Impaired inference in a case of developmental amnesia

Amnesia is associated with impairments in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm, we previously showed that age‐related impairments in inference were mitigated when judgments could be predicated on known pairwise relations, however, such advantages were not observed in the adult‐onset amnesic case D.A. Here, we replicate and extend this finding in a developmental amnesic case (N.C.), who also shows impaired relational learning and transitive expression. Unlike D.A., N.C.'s damage affected the extended hippocampal system and diencephalic structures, and does not extend to neocortical areas that are affected in D.A. Critically, despite their differences in etiology and affected structures, N.C. and D.A. perform similarly on the task. N.C. showed intact pairwise knowledge, suggesting that he is able to use existing semantic information, but this semantic knowledge was insufficient to support transitive expression. The present results suggest a critical role for regions connected to the hippocampus and/or medial prefrontal cortex in inference beyond learning of pairwise relations. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Extensive temporally graded retrograde amnesia for personal-episodic facts in transient global amnesia

Abstract

Transient global amnesia (TGA) is characterized by an impairment of episodic memory resulting both in anterograde and retrograde amnesia. Few studies have assessed retrograde amnesia in TGA. Only Evans et al. (Journal of Neurology, Neurosurgery and Psychiatry 1993; 56: 1227-30) have distinguished between the episodic and semantic components of autobiographical memory, suggesting a disturbance of autobiographical incident recollection. A patient was tested during the acute phase of TGA with a sophisticated autobiographical event interview [derived from Kopelman et al. (Journal of Clinical and Experimental Neuropscyhology 1989; 11: 724-44) and Borrini et al. (Psychological Medicine 1989; 19: 215-24)], designed to replicate and extend this study of autobiographical memory. The autobiographical event interview disclosed an extensive disturbance in recalling memories with a temporal gradient, sparing earliest memories compared to more recent ones.     

Long-term memory following transient global amnesia: an investigation of episodic and semantic memory

BACKGROUND: Several studies noted persistence of memory impairment following an episode of transient global amnesia (TGA) with standard tests. AIM: To specify long-term memory impairments in a group of patients selected with stringent criteria. METHODS: Both retrograde and anterograde memory were investigated in 32 patients 13-67 months after a TGA episode with original tasks encompassing retrograde semantic memory (academic, public and personal knowledge), retrograde episodic memory (autobiographical events) and anterograde episodic memory. RESULTS: Patients had preserved academic and public knowledge. Pathological scores were obtained in personal verbal fluency for the two most recent periods, and patients produced less autobiographical events than controls. However, when they were provided time to detail, memories were as episodic as in controls regardless of their remoteness. Anterograde episodic tasks revealed a mild but significant impairment of the capacity of re-living the condition of encoding, i.e. the moment at which words were presented. CONCLUSIONS: Patients who have suffered from an episode of TGA manifest deficits of memory focused on the retrieval of both recent semantic information and episodic memories and especially the capacity of re-living. These deficits may not result from a deterioration of memory per se but rather from difficulties in accessing memories.     

Preserved semantic learning in an amnesic patient

A case study is reported of an amnesic patient (KN), who displayed an ability to learn a substantial body of new visual and verbal semantic concepts, despite having a severe deficit in episodic memory. In two experiments, using an errorless learning paradigm, he was able to perform at a level close to that of his wife, who served as a control subject. When recall of material was retested after a delay of several months, during which time there were no further learning sessions, his retention was at least as good as, if not better, than that of his wife. This is taken as further evidence for the dissociation of semantic and episodic processes in amnesia. It also provides further evidence for the role of "errorless learning" in efficient acquisition of new facts in amnesia.     

Two cases of functional focal retrograde amnesia with impairment of object use

We report on two patients, TH and KN, with focal retrograde amnesia (FRA). Their memory loss regarding life events extended to their whole lives, whereas they could acquire and retain new information. They also showed prominent deficits in production and comprehension of common words. In addition, at least in the testing situation, they were impaired in their recognition and use of familiar objects. Although both cases of FRA followed an episode that can cause brain pathology, MRI revealed no structural abnormality in either patient. Stressful situations preceding the onset were evident in KN, but not in TH. We discuss their impairments of object knowledge from a neuropsychological perspective, and we interpret the etiology of their condition as a functional rather than a psychogenic amnesia.     

Amnesia and the organization of the hippocampal system

Early hippocampal injury in humans has been found to result in a limited form of global anterograde amnesia. At issue is whether the limitation is qualitative, with the amnesia reflecting substantially greater impairment in episodic than in semantic memory, or only quantitative, with both episodic and semantic memory being partially and equivalently impaired. Evidence from neuroanatomical and lesion studies in animals suggests that the hippocampus and subhippocampal cortices form a hierarchically organized system, such that the greatest convergence of information (and, by implication, the richest amount of association) takes place within the hippocampus, located at the top of the hierarchy. On the one hand, this evidence is consistent with the view that selective hippocampal damage produces a differential impairment in context-rich episodic memory as compared with context-free semantic memory, because only the latter can be supported by the subhippocampal cortices. On the other hand, given the system's hierarchical form of organization, this dissociation of deficits is difficult to prove, because a quantitatively limited deficit will nearly always be a viable alternative. A final choice between the alternative views is therefore likely to depend less on further evidence gathered in brain-injured patients than on which view accounts for more of the data gathered from converging approaches to the problem. Hippocampus 1998;8:212–216. © 1998 Wiley-Liss, Inc.     

Semantic amnesia without dementia: documentation of a case

We described the case of a patient affected by a progressive semantic memory disorder associated with prevalent temporal lobe atrophy. This deficit seems to be pure in the sense that it has not been found to overlap with other cognitive deficits (intellectual, linguistic, perceptual, visuo-spatial etc.) for a long time. Furthermore, despite his impaired semantic knowledge, the autobiographical memory of the patient was largely intact. This case therefore represents a form of semantic amnesia without dementia, and supports the hypothesis that there is a partial distinction between semantic and episodic memory.

---

Sommario Descriviamo il caso di un paziente con atrofia bilaterale (prevalentemente temporale) affetto da un deficit progressivo semantico. Non si evidenziarono (almeno per lungo tempo) altri deficit cognitivi e la memoria autobiografica/episodica, in contrasto a quella semantica, risultò sufficientemente conservata. Il caso rappresenta, perciò, una forma di amnesia semantica in assenza di deterioramento cognitivo e sostiene l'ipotesi della distinzione tra memoria semantica ed episodica.

     

Time estimation and amnesia: A case study

Abstract

The present experiment investigates the ability of an amnesic patient (AC) to estimate three durations (5, 14 or 38 s) in two different temporal tasks (reproduction and production). In the reproduction task, AC and control subjects first had to encode one of the three durations and then to reproduce it. In the production task, they were asked to produce one of the three durations given in chronometric units. AC's performance showed a clear dissociation according to the tasks and the durations. His productions of the three durations and his reproductions of 5 s did not differ from those of the controls, whilst his reproductions of longer durations (14 and 38 s) were systematic underestimations. The results suggest that reproduction involves a long-term storage in episodic memory for durations exceeding the short-term memory capacity, whereas production of durations given in chronometric units involves semantic memory, which contains the representation of several durations, and working memory, which permits the maintenance of temporal information throughout each trial.     

Counterfactual thinking in patients with amnesia

We often engage in counterfactual (CF) thinking, which involves reflecting on “what might have been.” Creating alternative versions of reality seems to have parallels with recollecting the past and imagining the future in requiring the simulation of internally generated models of complex events. Given that episodic memory and imagining the future are impaired in patients with hippocampal damage and amnesia, we wondered whether successful CF thinking also depends upon the integrity of the hippocampus. Here using two nonepisodic CF thinking tasks, we found that patients with bilateral hippocampal damage and amnesia performed comparably with matched controls. They could deconstruct reality, add in and recombine elements, change relations between temporal sequences of events, enabling them to determine plausible alternatives of complex episodes. A difference between the patients and control participants was evident, however, in the patients' subtle avoidance of CF simulations that required the construction of an internal spatial representation. Overall, our findings suggest that mental simulation in the form of nonepisodic CF thinking does not seem to depend upon the hippocampus unless there is the added requirement for construction of a coherent spatial scene within which to play out scenarios. © 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Hand gestures support word learning in patients with hippocampal amnesia

Co‐speech hand gesture facilitates learning and memory, yet the cognitive and neural mechanisms supporting this remain unclear. One possibility is that motor information in gesture may engage procedural memory representations. Alternatively, iconic information from gesture may contribute to declarative memory representations mediated by the hippocampus. To investigate these alternatives, we examined gesture's effects on word learning in patients with hippocampal damage and declarative memory impairment, with intact procedural memory, and in healthy and in brain‐damaged comparison groups. Participants learned novel label‐object pairings while producing gesture, observing gesture, or observing without gesture. After a delay, recall and object identification were assessed. Unsurprisingly, amnesic patients were unable to recall the labels at test. However, they correctly identified objects at above chance levels, but only if they produced a gesture at encoding. Comparison groups performed well above chance at both recall and object identification regardless of gesture. These findings suggest that gesture production may support word learning by engaging nondeclarative (procedural) memory.     

Novelty preference in patients with developmental amnesia

To re‐examine whether or not selective hippocampal damage reduces novelty preference in visual paired comparison (VPC), we presented two different versions of the task to a group of patients with developmental amnesia (DA), each of whom sustained this form of pathology early in life. Compared with normal control participants, the DA group showed a delay‐dependent reduction in novelty preference on one version of the task and an overall reduction on both versions combined. Because VPC is widely considered to be a measure of incidental recognition, the results appear to support the view that the hippocampus contributes to recognition memory. A difficulty for this conclusion, however, is that according to one current view the hippocampal contribution to recognition is limited to task conditions that encourage recollection of an item in some associated context, and according to another current view, to recognition of an item with the high confidence judgment that reflects a strong memory. By contrast, VPC, throughout which the participant remains entirely uninstructed other than to view the stimuli, would seem to lack such task conditions and so would likely lead to recognition based on familiarity rather than recollection or, alternatively, weak memories rather than strong. However, before concluding that the VPC impairment therefore contradicts both current views regarding the role of the hippocampus in recognition memory, two possibilities that would resolve this issue need to be investigated. One is that some variable in VPC, such as the extended period of stimulus encoding during familiarization, overrides its incidental nature, and, because this condition promotes either recollection‐ or strength‐based recognition, renders the task hippocampal‐dependent. The other possibility is that VPC, rather than providing a measure of incidental recognition, actually assesses an implicit, information‐gathering process modulated by habituation, for which the hippocampus is also partly responsible, independent of its role in recognition. © 2010 Wiley Periodicals, Inc.     

Transient topographical amnesia: A case report

We describe the case of a 56 year old female, with a history of migraine since adolescence, who experienced two episodes of transient topographical disorientation in the absence of intellectual deterioration or evident focal cerebral lesions.

---

Sommario Viene descritto il caso di una paziente di 56 anni, con storia di emicrania fin dall'adolescenza, caratterizzato da due episodi di disorientamento topografico transitorio, in assenza di deterioramento mentale e di evidenti lesioni cerebrali focali.

     

Relational learning and transitive expression in aging and amnesia

Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255‐257) , which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A‐>B, B‐>C, C‐>D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A‐>C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre‐experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre‐experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to‐be‐learned relations were arbitrary. However, accuracy improved for older adults when they could use pre‐experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and anterior temporal regions may have resulted in an inability to use prior knowledge to flexibly express indirect relational knowledge. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.     

Two further investigations of autobiographical memory in semantic dementia

A number of investigations in semantic dementia have documented better retrieval of recent personal events compared to those in the more distant past (Graham and Hodges, 1997). Westmacott et al. (2001) challenged this result, however, finding relative preservation of remote memories in a single case of semantic dementia when he was tested using family photographs. In Experiment 1, we tested two possible explanations for the discrepancy between the published papers: (a) that there is a significant effect of modality in autobiographical retrieval in semantic dementia (e.g., patients will show better, or even preserved, remote memory when tested on nonverbal, compared to verbal, tasks); and (b) that the distinct pattern seen between patients is attributable to the different methods adopted for scoring the episodic quality of the memories. A patient with semantic dementia, AM, produced autobiographical memories to both words and family photographs. These personal events were scored by two raters using the scoring method described by Westmacott et al. (2001) and that reported by Graham and Hodges (1997). It was found that AM showed similar levels of remote memory impairment regardless of whether the cue was verbal or nonverbal. In addition, significant effects of time were revealed in AM's performance on the verbal memory test, regardless of which method was used to score the memories. In Experiment 2, we investigated a related question: whether the relatively better retrieval of memories in semantic dementia could be due to over rehearsal of highly salient recent experiences? Four patients were tested on their ability to remember a recent event (either a trip to London or events from a Formula One Grand Prix race) using specially designed autobiographical questionnaires. It was found that all four were able to perform this task, although one patient showed evidence of some forgetting over three months, and another exhibited difficulty discriminating between two similar events. Together, the two experiments further confirm that patients with semantic dementia show a modality independent autobiographical memory deficit, with better retrieval of recent events.     

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.     

Losing memories overnight: A unique form of human amnesia

Since an automobile accident in 2005, patient FL has reported difficulty retaining information from one day to the next. During the course of any given day, she describes her memory as normal. However, memory for each day disappears during a night of sleep. She reports good memory for events that occurred before the accident. Although this pattern of memory impairment is, to our knowledge, unique to the medical literature, it was depicted in the fictional film “50 First Dates”. On formal testing, FL performed moderately well when trying to remember material that she had learned during the same day, but she exhibited no memory at all for material that she knew had been presented on a previous day. For some tests, unbeknownst to FL, material learned on the previous day was intermixed with material learned on the same day as the test. On these occasions, FL's memory was good. Thus, she was able to remember events from earlier days when memory was tested covertly. FL performed differently in a number of ways from individuals who were instructed to consciously feign her pattern of memory impairment. It was also the impression of those who worked with FL that she believed she had the memory impairment that she described and that she was not intentionally feigning amnesia. On the basis of her neuropsychological findings, together with a normal neurological exam, normal MRI findings, and psychiatric evaluation, we suggest that FL exhibits a unique form of functional amnesia and that its characterization may have been influenced by knowledge of how amnesia was depicted in a popular film. She subsequently improved (and began retaining day-to-day memory) at Johns Hopkins University where she was in a supportive in-patient environment and was shown how to take control of her condition by interrupting her sleep at 4-h intervals.     

Deficits in egocentric-updating and spatial context memory in a case of developmental amnesia

Patients with developmental amnesia usually suffer from both episodic and spatial memory deficits. DM, a developmental amnesic, was impaired in her ability to process self-motion (i.e., idiothetic) information while her ability to process external stable landmarks (i.e., allothetic) was preserved when no self-motion processing was required. On a naturalistic and incidental episodic task, DM was severely and predictably impaired on both free and cued recall tasks. Interestingly, when cued, she was more impaired at recalling spatial context than factual or temporal information. Theoretical implications of that co-occurrence of deficits and those dissociations are discussed and testable cerebral hypothesis are proposed.     

A case of persistent retrograde amnesia following a dissociative fugue: neuropsychological and neurofunctional underpinnings of loss of autobiographical memory and self-awareness

Autobiographical memory relies on complex interactions between episodic memory contents, associated emotions and a sense of self-continuity over the course of one's life. This paper reports a study based upon the case of the patient NN who suffered from a complete loss of autobiographical memory and awareness of identity subsequent to a dissociative fugue. Neuropsychological, behavioral, and functional neuroimaging tests converged on the conclusion that NN suffered from a selective retrograde amnesia following an episode of dissociative fugue, during which he had lost explicit knowledge and vivid memory of his personal past. NN's loss of self-related memories was mirrored in neurobiological changes after the fugue whereas his semantic memory remained intact. Although NN still claimed to suffer from a stable loss of autobiographical, self-relevant memories 1 year after the fugue state, a proportionate improvement in underlying fronto-temporal neuronal networks was evident at this point in time. In spite of this improvement in neuronal activation, his anterograde visual memory had been decreased. It is posited that our data provide evidence for the important role of visual processing in autobiographical memory as well as for the efficiency of protective control mechanisms that constitute functional retrograde amnesia.