiculum representation predicted faster and more accurate inference (AC) decisions. These data show that reactivation of related memories during new learning leads to dissociable coding strategies in hippocampal subfields, in line with computational theories.SIGNIFICANCE STATEMENT The flexibility of episodic memory allows us to remember both the details that differentiate similar events and the commonalities among them. Here, we tested how reactivation of past experience during new learning promotes formation of neural representations that might serve these two memory functions. We found that memory reactivation during learning promoted formation of differentiated representations for overlapping memories in the dentate gyrus/CA2,3 and subiculum subfields of the hippocampus, while simultaneously leading to the formation of integrated representations of related events in subfield CA1 Furthermore, memory reactivation and subiculum representation predicted success when inferring indirect relationships among events. These findings indicate that memory reactivation is an important learning signal that influences how overlapping events are represented within the hippocampal circuit.

There and Back Again: Hippocampus and Retrosplenial Cortex Track Homing Distance during Human Path Integration.

Path integration, the updating of position and orientation during movement, often involves tracking a home location. Here, we examine processes that could contribute to successful location tracking in humans. In particular, we investigate a homing vector model of path integration, whereby a navigator continuously tracks a trajectory back to the home location. To examine this model, we developed a loop task for fMRI, in which participants viewed movement that circled back to a home location in a sparse virtual environment. In support of a homing vector system, hippocampus, retrosplenial cortex, and parahippocampal cortex were responsive to Euclidean distance from home. These results provide the first evidence of a constantly maintained homing signal in the human brain. In addition, hippocampus, retrosplenial cortex, and parahippocampal cortex, as well as medial prefrontal cortex, were recruited during successful path integration. These findings suggest that dynamic processes recruit hippocampus, retrosplenial cortex, and parahippocampal cortex in support of path integration, including a homing vector system that tracks movement relative to home. SIGNIFICANCE STATEMENT: Path integration is the continual updating of position and orientation during navigation. Animal studies have identified place cells and grid cells as important for path integration, but underlying models of path integration in humans have rarely been studied. The results of our novel loop closure task are the first to suggest that a homing vector tracks Euclidean distance from the home location, supported by the hippocampus, retrosplenial cortex, and parahippocampal cortex. These findings suggest a potential homing vector mechanism supporting path integration, which recruits hippocampus and retrosplenial cortex to track movement relative to home. These results provide new avenues for computational and animal models by directing attention to homing vector models of path integration, which differ from current movement-tracking models.

Which way and how far? Tracking of translation and rotation information for human path integration.

Path integration, the constant updating of the navigator's knowledge of position and orientation during movement, requires both visuospatial knowledge and memory. This study aimed to develop a systems-level understanding of human path integration by examining the basic building blocks of path integration in humans. To achieve this goal, we used functional imaging to examine the neural mechanisms that support the tracking and memory of translational and rotational components of human path integration. Critically, and in contrast to previous studies, we examined movement in translation and rotation tasks with no defined end-point or goal. Navigators accumulated translational and rotational information during virtual self-motion. Activity in hippocampus, retrosplenial cortex (RSC), and parahippocampal cortex (PHC) increased during both translation and rotation encoding, suggesting that these regions track self-motion information during path integration. These results address current questions regarding distance coding in the human brain. By implementing a modified delayed match to sample paradigm, we also examined the encoding and maintenance of path integration signals in working memory. Hippocampus, PHC, and RSC were recruited during successful encoding and maintenance of path integration information, with RSC selective for tasks that required processing heading rotation changes. These data indicate distinct working memory mechanisms for translation and rotation, which are essential for updating neural representations of current location. The results provide evidence that hippocampus, PHC, and RSC flexibly track task-relevant translation and rotation signals for path integration and could form the hub of a more distributed network supporting spatial navigation. Hum Brain Mapp 37:3636-3655, 2016. © 2016 Wiley Periodicals, Inc.

Functional connections between optic flow areas and navigationally responsive brain regions during goal-directed navigation.

Recent computational models suggest that visual input from optic flow provides information about egocentric (navigator-centered) motion and influences firing patterns in spatially tuned cells during navigation. Computationally, self-motion cues can be extracted from optic flow during navigation. Despite the importance of optic flow to navigation, a functional link between brain regions sensitive to optic flow and brain regions important for navigation has not been established in either humans or animals. Here, we used a beta-series correlation methodology coupled with two fMRI tasks to establish this functional link during goal-directed navigation in humans. Functionally defined optic flow sensitive cortical areas V3A, V6, and hMT+ were used as seed regions. fMRI data was collected during a navigation task in which participants updated position and orientation based on self-motion cues to successfully navigate to an encoded goal location. The results demonstrate that goal-directed navigation requiring updating of position and orientation in the first person perspective involves a cooperative interaction between optic flow sensitive regions V3A, V6, and hMT+ and the hippocampus, retrosplenial cortex, posterior parietal cortex, and medial prefrontal cortex. These functional connections suggest a dynamic interaction between these systems to support goal-directed navigation.

Hippocampus and retrosplenial cortex combine path integration signals for successful navigation.

The current study used fMRI in humans to examine goal-directed navigation in an open field environment. We designed a task that required participants to encode survey-level spatial information and subsequently navigate to a goal location in either first person, third person, or survey perspectives. Critically, no distinguishing landmarks or goal location markers were present in the environment, thereby requiring participants to rely on path integration mechanisms for successful navigation. We focused our analysis on mechanisms related to navigation and mechanisms tracking linear distance to the goal location. Successful navigation required translation of encoded survey-level map information for orientation and implementation of a planned route to the goal. Our results demonstrate that successful first and third person navigation trials recruited the anterior hippocampus more than trials when the goal location was not successfully reached. When examining only successful trials, the retrosplenial and posterior parietal cortices were recruited for goal-directed navigation in both first person and third person perspectives. Unique to first person perspective navigation, the hippocampus was recruited to path integrate self-motion cues with location computations toward the goal location. Last, our results demonstrate that the hippocampus supports goal-directed navigation by actively tracking proximity to the goal throughout navigation. When using path integration mechanisms in first person and third person perspective navigation, the posterior hippocampus was more strongly recruited as participants approach the goal. These findings provide critical insight into the neural mechanisms by which we are able to use map-level representations of our environment to reach our navigational goals.

Structural Differences in Hippocampal and Entorhinal Gray Matter Volume Support Individual Differences in First Person Navigational Ability.

The ability to update position and orientation to reach a goal is crucial to spatial navigation and individuals vary considerably in this ability. The current structural MRI study used voxel-based morphometry (VBM) analysis to relate individual differences in human brain morphology to performance in an active navigation task that relied on updating position and orientation in a landmark-free environment. Goal-directed navigation took place from either a first person perspective, similar to a person walking through the landmark-free environment, or Survey perspective, a bird's eye view. Critically, the first person perspective required a transformation of spatial information from an allocentric into an egocentric reference frame for goal-directed navigation. Significant structural volume correlations in the hippocampus, entorhinal cortex, and thalamus were related to first person navigational accuracy. Our results support the theory that hippocampus, entorhinal cortex, and thalamus are key structures for updating position and orientation during ground-level navigation. Furthermore, the results suggest that morphological differences in these regions underlie individual navigational abilities, providing an important link between animal models of navigation and the variability in human navigation.

Memory integration constructs maps of space, time, and concepts.

Recent evidence demonstrates that new events are learned in the context of their relationships to existing memories. Within the hippocampus and medial prefrontal cortex, related memories are represented by integrated codes that connect events experienced at different times and places. Integrated codes form the basis of spatial, temporal, and conceptual maps of experience. These maps represent information that goes beyond direct experience and support generalization behaviors that require knowledge be used in new ways. The degree to which an individual memory is integrated into a coherent map is determined by its spatial, temporal, and conceptual proximity to existing knowledge. Integration is observed over a wide range of scales, suggesting that memories contain information about both broad and fine-grained contexts.

Individual Differences in Human Path Integration Abilities Correlate with Gray Matter Volume in Retrosplenial Cortex, Hippocampus, and Medial Prefrontal Cortex.

Humans differ in their individual navigational abilities. These individual differences may exist in part because successful navigation relies on several disparate abilities, which rely on different brain structures. One such navigational capability is path integration, the updating of position and orientation, in which navigators track distances, directions, and locations in space during movement. Although structural differences related to landmark-based navigation have been examined, gray matter volume related to path integration ability has not yet been tested. Here, we examined individual differences in two path integration paradigms: (1) a location tracking task and (2) a task tracking translational and rotational self-motion. Using voxel-based morphometry, we related differences in performance in these path integration tasks to variation in brain morphology in 26 healthy young adults. Performance in the location tracking task positively correlated with individual differences in gray matter volume in three areas critical for path integration: the hippocampus, the retrosplenial cortex, and the medial prefrontal cortex. These regions are consistent with the path integration system known from computational and animal models and provide novel evidence that morphological variability in retrosplenial and medial prefrontal cortices underlies individual differences in human path integration ability. The results for tracking rotational self-motion-but not translation or location-demonstrated that cerebellum gray matter volume correlated with individual performance. Our findings also suggest that these three aspects of path integration are largely independent. Together, the results of this study provide a link between individual abilities and the functional correlates, computational models, and animal models of path integration.

The hippocampus is functionally connected to the striatum and orbitofrontal cortex during context dependent decision making.

Many of our everyday actions are only appropriate in certain situations and selecting the appropriate behavior requires that we use current context and previous experience to guide our decisions. The current study examined hippocampal functional connectivity with prefrontal and striatal regions during a task that required participants to make decisions based on the contextual retrieval of overlapping sequential representations. Participants learned four sequences comprised of six faces each. An overlapping condition was created by having two sequences with two identical faces as the middle images. A non-overlapping condition contained two sequences that did not share any faces between them. Hippocampal functional connectivity was assessed during the presentation period and at the critical choice, where participants had to make a contextually dependent decision. The left hippocampus showed significantly increased functional connectivity with dorsal and ventral striatum and anterior cingulate cortex during the presentation period of the overlapping compared to the non-overlapping condition after participants knew the sequences. At the critical choice point of the overlapping condition, the left hippocampus showed stronger functional connectivity with the orbitofrontal cortex. These functional connectivity results suggest that the hippocampus may play a role in decision making by predicting the possibilities of what might come next, allowing orbitofrontal and striatal regions to evaluate the expected choice options in order to make the correct action at the choice point.