Impaired allocentric spatial memory underlying topographical disorientation

The cognitive processes supporting spatial navigation are considered in the context of a patient (CF) with possible very early Alzheimer's disease who presents with topographical disorientation. Her verbal memory and her recognition memory for unknown buildings, landmarks and outdoor scenes was intact, although she showed an impairment in face processing. By contrast, her navigational ability, quantitatively assessed within a small virtual reality (VR) town, was significantly impaired. Interestingly, she showed a selective impairment in a VR object-location memory test whenever her viewpoint was shifted between presentation and test, but not when tested from the same viewpoint. We suggest that a specific impairment in locating objects relative to the environment rather than relative to the perceived viewpoint (i.e. allocentric rather than egocentric spatial memory) underlies her topographical disorientation. We discuss the likely neural bases of this deficit in the light of related studies in humans and animals, focusing on the hippocampus and related areas. The specificity of our test indicates a new way of assessing topographical disorientation, with possible application to the assessment of progressive dementias such as Alzheimer's disease.     

Charting the acquisition of semantic knowledge in a case of developmental amnesia

We report the acquisition and recall of novel facts by Jon, a young adult with early onset developmental amnesia whose episodic memory is gravely impaired due to selective bilateral hippocampal damage. Jon succeeded in learning some novel facts but compared with a control group his intertrial retention was impaired during acquisition and, except for the most frequently repeated facts, he was also less accurate in correctly sourcing these facts to the experiment. The results further support the hypothesis that despite a severely compromised episodic memory and hippocampal system, there is nevertheless the capacity to accrue semantic knowledge available to recall.     

Preserved recognition in a case of developmental amnesia: implications for the acquisition of semantic memory?

We report the performance on recognition memory tests of Jon, who, despite amnesia from early childhood, has developed normal levels of performance on tests of intelligence, language, and general knowledge. Despite impaired recall, he performed within the normal range on each of six recognition tests, but he appears to lack the recollective phenomenological experience normally associated with episodic memory. His recall of previously unfamiliar newsreel events was impaired, but gained substantially from repetition over a 2-day period. Our results are consistent with the hypothesis that the recollective process of episodic memory is not necessary either for recognition or for the acquisition of semantic knowledge.     

Human hippocampus and viewpoint dependence in spatial memory

Virtual reality was used to sequentially present objects within a town square and to test recognition of object locations from the same viewpoint as presentation, or from a shifted viewpoint. A developmental amnesic case with focal bilateral hippocampal pathology showed a massive additional impairment when tested from the shifted viewpoint compared with a mild, list length-dependent, impairment when tested from the same viewpoint. While the same-view condition could be solved by visual pattern matching, the shifted-view condition requires a viewpoint independent representation or an equivalent mechanism for translating or rotating viewpoints in memory. The latter mechanism was indicated by control subjects' response latencies in the shifted-view condition, although the amnesic case is not impaired in tests of mental rotation of single objects. These results show that the human hippocampus supports viewpoint independence in spatial memory, and suggest that it does so by providing a mechanism for viewpoint manipulation in memory. In addition, they suggest an extremely sensitive test for human hippocampal damage, and hint at the nature of the hippocampal role in episodic recollection.     

Selective sparing of topographical memory

The case of a 61 year old patient with Pick's diseaseinvolving predominantly the left temporal lobe, who has been studied over a 5 year period, is reported. She presented with a grave impairment of both verbal and non-verbal memory functions. Her non-verbal memory deficits included profound impairments on the recognition of unfamiliar faces and the recall of abstract designs. Remarkably, her visual recognition memory performance for unknown buildings, landscapes, and outdoor scenes was preserved. Strikingly, her ability to recall familiar routes and learn new ones through acomplex virtual reality town was also entirely normal. This seems to bethe first case documenting the selective preservation of topographicalmemory in the context of severe non-verbal and verbal memoryimpairments. These findings imply that topographical memory andnon-verbal memory are subserved by separable neural systems.

     

The contribution of executive functions deficits to impaired episodic memory in individuals with alcoholism

Individuals with alcoholism commonly exhibit impaired performance on episodic memory tasks. However, the contribution of their impaired executive functioning to poor episodic memory remains to be clarified. Thirty-six recently detoxified and sober asymptomatic alcoholic men and 36 matched non-alcoholic participants were tested for processing speed, prepotent response inhibition, mental flexibility, coordination of dual-task and a verbal episodic memory task. Compared with non-alcoholic individuals, the alcoholic patients showed impaired executive functions combined with below normal performance on both free and delayed recall. In contrast, processing speed, cued recall and recognition were preserved. Regression analyses revealed that 47% of alcoholics' episodic memory's free recall performance was predicted by mental flexibility and that 49% of their delayed recall performance was predicted by mental flexibility, manipulation of dual-task and prepotent response inhibition. Regarding participants' executive predictors of episodic memory performance, the slopes of β coefficients were significantly different between the two groups, with alcoholics requiring more their executive system than non-alcoholics. Once detoxified, alcoholic patients showed episodic memory deficits mainly characterized by impaired effortful (executive) processes. Compared with controls, patients used effortful learning strategies, which are nonetheless less efficient.     

Active versus passive exploration of virtual environments modulates spatial memory in MS patients: a yoked control study

This study investigated whether exploration of computer-generated environments can selectively enhance spatial memory in patients with multiple sclerosis (MS). Fifteen patients and 15 healthy subjects who controlled their movements in a virtual house using a joystick recalled the spatial layout of the environments better than 15 patients and 15 controls who merely watched the active participants' progress. Among passive subjects, only healthy controls did significantly better than active participants in the recall of virtual objects. There were no significant differences between active and passive participants' recall of correct object locations in the virtual environments. MS patients' recall of the spatial layout and of the virtual objects was significantly worse than that of healthy subjects, but patients' data did not correlate with traditional neuropsychological measures of spatial memory. It is suggested that virtual reality can be used in MS patients to assess aspects of spatial memory that are not measured by traditional tests.     

Topographical memory impairments after unilateral lesions of the anterior thalamus and contralateral inferotemporal cortex

Monkeys with crossed unilateral excitotoxic lesions of the anterior thalamus and unilateral inferotemporal cortex ablation were severely impaired at learning two tasks which required the integration of information about the appearance of objects and their positions in space. The lesioned monkeys were also impaired at learning a spatial task and a task which required the integration of information about the appearance of objects and the background on which the objects were situated. Monkeys with only one of the unilateral lesions were not impaired and previous work has shown that monkeys with bilateral lesions of the anterior thalamus were not impaired on these tasks. These results indicate that the whole of the inferotemporal cortex-anterior thalamic circuit, which passes via the hippocampus, fornix, mamillary bodies and mamillothalamic tract, is essential for the topographical analysis of information about specific objects in different positions in space. Together with previous work, the results show that a unilateral lesion may affect cognition in the presence of other brain damage when an equivalent bilateral lesion alone does not. The tasks required the slow acquisition of information into long term memory and therefore assessed semantic knowledge although other research has shown impairment on topographical processing within working or episodic memory following lesions of the hippocampal-diencephalic circuit. It is argued that the hippocampal-diencephalic circuit does not have a role in a specific form of memory such as episodic memory but rather is involved in topographical analysis of the environment in perception and across all types of declarative memory.     

Impaired recognition memory on the Doors and People Test after damage limited to the hippocampal region

There have been conflicting reports about the importance of the hippocampal region for recognition memory. Vargha-Khadem et al. (1997) described three patients who became amnesic early in life as a result of damage apparently limited to the hippocampal region. One of these patients (Jon) performed normally on the recognition portion of the Doors and People Test but was severely impaired in recall. To compare adult-onset amnesia directly with these early-onset cases, we tested six amnesic patients on the Doors and People Test. Three of the patients have damage thought to be limited to the hippocampal region. All six patients were markedly impaired on both the recall and recognition portions of the test. To account for the difference between our adult-onset cases and the early-onset case (Jon), we suggest that some compensation for Jon's injury occurred during development, either due to functional reorganization of cortex adjacent to the hippocampus or as the result of learned strategies.     

Growing up with bilateral hippocampal atrophy: from childhood to teenage

The respective roles of the medial temporal lobe (MTL) structures in memory are controversial. Some authors put forward a modular account according to which episodic memory and recollection-based processes are crucially dependent on the hippocampal formation whereas semantic acquisition and familiarity-based processes rely on the adjacent parahippocampal gyri. Others defend a unitary view.We report the case of VJ, a boy with developmental amnesia of most likely perinatal onset diagnosed at the age of 8. Magnetic resonance imaging (MRI), including quantitative volumetric measurements of the hippocampal formation and of the entorhinal, perirhinal, and temporopolar cortices, showed severe, bilateral atrophy of the hippocampal formation, fornix and mammillary bodies; by contrast, the perirhinal cortex was within normal range and the entorhinal and temporopolar cortex remained within two standard deviations (SDs) from controls’ mean. We examined the development of his semantic knowledge from childhood to teenage as well as his recognition and cued recall memory abilities. On tasks tapping semantic memory, VJ increased his raw scores across years at the same rate as children from large standardisation samples, except for one task; he achieved average performance, consistent with his socio-educational background. He performed within normal range on 74% of recognition tests and achieved average to above average scores on 42% of them despite very severe impairment on 82% of episodic recall tasks. Both faces and landscapes-scenes gave rise to above average scores when tested with coloured stimuli. Cued recall, although impaired, was largely superior to free recall.This case supports a modular account of the MTL with episodic, but not semantic memory depending on the hippocampal formation. Furthermore, the overall pattern of findings is consistent with evidence from both brain-damaged and neuroimaging studies indicating that recollection requires intact hippocampal formation and familiarity relies, at least partly, on the adjacent temporal lobe cortex.     

A Consequence of Failed Sequential Learning: A Computational Account of Developmental Amnesia

Developmental amnesia, featured with severely impaired episodic memory and almost normal semantic memory, has been discovered to occur in children with hippocampal atrophy. Such amnesia seems to challenge the understanding that early loss of episodic memory may impede cognitive development and result in severe mental retardation. While the underlying mechanism is still unclear, no computational model has been reported to simulate developmental amnesia. A cognitive and computational system is presented, for the first time, to simulate the unique characteristics of the amnesia: impaired episodic recall, spared recognition, and spared semantic learning. The lesioned sequential/spatial learning ability of the hippocampus is suggested to be able to cause severe impairment of episodic recall, but affect neither recognition ability nor semantic learning. Semantic learning is generally thought to largely associate with the consolidation of episodic memory, a process in which sequential activation of episodic memory may not be necessary. Semantic learning through memory consolidation featured with random activation of stored experiences is performed, and the acquired knowledge is demonstrated to have the flexibility that is one of the key characteristics of semantic memory.     

Using semantic memory to boost 'episodic' recall in a case of developmental amnesia

We report two experiments that investigated factors that might boost 'episodic' recall for Jon, a developmental amnesic whose episodic memory is gravely impaired but whose semantic memory seems relatively normal. Experiment 1 showed that Jon's recall improved following a semantic study task compared with a non-semantic study task, as well as following four repeated study trials compared with only one. Experiment 2 additionally revealed that Jon's recall improved after acting compared with reading action phrases at study, but only if the phrases were well integrated semantically. The results provide some support for the hypothesis that Jon's 'episodic' recall depends on the extent to which he is able to retrieve events using semantic memory.     

The role of ventromedial prefrontal cortex in navigation: a case of impaired wayfinding and rehabilitation

A patient with ventromedial prefrontal damage, LG, is described who had a severe difficulty in wayfinding in his home town, despite intact knowledge for landmarks and routes in town. Although able to recall his spatial goals, LG often headed to familiar, "attractor" locations while navigating, losing his way in the process. Both a laboratory and an ecological study showed that spatial navigation improved when the patient was periodically reminded of, or asked to recall, the goal destination along his route. It is suggested that the ventromedial prefrontal cortex is necessary to maintain actively the goal destination in working memory, for use in navigation.     

A comparison of egocentric and allocentric spatial memory in a patient with selective hippocampal damage

The spatial memory of a single patient (YR) was investigated. This patient, who had relatively selective bilateral hippocampal damage, showed the pattern of impaired recall but preserved item recognition on standardised memory tests that has been suggested by Aggleton and Shaw [Aggleton JP, Shaw C. Amnesia and recognition memory: a reanalysis of psychometric data. Neuropsychologia 1996;34:51-62] to be a consequence of Papez circuit lesions. YR was tested on three recall tests and one recognition test for visuospatial information. The initial recall test assessed visuospatial memory over very short unfilled delays and YR was not significantly impaired. This test was then modified to test recall of allocentric and egocentric spatial information separately after filled delays of between 5 and 60 s. YR was found to be more impaired at recalling allocentric than egocentric information after a 60 s interval with a tendency for the impairment to increase up to this delay. Recognition of allocentric spatial information was also assessed after delays of 5 and 60 s. YR was impaired after the 60 s delay. The results suggest that the human hippocampus has a greater involvement in allocentric than egocentric spatial memory, and that this most likely concerns the consolidation of allocentric information into long-term memory rather than the initial encoding of allocentric spatial information. The findings also suggest that YR's item recognition/free recall deficit pattern reflects a problem retrieving or storing certain kinds of associative information.     

A role for right medial prefontal cortex in accurate feeling-of-knowing judgements: evidence from patients with lesions to frontal cortex

The hypothesis that prefrontal cortex plays a critical role in accurate predictions of episodic memory performance was tested using the feeling-of-knowing (FOK) paradigm. Fourteen patients with a broad spectrum of damage to the frontal cortex and matched controls read sentences and later were tested for recall memory, confidence judgments, and FOK accuracy using as cues the sentences with the final word missing. While frontal patients were impaired at recall and recognition memory, they were able to make accurate confidence judgments about their recall attempts. By contrast, as a group, the patients were markedly impaired in the accuracy of their prospective FOK judgments. Lesion analysis of frontal patients with clear FOK impairment revealed an overlapping region of damage in right medial prefrontal cortex. These findings provide functional and anatomical evidence for a dissociation between recall confidence and prospective memory monitoring and are discussed in terms of familiarity and access theories of FOK predictions.     

Episodic and semantic memory in mild cognitive impairment

Little is known about episodic and semantic memory in the early predementia stage of Alzheimer's disease (AD), which is referred to as mild cognitive impairment (MCI). To explore person knowledge, item recognition and spatial associative memory, we designed the Face Place Test (FPT). A total of 75 subjects participated: 22 patients with early AD, 24 with MCI and 29 matched controls. As predicted, AD patients showed significant deficits in person naming, item recognition and recall of spatial location (placing). Surprisingly, subjects with MCI were also impaired on all components. There was no significant difference between AD and MCI except on the placing component. Analysis of the relationship between semantic (naming) and episodic (recognition and placing) components of the FPT revealed a significant association between the two episodic tasks, but not between episodic and semantic performance. Patients with MCI show deficits of episodic and semantic memory. The extent of impairment suggests dysfunction beyond the medial temporal lobe. The FPT might form the basis of a sensitive early indicator of AD.     

Using virtual reality to characterize episodic memory profiles in amnestic mild cognitive impairment and Alzheimer's disease: influence of active and passive encoding

Most neuropsychological assessments of episodic memory bear little similarity to the events that patients actually experience as memories in daily life. The first aim of this study was to use a virtual environment to characterize episodic memory profiles in an ecological fashion, which includes memory for central and perceptual details, spatiotemporal contextual elements, and binding. This study included subjects from three different populations: healthy older adults, patients with amnestic mild cognitive impairment (aMCI) and patients with early to moderate Alzheimer's disease (AD). Second, we sought to determine whether environmental factors that can affect encoding (active vs. passive exploration) influence memory performance in pathological aging. Third, we benchmarked the results of our virtual reality episodic memory test against a classical memory test and a subjective daily memory complaint scale. Here, the participants were successively immersed in two virtual environments; the first, as the driver of a virtual car (active exploration) and the second, as the passenger of that car (passive exploration). Subjects were instructed to encode all elements of the environment as well as the associated spatiotemporal contexts. Following each immersion, we assessed the patient's recall and recognition of central information (i.e., the elements of the environment), contextual information (i.e., temporal, egocentric and allocentric spatial information) and lastly, the quality of binding. We found that the AD patients' performances were inferior to that of the aMCI and even more to that of the healthy aged groups, in line with the progression of hippocampal atrophy reported in the literature. Spatial allocentric memory assessments were found to be particularly useful for distinguishing aMCI patients from healthy older adults. Active exploration yielded enhanced recall of central and allocentric spatial information, as well as binding in all groups. This led aMCI patients to achieve better performance scores on immediate temporal memory tasks. Finally, the patients' daily memory complaints were more highly correlated with the performances on the virtual test than with their performances on the classical memory test. Taken together, these results highlight specific cognitive differences found between these three populations that may provide additional insight into the early diagnosis and rehabilitation of pathological aging. In particular, neuropsychological studies would benefit to use virtual tests and a multi-component approach to assess episodic memory, and encourage active encoding of information in patients suffering from mild or severe age-related memory impairment. The beneficial effect of active encoding on episodic memory in aMCI and early to moderate AD is discussed in the context of relatively preserved frontal and motor brain functions implicated in self-referential effects and procedural abilities.     

Memory lost and regained following bilateral hippocampal damage

We present a longitudinal neuropsychological study (31 examinations over a period of 18 months) of patient DE DF demonstrated bilateral atrophy of the hippocampal formation and globus pallidus resulting from carbon monoxide poisoning. Eighteen months after the event, the volume of the hippocampal formation was reduced by 42% on the left side and 28% on the right. The patient initially presented with a severe global amnesia. Then, he showed a gradual, yet selective recovery of episodic memory function. Verbal free recall and spatial memory performance remained reduced, whereas immediate word recall and recognition memory, as well as picture learning and memory, improved to levels at the lower range of normal performance. Interestingly, nonspatial associative learning was never much impaired and recovered completely by the end of testing. These data are taken as evidence that the human hippocampal formation does not equally support different forms of episodic memory.     

Impaired memory for scenes but not faces in developmental hippocampal amnesia: a case study

Item recognition for unfamiliar faces and scenes was tested in Jon, who has developmental amnesia resulting from bilateral hippocampal pathology. Performance and confidence judgements in healthy adults showed that both tests were equated for difficulty and had similar receiver operating characteristics (ROCs). Jon's performance on the faces test was indistinguishable from the controls, in both sensitivity and the shape of the ROC curve. In contrast his performance on the scenes test was markedly poor, and his ROC was inconsistent with both a standard dual process (DP; recollection and familiarity) model and an unequal variance signal detection model of recognition memory. Jon's data were as well fitted as controls' data by a DP model that included two recollection parameters, but required counter-intuitive parameter values corresponding to normal recollection and impaired familiarity, which likely reflect an idiosyncratic use of confidence judgements when his memory for the material is weak. The results highlight a limitation in using ROCs to estimate recollection and familiarity in patients who may have developed compensatory strategies for material that they have difficulty remembering (scenes, but not faces in this case). Overall, these data are difficult to reconcile with domain-general accounts of the hippocampal role in memory, including dual process models and the declarative model. Instead, the data indicate that the hippocampus plays a preferential role in the processing of topographical memoranda over faces memoranda.