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We investigated episodic future thinking (EFT) and future-based cognition and decision-making in patient SG, who developed a dense retrograde amnesia following hypoxia due to a cardiac arrest. Despite intact general cognitive and executive functioning, SG was unable to remember events from his entire lifetime. He had, however, relatively spared anterograde memory and general semantic knowledge. Voxel-based morphometry detected a reduction of gray matter in the thalamus, cerebellum and fusiform gyrus bilaterally, and, at a reduced threshold, in several regions of the autobiographical memory network, including the hippocampi. We show that SG is unable to imagine personal future events, but can imagine fictitious events not self-relevant and not located in subjective time. Despite severely impaired EFT, SG shows normal attitudes towards the future time, and normal delay discounting rates. These findings suggest that retrieval of autobiographical information from long-term memory is necessary for EFT. However, relatively spared anterograde memory and general semantic knowledge may be sufficient to allow construction of fictitious experiences. As well, EFT is not necessary to drive future-oriented cognition and choice. These findings highlight the relation between autobiographical memory and EFT, and the fractionation of human temporal consciousness. Moreover, they contribute to our understanding of retrograde amnesia as an impairment of memory as well as future thinking., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Andrew Mayes's contribution to the neuropsychology of memory has consisted in steadily teasing out the nature of the memory deficit in the amnesic syndrome. This has been done with careful attention to matters of method at all stages. This particularly applies to his investigations of forgetting rates in amnesia and to his studies of retrograde amnesia. Following a brief outline of his work, the main current theories of retrograde amnesia are considered: consolidation theory, episodic-to-semantic shift theory, and multiple trace theory. Findings across the main studies in Alzheimer dementia are reviewed to illustrate what appears to be consistently found, and what is much more inconsistent. A number of problems and issues in current theories are then highlighted--including the nature of the temporal gradient, correlations with the extent of temporal lobe damage, what we would expect 'normal' remote memory curves to look like, how they would appear in focal retrograde amnesia, and whether we can pinpoint retrograde amnesia to hippocampal/medial temporal damage on the basis of existing studies. A recent study of retrograde amnesia is re-analysed to demonstrate temporal gradients on recollected episodic memories in hippocampal/medial temporal patients. It is concluded that there are two requirements for better understanding of the nature of retrograde amnesia: (i) a tighter, Mayesian attention to method in terms of both the neuropsychology and neuroimaging in investigations of retrograde amnesia; and (ii) acknowledging that there may be multiple factors underlying a temporal gradient, and that episodic and semantic memory show important interdependencies at both encoding and retrieval. Such factors may be critical to understanding what is remembered and what is forgotten from our autobiographical pasts., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Patient M.L. [Levine, B., Black, S. E., Cabeza, R., Sinden, M., Mcintosh, A. R., Toth, J. P., et al. (1998). Episodic memory and the self in a case of isolated retrograde amnesia. Brain, 121, 1951-1973], lost memory for events occurring before his severe traumatic brain injury, yet his anterograde (post-injury) learning and memory appeared intact, a syndrome known as isolated or focal retrograde amnesia. Studies with M.L. demonstrated a dissociation between episodic and semantic memory. His retrograde amnesia was specific to episodic autobiographical memory. Convergent behavioral and functional imaging data suggested that his anterograde memory, while appearing normal, was accomplished with reduced autonoetic awareness (awareness of the self as a continuous entity across time that is a crucial element of episodic memory). While previous research on M.L. focused on anterograde memory of laboratory stimuli, in this study, M.L.'s autobiographical memory for post-injury events or anterograde autobiographical memory was examined using prospective collection of autobiographical events via audio diary with detailed behavioral and functional neuroanatomical analysis. Consistent with his reports of subjective disconnection from post-injury autobiographical events, M.L. assigned fewer "remember" ratings to his autobiographical events than comparison subjects. His generation of event-specific details using the Autobiographical Interview [Levine, B., Svoboda, E., Hay, J., Winocur, G., & Moscovitch, M. (2002). Aging and autobiographical memory: dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689] was low, but not significantly so, suggesting that it is possible to generate episodic-like details even when re-experiencing of those details is compromised. While listening to the autobiographical audio diary segments, M.L. showed reduced activation relative to comparison subjects in midline frontal and posterior nodes previously identified as part of the autobiographical memory network. Reductions were also evident in M.L. in association with personal semantic stimuli (e.g., recordings describing personal habits and routines). These data suggest an association between M.L.'s impoverished recollection of autobiographical material and reduced activation in midline sectors of the autobiographical memory network that support the autonoetic, first-person element of episodic memory.

Functional amnesia (FA) is characterized by an extensive retrograde memory loss in the absence of detectable structural brain damage. The two main hypotheses put forward to explain this disturbance involve a global retrieval deficit (affecting both pre- and post-onset memories) and a selective inability to explicitly retrieve pre-onset memories. Here, we extensively examined P.P., a patient with FA, with a view to obtaining additional insights into the cognitive and neural mechanisms underlying this disorder. In Experiments 1 and 2, post-onset memories were assessed using tasks focusing on the state of consciousness associated with their retrieval. Although subtle deficits in the ability to recollect post-onset personal events were detected, P.P.'s performances were normal when the encoding of the event was monitored in a laboratory setting. In Experiment 3, implicit recognition of pre-onset memories was tested using skin conductance responses. Results showed that P.P. responded implicitly to photographs of personal pre-onset events that were not explicitly recognized. In Experiment 4, designed to assess the patient's ability to suppress newly acquired information, P.P. suppressed more items than controls. Additionally, while no grey matter loss was evidenced with voxel-based morphometry, magnetic resonance spectroscopy and magnetization transfer imaging showed significant metabolic and structural changes within the white matter of the right prefrontal lobe. In conclusion, our results suggest that FA may result from a combination between two processes, a "hypo-retrieval" of pre-onset memories, tentatively due to white matter tract damage, and a "hyper-suppression" mechanism, concomitantly preventing the retrieval of pre-onset memories.

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.

Psychogenic fugue is a disorder of memory that occurs following emotional or psychological trauma and results in a loss of one's personal past including personal identity. This paper reports a case of psychogenic fugue in which the individual lost access not only to his autobiographical memories but also to his native German language. A series of experiments compared his performance on a variety of memory and language tests to several groups of control participants including German-English bilinguals who performed the tasks normally or simulated amnesia for the German language. Neuropsychological, behavioral, electrophysiological and functional neuroimaging tests converged on the conclusion that this individual suffered an episode of psychogenic fugue, during which he lost explicit knowledge of his personal past and his native language. At the same time, he appeared to retain implicit knowledge of autobiographical facts and of the semantic or associative structure of the German language. The patient's poor performance on tests of executive control and reduced activation of frontal compared to parietal brain regions during lexical decision were suggestive of reduced frontal function, consistent with models of psychogenic fugue proposed by Kopelman and Markovitsch.

Focal retrograde amnesia is an unusual and theoretically challenging form of memory disorder. The case of a 65-year-old woman presenting with focal retrograde amnesia is reported. Following a cardiac arrest and subsequent hypoxia she remained in a coma for 24 h with evidence of epileptiform activity during the early recovery period. MR scans, 4 and 7 months post-onset, showed mild bifrontal atrophic changes mainly affecting white matter areas. An [18F]fluorodeoxyglucose resting PET scan 1-year post-onset demonstrated right occipito-temporo-parietal hypometabolism. We were able to document the patient's performance on an extensive range of anterograde and retrograde tests and to monitor her recovery of function by assessing her performance at 4, 12 and 24 months post-onset. Spared anterograde memory was observed on a range of verbal and non-verbal tests, including matched tasks that compared pre-illness and post-illness onset recollections. In contrast, her performance on retrograde memory tests, using detailed autobiographical and public events verbal and photographic tasks, showed a temporally-graded retrograde amnesia, more particularly affecting memory for autobiographical episodes. Possible mechanisms underlying CH's focal retrograde amnesia are discussed in terms of Damasio's time-locked multiregional retroactivation model.

For patients with hippocampal pathology, disagreement exists in the literature over whether retrograde amnesia is temporally limited or very extensive depending on whether the anatomical damage is restricted to this structure or also involves additional temporal cortex. We report a comprehensive assessment of retrograde and anterograde memory functions of a severely global amnesic patient (VC). We found that he presented with a remarkably extensive and basically ungraded retrograde amnesia. This impairment profoundly affected four decades preceding the onset of his amnesia and encompassed both non personal and personal facts and events. VC also presented with a severe anterograde amnesia and a deficit in the acquisition of new semantic knowledge in the post-morbid period. Detailed MRI volumetric measurements revealed gross abnormalities in both hippocampi which were markedly shrunken. Of relevance to the debate on retrograde amnesia were the observations that the volumes of both entorhinal cortices and the remainder of both temporal lobes were normal. These data suggest that the hippocampus is critical not only for the efficient encoding and hence normal recall of new information but also for the recall of episodic information acquired before the onset of amnesia. Our results are compatible with the view that retrograde amnesia is both extensive and ungraded when the damage is limited to the hippocampus.

Several clinical and methodological caveats are outlined as they pertain to retrograde amnesia research, and data relevant to these caveats are presented. Three caveats in particular are noted in relation to recently published cases of marked retrograde amnesia; (i) temporal lobe epilepsy may influence memory for news events; (ii) there may be additional, unsuspected pathology in cases of amnesia, such as those with cerebral hypoxia; (iii) degree of media exposure is closely related to performance on the types of news events memory tests that are commonly used in retrograde amnesia research.

There are few clues as to the processes that underlie recovery of function from human amnesia. Evidence is offered from the perspective of a study of recovery of function during an episode of transient global amnesia (TGA) that occurred as a complication of a cerebral angiographic procedure being carried out in a neurosciences centre, and where there was therefore a unique opportunity to examine acute changes in memory function. This allowed us to conduct the first quantitative study where shrinkage of anterograde and retrograde memory loss was plotted at four separate intervals throughout the acute recovery process, and also 24 hr later. Recovery of retrograde amnesia preceded recovery from anterograde amnesia. Resolution of a naming deficit more closely paralleled recovery from retrograde amnesia rather than anterograde amnesia. Within retrograde amnesia for public events, there was a temporal gradient of memory loss, with more recent events affected to a greater degree than earlier events. Within anterograde amnesia, picture recognition memory preceded recovery of story recall memory. On the basis of these findings, and related observations in the published literature, it is proposed that recovery from some types of human amnesia, such as that associated with TGA, follows a 'lateral-to-medial' rule--lateral inferotemporal areas that play a major role in retrograde amnesia recover first from hypometabolism related to the TGA attack, followed by 'interface' areas such as the rhinal and parahippocampal cortices that are considered to have a role in both anterograde and retrograde memory functioning, with the last areas to recover physiological integrity being discrete limbic-diencephalic structures such as the hippocampus.

Following a car accident, a patient remained unconscious for approximately 20 min and confused for a few hours. When he could be questioned, he was found to have lost all past memories. The retrograde amnesia covered his whole life and concerned autobiographic events as well as famous facts and encyclopaedic knowledge. It also partially involved the verbal and visual lexicon. Reading, writing and counting were no longer possible. The profound impairment of retrograde memory contrasted with the preservation of anterograde memory, which permitted the patient to reacquire some of the notions he had lost, without, however, recovering the feeling of a personal experience of autobiographical information. Four years later, the retrograde deficit was unmodified, except for what had been relearnt. The search for data in support of an organic or psychological aetiology was negative. No signs of brain damage were apparent at the neurological examination and on CT, MRI and SPECT. On the other hand, there was no evidence of a psychiatric history, psychological stress or emotional precipitants that could substantiate the hypothesis that the patient derived a primary or secondary gain from amnesia. We propose that cases of focal retrograde amnesia, similar to the present one, deserve to be classified separately from organic and psychogenic forms under the label of 'functional' retrograde amnesia, a syndrome in which the threshold of activation of premorbid memories is abnormally raised by the trauma, leaving the encoding and retrieval of new memories unaffected.

This group study of 24 amnesic patients and 40 control subjects examined the hypothesis that retrograde memory deficits result from a combination of two impairment mechanisms: (1) a deficit in the retrieval of contents that is related to dysfunctioning of the hippocampal anterograde memory system, and (2) a deficit in the storage and/or retrieval of contents that is related to concomitant neocortical lesions. Retrograde amnesia was evaluated with the use of new Famous Persons and Autobiographical Memory Tests. The postulated components of retrograde memory impairment were assessed using the Wechsler Memory Scale and a new Semantic Memory Test, respectively. Regression analyses showed that recent episodic autobiography was exclusively related to the hippocampal component, while memory for famous persons and childhood autobiography was related to the neocortical component. In the case of details concerning people of recent fame, both components were identified as independent determinants. The temporal gradient of patients' impairment at the Famous Persons Test was marked for detailed knowledge, but small for overlearned knowledge. The present results thus support the combination hypothesis. They conform to the view that the transition from a hippocampus-dependent to a neocortex-dependent mnemonic representation of new contents is mediated by reiteration, and occurs within 5-10 years.

A case of pure retrograde amnesia following mild head injury is reported. Neuropsychological, psychodynamic and statistical approaches are employed in an attempt to disentangle the clinical picture presented by the patient. Focal retrograde amnesia, psychogenic retrograde amnesia and simulated amnesia are all taken into account. From a public events questionnaire and an inquiry about famous people, consistency analyses showed that the patient was able implicitly to use information she denied having, but at the same time, made us lower the probability of a simulated amnesia. Moreover, psychodynamic analysis showed that the patient's personality structure was compatible with hysterical patterns and we suggest that the patient's memory defect may be related to her personality. It seems less likely, though still possible, that the case may be explained in terms of deliberate simulation. In this case we conclude that the classification along the conscious/unconscious dimension seems more informative than the contrast between psychogenic and organic genesis.

In this paper we present data from a closed head injury patient who presents a striking example of what Kapur (Cortex 29, 217-234, 1993) has termed " focal retrograde amnesia". The patient, D.H., is unable to recollect any autobiographical incidents from the pre-morbid period, although he is able to provide personal and public information from this period. The data are discussed in relation to other reported instances of focal retrograde amnesia and a preliminary theoretical account is offered.

We describe our further investigations of the retrograde amnesia in a single case. R.F.R. became globally amnesic following an attack of Herpes Simplex Encephalitis. He could generate and recognize superordinate level information about the vast majority of proper names including the names of people but he was very impaired at giving information about what had "happened" to these same individuals. He could also provide detailed information about family friends but he could not recall salient major personal episodes in which these same individuals had been involved. Knowledge of people appears to be represented in a different way to that of events, even when a singular event has provided the main or only opportunity for learning about the individual.

The memory impairment of a patient suffering from functional retrograde amnesia was assessed both during the amnesic episode and after its termination. The patient's performance on a task tapping semantic memory was nearly identical on the two test occasions, but his performance on a task tapping episodic memory substantially changed across test sessions. Cueing procedures revealed that in spite of the patient's restricted access to episodic memory during the amnesic period, a relatively intact "island" of episodic memories could be uncovered. The distinction between episodic and semantic memory, as well as the relation between organic and functional retrograde amnesia, are discussed in light of the case study.

A case is reported of a patient who experienced numerous episodes of transient global amnesia (TGA) during which anterograde amnesia was less prominent than usual, and who developed a permanent selective retrograde amnesia. On formal testing, he performed well on traditional verbal memory tests, but showed marked retrograde amnesia for verbal material, including items on a famous voices recognition test. He was administered a paired-associate learning test where the names of famous personalities for which he was amnesic were associated with incongruous activities (e.g. John Newcombe-singing). Our patient performed better on this task than a group of five matched control subjects. Our observations indicate that in the organization of human memory retrograde amnesia may be fractionated from anterograde amnesia and that in certain situations specific types of amnesia can produce a facilitation effect compared to the performance of control subjects.

A patient with amnesia due to encephalitis was previously described in 1976 as having normal short-term memory and an intact ability to perform semantic analysis. Despite this ability, his retention beyond the limits of short-term memory was nearly nil. The present investigation sought to evaluate more completely the nature of this patient's retrieval deficit using a series of paradigms developed subsequent to his initial testing. Once again it was discovered that while his intact analytic abilities allowed retention of material in working memory, as soon as that working capacity was exceeded, retrieval of information became nearly impossible. It became apparent that the patient could not discriminate between a cue's most recently analyzed associate and the strongest existing associate to that cue in his semantic hierarchy. An analysis of his retrograde memory ability showed that he could retrieve almost no real episodes of either a public or private nature from his past. Instead, he seemed to rely on generalizations from his semantic memory to reconstruct "probable" events.

Recent work with amnesic patients has revealed a preserved capacity for acquiring and retaining new skills despite otherwise profound anterograde impairment. In addition to their anterograde impairment, amnesic patients also have retrograde memory loss for some information acquired prior to the amnesic event. The present experiment addresses for the first time the question of whether preservation of memory for skills is also a feature memory impairment. To determine the susceptibility of a recently learned skill to retrograde amnesia, we taught patients to read mirror-reversed words before and during the early part of a prescribed course of electroconvulsive therapy (ECT) and then tested retention of the skill after the course of treatment had been completed. Patients prescribed bilateral or right unilateral ECT and depressed patients not receiving ECT acquired the mirror-reading skill at the same rate and then retained it at the same level. For the patients prescribed ECT, intact learning and retention of the skill occurred despite retrograde amnesia for the previous testing sessions and for the words that they had read previously.