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Persistent post-traumatic retrograde amnesia: a neuropsychological and (18F)FDG PET study.

We report the case of a 48-year old woman who, after a severe closed head injury, developed a severe and persistent disruption of retrograde memory, associated with a mild impairment of learning abilities. The patient's dense amnesia spared only the childhood period and included both explicit memory (autobiographical and semantic) and procedural skills. Because of her partially spared learning ability and intact language, intensive training by family members resulted in the reacquisition and retention of many autobiographical events and of some skills she had lost after the accident. Brain CT scan and MRI were normal; a PET study with (18F)FDG revealed a significant bilateral reduction of metabolism in the hippocampus and anterior cingulate cortex, suggesting a role for these structures in memory for past events.

Amnesia↗

Remembering and knowing the past: a case study of isolated retrograde amnesia.

We describe a patient, RM, who suddenly became amnesic for premorbid autobiographic events in the absence of any known precipitating event. Learning abilities as well as semantic knowledge were normal. Knowledge of famous facts and persons was good, although not perfect. Whether RM suffered from organic or psychogenic isolated retrograde amnesia (IRA) could not be established on the basis of available clinical and neuropsychological elements. Regardless of its aetiology, RM's case respects the boundaries between semantic and episodic memory and so gives further support to the distinction between these two memory systems.

Adolescent↗

The effects of some K(+) channel blockers on scopolamine- or electroconvulsive shock-induced amnesia in mice.

The effects of three K(+) channel blockers, 4-aminopyridine, 3, 4-diaminopyridine and apamin, on scopolamine- or electroconvulsive shock-induced amnesia were investigated in mice by using a one-trial step-down passive avoidance system. Scopolamine and electroconvulsive shock reduced the retention latency of passive avoidance, which indicated the amnestic effect of these treatments. 4-Aminopyridine, 3,4-diaminopyridine and apamin injected immediately after the acquisition trial, reversed the amnestic effect of scopolamine or electroconvulsive shock in a dose-dependent manner. None of the drugs or electroconvulsive shock treatment affected the rotarod or activity cage performance of the mice. These results indicate that K(+) channel blockers may improve cognitive deficits when memory is impaired by a drug or any other manipulation.

4-Aminopyridine↗

Stimulation of delta1- and delta2-opioid receptors produces amnesia in mice.

The effects of intracerebroventricular administration of delta1- and delta2-selective opioid receptor agonists on spontaneous alternation performance, elevated plus-maze behavior and passive avoidance learning including step-down and step-through types were examined in mice. Although the delta1-selective opioid receptor agonist, [D-Pen2,L-Pen5]enkephalin (DPLPE) (1-10 microg) or the delta2-selective opioid receptor agonist, [D-Ala2]deltorphin II (deltorphin) (1-10 microg) did not markedly affect spontaneous alternation performance or elevated plus-maze behavior, DPLPE (1, 3 and/or 10 microg) and deltorphin (3 and 10 microg) inhibited passive avoidance learning including step-down and step-through types. The delta1-selective opioid receptor antagonist, 7-benzylidenenaltrexone (3.5 ng), and the delta2-selective opioid receptor antagonist, naltriben (19 ng), significantly antagonized the inhibitory effects of DPLPE (3 microg) and deltorphin (3 microg) on passive avoidance learning, respectively. In contrast, DPLPE (3 microg) or deltorphin (3 microg) did not markedly influence behavioral responses induced by electroshocks during training of passive avoidance learning. Moreover, DPLPE (0.3-3 microg) or deltorphin (0.3-3 microg) failed to significantly affect the radiant heat-induced nociceptive responses. These results suggest that stimulation of delta1- and delta2-opioid receptors produces amnesia, depending on the learning tasks used.

Amnesia↗

Dissociating habit and recollection: evidence from Parkinson's disease, amnesia and focal lesion patients.

We investigated the role played by the striatum and the medial temporal lobes (MTL) in memory performance by testing patients with Parkinson's disease (PD) and amnesia with Hay and Jacoby's habit-learning task [Journal of Experimental Psychology: Learning, Memory and Cognition 22 (1996) 1323]. Using equations from Jacoby's process-dissociation procedure [Journal of Memory and Language 30 (1991) 513], we were able to separate out the contribution of habit (automatic memory) and recollection (intentional memory) to performance within a single probability-learning paradigm. Amnesics showed the expected dissociation of impaired recollection and intact habit, highlighting the important role of the MTL in recollective processing. Mild PD patients did not perform differently than matched controls for habit or recollection, however, moderate PD patients were impaired in their ability to rely on habit and in their ability to recollect specific information. The performance of focal lesion patients further supported the interpretation that PD patients have a significant deficit in automatic, habit-learning due to striatal dysfunction while their deficit in recollection may arise from impoverished frontal lobe contributions.

Aged↗

Perceptual learning in amnesia.

Evidence from experiments on perceptual learning, accumulated during the last few years, increasingly indicates that the relative 'front end' parts of the visual system are more plastic even in adults than was previously expected. Hence, it might be possible that perceptual learning is similar in several respects to procedural learning and may be achieved even without (declarative) memory traces present. Results on six patients suffering from global amnesia due to damage to hippocampal-diencephalic systems demonstrate, for the first time, that at least some amnesic patients are able to significantly improve performance in a visual hyperacuity task as a result of training, showing improvement as good as the observers in the control group. This result corroborates the notion of a relatively 'front end' location of at least some forms of perceptual learning.

Adult↗

Is implicit learning spared in amnesia? Rule abstraction and item familiarity in artificial grammar learning.

We examined implicit learning of an artificial grammar in amnesic and control participants. The "biconditional" grammar used to generate study and test strings allows two potential sources of judgements in artificial grammar learning to be unconfounded: participants could either learn the abstract biconditional rules or could learn about the distributional statistics of the surface elements (e.g. bigrams) composing the study items. Test strings varied these two sources orthogonally. We found no evidence of abstract rule learning either in the control or amnesic groups. In contrast, both groups learned about the surface elements and tended to call test strings "grammatical" when they were composed of familiar bigrams. However, this sensitivity to bigram familiarity was significantly reduced in the amnesic compared to the control group. The results challenge the claim that implicit learning is intact in amnesia.

Amnesia↗

The contribution of autobiographical significance to semantic memory: evidence from Alzheimer's disease, semantic dementia, and amnesia.

In a previous study [Memory Cognit., in press], we demonstrated that some semantic concepts are more likely than others to be associated with specific personal memories, and that this autobiographical significance gives these concepts special status in long-term memory. In this paper, we explore the possible neural correlates of autobiographically significant semantic knowledge and examine whether or not autobiographical significance is a factor in determining patterns of semantic memory loss caused by brain damage. Using famous names that were rated on various attributes, including autobiographical significance, by control participants in a norming study [Memory Cognit., in press], we found that semantic dementia (SD) patients were more likely to recognize, identify and remember autobiographically significant episodes involving famous names that were rated high in autobiographical significance as compared to equally familiar names that were rated low. By contrast, people with Alzheimer's disease (AD) and people with medial temporal lobe (MTL) amnesia did not exhibit this preference for names rated high in autobiographical significance. Furthermore, in tests of free recall, recognition, fame judgment and speeded reading, semantic dementia patients demonstrated a performance advantage for autobiographically significant famous names, whereas the other patient groups did not. These findings suggest a critical role for medial temporal regions in the mediation of autobiographical memory and the interaction between personal experience and semantic memory. Theoretical implications are discussed.

Adult↗

Strategic retrieval and the frontal lobes: evidence from confabulation and amnesia.

Confabulation and amnesia are considered disorders of episodic but not of semantic memory. To test the limits of this view, retrieval from episodic and semantic memory was investigated in eight confabulating and nine non-confabulating amnesic subjects, and in 17 matched control subjects, by using a personal and an historical version of the Crovitz [Unconstrained search in long-term memory, Paper presented at the meeting of the Psychonomic Society, St Louis, MO, 1973] cue-word test. In response to cue words such as letter or battle subjects had to describe in detail, respectively, a related event from their personal lives or from history before their birth. We found that a subset of amnesic subjects, those with presumed damage or dysfunction in the region of the ventromedial frontal cortex, would confabulate in response to these cues. Their confabulations involved semantic, historical memories, as much as episodic, personal ones: and that distortions of content were at least as common as those of time. Even when not confabulating, they had much more difficulty than other amnesic subjects in recovering memories related to these cues. In confabulating, as compared to non-confabulating, amnesic subjects, prompting led to an increase in confabulations but also to greater recovery of veridical memories. By comparison, non-confabulating amnesic subjects whose memory loss was as severe as that of the confabulators, had a milder deficit on the personal as well as the historical cue-word test. They benefited from prompting somewhat more than matched control subjects. These results suggest that confabulation is associated with impaired strategic retrieval processes resulting from damage in the region of the ventromedial frontal cortex. These strategic retrieval processes help initiate and guide search in episodic and in semantic memory and they help monitor and organize the output from those systems.

Adult↗

Retrograde amnesia in patients with diencephalic, temporal lobe or frontal lesions.

Patients with focal diencephalic, temporal lobe, or frontal lobe lesions were examined on various measures of remote memory. Korsakoff patients showed a severe impairment with a characteristic 'temporal gradient', whereas two patients with focal diencephalic damage (and anterograde amnesia) were virtually unimpaired on remote memory measures. Patients with frontal lobe pathology were severely impaired in the recall of autobiographical incidents and famous news events. Patients with temporal lobe pathology showed severe impairment but a relatively 'flat' temporal gradient, largely attributable to herpes encephalitis patients. From recognition and cued recall tasks, it is argued that there is an important retrieval component to the remote memory deficit across all the lesion groups. In general, the pattern of performance by the frontal lobe and temporal lobe groups was closely similar, and there was no evidence of any major access/storage difference between them. However, laterality comparisons across these groups indicated that the right temporal and frontal lobe regions may make a greater contribution to the retrieval of past episodic (incident and event) memories, whereas the left temporal region is more closely involved in the lexical-semantic labelling of remote memories.

Adolescent↗

The mesograde amnesia of sleep may be attenuated in subjects with primary insomnia.

In this study, we pilot tested one of the more controversial components of the Neurocognitive Model of Insomnia; the proposition that subjects with chronic primary insomnia are better able to recall and/or recognize information from sleep onset intervals than good sleeper controls. Nine subjects participated in this pilot study, five of whom had a complaint of insomnia. The remaining four subjects were self-reported good sleeper controls. Subjects were matched for age, sex, and body mass. All subjects spent two nights in the sleep laboratory. The first night served as an adaptation night. The second night served as the experimental night during which a forced awakening and memory task was deployed. In this procedure, subjects were played single-word stimuli across four time periods: at natural sleep onset (Trial 1) and at the sleep onset transitions following three forced awakenings (Trials 2-4 from Stage 2 sleep). All subjects were awakened after about 6 h had elapsed from lights out and were tested for free recall and recognition memory for the word stimuli. The insomnia subjects, tended to identify more of the word stimuli on the recognition task (average for the four trials) and recognized significantly more of the words that were presented at sleep onset proper (Trial 1). This finding suggests that the natural mesograde amnesia of sleep may be attenuated in subjects with insomnia.

Acoustic Stimulation↗

Temporary amnesia induced by cold anesthesia and hypoxia in Drosophila.

Memory consolidation in Drosophila was investigated using cold anesthesia- and hypoxia-induced amnesia. Individual flies were operantly trained to avoid the specific flight orientations with respect to the landmarks surrounding them when paired with heat reinforcement at a flight simulator. Cold anesthesia, introduced immediately after training, exerted a significantly diminishing effect on memory between 15 and 150 min after training. Hypoxia delivered immediately after training had a significantly diminishing effect on memory between 30 and 150 min after training. In addition, cold anesthesia disrupted memory only when introduced within the first 20 min, while hypoxia worked only when delivered within the first 2 min after training. When interpreted in the context of a four-phase model of memory consolidation, the results suggest that 1) cold anesthesia disrupts both short-term memory (STM) and anesthesia-resistant memory (ARM), 2) hypoxia disrupts ARM specifically, 3) both of them leave long-term memory (LTM) intact, and 4) LTM may be independent of availability of STM and ARM in flies.

Amnesia↗

Bovine brain phosphatidylserine attenuates scopolamine-induced amnesia.

The effects of bovine cerebral cortex phosphatidylserine (BCPS) on the memory impairment induced by scopolamine in mice tested in the plus-maze discriminative avoidance task were investigated. Swiss male mice received daily i.p. 50 mg/kg BCPS or 0.2 M Tris pH 7.4 (TRIS) for 5 days. Twenty-four hours after the last injection, the animals received 1 mg/kg scopolamine (BCPS-SCO and TRIS-SCO) or saline (BCPS-SAL and TRIS-SAL) i.p. After 20 min, the animals were submitted to discriminative avoidance conditioning. In the test, performed 24 h later, BCPS-SCO, BCPS-SAL, and TRIS-SAL (but not TRIS-SCO) mice spent significantly less time in the aversive enclosed arm of the discriminative avoidance apparatus when compared to the time spent in the nonaversive enclosed arm. The results suggest that BCPS attenuates scopolamine-induced amnesia in a discriminative avoidance task.

Amnesia↗

Disturbance of venous flow patterns in patients with transient global amnesia.

Transient global amnesia (TGA) is an inability to form new memories. The pathophysiology and cause of TGA have not been defined. We examined the changes of internal jugular venous flow patterns in 21 patients with TGA and 21 age-matched and sex-matched controls using duplex ultrasonography during two Valsalva manoeuvres (blocking venous return through the superior vena cava). During both manoeuvres a retrograde flow component was seen significantly more frequently in the TGA group than in the controls. Ten patients reported Valsalva-like activities preceding TGA. In these patients a retrograde flow component took place more frequently than in those who did not report preceding Valsalva-like activities. Our results lend support to the hypothesis that TGA may be attributable to venous congestion, and consequent venous ischaemia to bilateral diencephalic or hippocampal structures.

Aged↗

Aetiology of transient global amnesia.

The pathophysiology of transient global amnesia (TGA) has been obscure since the definition of this syndrome more than 30 years ago. Current hypotheses include migraine, seizure, or transient cerebral arterial ischaemia. However, none of these potential mechanisms explain both the absence of other neurological signs or symptoms during TGA, and its frequent precipitating activities: many of which would be expected to result in marked increases in venous return from the arms to the superior vena cava. Patients with TGA also commonly have a Valsalva manoeuvre at the onset of attacks. I suggest that a Valsalva manoeuvre, blocking venous return through the superior vena cava, may allow brief retrograde transmission of high venous pressure from the arms to the cerebral venous system, resulting in venous ischaemia to the diencephalon or mesial temporal lobes and to TGA.

Amnesia↗

False attribution of suggestibility to explain recovered memory of childhood sexual abuse following extended amnesia.

Suggestibility is central to arguments proffered by critics of recovered memory of childhood sexual abuse who believe that memories involving amnesia are false creations of treatment. The present study represents the first direct investigation of suggestibility among patients who report recovered memory. Suggestibility was measured in 44 patients who recovered memories and in a 31 patient comparison group without a history of sexual trauma using the Gudjonsson Suggestibility Scale. Results indicated that patients who recover memories were remarkably less suggestible than the clinical field has been led to believe by advocates of false memory. As a group, they scored low on suggestibility. Recovered Memory patients yielded to suggested prompts an average of 6.7 times per case. This compares to an average of 10.6 in the Psychiatric comparison group. Paradoxically, patients without a history of sex abuse were more at risk for altering memory to suggestive prompts. These findings appreciably challenge advocated theories of suggested memory.

Adult↗

Intrahippocampal or intraamygdala infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II, causes retrograde amnesia in the rat.

We investigated the effect of a bilateral post-training intracerebral infusion of KN62, a specific inhibitor of calcium/calmodulin-dependent protein kinase II (CaM-II), on memory. This enzyme plays a crucial role in the early phases of long-term potentiation. Male Wistar rats were implanted bilaterally with cannulae aimed at the CA1 region of the dorsal hippocampus or at the junction between the central and the basolateral nuclei of the amygdala. After recovery, rats were trained in step-down inhibitory avoidance using a 0.5-mA footshock and tested for retention 24 h later. At various times after training (0, 30, 120, or 240 min for the animals implanted into the hippocampus; 0 or 240 min for the animals implanted in the amygdala) they received, through the cannulae, an infusion of vehicle (0.1% dimethylsulfoxide in water) or KN62 (100 mumol/side). KN62 caused full retrograde amnesia when given 0 min after training into either the amygdala or the hippocampus. When given into the hippocampus 30 min post-training it had a partial amnestic effect. When given 120 min after training into the hippocampus, or 240 min after training into either structure, KN62 had no effect. The data suggest that the early phase of memory requires intact CaM-II activity in the amygdala and hippocampus and support the hypothesis that memory involves long-term potentiation initiated at the time of training in both structures.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Effects of central muscarinic blockade on passive avoidance: anterograde amnesia, state dependency, or both?

It was recently reported that administration of relatively high intensities of footshock (overreinforcement) during training of passive avoidance protected animals against the amnesic effect of scopolamine, injected 5 min after training. This was interpreted in terms of a lesser involvement of acetylcholine in memory consolidation. An alternative explanation was that overreinforcement accelerated the consolidation process, which could have taken place before the injection of scopolamine. To test for this possibility, male Wistar rats were injected with 4, 8, or 12 mg/kg of scopolamine, 5 min before training with low or high levels of footshock and then tested for retention of the task. Scopolamine induced the expected memory deficit after the low-intensity footshock; after overreinforcement the higher doses of scopolamine induced state dependency, while no deficits were produced with the lower dose. It was concluded that: (a) acetylcholine is indeed involved in memory consolidation of passive avoidance; (b) scopolamine interacts with high footshock levels to produce state dependency; and (c) when relatively low doses of scopolamine are used in conditions of overreinforcement, protection against scopolamine-induced amnesia becomes evident.

Amnesia↗