Impact of schizophrenia on anterior and posterior hippocampus during memory for complex scenes.

ObjectivesHippocampal dysfunction has been proposed as a mechanism for memory deficits in schizophrenia. Available evidence suggests that the anterior and posterior hippocampus could be differentially affected. Accordingly, we used fMRI to test the hypothesis that activity in posterior hippocampus is disproportionately reduced in schizophrenia, particularly during spatial memory retrieval.Methods26 healthy participants and 24 patients with schizophrenia from the UC Davis Early Psychosis Program were studied while fMRI was acquired on a 3 Tesla Siemens scanner. During encoding, participants were oriented to critical items through questions about item features (e.g., "Does the lamp have a square shade?") or spatial location (e.g., "Is the lamp on the table next to the couch?"). At test, participants determined whether scenes were changed or unchanged. fMRI analyses contrasted activation in a priori regions of interest (ROI) in anterior and posterior hippocampus during correct recognition of item changes and spatial changes.ResultsAs predicted, patients with schizophrenia exhibited reduced activation in the posterior hippocampus during detection of spatial changes but not during detection of item changes. Unexpectedly, patients exhibited increased activation of anterior hippocampus during detection of item changes. Whole brain analyses revealed reduced fronto-parietal and striatal activation in patients for spatial but not for item change trials.ConclusionsResults suggest a gradient of hippocampal dysfunction in which posterior hippocampus - which is necessary for processing fine-grained spatial relationships - is underactive, and anterior hippocampus - which may process context more globally - is overactive

A Role for the Longitudinal Axis of the Hippocampus in Multiscale Representations of Large and Complex Spatial Environments and Mnemonic Hierarchies

The hippocampus is involved in spatial navigation and memory in rodents and humans. Anatomically, the hippocampus extends along a longitudinal axis that shows a combination of graded and specific interconnections with neocortical and subcortical brain areas. Functionally, place cells are found all along the longitudinal axis and exhibit gradients of properties including an increasing dorsal-to-ventral place field size. We propose a view of hippocampal function in which fine-dorsal to coarse-ventral overlapping representations collaborate to form a multi-level representation of spatial and episodic memory that is dominant during navigation in large and complex environments or when encoding complex memories. This view is supported by the fact that the effects of ventral hippocampal damage are generally only found in larger laboratory-scale environments, and by the finding that human virtual navigation studies associate ventral hippocampal involvement with increased environmental complexity. Other mechanisms such as the ability of place cells to exhibit multiple fields and their ability to scale their fields with changes in environment size may be utilized when forming large-scale cognitive maps. Coarse-grained ventral representations may overlap with and provide multi-modal global contexts to finer-grained intermediate and dorsal representations, a mechanism that may support mnemonic hierarchies of autobiographical memory in humans

Allocentric representation in the human amygdala and ventral visual stream

The hippocampus and the entorhinal cortex are considered the main brain structures for allocentric representation of the external environment. Here, we show that the amygdala and the ventral visual stream are involved in allocentric representation. Thirty-one young men explored 35 virtual environments during high-resolution functional magnetic resonance imaging (fMRI) of the medial temporal lobe (MTL) and were subsequently tested on recall of the allocentric pattern of the objects in each environment-in other words, the positions of the objects relative to each other and to the outer perimeter. We find increasingly unique brain activation patterns associated with increasing allocentric accuracy in distinct neural populations in the perirhinal cortex, parahippocampal cortex, fusiform cortex, amygdala, hippocampus, and entorhinal cortex. In contrast to the traditional view of a hierarchical MTL network with the hippocampus at the top, we demonstrate, using recently developed graph analyses, a hierarchical allocentric MTL network without a main connector hub

A Neurocognitive Perspective on the Forms and Functions of Autobiographical Memory Retrieval

Autobiographical memory retrieval involves constructing mental representations of personal past episodes by associating together an array of details related to the retrieved event. This construction process occurs flexibly so that the event details can be associated together in different ways during retrieval. Here, we propose that differences in how this association occurs support a division in autobiographical remembering. We first review theories of autobiographical memory organization that suggest that episodic details of an experience are processed along a gradient of abstraction. This organization allows for the same autobiographical event to be recalled as either a conceptualized or perceptually-based episodic memory. We then use neuroimaging evidence to show how this division within episodic autobiographical memory is also present in the brain, both at a network level and within the hippocampus. Specifically, we suggest that the anterior and posterior hippocampus are obligatorily tuned towards constructing conceptual vs. perceptual episodic representations of autobiographical memories. Finally, we discuss the directive purpose of this proposed division of episodic remembering by reviewing decision scenarios that benefit from recalling the past as a conceptual vs. a perceptual episode. Conceptual remembering is useful to guide ambiguous decisions that have yet to be encountered whereas perceptual remembering is useful to guide decisions for well-structured tasks that have been previously experienced. We emphasize that the ability to shift between conceptual and perceptual forms of remembering, by virtue of hippocampal specialization, during decision-making and other memory-guided actions is the key to adaptive behavior

The hippocampus and entorhinal cortex encode the path and Euclidean distances to goals during navigation

BACKGROUND Despite decades of research on spatial memory, we know surprisingly little about how the brain guides navigation to goals. While some models argue that vectors are represented for navigational guidance, other models postulate that the future path is computed. Although the hippocampal formation has been implicated in processing spatial goal information, it remains unclear whether this region processes path- or vector-related information. RESULTS We report neuroimaging data collected from subjects navigating London's Soho district; these data reveal that both the path distance and the Euclidean distance to the goal are encoded by the medial temporal lobe during navigation. While activity in the posterior hippocampus was sensitive to the distance along the path, activity in the entorhinal cortex was correlated with the Euclidean distance component of a vector to the goal. During travel periods, posterior hippocampal activity increased as the path to the goal became longer, but at decision points, activity in this region increased as the path to the goal became closer and more direct. Importantly, sensitivity to the distance was abolished in these brain areas when travel was guided by external cues. CONCLUSIONS The results indicate that the hippocampal formation contains representations of both the Euclidean distance and the path distance to goals during navigation. These findings argue that the hippocampal formation houses a flexible guidance system that changes how it represents distance to the goal depending on the fluctuating demands of navigation

Investigating Spatial Memory and Navigation in Developmental Amnesia: Evidence from a Google Street View Paradigm, Mental Navigation Tasks, and Route Descriptions

This dissertation examined the integrity of spatial representations of extensively travelled environments in developmental amnesia, thereby elucidating the role of the hippocampus in forming and retrieving spatial memories that enable flexible navigation. Previous research using mental navigation tasks found that developmental amnesic case H.C., an individual with atypical hippocampal development, could accurately estimate distance and direction between landmarks, but her representation of her environment was fragmented, inflexible, and lacked detail (Rosenbaum, Cassidy, & Herdman, 2015). Study 1 of this dissertation examined H.C.s spatial memory of her home environment using an ecologically valid virtual reality paradigm based on Google Street View. H.C. and control participants virtually navigated routes of varying familiarity within their home environment. To examine whether flexible navigation requires the hippocampus, participants also navigated familiar routes that had been mirror-reversed. H.C. performed similarly to control participants on all route conditions, suggesting that spatial learning of frequently travelled environments can occur despite compromised hippocampal system function. H.C.s unexpected ability to successfully navigate mirror-reversed routes might reflect the accumulation of spatial knowledge of her environment over the 6 years since she was first tested with mental navigation tasks. As such, Study 2 investigated how spatial representations of extensively travelled environments change over time in developmental amnesia by re-testing H.C. on mental navigation tasks 8 years later. H.C. continued to draw sketch maps that lacked cohesiveness and detail and had difficulty sequencing landmarks and generating detours on a blocked route task, suggesting that her overall representation of the environment did not improve over 8 years. Study 3 thoroughly examined the integrity of H.C.s detailed representation of the environment using a route description task. H.C. accurately described perceptual features of landmarks along a known route, but provided inaccurate information regarding the spatial relations of landmarks, resulting in a fragmented mental representation of the route. Taken together, these results contribute meaningfully to our current understanding of the integrity of spatial representations of extensively travelled environments in developmental amnesia. Non-spatial factors that could influence performance on navigation and spatial memory tasks are discussed, as is the impact of these results on theories of hippocampal function

Age-related changes in memory for object locations across different perspectives.

One important aspect of spatial cognition is the ability to recognize and remember spatial locations across different viewpoints. Previous research has suggested that those abilities decline in older adults. The aim of the current PhD project is to develop a clearer understanding of what may be contributing to age-related declines in recognising object locations from different perspectives. Specifically, focusing on how ageing effects encoding strategies that are used to memorize spatial configurations and the precision with which object/landmark locations are remembered. In Chapter 2, gaze behaviour was recorded during a task in which young and older adults judged whether previously encoded objects have remained in the same position or were displaced following perspective shifts. Ageing was associated with declines in spatial processing abilities. Additionally, older adults displayed a more conservative decision style and relied more on encoding object positions using room-based cues compared to young adults, who focused on the spatial relations among the to-be remembered objects during encoding. In Chapter 3, age-related differences in encoding strategies were further investigated using a modified version of the task used in Chapter 2 in which the availability and utility of the room- based cues was manipulated. Performance accuracy was similar across both age groups, yet, older adults displayed a greater preference towards a more categorical encoding strategy in which they formed spatial relations between objects and room-based cues. In the remaining chapters the focus shifted to investigating the precision with which object locations are remembered across different perspectives. In Chapter 4 participants memorized the position of an object in a virtual room and then judged from a different perspective, whether the object has moved to the left or to the right. Results revealed that participants exhibited a systematic bias in their responses that was termed the reversed congruency effect. Specifically, participants performed worse when the camera and the object moved in the same direction than when they moved in opposite directions. In Experiment 2, it was shown that the presence of additional objects in the environment reduced the reversed congruency effect whilst in Experiment 3 the reversed congruency effect was greater in older adults, suggesting that the quality of spatial memory and perspective-taking abilities are critical in mediating the reversed congruency effect. In Chapter 5, a novel task was used to investigate the systematic bias reported in Chapter 4. In this task participants encoded the position of an object in a virtual room and then estimated the object’s position following a perspective shift. In addition, memory load was manipulated. Overall, participants systematically overestimated the position of the object in the direction of the perspective shift. This bias was present in both memory and perception conditions. In Chapter 6, these results were replicated in an online-based version of the study. Lastly in Chapter 7, the influence of camera translations and camera rotations on the perspective shift related bias was decoupled. Additionally, the study investigated whether adding more information into the scene would reduce the bias and if there are age-related differences in the precision of object location estimates and the tendency to display the bias related to perspective shift. Overall, camera translations led to a greater systematic bias than camera rotations. Furthermore, the use of additional spatial information improved the precision with which object locations were estimated and reduced the bias associated with camera translation. Finally, although older adults were as precise as younger participants when estimating object locations, they benefited less from additional spatial information and their responses were more biased in the direction of camera translations. Overall, by combining eye-tracking and diffusion modelling the current thesis shows that ageing is associated with changes in the type of information that is used to encode object locations across different perspectives. Additionally, ageing was found to be particularly associated with impairments in the formation of fine-grained spatial representations. Furthermore, a novel bias in spatial memory across different perspectives has been identified. It is proposed that the perspective shift related bias is driven by uncertainty about object position following a perspective shift that leads participants to rely on an egocentric anchor when estimating the location of an object

Neural Representations of a Real-World Environment

The ability to represent the spatial structure of the environment is critical for successful navigation. Extensive research using animal models has revealed the existence of specialized neurons that appear to code for spatial information in their firing patterns. However, little is known about which regions of the human brain support representations of large-scale space. To address this gap in the literature, we performed three functional magnetic resonance imaging (fMRI) experiments aimed at characterizing the representations of locations, headings, landmarks, and distances in a large environment for which our subjects had extensive real-world navigation experience: their college campus. We scanned University of Pennsylvania students while they made decisions about places on campus and then tested for spatial representations using multivoxel pattern analysis and fMRI adaptation. In Chapter 2, we tested for representations of the navigator\u27s current location and heading, information necessary for self-localization. In Chapter 3, we tested whether these location and heading representations were consistent across perception and spatial imagery. Finally, in Chapter 4, we tested for representations of landmark identity and the distances between landmarks. Across the three experiments, we observed that specific regions of medial temporal and medial parietal cortex supported long-term memory representations of navigationally-relevant spatial information. These results serve to elucidate the functions of these regions and offer a framework for understanding the relationship between spatial representations in the medial temporal lobe and in high-level visual regions. We discuss our findings in the context of the broader spatial cognition literature, including implications for studies of both humans and animal models