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Biomedical subjects

E A Maguire

Publications and source records attributed to E A Maguire.

At least 19 recordsLinked to original sources

Anterior prefrontal involvement in episodic retrieval reflects contextual interference.

Different patterns of prefrontal activation are commonly found in studies of episodic and source memory (typically anterior and lateral) compared to those found in studies of autobiographical memory (typically ventromedial). We investigated a proposal that the former pattern reflects contextual interference when retrieving events that occurred in similar contexts. We used virtual reality to simulate contextually varied life-like events, in which subjects received distinct objects from a number of people in a number of locations. We compared fMRI data from two experiments in which the number of events per context varied. The first experiment (Burgess, N., Maguire, E.A., Spiers, H.J., and O'Keefe, J. 2001. A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events. Neuroimage 14, 439-453) involved 16 objects received from one of two people in one of two locations. The second experiment involved 20 objects, each received from a different person in a different location. The first experiment showed extensive bilateral activation of anterior and lateral prefrontal cortex, as well as a medial temporal and parietal network characteristic of both autobiographical and episodic memory. In the second study, the prefrontal activations were largely absent, while the medial parietal and temporal activations remained, and a ventromedial prefrontal area was additionally activated. Direct comparisons revealed large areas of significantly reduced activation in BA10, with lesser reductions in lateral prefrontal regions. We suggest that involvement of these prefrontal regains in episodic and source memory reflects the use of paradigms involving many events and few sources rather than any fundamental processing requirement of contextual retrieval in the absence of interference.

Adolescent↗

Remembering the past: neuroimaging studies of human memory.

The ability to find our way around an environment and to remember the events that occur within it are fundamental to normal functioning in daily life. Impairment of these abilities are among the first symptoms to be reported in patients with pathologies such as Alzheimer's disease and anoxia that are linked to the hippocampus and other limbic structures. However, many questions remain unanswered regarding the nature and neural bases of these memories. Findings from functional neuroimaging studies offer insights into the anatomy of memory and the presentation of memory impairments. In particular, neuroimaging is well placed to inform about the functionality of residual brain tissue, and the plasticity of memory anatomy in the context of hippocampal damage, and normal ageing.

Brain↗

A combined neuropsychological and neuroimaging study of topographical and non-verbal memory in semantic dementia.

A combined neuropsychological and neuroimaging investigation was carried out on a patient (O.I.) with semantic dementia who had asymmetrical temporal lobe atrophy, greater on the left. His performance on tests of verbal memory was gravely impaired. Similarly, his visual memory as indexed by recognition of unfamiliar faces was impaired. By contrast, his recognition memory for topographical memoranda (e.g. buildings, landscapes) and ability to find his way around was preserved. In order to identify the neural substrates supporting the preserved recognition of static topographical memoranda, O.I. was scanned using positron emission tomography (PET) during the encoding and recognition of building and landscape stimuli. In common with control subjects, during encoding O.I. activated parahippocampal cortex bilaterally, along with bilateral temporo-parietal, retrosplenial and left frontal cortices. During recognition, both patient and controls activated right parahippocampal, right superior parietal and right frontal cortices. Notably, control subjects, but not O.I., also activated at encoding the precuneus and at recognition the retrosplenial cortex. This allows the conclusion that these two areas while involved may not be necessary for topographical memory. Interestingly, the patient also activated regions that were not evident in control subjects both during encoding and recognition. These additional areas of activation may be necessary in a compensatory role. Overall, these data represent the first reported assessment of the functional integrity of degenerating brain tissue and its contribution to preserved topographical memory. The combination of the neuropsychological and neuroimaging approaches may provide insights into the functional-anatomy of memory while having clinical utility for the assessment of residual brain tissue.

Aged↗

Neuroimaging studies of autobiographical event memory.

Commonalities and differences in findings across neuroimaging studies of autobiographical event memory are reviewed. In general terms, the overall pattern across studies is of medial and left-lateralized activations associated with retrieval of autobiographical event memories. It seems that the medial frontal cortex and left hippocampus in particular are responsive to such memories. However, there are also inconsistencies across studies, for example in the activation of the hippocampus and dorsolateral prefrontal cortex. It is likely that methodological differences between studies contribute to the disparate findings. Quantifying and assessing autobiographical event memories presents a challenge in many domains, including neuroimaging. Methodological factors that may be pertinent to the interpretation of the neuroimaging data and the design of future experiments are discussed. Consideration is also given to aspects of memory that functional neuroimaging might be uniquely disposed to examine. These include assessing the functionality of damaged tissue in patients and the estimation of inter-regional communication (effective connectivity) between relevant brain regions.

Autobiographies as Topic↗

Methods for developmental studies of fear conditioning circuitry.

Psychophysiologic studies use air puff as an aversive stimulus to document abnormal fear conditioning in children of parents with anxiety disorders. This study used functional magnetic resonance imaging (fMRI) to examine changes in amygdala activity during air-puff conditioning among adults. Blood oxygen level-dependent (BOLD) signal was monitored in seven adults during 16 alternating presentations of two different colored lights (CS+ vs. CS-), one of which was consistently paired with an aversive air puff. A region-of-interest analysis demonstrated differential change in BOLD signal in the right but not left amygdala across CS+ versus CS- viewing. The amygdala is engaged by pairing of a light with an air puff. Given that prior studies relate air-puff conditioning to risk for anxiety in children, these methods may provide an avenue for directly studying the developmental neurobiology of fear conditioning.

Adult↗

Activity in prefrontal cortex, not hippocampus, varies parametrically with the increasing remoteness of memories.

The time-scale of hippocampal and neocortical involvement in memory retrieval is keenly debated. Using event-related fMRI we examined whether recollecting autobiographical and public event memories, ranging from the recent to the very remote, was associated with parametric changes in brain activity. A ventrolateral prefrontal region was sensitive to memory age, showing increased activation during retrieval of recent autobiographical events and subsequent parametric decrease with remoteness. While we observed modulation of hippocampal activity in relation to memory type (autobiographical events in particular), there was no evidence for sensitivity of this region to memory age. These findings are concordant with a view of hippocampal involvement in autobiographical memory retrieval throughout the lifetime.

Adult↗

Distinct neural systems for the encoding and recognition of topography and faces.

In a series of three positron emission tomography experiments the functional neuroanatomy of four different types of visual stimuli was investigated within the same experimental context. The stimuli were unknown buildings, landscapes, human faces, and animal faces. The purpose of the present study was to compare the stimulus types, both within the same category and across category, by examining if, at encoding (with several seconds exposure to each stimulus) or recognition (over time scales of minutes compared to the seconds of usual perception/one-back studies), common or different neural circuits were activated for all types/categories of stimuli. Within category and although visually very different, the encoding of both buildings and landscapes activated a similar set of brain regions, including bilateral parahippocampal gyrus. This was in contrast to the encoding of both human and animal faces, both of which resulted in activation of the fusiform gyrus bilaterally. Despite the perceptual inputs being identical to those during encoding, the recognition of both buildings and landscapes activated only unilateral right parahippocampal gyrus, while recognition of both human and animal faces activated unilateral right fusiform gyrus. In addition, right superior frontal gyrus and right inferior and medial parietal areas were more active during recognition compared with encoding for all stimulus types. Overall the data identify differential patterns of activation for encoding compared with retrieval of visual stimuli. Furthermore, medial temporal structures specifically are involved in the explicit learning and long-term recognition of topographically relevant stimuli, be they buildings or landscapes, while lateral temporal structures support nontopographical learning and recognition, in this case either human or animal faces.

Adult↗

A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events.

Virtual reality (VR) and event-related functional magnetic resonance imaging were used to study memory for the spatial context of controlled but lifelike events. Subjects received a set of objects from two different people in two different places within a VR environment. Memory for the objects, and for where and from whom they were received was tested by putting the subject back into a place in the company of a person and giving a paired forced choice of objects. In four conditions objects had to be chosen according to different criteria: which was received in that place, which was received from that person, which object was recognized, and which object was widest. Event-related functional magnetic resonance imaging was performed during testing to identify areas involved in retrieval of the spatial context of an event. A network of areas was identified consisting of a temporoparietal pathway running between the precuneus and parahippocampi via retrosplenial cortex and the parieto-occipital sulcus, left hippocampus, bilateral posterior parietal, dorsolateral, ventrolateral and anterior prefrontal cortices, and the anterior cingulate. Of these areas the parahippocampal, right posterior parietal, and posteriodorsal medial parietal areas were specifically involved in retrieval of spatial context compared to retrieval of nonspatial context. The posterior activations are consistent with a model of long-term storage of allocentric representations in medial temporal regions with translation to body-centered and head-centered representations computed in right posterior parietal cortex and buffered in the temporoparietal pathway so as to provide an imageable representation in the precuneus. Prefrontal activations are consistent with strategic retrieval processes, including those required to overcome the interference between the highly similar events.

Adult↗

Hippocampal amnesia.

This article reviews 147 cases of amnesia following damage including the hippocampus or fornix as reported in 179 publications. The aetiology, mnestic abilities and reference(s) are tabulated for each case. Consistent findings across cases include the association of bilateral hippocampal damage with a deficit in anterograde episodic memory combined with spared procedural and working memory. The limited nature of retrograde amnesia following lesions to the fornix is also noted. Less consistent and thus more controversial findings, include effects of lesion size or laterality, deficits in semantic memory or familiarity-based recognition and the extent of retrograde amnesia. The evidence concerning these issues is reviewed across cases.

Amnesia↗

Unilateral temporal lobectomy patients show lateralized topographical and episodic memory deficits in a virtual town.

A large-scale virtual reality town was used to test the topographical and episodic memory of patients with unilateral temporal lobe damage. Seventeen right and 13 left temporal lobectomy patients were compared with 16 healthy matched control subjects. After they had explored the town, subjects' topographical memory was tested by requiring them to navigate to specific locations in the town. The ability to recognize scenes from and draw maps of the virtual town was also assessed. Following the topographical memory tests, subjects followed a route around the same town but now collected objects from two different characters in two different locations. Episodic memory for various aspects of these events was then assessed by paired forced-choice recognition tests. The results showed an interaction between laterality and test type such that the right temporal lobectomy (RTL) patients were worse on tests of topographical memory, and the left temporal lobectomy (LTL) patients worse on tests of context-dependent episodic memory. Specifically, the RTL group was impaired on navigation, scene recognition and map drawing relative to control subjects. They were also impaired on recognition of objects in the episodic memory task. The LTL group was impaired relative to control subjects on their memory for contextual aspects of the events, such as who gave them the objects, the order in which objects were received and the locations in which they received them. They were also mildly impaired on topographical memory, but less so than the RTL group. These results suggest that topographical memory is predominately mediated by structures in the right medial temporal lobe, whereas the context-dependent aspects of episodic memory in this non-verbal test are more dependent on the left medial temporal lobe.

Adult↗

The effects of bilateral hippocampal damage on fMRI regional activations and interactions during memory retrieval.

Using functional magnetic resonance imaging (fMRI) we examined successful retrieval of real-world memories in a patient (Jon) with selective bilateral hippocampal pathology resulting from perinatal hypoxia compared with healthy control subjects. Jon activated the same brain regions during memory retrieval as control subjects, both medial and lateral on the left. In contrast to controls, Jon also activated many homologous regions on the right. In spite of having 50% volume loss bilaterally in his hippocampi, retrieval in Jon was associated with increased activation of the hippocampi. Furthermore, hippocampal activity, as with the controls, was differential, being most responsive to retrieval of autobiographical events compared with other memory types (autobiographical facts, public events, general knowledge). Jon made a distinction between events that the control subjects did not make, namely that some of the autobiographical and public events he clearly remembered, while others he found that he knew about but did not truly remember. His hippocampi and medial frontal cortex were significantly more active during retrieval of events for which he had clear and conscious recollection compared with those he knew as much about, including the context, but could not remember experiencing. Although Jon activates the same network of brain regions as the controls (albeit bilaterally), and with the same pattern of response in the hippocampus, the communication between regions differs from controls with regard to hippocampal-cortical connectivity. In controls there was increased effective connectivity between parahippocampal cortex and hippocampus, specifically during the retrieval of autobiographical events. In contrast, this increase was not apparent in Jon; rather, retrieval of autobiographical events elicited greater interaction between the hippocampus and retrosplenial cortex, and also increased interaction between retrosplenial and medial frontal cortex. This study underlines the value of scanning patients using fMRI while they undertake tasks they can perform, in this case allowing us to confirm the functionality of remaining tissue in the damaged hippocampi, and to appreciate the neural basis of a distinction (remember/know) that control subjects do not make. Besides refining our knowledge of the hippocampal role in autobiographical event memory, this study indicates that recruitment of bilateral regions during memory retrieval, and altered patterns of effective connectivity between brain regions may be important indicators of disordered memory.

Adult↗

The retrosplenial contribution to human navigation: a review of lesion and neuroimaging findings.

The clinical and neuroimaging literatures are surveyed in order to collate for the first time the available data on retrosplenial involvement in human navigation. Several notable features emerge from consideration of the case reports of relatively pure topographical disorientation in the presence of a retrosplenial lesion. The majority of cases follow damage to the right retrosplenial cortex, with Brodmann's area 30 apparently compromised in most cases. All patients displayed impaired learning of new routes, and defective navigation in familiar environments complaining they could not use preserved landmark recognition to aid orientation. The deficit generally resolved within eight weeks of onset. The majority of functional neuroimaging studies involving navigation or orientation in large-scale space also activate the retrosplenial cortex, usually bilaterally, with good concordance in the locations of the voxel of peak activation across studies, again with Brodmann's area 30 featuring prominently. While there is strong evidence for right medial temporal lobe involvement in navigation, it now seems that the inputs the hippocampus and related structures receive from and convey to right retrosplenial cortex have a similar spatial preference, while the left medial temporal and left retrosplenial cortices seem primarily concerned with more general aspects of episodic memory.

Animals↗

Neuroimaging, memory and the human hippocampus.

The hippocampus has long been implicated in mnemonic function, although its precise role is still keenly debated. Neuroimaging techniques such as positron emission tomography, functional magnetic resonance imaging and structural MRI, provide the means to examine in vivo the dynamic nature of human memory. Here, I briefly discuss how neuroimaging has investigated complex real-world memories of the kind typically reported lost by patients in the clinical context. A role, paralleling that documented in animals, for the right hippocampus in navigation is clearly apparent from functional and structural neuroimaging findings. In contrast, the left hippocampus is more responsive to memories for events that occur in a specific time and place (episodic memory) that characterise one's personal, or autobiographical, memory store from throughout the lifetime. Neuroimaging is well-placed to extend our understanding of the differential contributions the left and right hippocampi make to aspects of memory and how they interface to produce a unitary representation of the past.

Amnesia↗

Navigation-related structural change in the hippocampi of taxi drivers.

Structural MRIs of the brains of humans with extensive navigation experience, licensed London taxi drivers, were analyzed and compared with those of control subjects who did not drive taxis. The posterior hippocampi of taxi drivers were significantly larger relative to those of control subjects. A more anterior hippocampal region was larger in control subjects than in taxi drivers. Hippocampal volume correlated with the amount of time spent as a taxi driver (positively in the posterior and negatively in the anterior hippocampus). These data are in accordance with the idea that the posterior hippocampus stores a spatial representation of the environment and can expand regionally to accommodate elaboration of this representation in people with a high dependence on navigational skills. It seems that there is a capacity for local plastic change in the structure of the healthy adult human brain in response to environmental demands.

Adult↗

Patterns of hippocampal-cortical interaction dissociate temporal lobe memory subsystems.

A distributed network of brain regions supports memory retrieval in humans, but little is known about the functional interactions between areas within this system. During functional magnetic resonance imaging (fMRI), subjects retrieved real-world memories: autobiographical events, public events, autobiographical facts, and general knowledge. A common memory retrieval network was found to support all memory types. However, examination of the correlations (i.e., effective connectivity) between the activity of brain regions within the temporal lobe revealed significant changes dependent on the type of memory being retrieved. Medially, effective connectivity between the parahippocampal cortex and hippocampus increased for recollection of autobiographical events relative to other memory types. Laterally, effective connectivity between the middle temporal gyrus and temporal pole increased during retrieval of general knowledge and public events. The memory types that dissociate the common system into its subsystems correspond to those that typically distinguish between patients at initial phases of Alzheimer's disease or semantic dementia. This approach, therefore, opens the door to new lines of research into memory degeneration, capitalizing on the functional integration of different memory-involved regions. Indeed, the ability to examine interregional interactions may have important diagnostic and prognostic implications.

Adult↗

Fixation-off sensitivity as a model of continuous epileptiform discharges: electroencephalographic, neuropsychological and functional MRI findings.

A case of fixation-off sensitivity (FOS) in an asymptomatic adult is presented and studied as a model for continuous epileptiform discharges. Video-electroencephalographic (EEG) revealed continuous bilateral occipital spike wave discharges during elimination of central vision, which were shown to be associated with transitory cognitive impairment demonstrated by neuropsychological testing. Functional MRI showed activation of parieto-occipital and frontal brain areas during the fixation-off discharges. This localization was confirmed with 64-channel EEG source analysis. The applied methods provided additional information on the pathophysiology of epileptiform discharges.

Adult↗

Differential modulation of a common memory retrieval network revealed by positron emission tomography.

Functional neuroimaging is uniquely placed to examine the dynamic nature of normal human memory, the distributed brain networks that support it, and how they are modulated. Memory has traditionally been classified into context-specific memories personally experienced ("episodic memory") and impersonal non-context-specific memories ("semantic memory"). However, we suggest that another useful distinction is whether events are personally relevant or not. Typically the factors of personal relevance and temporal context are confounded, and it is as yet not clear the precise influence of either on how memories are stored or retrieved. Here we focus on the retrieval of real-world memories unconfounding personal relevance and temporal context during positron emission tomography (PET) scanning. Memories differed along two dimensions: They were personally relevant (or not) and had temporal specificity (or not). Recollection of each of the resultant four memory subtypes-autobiographical events, public events, autobiographical facts, and general knowledge-was associated with activation of a common network of brain regions. Within this system, however, enhanced activity was observed for retrieval of personally relevant, time-specific memories in left hippocampus, medial prefrontal cortex, and left temporal pole. Bilateral temporoparietal junctions were activated preferentially for personal memories, regardless of time specificity. Finally, left parahippocampal gyrus, left anterolateral temporal cortex, and posterior cingulate cortex were involved in memory retrieval irrespective of person or time. Our findings suggest that specializations in memory retrieval result from associations between subsets of regions within a common network. We believe that these findings throw new light on an old debate surrounding episodic and declarative theories of memory and the precise involvement of the hippocampus.

Adult↗

Human spatial navigation: cognitive maps, sexual dimorphism, and neural substrates.

Recent research on navigation has been particularly notable for the increased understanding of the factors affecting human navigation and the neural networks supporting it. The use of virtual reality environments has made it possible to explore the effect of environment layout and content on way-finding performance, and it has shown that these effects may interact with the sex and age of subjects. Functional brain imaging, combined with the use of virtual environments, has revealed strong parallels between humans and other animals in the neural basis of navigation.

Aging↗