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Biomedical subjects

Eleanor A Maguire

Publications and source records attributed to Eleanor A Maguire.

18 recordsLinked to original sources
PubMed2007

Patients with hippocampal amnesia cannot imagine new experiences.

Amnesic patients have a well established deficit in remembering their past experiences. Surprisingly, however, the question as to whether such patients can imagine new experiences has not been formally addressed to our knowledge. We tested whether a group of amnesic patients with primary damage to the hippocampus bilaterally could construct new imagined experiences in response to short verbal cues that outlined a range of simple commonplace scenarios. Our results revealed that patients were markedly impaired relative to matched control subjects at imagining new experiences. Moreover, we identified a possible source for this deficit. The patients' imagined experiences lacked spatial coherence, consisting instead of fragmented images in the absence of a holistic representation of the environmental setting. The hippocampus, therefore, may make a critical contribution to the creation of new experiences by providing the spatial context into which the disparate elements of an experience can be bound. Given how closely imagined experiences match episodic memories, the absence of this function mediated by the hippocampus, may also fundamentally affect the ability to vividly re-experience the past.

Adult↗
PubMed2006

Spontaneous mentalizing during an interactive real world task: an fMRI study.

There are moments in everyday life when we need to consider the thoughts and intentions of other individuals in order to act in a socially appropriate manner. Most of this mentalizing occurs spontaneously as we go about our business in the complexity of the real world. As such, studying the neural basis of spontaneous mentalizing has been virtually impossible. Here we devised a means to achieve this by employing a unique combination of functional magnetic resonance imaging (fMRI), a detailed and interactive virtual reality simulation of a bustling familiar city, and a retrospective verbal report protocol. We were able to provide insights into the content of spontaneous mentalizing events and identify the brain regions that underlie them. We found increased activity in a number of regions, namely the right posterior superior temporal sulcus, the medial prefrontal cortex and the right temporal pole associated with spontaneous mentalizing. Furthermore, we observed the right posterior superior temporal sulcus to be consistently active during several different subtypes of mentalizing events. By contrast, medial prefrontal cortex seemed to be particularly involved in thinking about agents that were visible in the environment. Our findings show that it is possible to investigate the neural basis of mentalizing in a manner closer to its true context, the real world, opening up intriguing possibilities for making comparisons with those who have mentalizing problems.

Adult↗
PubMed2006

Thoughts, behaviour, and brain dynamics during navigation in the real world.

How does the human brain allow us to interact with and navigate through a constantly changing world? Whilst controlled experiments using functional brain imaging can give insightful snapshots of neuronal responses to relatively simplified stimuli, they cannot hope to mirror the challenges faced by the brain in the real world. However, trying to study the brain mechanisms supporting daily living represents a huge challenge. By combining functional neuroimaging, an accurate interactive virtual simulation of a bustling central London (UK), and a novel means of 'reading' participants' thoughts whilst they moved around the city, we ascertained the online neural correlates underpinning navigation in this real-world context. A complex choreography of neural dynamics was revealed comprising focal and distributed, transient and sustained brain activity. Our results provide new insights into the specific roles of individual brain areas, in particular the hippocampus, retrosplenial, and frontal cortices, as well as offering clues about how functional specialisations operate within dynamic brain systems.

Adult↗
PubMed2006

The dynamics of hippocampal activation during encoding of overlapping sequences.

Sequence disambiguation, the process by which overlapping sequences are kept separate, has been proposed to underlie a wide range of memory capacities supported by the hippocampus, including episodic memory and spatial navigation. We used functional magnetic resonance imaging (fMRI) to explore the dynamic pattern of hippocampal activation during the encoding of sequences of faces. Activation in right posterior hippocampus, only during the encoding of overlapping sequences but not nonoverlapping sequences, was found to correlate robustly with a subject-specific behavioral index of sequence learning. Moreover, our data indicate that hippocampal activation in response to elements common to both sequences in the overlapping sequence pair, may be particularly important for accurate sequence encoding and retrieval. Together, these findings support the conclusion that the human hippocampus is involved in the earliest stage of sequence disambiguation, when memory representations are in the process of being created, and provide empirical support for contemporary computational models of hippocampal function.

Adult↗
PubMed2006

London taxi drivers and bus drivers: a structural MRI and neuropsychological analysis.

Licensed London taxi drivers show that humans have a remarkable capacity to acquire and use knowledge of a large complex city to navigate within it. Gray matter volume differences in the hippocampus relative to controls have been reported to accompany this expertise. While these gray matter differences could result from using and updating spatial representations, they might instead be influenced by factors such as self-motion, driving experience, and stress. We examined the contribution of these factors by comparing London taxi drivers with London bus drivers, who were matched for driving experience and levels of stress, but differed in that they follow a constrained set of routes. We found that compared with bus drivers, taxi drivers had greater gray matter volume in mid-posterior hippocampi and less volume in anterior hippocampi. Furthermore, years of navigation experience correlated with hippocampal gray matter volume only in taxi drivers, with right posterior gray matter volume increasing and anterior volume decreasing with more navigation experience. This suggests that spatial knowledge, and not stress, driving, or self-motion, is associated with the pattern of hippocampal gray matter volume in taxi drivers. We then tested for functional differences between the groups and found that the ability to acquire new visuo-spatial information was worse in taxi drivers than in bus drivers. We speculate that a complex spatial representation, which facilitates expert navigation and is associated with greater posterior hippocampal gray matter volume, might come at a cost to new spatial memories and gray matter volume in the anterior hippocampus.

Adult↗
PubMed2006

Navigation around London by a taxi driver with bilateral hippocampal lesions.

The time-scale of hippocampal involvement in supporting episodic memory remains a keenly debated topic, with disagreement over whether its role is temporary or permanent. Recently, there has been interest in how navigation by hippocampally-compromised patients in environments learned long ago speaks to this issue. However, identifying patients with damage that is primarily hippocampal, control subjects matched for navigation experience, and testing their in situ navigation, present substantial problems. We met these challenges by using a highly accurate and interactive virtual reality simulation of central London (UK) to assess the navigation ability of a licensed London taxi driver who had sustained bilateral hippocampal damage. In this test, patient TT and matched control taxi drivers drove a virtual London taxi along the streets they had first learned 40 years before. We found that the hippocampus is not required for general orientation in the city either in first person or survey perspectives, detailed topographical knowledge of landmarks and their spatial relationships, or even for active navigation along some routes. However, in his navigation TT was very reliant on main artery or 'A' roads, and became lost when navigation depended instead on non-A roads. We conclude that the hippocampus in humans is necessary for facilitating navigation in places learned long ago, particularly where complex large-scale spaces are concerned, and successful navigation requires access to detailed spatial representations.

Aged↗
PubMed2006

An unexpected sequence of events: mismatch detection in the human hippocampus.

The ability to identify and react to novelty within the environment is fundamental to survival. Computational models emphasize the potential role of the hippocampus in novelty detection, its unique anatomical circuitry making it ideally suited to act as a comparator between past and present experience. The hippocampus, therefore, is viewed to detect associative mismatches between what is expected based on retrieval of past experience and current sensory input. However, direct evidence that the human hippocampus performs such operations is lacking. We explored brain responses to novel sequences of objects using functional magnetic resonance imaging (fMRI), while subjects performed an incidental target detection task. Our results demonstrate that hippocampal activation was maximal when prior predictions concerning which object would appear next in a sequence were violated by sensory reality. In so doing, we establish the biological reality of associative match-mismatch computations within the human hippocampus, a process widely held to play a cardinal role in novelty detection. Our results also suggest that the hippocampus may generate predictions about how future events will unfold, and critically detect when these expectancies are violated, even when task demands do not require it. The present study also offers broader insights into the nature of essential computations carried out by the hippocampus, which may also underpin its unique contribution to episodic memory.

Adolescent↗
PubMed2005

The human hippocampus: cognitive maps or relational memory?

The hippocampus is widely accepted to play a pivotal role in memory. Two influential theories offer competing accounts of its fundamental operating mechanism. The cognitive map theory posits a special role in mapping large-scale space, whereas the relational theory argues it supports amodal relational processing. Here, we pit the two theories against each other using a novel paradigm in which the relational processing involved in navigating in a city was matched with similar navigational and relational processing demands in a nonspatial (social) domain. During functional magnetic resonance imaging, participants determined the optimal route either between friends' homes or between the friends themselves using social connections. Separate brain networks were engaged preferentially during the two tasks, with hippocampal activation driven only by spatial relational processing. We conclude that the human hippocampus appears to have a bias toward the processing of spatial relationships, in accordance with the cognitive map theory. Our results both advance our understanding of the nature of the hippocampal contribution to memory and provide insights into how social networks are instantiated at the neural level.

Adult↗
PubMed2005

The effect of adult-acquired hippocampal damage on memory retrieval: an fMRI study.

Bilateral hippocampal pathology typically results in significant memory problems. Despite apparently similar structural damage, patients with such lesions can differ in the pattern of impairment and preservation of memory functions. Previously, an fMRI study of a developmental amnesic patient whose anoxic hippocampal damage was incurred perinatally revealed his residual hippocampal tissue to be active during memory retrieval. This hippocampal activity was apparent during the retrieval of personal and general facts relative to a control task. In this study, we used a similar fMRI paradigm to investigate whether residual hippocampal activation was present also in patient VC with adult-acquired anoxic hippocampal pathology. VC's performance and reaction times on the experimental personal and general fact tasks were comparable to age-matched control subjects. However, in contrast to the elderly control sample and the previous developmental amnesic patient, his residual hippocampal tissue did not show activation changes during the experimental tasks. This finding indicates that patient VC's successful retrieval of personal and general facts was achieved without a significant hippocampal contribution. It further suggests that the hippocampal activation observed in the elderly controls and previous developmental amnesic patient was not necessary for successful task performance. The reason for this difference in hippocampal responsivity between VC and the developmental amnesic patient remains to be determined. We speculate that it may relate to the age at which hippocampal damage occurred reflecting plasticity within the developing brain, or to cognitive differences between VC, the developmental amnesic patient, and the control subjects.

Aged↗
PubMed2004

The brain network associated with acquiring semantic knowledge.

There is ongoing debate about how semantic information is acquired, whether this occurs independently of episodic memory, and what role, if any, brain areas such as hippocampus are required to play. We used auditory stimuli and functional MRI (fMRI) to assess brain activations associated with the incidental acquisition of new and true facts about the world of the sort we are exposed to day to day. A control task was included where subjects heard sentences that described novel scenarios involving unfamiliar people, but these did not convey general knowledge. The incidental encoding task was identical for two stimulus types; both shared the same episodic experience (lying in the brain scanner) and conveyed complex information. Despite this, and considering only those stimuli successfully encoded, compared to a baseline task, a more extensive network of brain regions was found to be associated with exposure to new facts including the hippocampus. Direct comparison between the two stimulus types revealed greater activity in dorsal, ventrolateral and dorsomedial prefrontal cortex, medial dorsal nucleus of the thalamus, and temporal cortex for fact stimuli. The findings suggest that successful encoding is not invariably associated with activation of one particular brain network. Rather, activation patterns may depend on the type of materials being acquired, and the different processes they engender when subjects encode. Qualitatively, from postscan debriefing sessions, it emerged that the factual information was found to be potentially more useful. We suggest that current or prospective utility of incoming information may be one factor that influences the processes engaged during encoding and the concomitant neuronal responses.

Adult↗
PubMed2003

Lateral asymmetry in the hippocampal response to the remoteness of autobiographical memories.

The time scale of hippocampal involvement in retrieving memories, particularly those more remote, is still a matter of debate. Some propose that the hippocampus is not involved in the retrieval of remote memories, whereas others assert that it is necessary for memory retrieval in perpetuity. Functional magnetic resonance imaging was used to examine the effect of remoteness on the neural basis of memory. We used a parametric event-related random-effects design in a large group of subjects to overcome some of the limitations of previous neuroimaging studies. We found that the hippocampi were significantly active during the retrieval of autobiographical memories. Notably, the two hippocampi diverged in their responses to remoteness. The right hippocampus showed a temporal gradient, decreasing in activity the more remote the autobiographical memories. No such effect was apparent in the left hippocampus, suggesting its invariant involvement in remembering autobiographical events throughout the lifespan. The dorsal amygdalas showed a temporal gradient similar to the right hippocampus, but emotional valence and intensity were not directly associated with changes in activity. The current results indicate that consideration of lateral asymmetry may help to broaden the scope of theoretical interpretations concerning hippocampal involvement in remote memory.

Acoustic Stimulation↗
PubMed2003

Aging affects the engagement of the hippocampus during autobiographical memory retrieval.

Surprisingly little is known about the neural correlates of remembering real life events in the context of normal aging. We therefore asked young and older adults to retrieve real life autobiographical event memories accrued over decades, while their brains were scanned using functional MRI. There were many commonalities between the groups in the wider network of brain areas active during retrieval. Nevertheless, one key difference emerged; while left hippocampal activation was apparent in the young, bilateral hippocampal activation was evident in older adults and direct comparison between the groups confirmed significantly greater right hippocampal activation in older adults. Notably, this difference was specific to autobiographical event memory retrieval, as the groups were comparable in the areas active during semantic memory retrieval. The present findings show that even when stimuli, tasks and performance appear indistinguishable between young and older adults, neural changes occur in aging with specificity in both the memory type and the brain regions affected. In particular, the results reveal that age-related effects are detectable in the hippocampus. This highlights the need to consider how the dynamic course of normal aging interacts with pathological processes that might also affect the hippocampus. Understanding this relationship may aid prognosis, as well as providing insights into plasticity in the anatomy of memory.

Adult↗
PubMed2003

The well-worn route and the path less traveled: distinct neural bases of route following and wayfinding in humans.

Finding one's way in a large-scale environment may engage different cognitive processes than following a familiar route. The neural bases of these processes were investigated using functional MRI (fMRI). Subjects found their way in one virtual-reality town and followed a well-learned route in another. In a control condition, subjects followed a visible trail. Within subjects, accurate wayfinding activated the right posterior hippocampus. Between-subjects correlations with performance showed that good navigators (i.e., accurate wayfinders) activated the anterior hippocampus during wayfinding and head of caudate during route following. These results coincide with neurophysiological evidence for distinct response (caudate) and place (hippocampal) representations supporting navigation. We argue that the type of representation used influences both performance and concomitant fMRI activation patterns.

Adult↗
PubMed2003

Navigation expertise and the human hippocampus: a structural brain imaging analysis.

Grey matter volume in the posterior hippocampus of London taxi drivers is greater than in age-matched controls, and the size of this increase correlates positively with time spent taxi driving (E.A. Maguire et al., 2000. Proc Natl Acad Sci USA 97: 4398-4403). This change suggests that increased posterior hippocampal grey matter volume is acquired in response to increased taxi driving experience, perhaps reflecting their detailed representation of the city. However, an alternate hypothesis is that the difference in hippocampal volume is instead associated with innate navigational expertise, leading to an increased likelihood of becoming a taxi driver. To investigate this possibility, we used structural brain imaging and voxel-based morphometry (VBM) to examine a group of subjects who were not taxi drivers. Despite this group showing a wide range of navigational expertise, there was no association between expertise and posterior hippocampal grey matter volume (or, indeed, grey matter volume throughout the brain). This failure to find an association between hippocampal volume and navigational expertise thus suggests that structural differences in the human hippocampus reflect the detail and/or duration of use of the spatial representation acquired, and not innate navigational expertise per se.

Adolescent↗
PubMed2003

Routes to remembering: the brains behind superior memory.

Why do some people have superior memory capabilities? We addressed this age-old question by examining individuals renowned for outstanding memory feats in forums such as the World Memory Championships. Using neuropsychological measures, as well as structural and functional brain imaging, we found that superior memory was not driven by exceptional intellectual ability or structural brain differences. Rather, we found that superior memorizers used a spatial learning strategy, engaging brain regions such as the hippocampus that are critical for memory and for spatial memory in particular. These results illustrate how functional neuroimaging might prove valuable in delineating the neural substrates of mnemonic techniques, which could broaden the scope for memory improvement in the general population and the memory-impaired.

Adult↗
PubMed2002

The human hippocampus and spatial and episodic memory.

Finding one's way around an environment and remembering the events that occur within it are crucial cognitive abilities that have been linked to the hippocampus and medial temporal lobes. Our review of neuropsychological, behavioral, and neuroimaging studies of human hippocampal involvement in spatial memory concentrates on three important concepts in this field: spatial frameworks, dimensionality, and orientation and self-motion. We also compare variation in hippocampal structure and function across and within species. We discuss how its spatial role relates to its accepted role in episodic memory. Five related studies use virtual reality to examine these two types of memory in ecologically valid situations. While processing of spatial scenes involves the parahippocampus, the right hippocampus appears particularly involved in memory for locations within an environment, with the left hippocampus more involved in context-dependent episodic or autobiographical memory.

Animals↗
PubMed2002

Neurodevelopmental aspects of spatial navigation: a virtual reality fMRI study.

Navigation in spatial contexts has been studied in diverse species, yielding insights into underlying neural mechanisms and their phylogenetic progression. Spatial navigation in humans is marked by age-related changes that may carry important implications for understanding cortical development. The emergence of "allocentric" processing, reflecting that ability to use viewer-independent spatial abstractions, represents an important developmental change. We used fMRI to map brain regions engaged during memory-guided navigation in a virtual reality environment in adolescents and adults. Blood oxygen level-dependent (BOLD) signal was monitored in eight adolescents and eight adults in a 1.5-T MRI scanner during three conditions: (1) memory-guided navigation (NAV); (2) arrow-guided navigation (ARROW); and (3) fixation (FIX). We quantified navigation ability during scanning and allocentric memory after scanning, based on subjects' ability to label a previously unseen, aerial view of the town. Adolescents and adults exhibited similar memory-guided navigation ability, but adults exhibited superior allocentric memory ability. Memory-guided navigation ability during scanning correlated with BOLD change between NAV/ARROWS in various regions, including a right frontal and right-anterior medial temporal lobe region. Age group and allocentric memory together explained significant variance in BOLD change in temporoparietal association cortex and the cerebellum, particularly in the left hemisphere. Consistent with developmental models, these findings relate maturation in the coding of spatial information to functional changes in a distributed, left-lateralized neural network.

Adolescent↗