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Hypothermia-induced anterograde amnesia: is memory loss attributable to impaired acquisition?

The present investigation examined whether the poor test performance observed in studies of anterograde amnesia reflects a memory deficit or is a by-product of weaker initial learning resulting from impaired sensory, motivational, or associative processes. Two experiments were performed which utilized latent extinction (Experiment 1) and delay of punishment (Experiment 2) manipulations in order to assess the nature of original learning in rats trained under either hypothermic (29 degrees C) or normothermic conditions. Results from both experiments provided evidence that hypothermia treatment administered prior to training had relatively little influence on the animal's ability to acquire a passive avoidance response. Therefore, the rapid forgetting observed in hypothermia-induced anterograde amnesia is most likely due to memory deficits rather than an artifact of poorer acquisition.

Amnesia↗

Passive avoidance learning produces focal elevation of bursting activity in the chick brain: amnesia abolishes the increase.

Presentation of a bright bead to day-old chicks (Gallus domesticus: Ross 1 Chunky Chicks) elicits spontaneous pecking. If the bead is coated with an aversive substance (e.g., methylanthranilate), they will avoid similar beads subsequently; if it is coated with water, they peck avidly on re-presentation. Formation of a memory for this one-trial passive avoidance task is unaffected by subconvulsive transcranial electroshock when applied 10 min after training in 60% of birds, whereas "immediate" post-training electroshock renders 63% of chicks amnesic. Memory formation and retention is associated with a large bilateral enhancement in trained over control chicks (320 and 350% in left and right hemispheres, respectively; p less than 0.001) of a particular spontaneous multi-unit activity firing pattern, that is, short-duration (15-40 ms) bursts of large-amplitude (greater than or equal to 200 microV, 450 microV max p-p), high-frequency (400-450 Hz) spiking in anesthetized chicks. This effect is observed in data lumped from 1-13 h after training and is restricted to the intermediate medial hyperstriatum ventrale. When chicks are rendered amnesic by electroshock immediately following training, there is a complete abolition of this increase in burst firing; in those chicks where this treatment fails to elicit amnesia, the increase in bursting is still observed. In birds in which the shock is delayed and memory formation occurs, the increase in bursting activity is maintained; however, if the delayed shock produces apparent amnesia, then the increase is once again abolished. The electroshock had no effect on bursting per se in untrained chicks. There was no significant difference in tonic spiking between the chicks. A marked increase in the occurrence of bursting epochs in the IMHV of anesthetized chicks following passive avoidance training is therefore closely associated with memory formation, but not with the nonspecific concomitants of the training procedure.

Amnesia↗

Anesthesia induced retrograde amnesia is ameliorated by ephrinA5-IgG in mice: EphA receptor tyrosine kinases are involved in mammalian memory.

EphA receptors and their ephrin-A ligands were previously thought to play a role only in embryonic development of the brain. Recently, however, these proteins were shown to be expressed in the adult mouse brain, primarily in the hippocampus, and were implicated in hippocampal synaptic plasticity and learning. What aspects of learning EphA receptors mediate have not been studied? Using the fear conditioning paradigm we demonstrate that EphA receptors play roles in memory. We show that post-training surgical anesthesia leads to robust context specific retrograde amnesia in mice, and post-anesthesia activation of EphA receptors induces a significant amelioration of this amnesia. As acquisition was left unaffected and performance factors were found unaltered, we suggest that the amelioration was due to changes in cognition leading to improved memory. Our data represent the first pieces of evidence for the involvement of EphA receptor tyrosine kinase receptors in mammalian memory, a finding that opens a new avenue into the functional analysis of the largest receptor tyrosine kinase subfamily in the brain.

Amnesia, Retrograde↗

ED evaluation of transient global amnesia.

Transient global amnesia is an unusual syndrome involving a transient memory loss and inability to form new memories, without affecting other cognitive functions. Although the patient often lacks insight into the problem, the syndrome is very frightening for family members, who frequently present to the ED. The evaluation of the syndrome is the subject of some controversy. This review presents current understanding about the causes of transient global amnesia and an approach to the ED evaluation of the syndrome.

Amnesia↗

Memory impairment in amnesia and dementia: implications for the use of animal models.

Cases of amnesia, in which there is a stable memory impairment with sparing of other cognitive functions, have taught us a great deal about the neuroanatomic basis of memory storage and retrieval; animal models of amnesia have provided even more precise information about the brain mechanisms responsible for specific aspects of memory functioning. Amnestic syndromes are rare, however, and constitute only a tiny fraction of the clinical cases in which memory is impaired. Dementia, particularly that due to Alzheimer's disease, is much more common but differs from the amnestic syndromes in three important ways: (1) a variety of of cognitive functions including language and praxis are affected, (2) the condition is usually progressive with gradual loss of several neuronal populations, and (3) the etiology of dementia is not well understood at present but clinical data suggest some role for genetic, viral, vascular and toxic environmental factors. It is argued that animal models should give greater attention to these important features of the common clinical dementias.

Amnesia↗

Preservation of autobiographical memory in a case of pure progressive amnesia.

G.D., a 79 year-old female, presents with a severe and slowly progressive amnesia although she remains entirely independent in daily life and is perfectly well spatially oriented. Her amnesia is relatively isolated and her deficit does not embrace other cognitive domains. G.D. underwent extensive neuropsychological evaluation including language, executive functions, perceptual, and memory tests. Based on clinical observation, the purpose of this study was to determine whether there was a dissociation between her autobiographical and semantic memory. Results point out a severely degraded semantic knowledge of famous public events and persons while autobiographical memory of personally experienced and relevant information remains intact. Results from this study and from previous studies seem to suggest that relative sparing of hippocampal structures may be related to the preservation of autobiographical memory.

Aged↗

Amnesia following infarction in the right retrosplenial region.

We present a case of retrosplenial amnesia following an infarction in the right retrosplenial region. A 62-year-old male showed mild weakness of the left hand, dizziness and gait disturbance. He also noticed that he could not perceive objects that he saw as real, but could perceive an object as real only by touching it. Magnetic resonance imaging (MRI) showed an infarction in the splenium of the corpus callosum and retrosplenial region on the right side. There was no aphasia or apraxia, but mild topographic disturbance was present. Intelligence was normal, but amnesia was noted. Both verbal and visual memory were disturbed equally. This case suggests that memory plays a role in the right retrosplenial region.

Amnesia↗

Sigma1 (sigma 1) receptor agonists and neurosteroids attenuate B25-35-amyloid peptide-induced amnesia in mice through a common mechanism.

The sigma1 (sigma 1) receptor agonists exert potent anti-amnesic effects, as they apparently block the learning impairments either induced by the muscarinic receptor antagonist scopolamine, the N-methyl-D-aspartate receptor antagonist dizocilpine or inherently due to the age-related deficits in senescence-accelerated mice. We recently described the amnesia induced by the beta-amyloid-related peptide beta 25-35, administered centrally in an aggregated form, in mice. The deficits were sensitive to cholinomimetics or to N-methyl-D-aspartate/glycine modulatory site agonists. Herein, we examined the effects of sigma 1 receptor ligands on the beta 25-35 peptide-induced amnesia. The effects of neuro(active) steroids, which interact in vitro and in vivo with sigma 1 receptors were examined in parallel. Mnesic capacity was evaluated seven days after administration of aggregated beta 25-35 peptide (3 nmol), using spontaneous alternation in the Y-maze for spatial short-term memory, or after 14 days, using the step-down type passive avoidance test for long-term memory. The sigma 1 receptor agonists (+)-pentazocine, PRE-084, or SA4503 attenuated, in a dose-dependent and bell-shaped manner, the beta 25-35 peptide-induced deficits on both tests. These effects were antagonized by haloperidol or BMY-14802, confirming the sigma 1 receptor pharmacology. Pregnenolone, dehydroepiandrosterone, and their sulphate esters, but not progesterone, also dose-dependently attenuated the beta 25-35 peptide-induced deficits. Progesterone blocked the beneficial effects of each other neurosteroid, behaving as an antagonist. Furthermore, haloperidol blocked the effects induced by neurosteroids, whereas progesterone antagonized the effects of the non-steroidal sigma 1 receptor agonists, showing a clear crossed pharmacology of different drug classes. These results demonstrate that: (i) the anti-amnesic effect of sigma 1 receptor agonists may be of therapeutic relevance in pathological states affecting the cholinergic and/or glutamatergic systems, such as in pathological aging; (ii) neurosteroids play an important role in learning processes and may collectively constitute a therapeutic target; (iii) the interaction between sigma 1 systems and neurosteroids appears indeed of behavioural relevance.

Amnesia↗

Functional anatomical study of psychogenic amnesia.

Psychogenic amnesia is characterized by an inability to recall information already stored in the patient's memory. It is usually related to a stressful or traumatic event that cannot be explained by manifest brain damage. To examine the underlying functional disturbance of brain areas in this condition, we performed a positron emission tomography (PET) activation study on a psychogenic amnesic patient and on 12 normal control subjects. A task requiring explicit retrograde memory of faces was compared with a control task. To assess functional modifications associated with the processes of recovery, a second PET study was performed on the patient 12 months after onset. During the task, activation of the right anterior medial temporal region including the amygdala was increased in the psychogenic amnesic patient. Activation of the bilateral hippocampal regions increased only in the control subjects. During recovery, the right anterior medial temporal region became less active while the right hippocampal region became more active. Activation levels also differed in the anterior cingulate cortex, prefrontal cortex and some other cortical regions between control subjects and the patient. These findings suggest that the changes in these limbic and limbic-cortical functions are related to symptoms of the psychogenic amnesia.

Adult↗

Memory consolidation, retrograde amnesia and the hippocampal complex.

Results from recent studies of retrograde amnesia following damage to the hippocampal complex of human and non-human subjects have shown that retrograde amnesia is extensive and can encompass much of a subject's lifetime; the degree of loss may depend upon the type of memory assessed. These and other findings suggest that the hippocampal formation and related structures are involved in certain forms of memory (e.g. autobiographical episodic and spatial memory) for as long as they exist and contribute to the transformation and stabilization of other forms of memory stored elsewhere in the brain.

Amnesia↗

Decursin from Angelica gigas mitigates amnesia induced by scopolamine in mice.

We previously reported that a total methanolic extract of the underground part of Angelica gigas Nakai (Umbelliferae) (here-in-after abbreviated AG) significantly inhibited acetylcholinesterase (AChE) activity. We characterized 12 coumarin derivatives including both decursin and decursinol from extracts of AG. In this study, we evaluated the anti-amnestic activity of decursin, a major coumarin constituent isolated from AG, in vivo using ICR mice with amnesia induced by scopolamine (1 mg/kg body weight, s.c.). Decursin, when administered to mice at 1 and 5 mg/kg body weight i.p., significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance test and the Morris water maze test. Moreover, decursin significantly inhibited AChE activity by 34% in the hippocampus of treated mice. These results indicate that decursin may exert anti-amnestic activity in vivo through inhibition of AChE activity in the hippocampus.

Acetylcholinesterase↗

Inter-identity amnesia in dissociative identity disorder: a simulated memory impairment?

BACKGROUND: Although included in the current edition of the DSM, there does not seem to be consensus among mental health professionals regarding the diagnostic status and scientific validity of dissociative identity disorder (DID). This study was aimed at the detection of simulation of inter-identity amnesia in DID. METHOD: A sample of 22 DID patients was included, together with a matched control sample of subjects instructed to simulate inter-identity amnesia, a guessor group that had no knowledge of the stimulus material and a normal control group. A multiple-choice recognition test was included. The rate of incorrect answers was determined. Moreover, the specific simulation strategy used was examined by providing subjects with a range of choices that varied in extent of disagreement with the correct answer and determining whether plausible or implausible answer alternatives were selected. RESULTS: On the recognition test DID patients selected incorrect answers above chance like simulators. Patients thus seem to use their knowledge of the correct answer in determining their given answer. They were not characterized by a well-thought-out simulating behaviour style, as indicated by the differences in selection of specific answer alternatives found between patients and simulators. CONCLUSIONS: DID patients were found not to be characterized by an actual memory retrieval inability, in contrast to their subjective reports. Instead, it is suggested that DID may more accurately be considered a disorder characterized by meta-memory problems, holding incorrect beliefs about their own memory functioning.

Adult↗

Enhanced emotion-induced amnesia in borderline personality disorder.

BACKGROUND: Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion-episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. METHOD: To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. RESULTS: BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. CONCLUSION: These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD.

Adult↗

The course of post-traumatic amnesia: three little words.

OBJECTIVE: To provide a simple means of "real time" recognition of emergence from post-traumatic amnesia (PTA). METHODS: Ninety-one patients with traumatic brain injury (PBI); 53 minor (GCS 13-15), 19 moderate (GCS 9-12), 18 severe (GCS 3-8). Twenty-seven control subjects treated at two regional trauma units for their acute phase and followed in a hospital-based research institute were studied prospectively. Subjects were examined repeatedly following injury with the Galveston Orientation and Amnesia Test (GOAT) and tests of their ability to learn and retain new information. Word triplets balanced for concreteness and frequency were presented. Immediate and 24-hour recall were tested. If 24-hour recall was imperfect, recognition was tested by presenting the 3 target words and 6 distracters. The target words were then re-presented and recall was tested the next day. The time intervals to first perfect recognition and first free perfect recall were compared with the patients' first GOAT score of 75 or greater on 2 successive days. Simple line drawings of common objects were also presented to the subjects using an identical paradigm. The outcome measures were GOAT, 3-word recognition and recall, 3 picture recognition and recall. RESULTS: For all categories of head injury severity, the median interval to perfect free recall of words followed the achievement GOAT criterion by a significant interval. The mean GOAT scores for perfect 3-word recall and recognition corresponding to minor, moderate and severe injuries were 97, 90 and 88, and 97, 76 and 68 respectively. The recognition and recall of pictures preceded the recognition and recall of words by approximately 1 day. CONCLUSIONS: The orientation measures of the GOAT that contain material that the patient knew prior to injury obscure the determination of recovery of continuous memory and should be tested separately. Three-word recall which is simpler to administer than the GOAT is a more reliable measure of emergence from PTA. For patients who are dysphasic or who do not share a common language with the examiner, 3-picture recognition and recall may substitute for word recognition and recall.

Adolescent↗

Magnetic resonance imaging changes in a patient with migraine attack and transient global amnesia after cardiac catheterization.

The presence of magnetic resonance imaging (MRI) abnormalities in patients with transient global amnesia has been an interesting phenomenologic finding. Several theories surround the occurrence of this syndrome, but little is known about its true physiopathology. We present a case of transient global amnesia after cardiac catheterization associated with migraine headache and MRI changes compatible with an ischemic insult. A discussion on potential explanations for this finding is made, as well as a review of the pertinent literature.

Amnesia, Transient Global↗

Dissociation of implicit and explicit knowledge in a case of psychogenic retrograde amnesia.

There have been few studies of psychogenic amnesia based on a cognitive or neuropsychological framework. In the present study, a patient with acute onset of profound psychogenic retrograde amnesia was examined. Although her performance on neuropsychological tasks revealed intact anterograde memory, language functioning, visuospatial and constructional skills, and mental speed and flexibility, she displayed severe impairments on a variety of retrograde memory tasks. Furthermore, initial observations revealed inconsistencies between the patient's recall of semantic knowledge on direct questioning and her ability to demonstrate the use of this knowledge on indirect tasks. To test this formally, we devised an indirect remote knowledge task to examine a possible dissociation between explicit and implicit memory. Two healthy subjects matched for age, gender, education, occupation, and estimated IQ were also tested. As predicted, the findings demonstrate implicit knowledge despite impaired explicit recall for the same material.

Amnesia, Retrograde↗

Comparison of the serial position effect in very mild Alzheimer's disease, mild Alzheimer's disease, and amnesia associated with electroconvulsive therapy.

Individuals given a series of words to memorize normally show better immediate recall for items from the beginning and end of the list than for mid-list items. This phenomenon, known as the serial position effect, is thought to reflect the concurrent contributions of secondary and primary memory, respectively, to recall performance. The present study compared the serial position effects produced on Trial 1 of the California Verbal Learning Test (CVLT) in mildly demented (N = 25; M MMSE = 20.0) and very mildly demented (N = 25; M MMSE = 25.5) patients with Alzheimer's disease (AD), and age- and education-matched normal control (NC) participants (N = 50). In addition, the serial position effects of the very mildly demented AD patients were compared to those of patients with a transient, circumscribed amnesia arising from a prescribed series of electroconvulsive therapy (ECT) treatments for the relief of depressive illness (N = 11). While the NC group exhibited the typical serial position effect, AD patients recalled significantly fewer words than NC participants overall, and exhibited a significantly reduced primacy effect (i.e., recall of the first 2 list items) with a normal recency effect (i.e., recall of the last 2 list items). Patients with circumscribed amnesia due to ECT were as impaired as the very mildly demented AD patients on most standard CVLT measures of learning and memory, but exhibited primacy and recency effects, which were within normal limits. These results suggest that a reduction in the primacy effect, but not the recency effect, is an early and ubiquitous feature of the memory impairment of AD. It is not, however, a necessary feature of all causes of memory impairment.

Adult↗

Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam.

A series of N-[(dialkylamino)alkyl]-2-oxo-1- pyrrolidineacetamides was synthesized. The title compounds reversed electroconvulsive shock (ECS) induced amnesia in mice when administered subsequent to the ECS treatment and were inactive in a general observational test for central nervous system (CNS) activity. Active compounds exhibited an inverted U-shaped dose-response curve. Among the compounds with the broadest dose-response curve, as well as the most potent, were those with the N-[2-[bis(1-methylethyl)amino] ethyl] or 2,6- dimethylpiperidinoethyl residues as amide substituent. The N-(dialkylamino) substituent markedly enhances amnesia-reversal activity, with ethylene providing the optimal chain length. N-[2-[Bis(1-methylethyl)amino]ethyl] -2-oxo-1- pyrrolidineacetamide N-(dialkylamino) substituent was selected for preclinical toxicological evaluation, assigned the investigational number CI-879 and the U.S. adopted name ( USAN ) pramiracetam . Pramiracetam demonstrated a wide margin of safety in animals and was well tolerated in normal human volunteers. It has shown encouraging activity in an open label trial in patients with primary degenerative dementia (PDD or senile dementia of the Alzheimer's type).

Amnesia↗