The case of K.C.: contributions of a memory-impaired person to memory theory

K.C. has been investigated extensively over some 20 years since a motorcycle accident left him with widespread brain damage that includes large bilateral hippocampal lesions, which caused a remarkable case of memory impairment. On standard testing, K.C.'s anterograde amnesia is as severe as that of any other case reported in the literature, including H.M. However, his ability to make use of knowledge and experiences from the time before his accident shows a sharp dissociation between semantic and episodic memory. A good deal of his general knowledge of the world, including knowledge about himself, is preserved, but he is incapable of recollecting any personally experienced events. In displaying such "episodic amnesia," which encompasses an entire lifetime of personal experiences, K.C. differs from many other amnesic cases. Here, we document for the first time the full extent of K.C.'s brain damage using MRI-based quantitative measurements. We then review the many investigations with K.C. that have contributed to our understanding not only of episodic and semantic memory but also to the development of other aspects of memory theory. These include the distinction between implicit and explicit memory, the prospect of new learning in amnesia, and the fate of recent and remote memory for autobiographical and public events, people, and spatial locations.     

Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst.

Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans.     

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.

     

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.     

Acquired amnesia in childhood: a single case study

We report the case of C.L., an 8-year-old child who, following the surgical removal of an ependymoma from the left cerebral ventricle at the age of 4 years, developed significant difficulties in retaining day-to-day events and information. A thorough neuropsychological analysis documented in C.L. a severe anterograde amnesic syndrome, characterised by normal short-term memory, but poor performance on episodic long-term memory tests. In particular, C.L. demonstrated virtually no ability to recollect new verbal information several minutes after the presentation. As for semantic memory, C.L. demonstrated general semantic competencies, which, depending on the test, ranged from the level of a 6-year-old girl to a level corresponding to her actual chronological age. Finding a patient who, despite being severely impaired in the ability to recollect new episodic memories, still demonstrates at least partially preserved abilities to acquire new semantic knowledge suggests that neural circuits implicated in the memorisation of autobiographical events and factual information do not overlap completely. This case is examined in the light of growing literature concerned with the dissociation between episodic and semantic memory in childhood amnesia.     

The nature of anterograde and retrograde memory impairment after damage to the medial temporal lobe

The study of anterograde and retrograde amnesia (AA and RA) in the laboratory and the clinic has provided important information about the structure and organization of memory. The severity of AA is usually correlated with the severity of RA. Nevertheless, variations in the expression of AA and RA have been reported, which presumably reflect variation in the locus and extent of brain damage. The relationship between AA and RA has rarely been described quantitatively in groups of patients where detailed anatomical information is available. We have quantified the severity of AA and RA for factual information in 11 memory-impaired patients with bilateral medial temporal lobe lesions, including 5 for whom detailed post-mortem neurohistological information was available. The findings describe an orderly relationship between AA and RA, such that patients with more severe AA also had more extensive RA. In addition, RA was measurable only after AA reached a substantial level of severity. This relationship between AA and RA in patients with identified medial temporal lobe lesions appears to describe a general principle, which applies to a range of etiologies, including traumatic amnesia, where the locus and extent of brain damage is less well understood. Whenever patients deviate substantially from the relationship described here, one should be alert to the likelihood that significant damage has occurred outside or in addition to the structures in the medial temporal lobe.     

Influence of patients' emotional state on the recovery processes after a transient global amnesia

Introduction

Currently, there is no consensus on the delay necessary to a complete recovery after a transient global amnesia (TGA). However, it seems that slight episodic memory disorders extend beyond 24 h. Although this impairment is probably a consequence of the TGA attack, other factors such as patients’ emotional state can intervene in the slow recovery process.

Methods

In a first experiment, we studied the dynamic of recovery processes after a TGA. Thus, we assessed the anterograde and retrograde components of episodic memory in 19 patients one day, one month and one year after the attack. In a second experiment, we examined the impact of patients’ emotional state on memory disorders, in using an original neuropsychological protocol (using material with emotional features) and an assessment of anxiety and depressive mood. This protocol was carried out in 19 other patients examined four months and one year after TGA.

Results

In the first experiment, we highlighted mild memory disorders affecting the anterograde component of episodic memory one day after the episode. In the second experiment, we showed these mild memory disorders could be detected several months after TGA. Moreover, patients who had the more depressive tendencies recognized the fewer items and those who displayed the highest level of anxiety supplied the fewer specific remote memories.

Conclusions

Our results showed that patients displayed very mild memory disorders several months after the episode of TGA, not affecting the daily routine. This impairment was influenced by patients’ emotional state, which could suggest that a high level of anxiety or depression can slow down the recovery. However, we cannot be sure that the deleterious effect of patients’ emotional state on their cognitive performances is specific to TGA. Other investigations are necessary to unravel this issue.     

Visual memory loss and autobiographical amnesia: a case study

Amnesia typically results from trauma to the medial temporal regions that coordinate activation among the disparate areas of cortex that represent the information that make up autobiographical memories. We proposed that amnesia should also result from damage to these regions, particularly regions that subserve long-term visual memory [Rubin, D. C., & Greenberg, D. L. (1998). Visual memory-deficit amnesia: A distinct amnesic presentation and etiology. Proceedings of the National Academy of Sciences of the USA, 95, 5413-5416]. We previously found 11 such cases in the literature, and all 11 had amnesia. We now present a detailed investigation of one of these patients. M.S. suffers from long-term visual memory loss along with some semantic deficits; he also manifests a severe retrograde amnesia and moderate anterograde amnesia. The presentation of his amnesia differs from that of the typical medial-temporal or lateral-temporal amnesic; we suggest that his visual deficits may be contributing to his autobiographical amnesia.     

Disproportionate retrograde amnesia in a patient with herpes simplex encephalitis

We describe a patient who developed a severe but temporally limited retrograde amnesia coupled with a relatively mild anterograde amnesia following herpes simplex encephalitis. The patient showed a profound retrograde amnesia for autobiographical events extending for about 10 years prior to the disease onset. Her knowledge about public events and famous persons was also impaired for this period. An MRI and SPECT demonstrated bilateral medial temporal pathology. This case represents a further instance of a relatively focal retrograde amnesia following brain damage. We review other reported cases with focal retrograde amnesia and consider theoretical and neuroanatomical accounts for the present case. Two factors may account for her amnesic patterns: a partial disruption of the store for premorbid binding codes (i.e., information that multimodal feature representations occurred synchronously); along with a relative preservation of the encoding process required to develop new synchronous codes.     

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.     

Memory consolidation and the hippocampus: further evidence from studies of autobiographical memory in semantic dementia and frontal variant frontotemporal dementia.

Studies of autobiographical memory in semantic dementia have found relative preservation of memories for recent rather than remote events. As semantic dementia is associated with progressive atrophy to temporal neocortex, with early asymmetric sparing of the hippocampus, this neuropsychological pattern suggests that the hippocampal complex plays a role in the acquisition and retrieval of recent memories, but is not necessary for the recall of older episodic events. In an alternative view of memory consolidation, however, the hippocampus plays a role in the retrieval of all autobiographical memories, regardless of the age of the memory [Curr. Opin. Neurobiol. 7(1997)217]. This 'multiple trace theory' predicts that patients with semantic dementia should show no effects of time in their autobiographical recall. In this article, we ask whether it is possible to reconcile the data from semantic dementia with the multiple trace theory by investigating whether the time-dependent pattern of autobiographical retrieval seen in the disease is due to (i) patients showing this effect being exceptional in their presentation; and/or (ii) patients with semantic dementia exhibiting impaired strategic retrieval from concomitant frontal damage. A series of experiments in patients with semantic dementia, the frontal variant of frontotemporal dementia and Alzheimer's disease clearly demonstrates that neither of these two factors can explain the documented effect of time seen in semantic dementia. Nonetheless, we discuss how damage to semantic knowledge could result in an autobiographical memory deficit and suggest that data from semantic dementia may be consistent with both views of hippocampal involvement in long-term memory.     

Pure retrograde amnesia following a mild head trauma: a neuropsychological and metabolic study

After a minor closed head injury, a 33-year-old man acquired extensive retrograde amnesia (RA) covering the previous ten years and concerning autobiographical, semantic and procedural memories. The patient's learning abilities remained excellent and he recovered considerable information from his wife, the media and personal documents. This relearned information did not, however, provide a sense of personal experience in the first weeks. CT and MRI failed to show brain damage, but EEG and SPECT examination showed a marked right temporal dysfunction. After three months the patient had almost completely recovered from RA. Interestingly, a parallel recovery was observed in the second SPECT obtained at this period. There was clearly a blockade of retrieval, while the stored engrams were probably intact. The mechanisms underlying such a functional amnesia are discussed in the light of previous reports of amnesia without brain lesions.     

Recall and recognition memory in amnesia: patients with hippocampal, medial temporal, temporal lobe or frontal pathology

The relationship between recall and recognition memory impairments was examined in memory-disordered patients with either hippocampal, medial temporal, more widespread temporal lobe or frontal pathology. The Hirst [Hirst, W., Johnson, M. K., Phelps, E. A., & Volpe, B. T. (1988). More on recognition and recall in amnesics. Journal of Experimental Psychology: Learning, Memory, & Cognition, 14, 758-762] technique for titrating exposure times was used to match recognition memory performance as closely as possible before comparing recall memory scores. Data were available from two different control groups given differing exposure times. Each of the patient groups showed poorer recall memory performance than recognition scores, proportionate to the difference seen in healthy participants. When patients' scores were converted to Z-scores, there was no significant difference between mean Z-recall and Z-recognition scores. When plotted on a scatterplot, the majority of the data-points indicating disproportionately low recall memory scores came from healthy controls or patients with pathology extending into the lateral temporal lobes, rather than from patients with pathology confined to the medial temporal lobes. Patients with atrophy extending into the parahippocampal gyrus (H+) performed worse than patients with atrophy confined to the hippocampi (H-); but, when H- patients were given a shorter exposure time (5s) and compared with H+ at a longer exposure (10s), their performance was virtually identical and did not indicate any disproportionate recall memory impairment in the H- group. Parahippocampal volumes on MRI correlated significantly with both recall and recognition memory. The possibility that findings were confounded by inter-stimulus artefacts was examined and rejected. These findings argue against the view that hippocampal amnesia or memory disorders in general are typically characterised by a disproportionate impairment in recall memory. Disproportionate recall memory impairment has been observed in a number of published cases, and the reason for the varying pattern obtained across hippocampal patients requires further examination.     

Patients with heart attacks are not valid models for medial temporal lobe amnesia. A neuropsychological and FDG-PET study with consequences for memory research

Equating the condition after cardiac arrest with that of medial temporal damage, and consequently medial temporal lobe amnesia, is questioned on the basis of results from a patient who was studied neuropsychologically as well as with static and dynamic imaging methods (MRI, PET) 6–9 months after a heart attack. The patient manifested severe and persistent anterograde and retrograde amnesia, as well as further cognitive deteriorations. While MRI only indicated non-specific cortical atrophy, PET revealed a severe bilateral affection of the thalamus and of both medial and lateral temporal cortices as well as occipito-parietal hypometabolism. The neuropsychological status indicates that patients with a diagnosis of cardiac arrest may suffer very severe and persistent cognitive deficits; the imaging analyses show that cardiac arrests may lead to quite severe and widespread brain damage which, however, may not be visible with current magnetic resonance imaging technology, but which is clearly apparent from positron emission tomography. These data suggest that patients with a condition after a heart attack may not be valid models for pure hippocampal—or even medial temporal lobe—pathology, as they may suffer much more widespread brain damage.     

Amnesia as an impairment of detail generation and binding: Evidence from personal, fictional, and semantic narratives in K.C.

Autobiographical episodic recall involves active simultaneous generation and binding of various elements that were present during the initial experience. Deficits in this reconstructive process may account for some aspects of retrograde amnesia (RA) for personally experienced events. Constructive and reconstructive processes may involve similar mechanisms. If so, patients with extensive anterograde amnesia (AA) and RA should show deficits in non-recollective cognitive domains, such as imagining events that had never been experienced and recounting non-personal narratives, that presumably rely on constructive and re-constructive processes, respectively. To test these possibilities, patient K.C., who has severe AA and RA for personal episodes, was asked to generate fictional events and to recall and recognize details of well-known fairy tales and bible stories. K.C.’s performance on both tasks was better than expected given his severely impaired autobiographical episodic memory (AM), but significantly worse than that of control participants. K.C. was able to create a skeletal outline for both types of narratives, providing sufficient information to convey their gist, but the narratives were fragmented and lacking in detail. This deficit cannot be explained as resulting entirely from deficient stored semantic knowledge, because K.C. was able to discriminate between true and false details of non-personal semantic narratives on a recognition test, which he cannot do for personal events [Gilboa, A., Winocur, G., Rosenbaum, R.S., Poreh, A., Gao, F., Black, S.E., Westmacott, R., & Moscovitch, M. (2006a). Hippocampal contributions to recollection in retrograde and anterograde amnesia. Hippocampus, 16, 966-980]. Thus, retrograde AM impairment may be viewed as both a loss of information as well as a deficit in reconstructive processes that hamper or prevent the binding of information to generate a cohesive, detail-rich memory.     

Hippocampal lesions produce both nongraded and temporally graded retrograde amnesia in the same rat

Rats were administered contextual fear conditioning and trained on a water‐maze, spatial memory task 28 days or 24 h before undergoing hippocampal lesion or control surgery. When tested postoperatively on both tasks, rats with hippocampal lesions exhibited retrograde amnesia for spatial memory at both delays but temporally graded retrograde amnesia for the contextual fear response. In demonstrating both types of retrograde amnesia in the same animals, the results parallel similar observations in human amnesics with hippocampal damage and provide compelling evidence that the nature of the task and the type of information being accessed are crucial factors in determining the pattern of retrograde memory loss associated with hippocampal damage. The results are interpreted as consistent with our transformation hypothesis (Winocur et al. (2010a) Neuropsychologia 48:2339–2356; Winocur and Moscovitch (2011) J Int Neuropsychol Soc 17:766–780) and at variance with standard consolidation theory and other theoretical models of memory. © 2013 Wiley Periodicals, Inc.     

Retrograde amnesia in rats with lesions to the hippocampus on a test of spatial memory

The present study examined remote spatial memory in a test that spans several months to determine whether remote memories are spared relative to more recent ones, as predicted by models of memory consolidation. At 3, 6 or 12 months of age, groups of rats received forced-choice training as to the location of food reward in a cross maze. At 12.5 months, rats received bilateral neurotoxic lesions to the hippocampus or a control surgical procedure and 2 weeks later their memory for the spatial location was tested. Their performance was compared to that of rats with hippocampal or control lesions with no prior training on several measures of savings. The hippocampal group with no pre-training, as expected, was severely impaired in learning the location of the food reward. Compared to this group, rats with hippocampal lesions that were pre-trained consistently performed better at the shortest training-surgery interval but not at the longer ones. That is, rats with hippocampal lesions exhibited retrograde amnesia at all training-surgery intervals and a forgetting curve that paralleled that of the control groups. The results were interpreted within a framework that distinguishes between relational and associative context, and as providing evidence that the hippocampus is necessary for the retention and retrieval of memories that are bound to relational context, regardless of the age of the memory.     

Role of the medial temporal lobes in relational memory: neuropsychological evidence from a cued recognition paradigm

In this study, we examined the role of the hippocampus in relational memory by comparing item recognition performance in amnesic patients with medial temporal lobe (MTL) damage and their matched controls. Specifically, we investigated the contribution of associative memory to item recognition using a cued recognition paradigm. Control subjects studied cue-target pairs once, whereas amnesic patients studied cue-target pairs six times. Following study, subjects made recognition judgments about targets that were presented either alone (no cue), with the originally presented cue (same cue), or with a cue that had been presented with a different target (recombined cue). Controls had higher recognition scores in the same cue than in the recombined cue condition, indicating that they benefited from the associative information provided by the same cue. By contrast, amnesic patients did not. This was true even for a subgroup of patients whose recognition performance in the no cue condition was matched to that of the controls. These data provide further support for the idea that the hippocampus plays a critical role in relational memory, even when associative information need not be retrieved intentionally.     

Autobiographical memory and the self in a case of transient epileptic amnesia

Transient epileptic amnesia (TEA) is characterized by deficits in autobiographical memory (AM). One of the functions of AM is to maintain the self, suggesting that the self may undergo changes as a result of memory loss in temporal lobe epilepsy. To examine this, we used a modification of a task used to assess the relationship between self and memory (the IAM task) in a single case, E.B. Despite complaints of AM loss, E.B. had no difficulty in producing a range of self-images (e.g., I am a husband) and collections of self-defining AMs in support of these statements. E.B. produced fewer episodic memories at times of self-formation, but this did not seem to impact on the maintenance of self. The results support recent work suggesting the self may be maintained in the absence of episodic memory. The application of tasks such as that used here will further elucidate AM impairment in temporal lobe epilepsy.     

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.