Functional Retrograde Amnesia A Multiple Case Study
Functional Amnesia: Clinical Description and Neuropsychological Profile of 10 Cases
- Mark Kritchevsky1,4,6,
- Judy Chang5, and
- Larry R. Squire1,2,3,4
- 1Department of Neurosciences,2Department of Psychology, and3Department of Psychiatry, University of California, San Diego, La Jolla, California 92093, USA4VA San Diego Healthcare System, San Diego, California 92161, USA5Stanford Sleep Disorders Clinic, Stanford, California 94305, USA
We carried out the first neuropsychological study of a series of patients with functional amnesia. We evaluated 10 patients, first with a neurological examination and then with three tests of anterograde amnesia and four tests of retrograde amnesia. Excluding one patient who later admitted to malingering, all patients had a significant premorbid psychiatric history and one or more possible precipitating factors for their amnesia. Eight of the 10 patients still had persistent retrograde amnesia at our last contact with them (median = 14 mo after the onset of amnesia). On tests of anterograde amnesia, the patients performed normally as a group, though some patients scored poorly on tests of verbal memory. On tests of retrograde amnesia, all patients had difficulty recollecting well-formed autobiographical memories of specific events from their past. In contrast, patients performed as well as controls at distinguishing the names of cities from fictitious city names. On remote memory tests for past public events and famous faces, different patients exhibited different but internally consistent patterns of impaired and spared performance. The variability in the clinical and neuropsychological findings among our patients may be understood by supposing that memory performance is poor in proportion to how directly a test appears to assess a patient's commonsense concept of memory. The presentation of patients with functional amnesia is as variable as humankind's concept of what memory is and how it works.
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Bilateral damage to the medial temporal lobe or medial diencephalon is associated with a syndrome of amnesia that has been widely studied (Scoville and Milner 1957; Squire 1992; Zola-Morgan and Squire 1993). The memory impairment is characterized by intact immediate memory, marked anterograde amnesia (i.e., impaired new learning), and variable, usually temporally graded retrograde amnesia (i.e., loss of premorbid memory affecting recent memory more than remote memory). In addition, the amnesia is selective in the sense that it affects the capacity for conscious recollection of facts and events (termed declarative memory) but spares nondeclarative forms of memory that are expressed through performance, such as skills, habits, simple forms of conditioning, and the phenomenon of priming. This form of memory impairment is encountered in patients with stroke, traumatic brain injury, anoxia-ischemia, encephalitis, Korsakoff's syndrome, and most commonly, early Alzheimer's disease (Baddeley et al. 2002). Although memory impairment is often permanent, some forms, such as transient global amnesia, do resolve spontaneously (Kritchevsky et al. 1988).
In contrast to the memory impairment in these cases, which is due to neurological lesions, there is a less common condition in which patients develop severe retrograde amnesia in the absence of significant anterograde amnesia and without any known brain injury or disease. This non-neurological syndrome of memory impairment has been variously termed “hysterical amnesia,” “psychogenic amnesia,” or “dissociative amnesia” (American Psychiatric Association 1994), and we refer to it here as functional amnesia. Functional amnesia is the memory disorder that is most often popularized in literature and film, and it appears to be the condition that lay persons typically regard as “amnesia.”
In early descriptions of functional amnesia based on large numbers of cases (Abeles and Schilder 1935; Kanzer 1939; Wilson et al. 1950; Kennedy and Neville 1957), the typical patient had a sudden onset of amnesia in which the main symptom was considered to be loss of personal identity. In these early reports, memory functions were not evaluated systematically, but loss of knowledge about facts and personal events was sometimes noted, and memory was reported to be generally good for events occurring after the onset of amnesia (Abeles and Schilder 1935). Recovery from this condition was considered to have occurred in almost all the cases within one month. Uncommonly, cases were reported in which functional amnesia lasted longer (case #1 of Pratt 1977; Akhtar et al. 1981).
In 1982, the first case of functional amnesia was reported where extensive neuropsychological testing was carried out during amnesia (Schacter et al. 1982). In the years since, a number of other single-case studies have been reported that include neuropsychological findings from formal tests. In general, the findings from these case studies are in accord with the earlier clinical reports: sudden onset of retrograde amnesia, including a loss of personal identity, in the absence of significant anterograde amnesia.
Nevertheless, the findings from these newer cases raise two puzzling issues. First, in contrast to what was reported in the early clinical studies, many of the patients who were studied with neuropsychological testing did not recover from their condition, even after one or two years (e.g., Campodonico and Rediess 1996; Markowitsch et al. 1997). Second, the findings across patients were variable. Variability was apparent in the early clinical case reports and was particularly evident in the single cases studied with neuropsychological tests. Patients differed with respect to the severity of retrograde amnesia, the extent to which the amnesia affected general knowledge in addition to personal memories, and the extent to which the impairment extended beyond memory to include such things as knowledge of vocabulary, the names and functions of objects, and the ability to perform previously familiar skills. However, each of these single-case studies employed its own collection of neuropsychological tests and asked its own questions. Thus, it is difficult to compare the patients, and it is difficult to generalize across the studies. If common tests had been used, perhaps the variability among the patients would have been less striking.
We have carried out the first neuropsychological study of a series of patients with functional amnesia. We evaluated 10 patients, first with a neurological examination and then with formal tests: three tests of anterograde amnesia and four tests of retrograde amnesia. Patients were also given a personality inventory. In addition, insofar as was possible, we followed the patients to determine when and if recovery from amnesia occurred. One of the 10 patients confessed to malingering his amnesia, and his test scores are presented here so that they can be compared to the scores of the other patients. Preliminary findings for these patients appeared in an earlier report, which compared functional amnesia with transient global amnesia (Kritchevsky et al. 1997).
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As a group, the patients had little or no anterograde amnesia and marked retrograde amnesia. With respect to anterograde amnesia, all of the patients had good memory for events that occurred after the onset of amnesia. One patient (SF) did complain of difficulty with new learning and, in neurological examination, was poor at learning verbal (but not nonverbal) material. However, like the other patients, he did not appear to be forgetful and gave no sign of difficulty with attention or language. With respect to retrograde amnesia, nine of the patients had loss of past memories that extended into childhood (all but DS, whose retrograde amnesia was limited to 2-3 yrs). Seven of these nine patients did not know their name at the onset of amnesia (this information was unavailable for the remaining two). Some patients were aware of a few vague and incomplete memories within their period of retrograde amnesia. Before they were found amnesic in San Diego, California, two of the patients had periods of sudden and unexpected travel during which they apparently had exhibited normal behavior. SP traveled from another state to San Diego during a period of 2 d. JG traveled from a southern state to San Diego during a period of 11 d.
Nine of the patients (all but RW, who malingered his amnesia) had significant premorbid psychiatric histories that included one or more of the following: alcohol and/or other substance abuse (six patients), previous conversion symptoms (two patients), and diagnoses of anxiety disorder (one patient), posttraumatic stress disorder (one patient), chronic paranoid schizophrenia or psychosis due to longstanding alcohol and other substance abuse (one patient), depression and/or history of suicide attempt (four patients), and histrionic or borderline personality disorder (one patient). For these same nine patients, one or more possible precipitating factors could be identified, including intoxication with alcohol (three patients), mild closed head injury (two patients), active depression (five patients), witnessing a physical assault that was similar to previous repeated assaults committed against her (one patient), and involvement or alleged involvement in illegal activity (four patients). The tenth patient (RW) hit himself on the head to simulate a precipitating factor.
Eight of the patients (all but JG and DS) had one or more abnormalities, in addition to their amnesia, that were thought to be psychogenic. These included an inability to voluntarily move the eyes in formal testing, bilateral leg weakness with inability to walk independently, left-sided weakness that began shortly after the onset of amnesia, as well as anomia, inability to name numbers, difficulty with calculations, loss of ability to read and write, and loss of ability to carry out previously familiar activities (e.g., using a telephone, driving a car with manual transmission, or operating a motorcycle). One patient reported that he had to relearn the English language during the first 2 d of his amnesia by reading the dictionary. Another reported that she could no longer remember the Spanish language, though she had been raised in a bilingual home.
Only two patients (MD and RW, the malingerer) fully recovered from their condition. The extensive retrograde amnesia of another patient (JG) shrunk during a 6-mo period to involve only the 8 mo before the onset of amnesia. The eight patients who did not recover had significant and persistent retrograde amnesia at our last contact with them (range = 9 d to 42 mo, median = 14 mo after the onset of amnesia). Two of these patients had established new personalities at the onset of amnesia, which persisted through our last contact with them at 23 mo and 42 mo, respectively, after the onset of amnesia.
Tests of Anterograde Amnesia
Figure 1A shows performance on the test of story recall. The patients were marginally impaired at immediate recall (t  = 2.1, P < .06), and similar overall to controls at delayed recall (P > 0.10). Nevertheless, the patients exhibited considerable variability in their scores, and six of the 10 patients (MD, RW, JM, SF, DS, CB) had immediate recall scores that were more than two standard deviations below the control mean. Except for RW, all the patients obtained scores for delayed recall that were within two standard deviations of the control mean.
Performance of patients with functional amnesia (FA) and controls on tests of anterograde amnesia. (A) Story recall. Recall was tested immediately (Immed) and again after a delay of 10-20 min (Delay). (B) Paired-associate learning. Ten word pairs were presented on each of three study trials. (C) Copy of a complex figure and reconstruction from memory after 10-20 min (Delay). Maximum score = 36. Patient RW did not receive the diagram recall test. (•) indicate the scores for each participant. *indicates scores for patient RW.
Figure 1B shows performance on the test of paired-associate learning. A two-way analysis of variance (2 groups × 3 learning trials) indicated that the patients and the controls performed similarly overall (F [1,13] = 2.7, P > 0.10) and improved at a similar rate across the three trials (interaction of group X trials F [2,26] = 0.5, P > 0.10). Nevertheless, the patients exhibited some variability in their scores, and for four of them (MD, RW, SF, DG) the total number of words recalled across the three tests was more than two standard deviations below the overall control mean.
Figure 1C shows performance on the diagram recall test. The patients scored similarly to the controls, both when they copied the figure and when they reconstructed it from memory (Ps > 0.10).
Tests of Retrograde Amnesia
Figure 2 shows results for the cities tests. Overall, the patients performed similarly to the controls (U.S. cities; t  = 1.8, P = .09; California cities, P > 0.10). Nonetheless, two patients (JG, JM) scored more than two standard deviations below the control mean on both tests. Notably, one of these (JM) scored only 47% correct on the U.S. cities test and 30% correct on the California cities test (chance = 50% for each test).
Patients with functional amnesia (FA) and controls were asked to identify the names of cities in the United States (left two bars) and the names of cities in Southern California (right two bars) from lists of real and fictitious city names. Patient SP was not tested. Chance = 50%. (•) Indicates the scores for each participant. (*) Indicates scores for patient RW.
Figure 3 shows performance on the test of past autobiographical memory. Patient DS, whose retrograde amnesia was limited to the 2-3 yrs before the onset of amnesia, was not given this test. The patients performed markedly poorer than the controls, both when they were scored on the basis of their unaided recollections (no probe; t  = 3.2, P < 0.01) and when they were scored on the basis of what they could recollect after encouragement from the examiner (probe; t  = 2.7, P < 0.05). Of note, the two patients who obtained the best scores (CB, DG) were tested longer after the onset of their amnesia (3 and 9 mo) than the other patients (1 d to 10 wks, median = 7 d). The good performance of these two patients resulted from the fact that they were able to draw memories from the period after the onset of their amnesia. In neurological examination, both these patients exhibited significant loss of premorbid autobiographical memories.
Patients with functional amnesia (FA) and controls were asked to recollect 10 autobiographical episodes. Responses were scored (0 to 3) before (No Probe) and after (Probe) encouragement by the examiner to elicit as specific a recollection as possible. Patient DS was not tested. (•) (•) Indicates the scores for each participant. (*) Indicates scores for patient RW.
Figure 4 shows the percentage of well formed, 3-point episodic memories that were recalled from different past time periods (0 d to >20 yrs). One patient (RW, the malingerer) was unable to produce any well formed recollections and was not included in this analysis. The remaining patients each recalled from three to 10 memories. The patients differed markedly from the controls in that they recalled most of their memories (78%) from the most recent time period (controls = 24%; t  = 3.1, P < .01) and very few of their memories from the most remote time period (patients, 3%; controls, 36%; t  = 3.2, P < .01). All of the memories recalled by the patients from the most recent time period were drawn from the time after the onset of amnesia. Thus, compared with the controls, the patients had a striking tendency not to recall remote memories, but rather to draw their memories from the period after the onset of their amnesia.
Percentage of memories that were recalled from the indicated time periods for patients with functional amnesia (FA) and controls. The data are based only on those recollections given a maximum score of 3 on the 10-item test of past autobiographical memory (Fig. 3). Patient DS was not tested, and patient RW had no recollections that were given a 3-point score. For the 8 patients, all the memories from the 0-9-mo time period were taken from the period after the onset of amnesia.
Figure 5A,B shows performance on the public events test. The four patients who took this test (EC, DS, CB, DG) were impaired both at recall (16.7% correct for patients; 39.2% correct for controls; t  = 4.2, P < .01) and at recognition (44.8% correct for patients; 76.6% correct for controls; t  = 4.2, P < .01). Patient DS, whose retrograde amnesia was limited to events that occurred 2-3 yrs before the onset of his amnesia, performed better than the other patients. However, he still performed at the low end of the control range on recall (29.2%) and poorer than the controls on recognition (62.5%). Six other patients took a similar test involving 17-26 questions about the two most recent decades and also scored poorly at recall and at recognition (16.3% correct for recall; 48.3% correct for recognition; MD did not take the recall test). One of these five patients (JM) answered none of 18 recall questions correctly and scored only 11.1% correct on the multiple-choice recognition test (chance = 25%).
Performance on tests of remote memory for public events and famous faces. Participants were asked 24 questions about public events that had occurred during the two decades prior to testing (A) and then took a four-alternative, multiple-choice test about the same events (B). The FA data are for patients EC, DS, CB and DG. Participants also were asked to identify 19 photographs of famous people who came into the news during the two decades before testing (C) and then to recognize the names that they could not recall (D). The recognition score was based on the number of items recalled correctly plus the items that were recognized correctly. Chance = 41.7%. The FA data are for patients SF, EC, CB and DG. (•) Indicate the scores for each participant.
Figure 5C,D shows performance on the test of famous faces. As a group, the four patients who took this test (SF, EC, CB, DG) were impaired both at recall (40.8% correct for patients; 64.2% correct for controls; t  = 5.7, P < .01) and at recognition (80.2% correct for patients; 94.7% correct for controls; t  = 4.2, P < .01). Six other patients took a similar test involving 20-27 faces from the two most recent decades and also scored poorly as a group (39.1% correct for recall; 77.8% correct for recognition; SP did not take the recognition test). However, there was marked variability in the individual scores. Thus, both the recall and recognition scores of patients RW and JG were as good as or better than the control scores (RW: 85.2% and 98.1%; JG: 59.2% and 90.7%). Also, patient DS (whose retrograde amnesia was limited to 2-3 yrs) performed just below the controls at recall (55.0%) and obtained a perfect score at recognition (100%). EC scored well enough on the recognition test to reach the low end of the control range. Another patient (MD) scored 0% correct at recall but scored much better at recognition (81.5%). Lastly, patient JM performed very poorly, just as he did on the public events test. He scored 0% correct at recall and only 18.5% correct at recognition (chance = 41.7%). His overall score on both the public events and famous faces recognition tests (7/45 items correct) was 2.75 standard deviations below the score that would have been expected from guessing.
The nine patients (all except SP) who were administered the Mini-Mult Personality Test had abnormal profiles. Overall, compared to the controls, patients obtained significantly abnormal scores on the Depression scale and the Schizophrenia scale (ts  > 2.7, Ps < .02). Their scores on the Hypochondriasis scale were also marginally abnormal (t  = 1.89, P < .09). Every patient had an abnormal score (T score ≥ 70) on at least one scale (range = 1-6 scales). There appeared to be two patterns of scores among the patients. Three patients (RW, JM, EC) had abnormal scores on the Hypochondriasis, Depression, and Hysteria scales and not on the other scales. Five other patients (MD, JG, SF, DS, CB) had especially elevated scores on the Depression and Schizophrenia scales (mean T scores = 86 and 84, respectively). Among the other scales, three patients (MD, JG, and DS) obtained abnormal scores on the Psychopathic Deviate scale, and four patients (JG, SF, DS, CB) obtained abnormal scores on the Psychasthenia scale. One patient (DG) obtained an abnormal score only on the Schizophrenia scale.
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We have carried out the first study of a series of patients with functional amnesia, all of whom received extensive neuropsychological testing during the course of their amnesic condition. Clinically, all 10 patients had severe retrograde amnesia in the absence of significant anterograde amnesia. Of the nine patients whose amnesia extended into childhood, the seven for whom information was available did not know their name at the onset of amnesia. Excluding one patient who later admitted to malingering, all patients had a significant premorbid psychiatric history and one or more possible precipitating factors for their amnesia. Eight of the 10 patients also had one or more neurological abnormalities at the onset of amnesia, in addition to memory loss, that were thought to be psychogenic. Finally, eight of the 10 patients still had significant and persistent retrograde amnesia at our last contact with them.
The patients performed well as a group on tests of anterograde amnesia for verbal and nonverbal material (Fig. 1). However, performance was somewhat variable on the verbal memory tests. Whereas all the patients scored in the control range on the diagram recall test, several patients scored more than two standard deviations below the control mean on immediate recall of the short prose passage and on the paired-associate learning test. Yet, despite poor scores on some of the tests, it is important to emphasize that none of the patients exhibited any difficulty learning and remembering day-to-day events after the onset of amnesia.
In sharp contrast to their adequate capacity for new learning, the patients had difficulty recollecting well formed autobiographical memories of specific events from their past (Fig. 3). In addition, to the extent that personal memories could be recollected, the patients differed strikingly from controls by drawing most of their memories from the period after they became amnesic (Fig. 4).
The patients as a group were also significantly impaired on remote memory tests for public events and famous faces that covered the two decades prior to the onset of amnesia (Fig. 5). Three points are of interest. First, one patient (JM) scored so poorly on the multiple-choice versions of these tests (7 of 45 items correct; 2.75 standard deviations below the score that would be expected by chance), that one must consider the possibility that he intentionally chose the wrong answers. Second, three patients (JG, DS, and RW, the malingerer), performed particularly well on the recall and recognition portions of the famous faces test (66.5% correct for recall; 95.3% correct for recognition), despite performing poorly on the recall and recognition portions of the public events test (26.4% for recall; 57.9% for recognition). Also, one patient (MD) did rather well on the famous faces recognition test (81.5% correct) after failing altogether at recall (0% correct). Third, in contrast to their overall poor performance on these remote memory tests, the patients as a group performed as well as controls at distinguishing the names of cities from fictitious city names (Fig. 2). Two patients (JG and JM) did score more than two standard deviations below the control mean on both tests. Nevertheless, the good performance of the group is striking, when one considers that the names of cities, like the names of famous faces and facts about public events, must be learned and stored in long-term memory.
The findings for our patients are in broad agreement with what has been reported previously in single-case studies where neuropsychological tests were given during functional amnesia. Specifically, one finds good anterograde memory function and significant retrograde amnesia, usually including an inability to recall one's name (see, e.g., Schacter et al. 1982; patient K of Treadway et al. 1992; Kopelman et al. 1994; Barbarotto et al. 1996; Campodonico and Rediess 1996; Markowitsch et al. 1997). In other case reports, an unequivocal diagnosis was not reached, but the findings were similar to what we have described here, and we believe it likely that these other patients also had functional amnesia (e.g., De Renzi et al. 1995, 1997; patient MM of Lucchelli et al. 1995; Dalla Barba et al. 1997; Papagno 1998; Mackenzie-Ross 2000; Nakamura et al. 2002).
Although a typical presentation can be identified for functional amnesia (good anterograde memory, poor retrograde memory), there is considerable variability among patients, both in our own series and in the published cases. Thus, four of our 10 patients performed poorly on tests of autobiographical memory, past public events, and famous faces (for similar cases, see Campodonico and Rediess 1996; De Renzi et al. 1997; Papagno 1998). In contrast, of the nine patients given the recall and recognition famous faces test, five did well at recognizing the names of famous faces, and three of these five also did well at recalling the names (for a similar report of good performance on a famous faces test despite poor autobiographical memory, see Schacter et al. 1982; for good recognition of famous faces but poor recall of public events, see De Renzi et al. 1995). Another variation on the typical pattern is illustrated by our patient JM, who performed below chance levels on all the recognition tests (the cities tests, the public events recognition test, and the famous faces recognition test). This pattern of performance on a multiple-choice test also has been described previously (Barbarotto et al. 1996).
In most cases, memory for all or nearly all of one's personal past is initially lost. However one of our patient's retrograde amnesia, even initially, was limited to a time period of two to three years before the onset of amnesia (for another case of limited retrograde amnesia, see patient K of Treadway et al. 1992). There is also considerable variability in the extent to which memory loss extends into domains beyond autobiographical memory and fact memory. Thus, eight of our 10 patients variously exhibited anomia, difficulty in calculations, some loss of vocabulary, or inability to perform previously familiar activities. Similar descriptions are common in the published cases (De Renzi et al. 1995, 1997; patient MM of Lucchelli et al. 1995; Campodonico and Rediess 1996; Papagno 1998; Nakamura et al. 2002).
It is also worth mentioning that, even though anterograde memory function is generally intact in functional amnesia, one nevertheless finds variability among patients in this domain as well, particularly on verbal memory tests. Thus, the nine of our patients who took the diagram recall test did well at copying the figure and later reconstructing it from memory. Yet, six patients had poor immediate recall of a short prose passage (though delayed recall scores were adequate), and four had some difficulty with paired-associate learning. Among the published cases, most are reported to have fully intact anterograde memory function. Nevertheless, some patients have been reported to do poorly on immediate recall tests (Schacter et al. 1982; Barbarotto et al. 1996) or obtained poor scores on other tests of new learning (Schacter et al. 1982; De Renzi et al. 1997).
Lastly, one also finds variability with respect to recovery. Only two of our 10 patients fully recovered from their functional amnesia. Similarly, the majority of the patients in the published literature who have been studied with neuropsychological tests also had persistent retrograde amnesia, sometimes lasting several years (De Renzi et al. 1995, 1997; Barbarotto et al. 1996; Campodonico and Rediess 1996; Dalla Barba et al. 1997; Markowitsch et al. 1997; Mackenzie-Ross 2000; Nakamura et al. 2002). A few cases of recovery also have been reported, in these instances within 1 mo of the onset of amnesia (Schacter et al. 1982; patient MM of Lucchelli et al. 1995; Papagno 1998). It is striking that in the early clinical reports of functional amnesia, recovery from amnesia was considered to have occurred in almost all cases within 1 mo of onset (Abeles and Schilder 1935; Kanzer 1939; Wilson et al. 1950; Kennedy and Neville 1957). How can these reports be reconciled with our observation, and the observations of others, that the amnesic condition often persists? One possibility is that the early clinical studies focused on loss of personal identity as a key feature of the amnesia. Because the capacity for new learning is preserved, patients are able to learn their names after the onset of amnesia and also recover (relearn) a good deal of autobiographical and factual material that was initially inaccessible. In the absence of a careful follow-up examination, persistent gaps in memory function may be overlooked. A second possibility is that patients with retrograde amnesia lasting longer than 1 mo have sometimes not been given a diagnosis of functional amnesia and were therefore not included in the early clinical reports that described this disorder. A third possibility, perhaps less likely, is that the typical clinical course of functional amnesia has changed over the decades since the early clinical reports were published, for example, because of shifts in the culture or changes in the approach to treatment.
It is useful to contrast the condition of functional amnesia to focal retrograde amnesia, a rare neurological condition resulting most likely from bilateral damage to the anterior and inferior temporal lobes (Kapur et al. 1992; Markowitsch et al. 1993). Patients with focal retrograde amnesia typically have evidence of brain damage, minimal anterograde amnesia (which can be more severe at initial presentation), and extended retrograde amnesia for one to many decades (Kapur 1993). Loss of personal identity has not been commented upon. Previously learned skills may be spared though the patient cannot recall having learned the skill (Kapur et al. 1992). In contrast, in our cases of functional amnesia, as in previously published cases, there was no evidence of brain injury by history, neurological examination, or neuroimaging. In addition, significant anterograde amnesia was not evident at the time that neuropsychological testing revealed severe retrograde amnesia. Further, for most patients, the retrograde amnesia extended to all of the personal past and included loss of personal identity. Lastly, the presentation of retrograde amnesia was decidedly variable, with sparing of memory for famous faces in some cases, especially when testing occurred in a recognition (rather than recall) format.
The variability in the clinical and neuropsychological findings among our patients is especially helpful for reaching the conclusion that the amnesia was nonneurological, or functional, in origin. In comparison to the memory impairment in functional amnesia, the memory impairment associated with brain injury or disease presents a consistent picture. In contrast, the pattern of sparing and loss in our patients had no sound pathophysiological explanation. Even for the patients with evidence of head trauma, there was no suggestion that the injury was sufficiently severe to have caused brain damage. In addition, the presence of abnormal premorbid psychiatric histories in every patient except RW, the confessed malingerer, the evidence in many cases for psychological stress at the onset of amnesia, and the frequency of abnormalities, in addition to memory loss, that were thought to be psychogenic—all of these factors support the conclusion that the amnesia in our patients was functional and not due to a neurological lesion.
One important issue concerns the genuineness of the cases that we have reported. One patient (RW) admitted 5 d after the onset of his amnesia that he had malingered his condition. A second patient (JM) scored so poorly on the recognition versions of the remote memory tests (significantly below the score that could be obtained by guessing) that it is possible that he intentionally chose the incorrect answers. Is it possible that others of our patients were deliberately simulating a memory impairment? Although functional amnesia is readily distinguished from the known forms of neurological memory disorder, it is more difficult to distinguish functional amnesia with a psychogenic origin from malingering. The neuropsychological findings did not clearly discriminate between RW and the other patients, though RW did perform poorer than any of the other patients on one test of anterograde amnesia (Fig. 1A) and on one test of retrograde amnesia (Fig. 3). In fact, in the test of retrograde amnesia, he was the only patient who was unable to recall a single well formed (3-point) autobiographical memory. Lastly, RW was the only patient for whom we could not identify a significant premorbid psychiatric history.
Building on these observations, we suggest that three features of our patients' presentations favor the interpretation that they (excepting RW and possibly JM) had a genuine psychogenic or dissociative disorder that was not intentionally simulated. First, the scores on the tests that the patients performed poorly were almost never as low as they could have been. RW, the malingerer, sometimes performed worse than the others. Second, hypnosis (SP) and amytal interviews (MD, JG, and EC) improved access to past memories, and in three of these four cases access to past memories either completely recovered or continued to improve. Third, all of the patients except RW had significant premorbid psychiatric histories, including in two cases a history of conversion symptoms. Moreover, most of the patients also had significant abnormalities in addition to their memory disorder that were thought to be psychogenic. In contrast, the memory problems exhibited by RW were accompanied only by mild somatic complaints and mild difficulty with calculations.
We suggest that the striking variability in the presentation of patients with functional amnesia can be understood by supposing that performance is poor in proportion to how directly a test appears to assess a patient's commonsense concept of memory. At the heart of the condition is the severe difficulty that all patients have in recalling past personal memories. Most patients also have great difficulty remembering public events, perhaps because they are being asked to remember events that occurred in their past. In contrast to poor performance on public events tests, some patients do better at recalling the names of famous faces, and others do better still at recognizing the names of famous faces than at recalling the names, perhaps because these tests appear to assess general knowledge rather than the ability to retrieve memories. Most patients also recognize satisfactorily the names of cities, which also may be perceived as part of general knowledge. In addition, most patients do well at learning and remembering new material, perhaps because such tests appear to involve one's ability in the present moment rather than the ability to reach into the past. At the same time, for a few patients the amnesic condition is rather broad and includes loss of some vocabulary words, inability to identify common objects, as well as an inability to perform previously familiar skills. In the case of neurological amnesia, specific brain lesions are associated with consistent and specific syndromes of memory dysfunction. In the case of functional amnesia, the presentation is as variable as humankind's concept of what memory is and how it works.
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MATERIALS AND METHODS
We administered neuropsychological tests to all patients available to us (n = 10) who met clinical criteria for functional amnesia between 1982 and 1994. Testing occurred 1 d to 9 mo after the onset of their amnesia (median = 10 d). The procedure was approved by the Institutional Review Boards of the UCSD School of Medicine, and the VA San Diego Healthcare System. All participants gave written informed consent to participate in the study.
SP was a 46-yr-old Caucasian man who had been found by the police in an intoxicated state and brought to the Emergency Department one afternoon in 1982. In the Emergency Department, he said that he could not recall his name and that he had little recall for events that had occurred before being driven to the Emergency Department. By contacting individuals identified on business cards in the patient's wallet, it was learned that he was of Hungarian birth and had been in the United States since 1954. He had worked for at least 10 yrs as a ship's cook and had worked for approximately 6 yrs as a chef on a cruise ship. He had been diagnosed as a chronic alcoholic. He stated that he had once attempted to jump off the Golden Gate bridge to kill himself but had been stopped. Prior to his arrival in San Diego he had been living in a southwestern state for at least 8 mo. He had successfully completed a 3-wk detoxification program there, had obtained a job at a restaurant, and was living at a nearby halfway house. Three days before admission, he received his first paycheck. The following day, he told personnel at the restaurant that he had some errands to run. They had not heard from him since then.
Neurological evaluations on the date of admission revealed severe retrograde amnesia with mild and transient difficulty with calculations. Thus, he complained that he could not recall his past except that he had been a cook at some time and that he smoked cigarettes. He did not recognize his name when it was found in his wallet. He did not know his birthdate or birthplace. He did not know where he lived. He could not recall events of World War II. He was uncertain of who the president was but gave the correct name when encouraged to guess. When shown a picture of the current president standing with the two previous presidents, he was able to name all three. He was shown a hand-drawn sketch of the United States and asked to place five cities. He placed Los Angeles, Miami, and Chicago correctly. He placed San Diego in west Texas. He placed Dallas at the eastern border of Texas. On initial evaluation by the Emergency Department physician, he said that 100 minus 7 was 973 and that 5 × 5 was 45. On evaluation several hours later by the neurology resident, he correctly calculated 20 minus 4, 14 + 27, and 41 × 3. He appeared anxious throughout the day of admission and when asked to write a sentence he wrote, “I'm scared.” Digit span was five forward and three reversed. He recalled two of three words after a 3-min delay and recognized the third word. The remainder of his neurological examination was remarkable for mild ataxia, presumably due to his alcohol use, and decreased ankle jerks presumably due to a mild alcohol-related polyneuropathy. Admission laboratory tests were remarkable for a blood alcohol level of 0.13 mg/deciliter. CT head scan with and without contrast was normal.
During the first 5 d of his admission, he experienced the return of a few memories that had occurred prior to 1979. Thus, the fifth day following admission, he thought that he had spent 1959 and 1960 in Detroit, 1974 sailing in the Arctic, 1976 working on an oil tanker as a cook, and 1979 on a ship. He still could not recall his name, the names of his parents, when he had left Hungary, or whether he had a family. The following day, he was asked what he thought might have caused his memory loss. He said, “Either too much liquor, or a medical problem, or a mental stress—maybe a mental stress.” He had no idea what stress might have occurred. Formal neuropsychological tests were administered on the sixth and seventh days following admission when he still had severe but not complete retrograde amnesia.
Because of persistent retrograde amnesia, a 1-h interview was performed under hypnosis following our testing on the seventh day following admission. The psychiatrist considered him to be a good hypnotic subject. During the interview, he recalled many details of his past life, including the fact that he had been in the Hungarian Air Force in 1954, that his wife and 2-yr-old daughter had accidentally drowned in 1961, and that he had recently been in a halfway house for alcohol treatment. Over the subsequent 2 d, many additional past memories returned, including feelings of guilt and nightmares from combat in Hungary, guilt about the death of his wife and daughter, nightmares about their death, and a life of excessive alcohol use, wandering, and fearing close attachments. He described a suicide attempt by overdose in 1979. He said that his memory loss truly terrified him and that he was now motivated to obtain psychiatric help. He agreed to be transferred to the psychiatric ward for further work on regaining his memories. Later that day he disappeared unexpectedly from the hospital, did not return, and could not be found.
MD was a 32-yr-old Caucasian man with 9 yrs of education who was brought to the Emergency Department one morning in 1983. He complained of a generalized throbbing headache, could not recall his name or his past, and mentioned suicidal thoughts. He was intoxicated and had multiple abrasions on his head and face. Biographical information about the patient was obtained later from his father, after the patient's identity became known. The father stated that the patient had done poorly in junior high school and had dropped out during his first year of high school. His father said that the patient frequently lied, and that his biggest problem had always been that he “couldn't recall which lie he told last.”
During five separate evaluations in the Emergency Department over the next 14 h, MD presented a picture of profound retrograde amnesia with some other cognitive deficits. He told the Emergency Department physicians that his name might be Monty and that he may have fallen off a motorcycle (both of which proved to be incorrect). He said that he had a history of alcohol abuse. Ophthalmology evaluation was performed at 9:00 a.m. The patient could not recall why he had a prosthetic right eye. When visual acuity was tested using a standard test card for near vision (Rosenbaum card), the patient said that he saw the numbers but did not know their names. One hour later, the neurosurgery resident noted that the patient was unable to recall past events. The patient said incorrectly that he had not been drinking though he did report a history of alcohol abuse. He could not recall having expressed any suicidal thoughts but seemed to remember all of the other events that had occurred since he arrived at the hospital. He did not know the day, date, month, place, his last name, or how he had arrived at the hospital. He was able to recall three of three objects at 5 min. He said that his last memory before coming to the hospital was hitchhiking near some bushes. He correctly named Reagan as the president and said incorrectly that Nixon was the president before Reagan. He could not recall any details about Nixon. When asked about the Harley Davidson motorcycle tattooed on his chest, he said that he rode a Harley Davidson motorcycle “because that's all I've ever ridden, they're the best bike there is.” He could not name any other motorcycle or discuss the merits of the Harley Davidson. He could not name a pen and said that, “It's to write with.” He could not name a shoe and said that, “It's to walk on.” He could not name a watch. He correctly named numbers that were traced on his palms. On admission to the Neurology Service 12 h after his presentation to the Emergency Department, he named Reagan as president but could not name any previous president. General neurological examination was remarkable for absent ankle jerks, presumably due to a mild alcohol-related polyneuropathy. Admission laboratory tests were remarkable for a blood alcohol level of 0.26 mg/deciliter. CT head scan without contrast was normal.
By the following day, he was no longer intoxicated, his headache had resolved, and he exhibited severe retrograde amnesia with resolution of his other cognitive deficits. During the next 5 d, formal neuropsychological testing was administered. He remained in this state for 5 d, during which time he had occasional vague recollections about his personal past. For example, he was preoccupied one day with concerns over the whereabouts and welfare of his cousin S. He also expressed a few thoughts and opinions about his past without being able to recall any specific supportive events. Thus, he was certain that he used alcohol but not other drugs. He experienced a craving for a cigarette and thought that he probably was a smoker. During these 5 d, his retrograde amnesia included items of general knowledge. Thus, when told four brands of motorcycles, he recognized only two (Harley Davidson and Kawasaki, but not Honda or Yamaha). He did not recognize the word Chicago, but said that Los Angeles and New York City sounded familiar. In contrast to his poor recognition of these proper nouns, he recognized several other words (walkie-talkie, volcano, Kleenex, and Scotch tape). However, he could not say what a robin was and said that the word bluejay was “associated with birds.”
On the fifth day following admission, the hospital staff learned the patient's name, and this information was presented to him. This event appeared to prompt the return of many personal memories over the next 24 h. He was able to recall his name, where he grew up, and where he lived. He recalled little of the events that had occurred during the 2 wks prior to his hospitalization, but he did recall that he had been drinking heavily for 6 d up to and including the day of his admission. On the seventh day following his admission, an amobarbital interview was performed and yielded good recall of all previously unremembered events, including the events of the day preceding hospitalization. He had been drinking with his cousin, S. He recalled a fight with three unknown men. At some point he had fallen on his face, and he thought that his memory problems had probably started at that time. The day following the amobarbital interview, when his memory for the past appeared to have fully recovered, he was discharged. He agreed to come back in 2 wks for further follow-up testing but never returned.
RW was a 52-yr-old African-American man with 15 yrs of education who was brought to the Emergency Department one afternoon in 1985. In the Emergency Department, he complained of a painful lump on the right side of his head and stated that he could not recall what had happened to him. He was found to have severe retrograde amnesia. He stated that he knew his name only because it was on an identification card in his wallet. Additional history was subsequently obtained that shed some light on his amnesia. In 1982, he was robbed at knifepoint outside his apartment in New York City. He was brought into the bedroom and tied up while four to five people robbed him. He had felt fearful, worried, and angry since that incident. He left New York City shortly after the robbery, traveled for a year, then settled in Las Vegas for 1-1/2 yrs. Since arriving in San Diego in 1985, he had been unable to find work or an apartment that he could afford and so had lived in downtown hotels and at the downtown YMCA. He smoked marijuana 4-7 times each week but did not use alcohol or other drugs. He had presented to the Emergency Department 2 d previous to the present visit because of a concern about his physical health but had been reassured that he had only a musculoskeletal pain.
At the present visit, he told the Emergency Department nurse and physician that at 10:00 a.m. he had found himself sitting in a hallway at the YMCA with his toiletries next to him on the floor. He thought that he had suddenly lost consciousness and fallen to the floor and said that he might have hit his head against the wall or that someone might have hit him. He recalled walking to his room, dressing, reporting the incident to the hotel desk clerk, and being driven to the hospital. He complained of a painful lump on the back of his head on the right, an anterior chest pain that was worse when he took a deep breath, dizziness that occurred with standing and walking, possible slight weakness in his right arm and hand, and nausea. Although he would tell the neurologist who next saw him that he could not recall events that had occurred earlier in the morning, prior to his fall, he told the Emergency Department physician that he had not yet eaten that day, that he had not used drugs, and that nothing was missing from his possessions following his fall.
Neurological evaluations on the day of admission revealed severe retrograde amnesia for personal events, less severe retrograde amnesia for public events, and mild difficulties with calculation. When questioned about the past, he noted that some questions made him feel uncomfortable and that many questions evoked pictures in his mind with which he could not associate words. He could not recall his parents' names, his occupation, or how long he had been in San Diego. He thought that he might have been born in New York. (We later learned that this was correct.) He had no recall for events that had occurred prior to his fall and no recollection of the visit to the Emergency Department that he had made 2 d previously for evaluation of musculoskeletal pain. He correctly stated his birth year. He did not know his birth month, and when encouraged to guess, said June. (We later learned that he had been born in July.) He was uncertain of his level of education, but when encouraged he guessed that he had finished high school and college. (We later learned that he had graduated from high school and completed three years of college.) He knew that he was in San Diego, but thought he knew this because the person who had brought him to the hospital had told him. He thought that he had been staying at the downtown YMCA during his entire stay in San Diego because he could not picture anyplace else. He could not remember any of his past medical history.
He was able to correctly name the current president as Ronald Reagan, but not his political party, and noted that he had been an actor. He could not name the previous president. When asked to name any other presidents he could name only Kennedy and Roosevelt. When asked about any specific memories concerning these individuals, he recalled that he liked Kennedy. Later in the interview, he was asked whether he had any recollection of what had happened to Kennedy, and he said that he had been killed in Texas. When asked about the word Watergate, he said, “What comes to mind is a canal.” When asked what countries had borders with the United States, he correctly said Canada and Mexico. When asked about Cuba, he said, “Communist country, Castro, and cigars.” When asked about the World Series, he correctly noted that it was a baseball game played by the champions of the American and National Leagues. He correctly named the cities for whom the Yankees and Cubs played, but incorrectly said that the Dodgers played in Brooklyn. When asked if it were possible that the Brooklyn Dodgers had moved to Los Angeles, he said no. He correctly described a Hula-Hoop, a Frisbee, and a space shuttle. In the Emergency Department, he recalled two of three objects after a 5-min delay, and when asked to subtract serial 7s from 100 he said 100, 93, 85, 73, 62, 54 and then stated that he could not proceed further. On the neurology ward he recalled six of six words after 1-, 5-, and 10-min delays. A 2-cm tender scalp swelling was present in the occipital region. CT head scan with and without contrast was normal.
During the first 5 d of his hospitalization, he experienced no return of any lost memories that had occurred prior to the day of admission. Then, on the fifth day following hospital admission, he admitted that he had intentionally hit himself on the head with a bottle and faked his memory loss. He said that he had felt the need for “sanctuary” and so had sought admission to the hospital. We administered formal neuropsychological tests on the first and second days following his admission, during his malingered amnesia. Following his confession of feigned amnesia, he was transferred to the research Psychiatry Service with a diagnosis of adjustment disorder with depressed mood, and there he was treated with 8 wks of individual and group therapy. He was discharged to live in an apartment that he had rented.
JG was a 28-yr-old Caucasian woman with 16 yrs of education, whom we first evaluated on the Psychiatry Service in 1985. She stated that she had “psychogenic amnesia” and could not remember anything from before the onset of amnesia except how to “walk and talk and play a mean game of pool.” She also stated that she knew her name only because it had been told to her 2 d earlier. Past history was subsequently obtained from her hospital records and from her attorneys. She had obtained a Bachelor of Science degree in mathematics and subsequently served for 4 yrs in the Navy as a helicopter pilot. In 1982, during her final year in the Navy, she became depressed and suicidal following the dissolution of a previously stable, 5-yr relationship. She then, while intoxicated with alcohol, fired a pistol on the grounds of San Diego's Naval Hospital, put the gun to her head, and threatened to kill herself. She surrendered the gun to police and was hospitalized on the psychiatric unit. On the unit she was found to be dramatic, demanding, and manipulative. She had to be restrained on two occasions. Her discharge diagnosis was “histrionic personality disorder.” She did well for the next year and was able to work as a computer programmer in the Southwest. In 1984, she was hospitalized on a psychiatric service for depression and a suicide attempt. She was discharged the following month with a diagnosis of borderline personality disorder. She lived with her parents in the South for the next 3 mo, then lived and worked in a nearby city for 3 mo. Subsequently, during a period of 11 d, she drove from the southern state where she lived and worked to San Diego. She had no history of alcohol or other drug problems except for a period of excessive alcohol use in 1982.
On the day of her arrival in San Diego, in the course of being arrested for discharging her pistol on the grounds of San Diego's Naval Hospital (where she had previously discharged a firearm in 1982), she realized that she was unable to recall her past life. A forensic psychiatrist diagnosed her with malingering and she was incarcerated, but she was released after 5 wks when a polygraph test suggested that her amnesia was not malingered. She then was treated with individual psychotherapy and hypnosis with no improvement in her amnesia. Two months after her arrival in San Diego, her probation officer confronted her with her identity, which had been discovered after her gun was traced to the southern state where she had lived. She struck or attempted to strike her probation officer, said she would not go back to that state, and said she did not like her father even though she did not remember him. She refused to speak further, was brought to the Emergency Department for evaluation, and was admitted to the psychiatric service.
Neurological evaluation revealed that she had no recall for personal memories from before the onset of amnesia. After a review of hospital records indicated that she had been a Navy helicopter pilot, she was asked questions about helicopters on the following days. She was unable to answer these questions. She did not know if a checklist was used during the operation of a helicopter but did demonstrate a plausible sequence of hand and foot movements when asked to show how to fly a helicopter. The remainder of her neurological examination was normal. Formal neuropsychological tests were administered immediately following the neurological evaluation.
During the first 1-1/2 wks of her hospitalization, she had no return of old memories. She was observed to be sullen and withdrawn, and at times was manipulative, demanding, or impulsive. She sometimes expressed suicidal thoughts. During an amobarbital interview she recalled personal material up to 1-2 yrs before the interview. Thus, she discussed her family, young adulthood, and friends in the southern state where she had lived. She was able to describe extensively her helicopter training. She discussed different types of helicopters and stated that two different checklists were used in flying helicopters. Following the amobarbital interview, her severe retrograde amnesia returned and persisted through the remaining 6 wks of hospitalization. During this time her psychological status gradually improved, though on several occasions she became violent and required restraint and placement in seclusion. Finally, it was discovered that she was wanted in the southern state for a criminal offense committed on the day she began her trip to San Diego. She was discharged from the hospital. At this time she was escorted from the hospital by hospital security, turned over to San Diego police, and then extradited to her home state. It was learned later that by 6 mo following the onset of her amnesia her retrograde amnesia had shrunk and covered only the period of 8 mo before the onset of the amnesia. She subsequently pled guilty to a minor charge.
JM was a 37-yr-old Caucasian man whom we first evaluated in 1985. He complained of inability to recall his past and of left-sided weakness and sensory loss. He knew his name at the time we saw him, but it could not be determined whether he knew his name at the time his amnesia began, 8 d earlier.
Information subsequently obtained from hospital records and from his wife indicated that he was a Vietnam combat veteran and had served as a paratrooper in the Special Forces. He had 50% service-connected disability with a diagnosis of anxiety disorder. He had had many previous hospitalizations. On one occasion he had developed mild left-sided weakness following a cardiac catheterization and had been diagnosed with a stroke. On another occasion, he had been given a diagnosis of hysterical conversion reaction. He was married and had two young children. Four months before our evaluation, he and his family had moved from the Midwest to a western state. Here, he had been accused of a criminal offense.
Eight days before our evaluation, at about the time he was supposed to appear in court, he complained of a severe headache and said that he could not recognize his present surroundings or remember his past. He was taken to a local hospital, where he developed a paralysis of his left arm and leg. He was evaluated by a neurologist, who thought that his complaints were not neurological but rather due to conversion symptoms. Electroencephalogram and CT head scan were normal. He was referred for psychiatric evaluation. He was seen the following day and said that he had no independent recall for his past life previous to the onset of the headache and amnesia. He also complained of weakness on his left side. On examination, he appeared depressed, had psychomotor retardation, and spoke very softly with his head lowered. When walking he dragged his left foot and his left arm hung limply at his side. He was admitted that day for further evaluation of his retrograde amnesia and left-sided weakness.
We evaluated him with formal neuropsychological tests on the eighth and ninth days following the onset of his amnesia. He said that his left arm just hung “like dead meat,” he could feel touch but not pain from a pin on the left arm, and he dragged his left leg when he walked. He complained of inability to recall any events that had occurred before the onset of amnesia. Whenever he told us something about his past, he carefully qualified it by saying, “That's what they tell me,” “That's what my wife tells me,” or “That's what the paper in my wallet says.” His wife had told him that he rode a motorcycle. When she showed him his motorcycle, he had not recognized it. She showed him how to start it, but once the motorcycle was started he did not know how to operate it. He was impressed with the complexity of the motorcycle but was not able to recognize any of its parts or the function of these parts. When we asked him who Kennedy was, he said he did not know. When asked about the Beatles, he said that it sounded like a bug. When asked about Vietnam, he said that he had been told that there had been a war there. He added that he had never been there, though his hospital records indicated that he was a Vietnam combat veteran. He said that Scotch tape was clear tape to stick things up, Kleenex was a napkin, and a satellite was a transmitter launched into space. When asked about scissors, he said after a prolonged delay that they were “to cut paper with.”
During his hospitalization, he experienced no recovery of old memories. He was discharged on the twelfth day following the onset of amnesia, for outpatient psychiatric follow-up and went to court following his discharge. At this time, when he was accused of committing the criminal offense, he said, “I don't know what they are talking about.” He was found guilty and ordered to receive counseling. Our last report of him involved a hospitalization in the Midwest in 1987, for major depression. At this time, his retrograde amnesia apparently continued, as he claimed that he had lost most of his memories from childhood through 1985 as a result of a “stroke” that he had suffered in 1985.
Retrograde amnesia (RA) is a loss of memory-access to events that occurred, or information that was learned, before an injury or the onset of a disease. It tends to negatively affect episodic, autobiographical, and declarative memory while usually keeping procedural memory intact with no difficulty for learning new knowledge. RA can be temporally graded or more permanent based on the severity of its cause and is usually consistent with Ribot's Law: where subjects are more likely to lose memories closer to the traumatic incident than more remote memories. The type of information that is forgotten can be very specific, like a single event, or more general, resembling generic amnesia. It is not to be confused with anterograde amnesia, which deals with the inability to form new memories following the onset of an injury or disease.
The most commonly affected areas are associated with episodic and declarative memory such as the hippocampus, the diencephalon, and the temporal lobes.
- The hippocampus deals largely with memory consolidation, where information from the working memory and short-term memory is encoded into long-term storage for future retrieval. Amnesic patients with damage to the hippocampus are able to demonstrate some degree of unimpaired semantic memory, despite a loss of episodic memory, due to spared parahippocampal cortex. In other words, retrograde amnesics "know" an information or skill, but cannot "remember" how they do.
- The diencephalon and the surrounding areas' role in memory is not well understood. However, this structure appears to be involved in episodic memory recall.
- The temporal lobes are essential for semantic and factual memory processing. Aside from helping to consolidate memory with the hippocampus, the temporal lobes are extremely important for semantic memory. Damage to this region of the brain can result in the impaired organization and categorization of verbal material, disturbance of language comprehension, and impaired long-term memory. The right frontal lobe is critical for the retrieval of episodic information, while the left frontal region is more active for the retrieval of semantic information.  Lesions in the right hemisphere and right frontal lobes result in the impaired recall of non-verbal material, such as music and drawings. Difficulties in studying this region of the brain extends to its duties in comprehension, naming objects, verbal memory, and other language functions.
Brain plasticity has helped explain the recovery process of brain damage induced retrograde amnesia, where neuro-structures use different neural pathways to avoid the damaged areas while still performing their tasks. Thus, the brain can learn to be independent of the impaired hippocampus, but only to a certain extent. For example, older memories are consolidated over time and in various structures of the brain, including Wernicke's area and the neocortex, making retrieval through alternate pathways possible.
Types of retrograde amnesia
As previously mentioned, RA commonly results from damage to the brain regions most closely associated with episodic and declarative memory, including autobiographical information. In extreme cases, individuals may completely forget who they are. Generally, this is a more severe type of amnesia known as global or generalized amnesia. However, memory loss can also be selective or categorical, manifested by a person's inability to remember events related to a specific incident or topic. Patients also differ in durations of RA (how long they can't recall information) and durations of what is forgotten (past time frame for which information is unavailable).
Temporally graded retrograde amnesia
In temporally graded retrograde amnesia, victims eventually recover most memories following the onset of RA. This suggests that the hippocampal formation is only used in systematic consolidation for temporary, and short periods of time, until long-term consolidation takes place in other brain structures. Here, the fact that damage to the hippocampal formation can eventually overcome RA suggests that other brain structures are able to take over the jobs of the malfunctioning regions. RA can also progress and further deteriorate memory recollection, as in the case of Korsakoff syndrome and Alzheimer's disease, due to the ongoing nature of the damage caused by the illnesses. The degree to which different patients recover from RA differs in time (some take a few days while others a few decades) and content (some will only remember certain specific instances while others more).
Focal, isolated, and pure retrograde amnesia
These terms are used to describe a pure form of RA, with an absence of anterograde amnesia (AA). In addition, Focal RA in particular, has also been used to describe a RA situation in which there is a lack of observable physical deficit as well. This could be described as a psychogenic form of amnesia with mild anterograde and retrograde loss. A case study of DH revealed that the patient was unable to provide personal or public information, however there was no parahippocampal or entorhinal damage found. Individuals with focal brain damage have minimal RA.
Isolated RA is associated with a visible thalamic lesion. Consistent with other forms of RA, the isolated form is marked by a profound inability to recall past information.
Pure retrograde amnesia (PRA) refers to the behavioral syndrome that is characterized by the inability to retrieve remote information in the face of a normal ability to learn new information, with no other ecological or psychometric evidence of cognitive impairment. It should not be confused with the brief periods of peritraumatic amnesia that are common in mild concussive head traumas. The findings of pure retrograde amnesia have helped form the dissociation between mechanisms for RA and AA. Several studies have found numerous causes for PRA like vascular diseases, head traumas ranging from mild to severe, encephalitis, as well as purely psychological conditions and totally unidentifiable aetiologies. Most people who suffer from PRA can function normally and learn new information and therefore are not severely set back in life.  (Lucchelli, Muggia, & Spinnler, 1998).
A pure form of RA is rare as most cases of RA co-occur with AA. A famous example is that of patient ML. The patient's MRI revealed damage to the right ventral frontal cortex and underlying white matter, including the uncinate fasciculus, a band of fibres previously thought to mediate retrieval of specific events from one's personal past.
The causal explanation of retrograde amnesia is still under investigation.
The three main models used to explain RA assume that the hippocampus is one of the main areas of the brain used in memory consolidation. During consolidation, the hippocampus acts as an intermediate tool that quickly stores new information until it is transferred to the neocortex for the long-term. The temporal lobe, which holds the hippocampus, entorhinal, perirhinal and parahippocampal cortices, has a reciprocal connection with the neocortex. The temporal lobe is temporarily needed when consolidating new information; as the learning becomes stronger, the neocortex becomes more independent of the temporal lobe.
Studies on specific cases demonstrate how particular impaired areas of the hippocampus are associated with the severity of RA. Damage can be limited to the CA1 field of the hippocampus, causing very limited RA for about 1 to 2 years. More extensive damage limited to the hippocampus causes temporally graded amnesia for 15 to 25 years. Another study also suggests that large medial temporal lobe lesions, that extend laterally to include other regions, produce more extensive RA, covering 40 to 50 years. These findings suggest that density of RA becomes more severe and long-term as the damage extends beyond the hippocampus to surrounding structures.
The common studied causes of RA do not always lead to the onset of RA. It may even be that in some cases both conscious feigning and unconscious processes are at play.
Traumatic brain injury (TBI) or post-traumatic amnesia
Traumatic brain injury (TBI), also known as post-traumatic amnesia, occurs from an external force that causes structural damage to the brain, such as a sharp blow to the head, a diffuse axonal injury, or childhood brain damage (e.g., shaken baby syndrome). In cases of sudden rapid acceleration, the brain continues moving around in the skull, harming brain tissue as it hits internal protrusions.
TBI varies according to impact of external forces, location of structural damage, and severity of damage ranging from mild to severe. Retrograde amnesia can be one of the many consequences of brain injury but it is important to note that it is not always the outcome of TBI. An example of a subgroup of people who are often exposed to TBI are individuals who are involved in high-contact sports. Research on football players takes a closer look at some of the implications to their high-contact activities. Enduring consistent head injuries can have an effect on the neural consolidation of memory.
Specific cases, such as that of patient ML, support the evidence that severe blows to the head can cause the onset of RA. In this specific case there was an onset of isolated RA following a severe head injury. The brain damage did not affect the person's ability to form new memories. Therefore, the idea that specific sections of retrograde memory are independent of anterograde is supported. Normally, there is a very gradual recovery, however, a dense period of amnesia immediately preceding the trauma usually persists.
RA can occur without any anatomical damage to the brain, lacking an observable neurobiological basis. Primarily referred to as psychogenic amnesia or psychogenic fugue, it often occurs due to a traumatic situation that individuals wish to consciously or unconsciously avoid through intrapsychic conflicts or unconscious repressions. The onset of psychogenic amnesia can be either global (i.e., individual forgets all history) or situation specific (i.e., individual is unable to retrieve memories of specific situations).
People experiencing psychogenic amnesia have impaired episodic memory, instances of wandering and traveling, and acceptance of a new identity as a result of inaccessible memories pertaining to their previous identity.
Recent research has begun to investigate the effects of stress and fear-inducing situations with the onset of RA. Long-term potentiation (LTP) is the process by which there is a signal transmission between neurons after the activation of a neuron, which has been known to play a strong role in the hippocampus in learning and memory. Common changes in the hippocampus have been found to be related to stress and induced LTP. The commonalities support the idea that variations of stress can play a role in producing new memories as well as the onset of RA for other memories. Also, the amygdala plays a crucial role in memory and can be affected by emotional stimuli, evoking RA.
Studies of specific cases, such as 'AMN', support evidence of traumatic experiences as a plausible cause of RA. AMN escaped a small fire in his house, did not inhale any smoke, and had no brain damage. Surprisingly, the next day, he was unable to recall autobiographical based knowledge. This case shows that RA can occur in the absence of structural brain damage.
After a traumatic head injury, emotional disturbances can occur at three different levels: neurological, reactionary, and long-term disturbances. Neurological disturbances can change emotional and motivational responses. Reactionary disturbances effect emotional and motivational responses as well, but they reflect failure to cope with environmental demands. Someone with this might withdraw from the environment that they are placed in because they no longer know how to handle the cognitive resources.
RA has been found among alcohol-dependent patients who suffer from Korsakoff's syndrome. Korsakoff's syndrome patients suffer from retrograde amnesia due to a thiamine deficiency (lack of vitamin B1). Also, chronic alcohol use disorders are associated with a decrease in volume of the left and right hippocampus.
These patients' regular diet consists mostly of hard alcohol intake, which lacks the necessary nutrients for healthy development and maintenance. Therefore, after a prolonged time consuming primarily alcohol, these people undergo memory difficulties and ultimately suffer from RA. However, some of the drawback of using Korsakoff patients to study RA is the progressive nature of the illness and the unknown time of onset.
Infections that pass the blood–brain barrier can cause brain damage (encephalitis), sometimes resulting in the onset of RA. In the case of patient 'SS', the infection led to focal or isolated retrograde amnesia where there was an absence of or limited AA. Brain scans show abnormalities in the bilateral medial temporal lobes, including two thirds of the hippocampal formation and the posterior part of the amygdala.
Henry Molaison suffered from epilepsy that progressed and worsened by his late twenties. The severity of his condition caused him to undergo surgery in an effort to prevent his seizures. Unfortunately, due to a lack of overall known neurological knowledge, Molaison's surgeons removed his bilateral medial temporal lobe, causing profound AA and RA. The removed brain structures included the hippocampus, the amygdala, and the parahippocampal gyrus, now called the medial temporal lobe memory system. HM was one of the most studied memory cases to date and started the examination of neurological structures in relation to memory.
Other patients who suffered RA due to surgery are 'P.B.' and 'F.C.' who had unilateral removal of the medial areas in the left temporal lobe.
Clinically induced RA has been achieved using different forms of electrical induction.
- Electroconvulsive therapy (ECT), used as a depression therapy, can cause impairments in memory. Tests show that information of days and weeks before the ECT can be permanently lost. The results of this study also show that severity of RA is more extreme in cases of bilateral ECT rather than unilateral ECT. Impairments can also be more intense if ECT is administered repetitively (sine wave simulation) as opposed to a single pulse (brief-pulse stimulation).
- Electroconvulsive shock (ECS): The research in this field has been advanced by using animals as subjects. Researchers induce RA in rats, for example, by giving daily ECS treatments. This is done to further understand RA.
Diagnosis and treatment
Testing for retrograde amnesia
As previously mentioned, RA can affect people's memories in different degrees, but testing is required to help determine if someone is experiencing RA. Several tests exist, for example, testing for factual knowledge such as known public events. A problem with this form of testing is that people generally differ in their knowledge of such subjects. Other ways to test someone is via autobiographical knowledge using the Autobiographical Memory Interview (AMI), comprising names of relatives, personal information, and job history. This information could help determine if someone is experiencing RA and the degree of memory affected. However, due to the nature of the information being tested, it is often difficult to verify the accuracy of the memories being recalled, especially if they are from a distant past. Some researchers have found that the time interval after the head injury occurred did not seem to matter. The effect of the memory loss was the same no matter how long it had been after from the injury.
Brain abnormalities can be measured using magnetic resonance imaging (MRI), computed tomography scan (CT) and electroencephalography (EEG), which can provide detailed information about specific brain structures. In many cases, an autopsy helps identify the exact brain region affected and the extent of the damage that caused RA once the patient has died.
There are some aspects essential to the patient that remain unaffected by RA. In many patients, their personality remains the same. Also, semantic memory, that is general knowledge about the world, is usually unaffected. However, episodic memory, which refers to one's life experiences, is impaired.
Another real life problem with RA is malingering, which is conceived as the rational output of a neurologically normal brain aiming at the surreptitious achievement of a well identified gain. Since it is common for people who have committed a crime to report having RA for that specific event in order to avoid their punishment, the legal system has pushed for the creation of a standardized test of amnesia. However, since most cases differ in onset, duration, and content forgotten, this task has shown to be a rather complex one.
When someone is suffering from RA, their memory cannot be recovered from simply being told personal experiences and their identity. This is called reminder effect or reminder treatment. The reminder effect consists of re-exposing the patient to past personal information, which cannot reverse RA. Thus, reminding the patient details of their life has no scientific bearings on recovering memory. Fortunately, memory can be and usually is recovered due to spontaneous recovery and plasticity.
Since researchers are interested in examining the effects of disrupted brain areas and conducting experiments for further understanding of an unaffected, normal brain, many individuals with brain damage have volunteered to undergo countless tests to advance our scientific knowledge of the human brain. For example, Henry Molaison (HM) was someone with significant brain damage and participated in a lot of neurological research. Furthermore, he was also the most tested person in neuropsychology. All living people who participate are referred to in literature using only their initials to protect privacy.
Each case of RA has led to different symptoms and durations, where some patients have exhibited an inability to describe future plans, whether in the near future (e.g., this afternoon) or in the distant future (e.g., next summer) because of their inability to consolidate memories. Furthermore, researchers have also found that some patients can identify themselves and loved ones in photographs, but cannot determine the time or place the photo was taken. It has also been found that patients with RA greatly differ from the general population in remembering past events.
A few case examples are:
- After a head injury, AB had to relearn personal information. Many of AB’s habits had also changed.
- Patient CD, reported disorientation of place and time following his injuries as well as relearning previously learned information and activities (e.g., using a razor).
- EF was examined and found to be very confused about social norms (e.g., appropriate attire outside his home). EF exhibited memory loss of his personal experiences (e.g., childhood), and the impaired ability to recognize his wife and parents.
- JG is the first recorded patient suffering from isolated RA.
- GH, a mother and a wife, had surgery in August 2002. When GH woke up after the surgery, she believed it was May 1989. Due to her amnesia, GH experienced great difficulty in her social environment, being overwhelmed by relationships to others.
- DH, a learning disabilities instructor and husband, suffered a closed head injury. He did not show any normal signs of memory loss but he could not recall anything prior to the accident.
- CDA is 20-year-old man who fell and experienced head trauma after being unconscious for a little less than an hour. He had a self-identity loss and a retrograde deficit limited to the autobiographical events 5 years before the trauma. He often showed signs of spontaneous speech that was iterative and sometimes incoherent. When he saw his family and friends, he was shocked at how old they looked because he remembered them from 5 years earlier. This case also included amnesia for procedural skills like the fear of shaving or driving, which ultimately was overcome. There were no psychological, neuropsychological, or brain damage problems. His recovery of memory was progressive and spontaneous, where after several months the amnesia was limited to the two years preceding the trauma. This was a classic case of PRA. 
- GC was a 38 year old accountant that was found in a town square unable to remember anything about himself and unaware of where he was and how he got there. He was eventually able to recall basic information about himself and his family, but could not recall emotionally charged autobiographical events pertaining to the last 7 years of his life. Within 3–4 days, it was determined that his autobiographical amnesia was clearly and strictly selective for professional events, as he could remember everything that was not related to his job. It was ultimately learned that the job had created severe emotional stress and anxiety due to the extreme hours that triggered a sudden fugue state. He was eventually able to recover most of his memories minus a single work event where he had stolen money from the company. This was a classic case of psychogenic amnesia. 
- AF is a 15-year-old boy who hit his head and lost consciousness. He could not remember anything but was able to play songs on the piano, showing that his procedural memory was still intact. He gradually recovered some memories within the first 2–3 days but had autobiographical amnesia as well as significant memory loss for famous public facts and events for the 2 years prior to the injury. 
Although it may seem that people living with brain damage have great difficulty continuing the usual day-to-day aspects, they still can accomplish many feats. People with RA are able to lead a normal life. For instance, KC is a man who has many functional aspects intact; normal intelligence, unaffected perceptual and linguistic skills, short-term memory, social skills, and reasoning abilities. All of these things are necessary in everyday life and contribute to normal living. KC also is fully capable of scripted activities (e.g., making reservations or changing a flat tire). In addition, patient HC successfully graduated high school and continued into post-secondary studies, an obvious accomplishment despite her condition. DH relearned his childhood memories from his parents and can retell the stories, but cannot recall specifics other than what has been told to him.
Other forms of amnesia
Other forms of amnesia exist and may be confused with RA. For instance, anterograde amnesia (AA) is the inability to learn new information. This describes a problem encoding, storing, or retrieving information that can be used in the future. It is important to note that these two conditions can, and often do both occur in the same patient simultaneously, but are otherwise separate forms of amnesia.
RA can also be an inherent aspect of other forms of amnesia, namely transient global amnesia (TGA). TGA is the sudden onset of AA and RA caused by a traumatic event, however it is short lived, typically lasting only 4 to 8 hours. TGA is very difficult to study because of the patients' quick recovery. This form of amnesia, like AA, remains distinct from RA.
Post-traumatic amnesia (PTA) is a state of confusion that occurs immediately following a traumatic brain injury in which the injured person is disoriented and unable to remember events that occur after the injury.
Psychogenic amnesia, or dissociative amnesia, is a memory disorder characterized by sudden retrograde autobiographical memory loss, said to occur for a period of time ranging from hours to years.
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