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The scope of preserved procedural memory in amnesia.

The finding that patients with amnesia retain the ability to learn certain procedural skills has provided compelling evidence of multiple memory systems in the human brain, but the scope, defining features and ecological significance of the preserved mnemonic abilities have not yet been explored. Here, we tested the hypothesis that subjects with amnesia would be able to learn and retain a broad range of procedural skills, by examining their acquisition and retention performance on five novel experimental tasks. The tasks are based on real-world activities and encompass a broad range of perceptual-motor demands: (i) the weaving task involves weaving pieces of fabric from woollen strings, using a manual weaver's loom; (ii) the geometric figures task consists of tracing geometric figures with a stylus as they move horizontally across a touch screen monitor; (iii) the control stick task involves tracking a sequence of visual target locations using a joystick control; (iv) the pouring task consists of pouring 200 ml of water from a watering can into a series of graduated cylinders, from a point 20 cm above the cylinders; and (v) the spatial sequence task involves learning an ordered sequence of pushing five spatially distributed buttons without visual guidance. Ten chronic and stable amnesic subjects (nine with bilateral medial temporal lobe damage due to herpes simplex encephalitis or anoxia, and one with thalamic stroke) and 25 matching normal comparison subjects were tested on three occasions: initial learning at time 1; retention at time 2 (24 h later); and retention at time 3 (2 months later). Despite impaired declarative memory for the tasks, the amnesic subjects demonstrated acquisition and retention of the five skills; their learning slopes over repeated trials were comparable with those of comparison subjects. These findings indicate that preserved learning of complex perceptual-motor skills in patients with amnesia is a robust phenomenon, and that it can be demonstrated across a variety of conditions and perceptual-motor demands. The comparability of the tasks employed in this study with real-world activities highlights the potential application of this memory dissociation in the rehabilitation of patients with amnesia.

Adult↗

Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome.

Anterograde amnesia in Wernicke-Korsakoff syndrome is associated with diencephalic lesions, mainly in the anterior thalamic nuclei. Whether diencephalic and temporal lobe amnesias are distinct entities is still not clear. We investigated episodic memory for faces using functional MRI (fMRI) in eight controls and in a 34-year-old man with Wernicke-Korsakoff syndrome and diencephalic lesions but without medial temporal lobe (MTL) involvement at MRI. fMRI was performed with a 1.5 tesla unit. Three dual-choice tasks were employed: (i) face encoding (18 faces were randomly presented three times and subjects were asked to memorize the faces); (ii) face perception (subjects indicated which of two faces matched a third face); and (iii) face recognition (subjects indicated which of two faces belonged to the group they had been asked to memorize during encoding). All activation was greater in the right hemisphere. In controls both the encoding and recognition tasks activated two hippocampal regions (anterior and posterior). The anterior hippocampal region was more activated during recognition. Activation in the prefrontal cortex was greater during recognition. In the subject with Wernicke-Korsakoff syndrome, fMRI did not show hippocampal activation during either encoding or recognition. During recognition, although behavioural data showed defective retrieval, the prefrontal regions were activated as in controls, except for the ventrolateral prefrontal cortex. fMRI activation of the visual cortices and the behavioural score on the perception task indicated that the subject with Wernicke-Korsakoff syndrome perceived the faces, paid attention to the task and demonstrated accurate judgement. In the subject with Wernicke-Korsakoff syndrome, although the anatomical damage does not involve the MTL, the hippocampal memory encoding has been lost, possibly as a consequence of the hippocampal-anterior thalamic axis involvement. Anterograde amnesia could therefore be the expression of damage to an extended hippocampal system, and the distinction between temporal lobe and diencephalic amnesia has limited value. In the subject with Wernicke-Korsakoff syndrome, the preserved dorsolateral prefrontal cortex activation during incorrect recognition suggests that this region is more involved in either the orientation or attention at retrieval than in retrieval. The lack of activation of the prefrontal ventrolateral cortex confirms the role of this area in episodic memory formation.

Adult↗

Lesions of the basolateral amygdala complex block propofol-induced amnesia for inhibitory avoidance learning in rats.

BACKGROUND: As the unitary theory of anesthesia gives way to the "multiple sites, multiple mechanisms" concept, the sites involved in mediating the components of anesthesia must be identified. In the current study, we test the hypothesis that the basolateral amygdala complex (BLAC) is a brain site involved with mediating propofol-induced amnesia. METHODS: Male Sprague-Dawley rats were divided into two groups, sham-operated control animals and rats given bilateral excitotoxic N-methyl-D-aspartate lesions of the BLAC. For each group, animals were given intraperitoneal saline or propofol (25 mg/kg) 5 min before inhibitory avoidance learning. Rats were given a foot shock (0.4 mA) upon entering the dark side of a two-sided apparatus. Rats could escape additional shock by returning to and staying in the light side. Training ended after shock avoidance for greater than 60 s. Memory was tested at 24 h. Longer latencies to enter the dark side 24 h after training imply better memory. RESULTS: Sham-saline-treated animals had a robust memory latency (median latency [interquartile range] = 300 [163-567] s). Sham-propofo-treated animals exhibited a significant anterograde amnesia (latency = 63 [14-111] s) (P < 0.05 vs. sham-saline-treated animal). Both the saline-injected and propofol-injected animals with BLAC lesions showed robust memory (latency = 300 [264-485] and 323 [143480] s, respectively). These latencies did not differ from performance in the sham-saline-treated group and were significantly higher than the latency of the sham-propofol-treated group (both P < 0.05). CONCLUSIONS: Discrete BLAC lesions blocked the amnestic effect of propofol. BLAC activity appears to be a requirement for propofol-induced amnesia. This finding suggests that the BLAC is a key brain site mediating anesthetic-induced amnesia.

Amnesia↗

Facilitation of serotonergic activity and amnesia in rats caused by intravenous anesthetics.

BACKGROUND: Midazolam and propofol often provoke retrograde amnesia after recovery from anesthesia in humans. Because an increase in central serotonergic activity impairs learning and memory, the authors examined the relation between changes in the serotonergic activity caused by intravenous anesthetics and memory. METHODS: Changes in extracellular concentrations of monoamines and their metabolites were investigated in rat striatum by a microdialysis procedure, and the effects of intraperitoneal injections of midazolam (5 mg/kg), propofol (60 mg/kg), and pentobarbital (15 mg/kg) were then examined. To evaluate the behavioral alteration with these agents, the authors used a step-through passive avoidance test. RESULTS: Midazolam and propofol slightly increased the extracellular concentration of 5-hydroxytryptamine in the striatum, although pentobarbital did not produce any changes. Midazolam and propofol increased the extracellular concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-hydroxytryptamine, with the peak values each 138% and 138% of that in saline-injected animals, respectively. However, pentobarbital decreased the 5-hydroxyindoleacetic acid concentration to 61% of that in the saline group. Administration of midazolam or propofol immediately after the completing the passive avoidance learning reduced step-through latencies after 24 h, although pentobarbital-injected animals maintained a consistent performance. The effects of midazolam and propofol on step-through latencies were completely antagonized by intracerebroventricular administration of spiroxatrine (5 microg), a 5-hydroxytryptamine 1A antagonist, 30 min before training. CONCLUSIONS: Midazolam and propofol increased central serotonergic activity and provoked retrograde amnesia. Because amnesia was completely diminished by a 5-hydroxytryptamine antagonist, facilitation of the serotonergic system may be involved in retrograde amnesia caused by these agents.

Amnesia↗

The complex episode of transient global amnesia.

In most reports, Transient Global Amnesia (TGA) consisted of a single episode of total amnesia. The detailed investigation on the process of recovery from amnesia in the present two cases of TGA indicated the existence of a complex episode of TGA which consisted of a sequence of episodes of total amnesia.

Amnesia↗

An experimental study of compliance and post-hypnotic amnesia.

A procedure was devised to test the hypothesis that the traditional measure of post-hypnotic amnesia, which involves determining the number of items recalled before and after a 'release' signal, may be significantly biased by compliance. One group of subjects (group B) was given an opportunity to 'own-up' to compliant behaviour before being tested for post-hypnotic amnesia. Another group (group A) was only given the opportunity to own-up after being tested for amnesia. Results indicated a very strong compliance effect, group A showed significantly more post-hypnotic amnesia than group B.

Adolescent↗

A multicentre, randomised trial examining the effect of test procedures measuring emergence from post-traumatic amnesia.

BACKGROUND: Post-traumatic amnesia (PTA) tests that record different PTA durations in the same patient, thereby raising measurement accuracy issues, have been reported previously. A major problem lies in determining the end point of PTA. AIMS: To delineate areas of discrepancy in PTA tests and to provide independent verification for a criterion signalling emergence from PTA. METHODS: In a randomised design, two related PTA procedures were compared, one purportedly more difficult (Westmead PTA Scale, WPTAS) than the other (Modified Oxford PTA Scale, MOPTAS). Eighty two patients in the early stages of PTA were examined daily until emergence, by using the Galveston Orientation and Amnesia Test (GOAT) and the WPTAS/MOPTAS. A short battery of cognitive and behavioural measurements was made on three occasions: at the early stage of PTA (time 1), towards the end of PTA when the maximum score (12/12) was first obtained (time 2) and at the traditional criterion for emergence (scoring 12/12 for 3 consecutive days; time 3). RESULTS: No significant difference was recorded in PTA duration between the MOPTAS and WPTAS. Both scales recorded longer PTA durations than the GOAT. By using Kaplan-Meier survival analyses, the WPTAS was found to show a more protracted pattern of emergence at the end stage of PTA than the MOPTAS. A time lag of > or = 1 week in the resolution of disorientation as compared with amnesia was observed in 59% cases. Significant improvements occurred on all independent measurements between time 1 and time 2, but on only 2 of 5 cognitive measurements between time 2 and time 3. CONCLUSIONS: Although no significant differences in the duration of PTA on the MOPTAS/WPTAS were recorded, emergence from the late stages of PTA occurred more promptly with the MOPTAS. The need for inclusion of both orientation and memory items in PTA tests is highlighted by the frequency of disorientation-amnesia dissociations. The patterns of results on the independent measures suggest that patients who are in PTA for > 4 weeks have probably emerged from PTA when they first score 12/12 on the MOPTAS/WPTAS, and this criterion can replace the traditional criterion.

Adolescent↗

Syndromes of transient amnesia: towards a classification. A study of 153 cases.

Of 153 patients presenting with acute transient amnesia, 114 fulfilled the proposed strict diagnostic criteria for transient global amnesia (TGA). The prognosis of this group was excellent with the exception of a small subgroup (7%), largely identifiable because of atypically brief or recurrent attacks, who developed epilepsy of temporal lobe type on follow up. Computerised tomography (CT) scans performed on 95 patients were normal, evidence for covert alcoholism was lacking and there was a familial incidence of approximately 2%. By contrast, the group of 39 patients who did not meet the criteria for TGA had a significantly worse prognosis with a high incidence of major vascular events. The groups could not be distinguished on the basis of behavioural characteristics during the attack. The following classification was proposed: 1) pure TGA--attacks fulfilling the strict criteria, and of more than one hour in duration which do not require detailed investigation, 2) probable epileptic amnesia--attacks of less than an hour or rapidly recurrent, 3) probable transient ischaemic amnesia, a minority of cases with additional focal neurological deficits during the attack.

Adult↗

Memory without context: amnesia with confabulations after infarction of the right capsular genu.

OBJECTIVE: To explore the mechanism of an amnesia marked by confabulations and lack of insight in a patient with an infarct of the right inferior capsular genu. The confabulations could mostly be traced back to earlier events, indicating that the memory disorder ensued from an inability to store the temporal and spatial context of information acquisition rather than a failure to store new information. METHODS: To test the patient's ability to store the context of information acquisition, two experiments were composed in which she was asked to decide when or where she had learned the words from two word lists presented at different points in time or in different rooms. To test her ability to store new information, two continuous recognition tests with novel non-words and nonsense designs were used. Recognition of these stimuli was assumed to be independent of the context of acquisition because the patient could not have an a priori sense of familiarity with them. RESULTS: The patient performed at chance in the experiments probing knowledge of the context of information acquisition, although she recognised the presented words almost as well as the controls. By contrast, her performance was normal in the recognition tests with non-words and nonsense designs. CONCLUSION: These findings indicate that the patient's amnesia was based on an inability to store the context of information acquisition rather than the information itself. Based on an analysis of her lesion, which disconnected the thalamus from the orbitofrontal cortex and the amygdala, and considering the similarities between her disorder, Wernicke-Korsakoff syndrome, and the amnesia after orbitofrontal lesions, it is proposed that contextual amnesia results from interruption of the loop connecting the amygdala, the dorsomedial nucleus, and the orbitofrontal cortex.

Amnesia↗

Temporal lobe hypoperfusion in isolated amnesia with slow onset: a single photon emission computer tomography study.

Single photon emission computer tomography (SPECT) applied early in the course of Alzheimer's disease (AD) may identify regions with impaired brain function. Moreover, it may be relevant to characterize SPECT perfusion patterns in patients with mild cognitive impairment (MCI), in particular the subgroup of MCI patients with isolated amnesia, as these patients have been demonstrated to convert to AD in more than half of the cases within 3 years. The primary aim of the present study was to characterize the regional cerebral blood flow (CBF) in patients with neuropsychologically verified isolated amnesia. We examined 32 patients (11 men/21 women) with isolated amnesia according to strict neuropsychological criteria and 15 healthy volunteers (11 men/4 women). All subjects had an SPECT-99mTc-d,l-HMPAO perfusion study and neuropsychological assessments. Cranial MRI or CT was performed in all subjects. Semiquantitative (cerebellar relative) flow values were calculated and statistically compared. Patients with isolated amnesia had significant hypoperfusion in several cortical regions of interest compared to control subjects, most prominently in the left temporal cortex. Additionally, there was a trend towards globally reduced CBF in the patients, although this was not significant. These findings may indicate the presence of a progressive degenerative illness affecting multiple brain regions at its early or preclinical stage.

Adult↗

Extracranial carotid artery in patients with transient global amnesia: evaluation by real-time B-mode ultrasonography with duplex Doppler flow.

Patients with transient global amnesia are often categorized as having cerebrovascular disease. Noninvasive carotid artery testing was performed in 56 patients with transient global amnesia to determine if they had the same incidence of extracranial atherosclerotic vascular disease as patients with focal cerebral transient ischemic attacks. Only 3 of 56 patients had hemodynamic obstruction of flow at the carotid artery bifurcation, and 41 of 56 had no evidence of any atherosclerotic disease. Other risk factors for cerebrovascular disease were present in 24 of 56 patients, but only 1 had a prior cerebrovascular event. The pathophysiology of transient global amnesia appears to differ from the pathophysiology of classical transient ischemic attacks in that there is no clear relation between transient global amnesia and the presence of extracranial atherosclerotic cerebrovascular disease.

Aged↗

Posterior ischemia during an attack of transient global amnesia.

BACKGROUND: The popular concept that cerebral ischemia causes transient global amnesia has been difficult to prove by cerebral blood flow studies during attacks because the transient global amnesia attacks are so short. CASE DESCRIPTION: We performed single-photon emission computed tomography (SPECT) of the brain and neuropsychological assessment in a 37-year-old woman during a 10-hour attack and twice thereafter. A neuropsychological evaluation 3 hours after the onset of transient global amnesia revealed severe impairment of recent memory and verbal fluency, both of which returned to normal 2 and 28 days later, respectively. A 99mTc-labeled hexamethylpropyleneamine oxime SPECT of the brain performed 6 hours after the onset showed multiple perfusion defects in both occipital lobes, the medial left temporal lobe, and the left thalamus. A second brain SPECT performed 3 days later showed perfusion defects in only the occipital regions. A third brain SPECT performed 28 days later was normal. The patient's brain computed tomographic scan, electroencephalogram, duplex ultrasound of the carotid artery, and echocardiogram were normal. CONCLUSIONS: The perfusion defects revealed by the brain SPECT during the transient global amnesia attack indicated ischemia in the territory of the posterior cerebral arteries, which partially resolved in 3 days and completely resolved by 28 days.

Adult↗

Diffusion-weighted MRI in transient global amnesia precipitated by cerebral angiography.

BACKGROUND: Transient global amnesia is a well-described complication of cerebral angiography. Speculation about the pathophysiology exists but is as yet unsubstantiated. Diffusion-weighted MRI is a new imaging technique that is very sensitive in detecting acute ischemia. Its use in the evaluation of transient amnesia precipitated by cerebral angiography has not previously been reported. CASE DESCRIPTION: A 44-year-old man underwent posterior circulation cerebral angiography for the investigation of episodic vertigo. Shortly after completion of the procedure, he was noted to have symptoms of transient global amnesia. Diffusion-weighted MRI at 6 and 44 hours after the procedure demonstrated increased signal in the right hippocampus and other areas within the posterior circulation bilaterally consistent with ischemia from emboli. Abnormalities on conventional MRI images performed at the same time points were noted only in retrospect. A follow-up MRI at 2 months was normal. CONCLUSIONS: Ischemia from cerebral emboli may cause transient global amnesia precipitated by cerebral angiography. Diffusion-weighted MRI may be useful in defining the pathophysiology.

Adult↗

Amnesia due to fornix infarction.

Background and Purpose-The fornix connects various structures involved in memory. We report a patient with anterograde amnesia after an acute ischemic infarct in the anterior fornix. Case Description-A 71-year-old female with acute-onset amnesia had neuroimaging studies showing ischemic infarction of both columns and the body of the fornix and the genu of the corpus callosum. Neuropsychological evaluation revealed anterograde amnesia without evidence of callosal disconnection. The patient showed marked improvement in her memory function on the follow-up visit. Conclusions-Amnesia in this case is likely due to infarction of the anterior fornix structures.

Aged↗

Predictors of retrograde amnesia following ECT.

OBJECTIVE: Substantial progress has been made in identifying how the treatment parameters used in ECT impact on cognitive side effects. However, there is limited information regarding individual differences in vulnerability to these side effects. The authors examined patients' pretreatment global cognitive status and postictal orientation recovery time as potential predictors of the magnitude of retrograde amnesia for autobiographical memories after ECT. METHOD: Seventy-one inpatients with major depressive disorder were randomly assigned to four ECT conditions that varied in electrode placement (right unilateral versus bilateral) and stimulus dosage (low versus high intensity). Orientation recovery time was assessed at virtually every session during the course of ECT. Global cognitive status was assessed with the modified Mini-Mental State examination before treatment, during the week after termination of treatment, and 2 months after treatment ended. Retrograde amnesia was assessed at these same time points with the Autobiographical Memory Interview. RESULTS: Pre-ECT global cognitive status and the duration of postictal disorientation were strong predictors of the magnitude of retrograde amnesia in the week after the course of ECT and at 2-month follow-up. In general, these relationships were maintained regardless of technical parameters in the administration of the ECT. CONCLUSIONS: Patients who manifest global cognitive impairment before treatment and patients who experience prolonged disorientation in the acute postictal period may be the most vulnerable to persistent retrograde amnesia for autobiographical information.

Amnesia, Retrograde↗

Study of cases of anterograde amnesia in a disease of mental disintegration.

Pierre Janet, in his famous paper (1892) on anterograde amnesia, is concerned with the theme of the disintegration of the human personality. He shows that the weakened personality may lose the power to assimilate memories of current events. After a severe shock, there may supervene not only a retrograde amnesia (a blotting out from memory from some period before the accident), but also a continued or anterograde amnesia, that is to say, an inability to remember events occurring after the accident. Janet details the circumstances of a very interesting case of amnesia resulting from an attack of hysteria, brought on by the shock of bad news. The patient, 'Mrs. D.', had wholly lost all memory of events that occurred during the month and a half before her attack, and since that time she had only been able to remember for a few moments what was going on around her. Janet shows that memories which appear not to be formed are in fact formed; that they exist somewhere in the patient's mind with the full vividness of ordinary recollections, and that they may spontaneously crop up in dreams, or may be called out by hypnotic suggestion, or by other methods.

Amnesia, Anterograde↗

Effect of hachimijiogan, an oriental herbal medicinal mixture, on experimental amnesia in mice.

The effect of Hachimijiogan on cognitive disturbance was investigated using step-through passive avoidance failure techniques: scopolamine-, cycloheximide- and cerebral ischemia-induced amnesia. Pre-acquisition trial administration of Hachimijiogan (0.5 g/kg, p.o.) prolonged the step-through latency reduced by scopolamine and cycloheximide. Hachimijiogan (0.5 and 1.0 g/kg, p.o.) also ameliorated the cerebral ischemia-induced amnesia. Physostigmine (0.1 mg/kg, i.p.) ameliorated all three amnesia models. The ameliorating effects of Hachimijiogan and physostigmine on cycloheximide-induced amnesia were diminished by the combination with scopolamine. These results suggest that Hachimijiogan possesses a wide-ranging pharmacological profile in anti-amnesic actions and that its anti-amnesic activities may be related to the cholinergic neuronal system.

Amnesia↗