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Amnesia produced by anisomycin in an appetitive task is not due to conditioned aversion.

Two experiments investigated the effects of lithium chloride (LiCl) and anisomycin (ANI) in a water reward Y-maze task. In Experiment 1, male CD-1 mice given weak or strong training were injected post-training with either saline or LiCl (150 mg/kg), which has been reported to produce conditioned aversion in mice. One day after training, both LiCl groups avoided the rewarded arm of the maze and drank less water than saline-injected controls. Two days after training, the strongly trained LiCl mice showed avoidance, while both LiCl groups drank less water. In Experiment 2, weakly trained mice given pre- and post-training ANI (30 mg/kg) were amnesic on the second test day compared to mice that received post-trial saline. However, water consumption was increased on the test day for both groups. LiCl produced a different pattern of results than ANI in this task. On the basis of these results, it is suggested that amnesia produced by ANI is due to impaired memory formation and not to conditioned aversion.

Amnesia↗

Oxiracetam prevents the MK-801 induced amnesia for the elevated plus-maze in mice.

We investigated the effect of the nootropic substance oxiracetam on the impairment of memory induced in mice by the non-competitive NMDA antagonist MK-801. Memory capacities of animals having different experience were evaluated using the elevated plus-maze test. Oxiracetam was injected immediately after the acquisition session(s), MK-801 was given 30 min before the retention session which followed 24 h after the acquisition session(s). In slightly experienced animals (Section 3.1), oxiracetam (3 and 30 mg/kg, s.c.) prevented MK-801 (0.15 mg/kg, i.p.) induced memory deficits characterized by a prolongation of the transfer latency. In well-trained animals (Section 3.2), oxiracetam (30 mg/kg, s.c.) attenuated MK-801 (0.15,0. 25 and 0.4 mg/kg, i.p.) induced amnesia for a spatial orientation in the elevated plus-maze. These results show that oxiracetam interacted with the glutamatergic NMDA receptor system and forestalled the impairment of retrieval of long-term memory. The results also justify the usage of the elevated plus-maze method in the evaluation of potential anti-amnesic or nootropic drugs.

Amnesia↗

Engram activation reinstates the susceptibility of consolidated memory traces to retrograde amnesia by functional blockade of parabrachial nuclei.

Previous studies have shown that in rats the acquisition of a step-through passive avoidance reaction (PAR) in the light-dark box apparatus is disrupted by tetrodotoxin (TTX) inactivation of the parabrachial nuclei (PBN) 24 but not 48 h after the acquisition trial. The present experiment shows that TTX induces retrograde amnesia even when applied to the PBN 48 h after PAR acquisition only if it is preceded by a 30-min confinement (extinction) or by a footshock (retraining) in the dark compartment. These stimuli, independently of their sign, induce quantitatively comparable TTX disrupting effects. This happens notwithstanding the fact that these stimuli are too weak to modify PAR under control conditions. This paradoxical finding suggests that engram vulnerability may not be a simple inverse function of its recency but that it may reflect a reactivation of the neural circuits involved in memory trace formation. Consolidated engrams become again vulnerable only when contextual cue stimuli are presented shortly before the application of the disrupting procedure.

Amnesia, Retrograde↗

The objective assessment of amnesia in dissociative identity disorder using event-related potentials.

Assessment of amnesia in Dissociative Identity Disorder (DID) typically relies on self-report, the veracity of which cannot often be independently verified. Memory in DID was therefore assessed using an objective method that involved event-related potentials (ERPs) as well as indirect behavioral measures of memory, and that provided statistically supported assessments for each participant. Four participants who met DSM-IV criteria for DID participated in an ERP memory assessment task, in which words learned by one identity (identity A) were then presented to a second identity (identity B). All four participants - tested as identity B - produced ERP and behavioral evidence consistent with recognition of the material learned by identity A. While it would be premature to generalize all cases of DID, the results suggest that there may be reasons to question the veracity of reports by individuals who meet diagnostic criteria for DID on the basis of a structured clinical interview.

Adult↗

P300 correlates of simulated malingered amnesia in a matching-to-sample task: topographic analyses of deception versus truthtelling responses.

Two experiments using a P300-enhanced Forced Choice Procedure (P3FCP) investigated simulated amnesia in a matching-to-sample task. In Experiment 1, successful manipulation of subjects towards different behavioral hit rates (75-80% vs. 85-90%) did not adversely affect the diagnostic sensitivity of match-mismatch Pz-P300 amplitude analyses, allowing detection of 69% of simulators. P300 amplitudes of simulators (Malinger group) were as large as those of truth-tellers (truth group, a control), indicating no dual task-related (Malingering) reduction across different behavioral hit rates. Experiment 2 found no main effect of oddball type, match vs. mismatch, on P300 (P3) amplitude with a mismatch-rare variant of the P3FCP. This study also revealed larger Pz-P3s in the Malingering (vs. Truth-telling) condition. Subsequent topographic analyses suggested different Truth and Malinger scaled P3 amplitude topographies in both these sets of P3FCP data and in those from a previous autobiographical memory paradigm. Further analysis yielded preliminary evidence for a common deception-related P3 amplitude topography across different paradigms/conditions.

Adult↗

Amnesia and Alzheimer's disease: which neurotransmitter system is responsible?

The cholinergic, noradrenergic, and serotonergic neurotransmitter systems show a consistent pattern of degeneration associated with Alzheimer's disease (AD) and, to a lesser extent, normal aging. The review articles in this section draw a relation between degeneration of one or more of these systems and impairments in learning and memory. Cholinergic hypofunction may underlie the amnesia associated with AD but not that associated with normal aging. The relevance of impaired serotonergic or noradrenergic function to any cognitive impairment associated with aging or AD remains undetermined.

Alzheimer Disease↗

Transient global amnesia and migraine in young people.

Two cases of transient global amnesia (TGA) in a 16-year-old boy and in a 13-year-old girl are reported; both occurred during competitive sport and were associated with migraine. TGA in young people could provide crucial information on the still equivocal pathogenesis, a vascular thromboembolic hypothesis being untenable in such cases. A migrainous mechanism is likely to underlie TGA in young people and "pure' TGA in general. TIA or stroke, like epilepsy or other pathological conditions, should concern the differential diagnosis of transient amnestic episodes rather than the pathogenesis of TGA.

Adolescent↗

Transient global amnesia: concomitant episodic memory and positron emission tomography assessment in two additional patients.

Transient global amnesia (TGA) is characterized by a profound but transient deficit of episodic memory. The study of cerebral blood flow and oxygen metabolism with positron emission tomography (PET) provides relevant pathophysiologic data, but only three patients have been reported so far and in only one was concomitant neuropsychological testing performed. We report here the concomitant neuropsychological and PET assessment of two additional patients. Episodic disturbance was characterized by a storage disturbance for one case and an incapacity to learn episodic associations in the other, illustrating cognitive heterogeneity despite similar neurological presentation. PET findings disclosed mild but significant changes in the amygdala (right or left) and left posterior hippocampus, which could account for both the storage disturbance and the inability to associate episodic components. The PET findings also argued in favor of a vascular disturbance accompanying TGA.

Aged↗

Delayed-onset amnesia caused by protein synthesis inhibition in odor-taste associative memory of the terrestrial slug Limax valentianus.

The terrestrial slug Limax avoids the odor of innately preferred food after it is presented with the aversive taste of quinidine. This type of associative memory persists for several weeks. We investigated effects of protein synthesis inhibitors on the retention of this odor-taste associative memory. Anisomycin or cycloheximide applied to the slug 30 min prior to conditioning impaired the memory retention as late as two or more days after the conditioning, while the retention of a short-term memory was normal for up to 24 h. In contrast, the inhibition of protein synthesis by these inhibitors decays within several hours. In Limax, the onset of amnesia is unusually delayed when protein synthesis is suppressed at the time of conditioning.

Amnesia↗

The GABA-B antagonist CGP 36742 prevent PTZ-kindling-provoked amnesia in rats.

Deficit in active and inhibitory avoidance behaviour has been found in pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the GABA B antagonist CGP 36742 on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in CGP 36742-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of CGP 36742 is considered. The favourable effect of the GABA B antagonist in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice.

Amnesia↗

Effect of the calcium channel blockers nifedipine and diltiazem on pentylenetetrazole kindling-provoked amnesia in rats.

A large body of research supports the view that memory disturbance is an integral part of epilepsy. Deficit in various behaviour tasks has been found in rats subjected to experimental epilepsy-pentylenetetrazole (PTZ) kindling. In the present study we examined the effect of post-training administered calcium channel blockers nifedipine (10 and 40 mg/kg) and diltiazem (10 and 30 mg/kg) on amnesia induced by PTZ kindling in shuttle-box- and step-down-trained rats. Retention in nifedipine- or diltiazem-treated kindled animals was significantly improved compared to the kindled controls. The mechanisms of action of calcium antagonists studied is considered. Taken together with the data about calcium channel blocker anticonvulsive activity, the results of this study further suggest that nifedipine and diltiazem might be useful in the treatment of cognitive disorders in epileptic patients.

Amnesia↗

Piracetam and fipexide prevent PTZ-kindling-provoked amnesia in rats.

Deficit in active and inhibitory avoidance behaviour has been pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the nootropic drugs piracetam and fipexide on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in piracetam- and fipexide-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of the two drugs are considered. The favourable of nootropic drugs in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice.

Amnesia↗

Transient global amnesia of epileptic origin accompanied by fever.

The case of a previously healthy 69-year-old female patient is described who presented, in a period of 6 months, 3 long-lasting (from 2 hour- to 10 hour-duration) episodes of transient global amnesia accompanied by a temperature rise. During one of these episodes an EEG was obtained, showing a diffuse alteration, focal slowing, and bitemporal asynchronous paroxysmal activity giving rise to electrical ictal discharges. Interictal EEGs were normal. Cerebral computed tomography was normal. Carbamazepine was given with complete control of the attacks. These episodes may be interpreted as complex partial status with unusual semeiology.

Aged↗

New insights into transient global amnesia: recent imaging and clinical findings.

Transient global amnesia (TGA) is one of the most striking syndromes in clinical neurology. Despite several new hypotheses concerning TGA pathogenesis-including psychological disturbances, personality traits, and hypoxic-ischaemic origin associated with venous congestion in memory relevant structures or small vessel changes-there is no consensus about the cause. New imaging techniques, particularly diffusion-weighted imaging, open up new insights into the location of TGA pathology. Studies with dynamic venous duplex sonography confirmed the importance of jugular-vein-valve insufficiency. We review these new findings and their implications for a better understanding of this remarkable syndrome. Although we still do not have all the answers, the use of new imaging modalities, neuropsychological findings, and epidemiological data may in future help to unravel the origin of TGA.

Amnesia, Transient Global↗

Priming deficits in amnesia: now you see them, now you don't.

The rate with which perceptual information becomes available was manipulated in 2 word naming experiments. Word priming effects, in terms of reduced naming latencies for repeated items, and recognition memory measures were obtained with matched groups of amnesic patients and control participants. In both experiments, the amnesic patients evidenced significantly reduced priming effects compared to control participants under difficult task conditions. Under easy task conditions the baseline naming latencies of the amnesics were significantly longer than those of controls, but the difference in priming effects failed to reach significance. The findings are consistent with the Information Availability model of priming positing that both priming and explicit memory are mediated by episodic information from a study or information processing episode. It is argued that word priming does not represent a memory function that is spared in amnesia.

Adult↗

Synthesis and amnesia-reversal activity of a series of 7- and 5-membered 3-acylamino lactams.

A series of 3-(acylamino)-epsilon-caprolactams and 3-(acylamino)-2-pyrrolidinones was synthesized. Some of these compounds reversed at different degrees electroconvulsive shock- and Scopolamine-induced amnesia, using a step-through passive avoidance in mice. Classical nootropic drugs, i.e., Aniracetam, Oxiracetam, and Piracetam, were used as reference compounds. Within the analyses of data performed, we introduced a new parameter, the confrontation index (CI), which is a function of Mann-Whitney's U statistic. The CI permits a common scale of activity of substances to be generated, independently of probabilistic hypotheses, with higher scores representing higher activities. The most active compounds were characterized by the formylamino and [3-(trifluoromethyl)benzoyl]amino groups in the 3-position of the ring. None of the substances assayed showed any effect on spontaneous behavior and neurovegetative system.

Amnesia↗

Amnesia-reversal activity of a series of cyclic imides.

A series of dihydro-1H-pyrrolizine-3,5(2H,6H)-diones were synthesized and evaluated for their ability to reverse electroconvulsive shock (ECS) induced amnesia in mice. Among the structure-activity relationships explored were the effects of ring size, the presence of heteroatoms (sulfur) in the ring system, and the introduction of alkyl substituents. The optimal ring size for the bicyclic system was 5.5 with dihydro-1H-pyrrolizine-3,5(2H,6H)-dione (3), although some activity was present in the corresponding 5.6 [hexahydro-3,5-indolizinedione (7)] and 6.6 [tetrahydro-2H-quinolizine-4,6(3H,7H)-dione (9)] analogues. Replacement of the C-1 carbon atom in compound 3 with a sulfur [dihydropyrrolo[2,1-b]thiazole-3,5(2H,6H)-dione (10)] abolished activity, and the introduction of methyl groups resulted in poorer biological profiles except when the substitution was made at the 7a position [dihydro-7a-methyl-1H-pyrrolizine-3,5(2H,6H)-dione (4)]. In several instances, hydrolysis of the parent bicyclic compound was carried out to furnish the corresponding lactam acids, which were further derivatized. Several exhibited interesting activity, especially the 5-oxo-2-pyrrolidinepropanoic acid derivatives such as 5-oxo-2-pyrrolidinepropanoic acid (12), 5-oxo-2-pyrrolidinepropanoic acid phenylmethyl ester (17), 5-oxo-2-pyrrolidinepropanoic acid (3-chlorophenyl)methyl ester (20), N-4-pyridyl-5-oxo-2-pyrrolidinepropanoic acid amide (25), and N-(2,6-dimethylphenyl)-5-oxo-2-pyrrolidinepropanoic acid amide (27). Compound 3 (CI-911; rolziracetam) was also observed to improve performance on a delayed-response task in aged rhesus monkeys and was selected for evaluation in cognitively impaired human subjects on the basis of its biological profile and a wide margin of safety in animals.

Amnesia↗

Transient global amnesia (TGA) in an MEG study.

A patient who had experienced an attack of transient global amnesia (TGA) was examined using neurophysiological methods. Magnetoencephalography (MEG) was performed and the Wechsler Memory Scale-Revised (WMS-R) test was administered at 5 days and at more than a month after the TGA episode. MEG data on neuronal activity obtained while the patient was undertaking a working memory task and during rest were analyzed using the wavelet-crosscorrelation method, which reveals time-lag and information flow between related sites in the brain. The WMS-R memory scores showed dramatic improvement when the test was administered a month following the attack, although no significant changes were observed in EEG, MRI and SPECT data. The MEG study revealed that under a working memory load how the neuron works functionally and the information propagates assembly within the right hemisphere, and that these brain functions were not performed adequately shortly after the TGA attack.

Amnesia, Transient Global↗