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PubMed2004

Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users.

RATIONALE: Ketamine is an N-methyl-d-aspartate (NMDA)-receptor antagonist that is increasingly being used as a recreational drug. Previous research has shown gross generalised verbal memory impairments persisting 3 days after ketamine use in chronic users, however episodic memory has not specifically investigated in this population. OBJECTIVE: To determine whether ketamine, on the night of drug use (day 0) and 3 days later, is associated with impaired episodic memory as assessed by a source memory task. METHODS: Twenty ketamine users and 20 poly-drug controls were compared on a source memory task both on day 0 and 3. Participants also completed questionnaires on both days indexing schizophrenic-like and dissociative symptoms. RESULTS: On day 0, ketamine abusers were impaired on both source memory and item recognition and scored more highly on schizophrenic and dissociative symptom scales compared to poly-drug controls. On day 3 ketamine abusers only displayed source memory impairments and these positively correlated with the level of schizophrenic-like symptoms on day 0. No differences on day 3 in schizophrenic-like or dissociative symptoms were observed. CONCLUSIONS: Ketamine abusers exhibit a persisting deficit in source memory on day 3 but not in item recognition. These findings suggest that repeated use of ketamine produces chronic impairments to episodic memory.

Adolescent↗

PubMed2006

Mnemonic intrusions into working memory in psychometrically identified schizotypal individuals.

Reduced working memory capacity seems to characterize the memory system of individuals from the schizophrenia spectrum. A probabilistic category learning task was designed in order to empirically test the hypothesis that deficient inhibitory control over the contents of working memory may be a fundamental cognitive abnormality of psychometrically identified schizotypal individuals. Two groups of participants were recruited on the basis of their responses on scales measuring psychotic-like experiences in a self-report schizotypy questionnaire. Simple stimuli were presented visually, and participants were instructed to glean the strength of the connection between pairs of stimuli. The experimental task comprised several learning conditions which were designed to assess predictions derived from the inhibition-deficit hypothesis. Working memory-dependent and working memory-independent task conditions allowed to examine the specificity of the putative inhibition deficit. The subjective strength of connections between pairs of stimuli was doubly dissociated as a function of schizotypy (low scorers, high scorers) and learning condition (discriminative, non-discriminative), but only when there was a delay between the to-be-associated stimuli, i.e. when the task was working memory-dependent. The pattern of results is consistent with the inhibition-deficit hypothesis which conjectures that the flow of information through short-term memory features one serious flaw in individuals from the schizophrenia spectrum, namely the occurrence of mnemonic intrusions from long-term memory into working memory.

Cues↗

PubMed2004

Multidisciplinary approaches for investigating the mechanisms of hippocampus-dependent memory: a focus on inbred mouse strains.

Inbred mouse strains differ in genetic makeup and display diverse learning and memory phenotypes. Mouse models of memory impairment can be identified by examining hippocampus-dependent memory in multiple strains. These mouse models may be used to establish the genetic, molecular, and cellular correlates of deficits in learning or memory. In this article, we review research that has characterized hippocampal learning and memory in inbred mouse strains. We focus on two well-established behavioral tests, contextual fear conditioning and the Morris water maze (MWM). Selected cellular and molecular correlates of good and poor memory performance in inbred strains are highlighted. These include hippocampal long-term potentiation, a type of synaptic plasticity that can influence hippocampal learning and memory. Further methods that might help to pinpoint the anatomical loci, and genetic and cellular/molecular factors that contribute to memory impairments in inbred mice, are also discussed. Characterization of inbred mouse strains, using multidisciplinary approaches that combine cellular, genetic, and behavioral techniques, can complement directed mutagenesis to help identify molecular mechanisms for normal and abnormal memory functions.

Animals↗

PubMed2005

Medial temporal lobe structures are needed to re-experience remote autobiographical memories: evidence from H.M. and W.R.

The nature and extent of retrograde amnesia in patients with medial temporal lobe (MTL) lesions is currently under debate. While some investigators propose a temporally limited role for the MTL in episodic and semantic memory, others claim that MTL structures are needed for episodic memories of one's entire lifetime, and that only semantic memory becomes independent of the MTL. To address this issue, we tested two amnesic patients, H.M. and W.R., with bilateral MTL lesions on a series of remote memory tests that together distinguished episodic memory from semantic memory performance. Notably, we used a new method to assess autobiographical memory that measured the degree of re-experiencing of personal happenings from the past. Both patients showed relatively spared semantic memory, but severe impairment on measures of autobiographical memory, with no temporal gradient. Our data support the view that MTL structures play a significant role in recalling specific personal episodes, not only from the recent past but from the distant past as well.

Aged↗

PubMed2005

Different mechanisms of episodic memory failure in mild cognitive impairment.

Mild cognitive impairment (MCI), defined as episodic memory impairment beyond what is expected in normal aging, is often associated with hippocampal atrophy (HA) and may represent incipient Alzheimer's disease. However, recent studies suggest that MCI is very heterogeneous and multiple etiologies likely exist. One possibility is small vessel cerebrovascular disease (CVD). Specifically, we hypothesized that white matter hyperintensities (WMH), an MRI marker for CVD, would lead to impairments in executive control processes critical for working memory that may, in turn, result in episodic memory impairment. To test this hypothesis, we examined a group of subjects clinically diagnosed with MCI and used MRI to further subcategorize individuals as either MCI with severe white matter hyperintensities (MCI-WMH) or MCI with severe hippocampal atrophy (MCI-HA). MCI-WMH, MCI-HA, and matched control subjects each performed a battery of working memory and episodic memory tasks. Results showed that MCI-HA and MCI-WMH were equally impaired on the episodic memory task relative to controls, but MCI-WMH were additionally impaired on tests tapping verbal and spatial working memory abilities and attentional control processes. These results suggest that CVD and hippocampal dysfunction are associated with distinct neuropsychological profiles. Although both syndromes are associated with episodic memory deficits, CVD is additionally associated with working memory and executive control deficits.

Aged↗

PubMed2005

Contrasting roles for beta1, beta2 and beta3-adrenoceptors in memory formation in the chick.

Noradrenaline plays distinct roles in the modulation and consolidation of memory for one-trial, discriminated, avoidance learning in the chick. We have previously shown that activation of beta2-, beta3- and alpha1-adrenoceptors (ARs) by injection into the multimodal forebrain association region (intermediate medial hyperstriatum ventrale [IMHV] or intermediate medial mesopallium [IMM]) is involved in the consolidation of memory 30 min after training and that activation of alpha2-ARs in the caudate putamen plays a role in the reinforcement of memory leading to consolidation in the IMM (IMHV). In this paper we provide evidence that noradrenaline acts at beta1-ARs in the basal ganglia (lobus parolfactorius or medial striatum) in short-term memory processing immediately post-training and demonstrate inhibition of memory by selective AR antagonists at particular times in the sequential memory processing sequence after training. These results support separate roles for beta2- and beta3-ARs in memory consolidation. Our studies suggest that, as a consequence of the learning experience, noradrenaline acts in different brain regions and at different times in memory processing, to enhance memory through distinct populations of ARs.

Adrenergic beta-Agonists↗

PubMed2006

Ketamine affects memory consolidation: differential effects in T-maze and passive avoidance paradigms in mice.

The effects of ketamine, an N-methyl-D-aspartate (NMDA) antagonist, on memory in animals have been limited to the sub-anesthetic dose given prior to training in previous studies. We evaluated the effects of post-training anesthetic doses of ketamine to selectively manipulate memory consolidation, and the effect of pre-retention sub-anesthetic doses of ketamine on memory retrieval in passive avoidance and T-maze tasks in mice. Repeated post-training anesthetic doses of ketamine impaired the consolidation of memory in the T-maze but not in passive avoidance paradigms. This impairment was not permanent but diminished 1-2 days after ketamine withdrawal. Sub-anesthetic post-training doses of ketamine (5 mg/kg) had no effect on memory consolidation, and larger doses (10, 20 and 50 mg/kg) did not influence the retrieval of memory in the T-maze. The data suggest that repeated anesthetic doses of ketamine block NMDA receptors and affect memory consolidation. Moreover, NMDA mechanisms antagonized by ketamine appear to be selectively involved in spatial (T-maze) memory mechanisms but may not be necessary for non-spatial (passive avoidance) memory consolidation.

Animals↗

PubMed2006

Cognitive rehabilitation of memory problems in patients with epilepsy.

People with epilepsy often complain about their memory. Memory deficits are also most commonly observed during neuropsychological evaluation. Many patients with memory problems ask for some kind of memory training. General memory improvement is not possible, but learning mnemonics clearly will help to solve some of the most common everyday memory problems of patients. Most mnemonics follow the general rules for good learning or memory. In the design of a memory rehabilitation program some specific aspect should be taken into account, such as the need for psycho-education into the effects of cognitive deficits in daily life, the impact of personality and emotional reactions, and the individual perception of memory problems. Training goals must be tailor-made, small and as concrete as possible and fully adjusted to the needs and wishes of the patients. Generalization of the learned mnemonics is mostly modest or even absent.

Emotions↗

PubMedDate not supplied

Two further investigations of autobiographical memory in semantic dementia.

A number of investigations in semantic dementia have documented better retrieval of recent personal events compared to those in the more distant past (Graham and Hodges, 1997). Westmacott et al. (2001) challenged this result, however, finding relative preservation of remote memories in a single case of semantic dementia when he was tested using family photographs. In Experiment 1, we tested two possible explanations for the discrepancy between the published papers: (a) that there is a significant effect of modality in autobiographical retrieval in semantic dementia (e.g., patients will show better, or even preserved, remote memory when tested on nonverbal, compared to verbal, tasks); and (b) that the distinct pattern seen between patients is attributable to the different methods adopted for scoring the episodic quality of the memories. A patient with semantic dementia, AM, produced autobiographical memories to both words and family photographs. These personal events were scored by two raters using the scoring method described by Westmacott et al. (2001) and that reported by Graham and Hodges (1997). It was found that AM showed similar levels of remote memory impairment regardless of whether the cue was verbal or nonverbal. In addition, significant effects of time were revealed in AM's performance on the verbal memory test, regardless of which method was used to score the memories. In Experiment 2, we investigated a related question: whether the relatively better retrieval of memories in semantic dementia could be due to over rehearsal of highly salient recent experiences? Four patients were tested on their ability to remember a recent event (either a trip to London or events from a Formula One Grand Prix race) using specially designed autobiographical questionnaires. It was found that all four were able to perform this task, although one patient showed evidence of some forgetting over three months, and another exhibited difficulty discriminating between two similar events. Together, the two experiments further confirm that patients with semantic dementia show a modality independent autobiographical memory deficit, with better retrieval of recent events.

Aged↗

PubMed2000

Prospective remembering of Korsakoffs and alcoholics as a function of the prospective-memory and on-going tasks.

Prospective memory is assumed to rely more on the frontal lobes than retrospective memory. Since Korsakoff patients are known to suffer from a general cerebral atrophy and a frontal lobe atrophy in particular, they are expected to show considerably impaired prospective memory. In Experiment 1, the performance of Korsakoff patients on a semantic prospective-memory task (which was embedded in a perceptual on-going task) was particularly bad in Session 1; in Session 2, the Korsakoff patients improved substantially, to reach the performance level of nonamnesic alcoholics. In Experiment 2, prospective memory of the Korsakoff patients and nonamnesic alcoholics was better when the on-going task was more similar to the prospective-memory task; particularly striking was the much better prospective memory in the semantic prospective-memory task when the on-going task requires a semantic analysis than when the on-going task requires perceptual processing. The findings are in agreement with a task-appropriate processing explanation but also in partial agreement with the attention hypothesis of the instance theory of automaticity. Contrary to the frontal lobe hypothesis, prospective memory of the Korsakoff patients was surprisingly good in several aspects of the two experiments.

Adult↗

PubMed1999

Fractionation of visual memory: evidence from a case with multiple neurodevelopmental impairments.

It is known that the adult visual memory system is fractionable into functionally independent cognitive subsystems, selectively susceptible to brain damage. However, it is unclear whether these cognitive subsystems can fractionate developmentally. The present study describes an investigation of visual memory of a patient (PE) with multiple developmental disorders. PE was congenitally deaf, had Gilles de la Tourette syndrome and autism, with non-verbal ability in the normal range. The patient presented with a recognition memory impairment for unknown human faces. This contrasted with his superior recognition memory for unknown buildings, landscapes and outdoor scenes. PE's memory impairment for faces could not be explained by a general deficit in face processing. Interestingly, PE also showed a recognition memory impairment for animals. These findings indicate that different domains of the visual memory system can be fractionated developmentally. In particular, it demonstrates that topographical memory can develop independently from other aspects of visual memory.

Adult↗

PubMed1988

The effect of scopolamine and physostigmine on working and reference memory in pigeons.

A comparison of the effects of scopolamine and physostigmine on working memory and reference memory in White Carneaux pigeons was undertaken. In Experiment 1, the pigeons received injections of scopolamine hydrobromide (0.03 mg/kg), or saline. Scopolamine hydrobromide had greater disruptive effects on working memory trials than on reference memory trials, and the centrally active form of scopolamine disrupted working memory trial accuracy more than the peripherally active form. The differential sensitivity of accuracy on working memory trials to disruption by central cholinergic blockade was obtained even though the discrimination required on reference memory trials was more difficult. In Experiment 2, the pigeons received injections of scopolamine hydrobromide (0.015 mg/kg), physostigmine (0.075 mg/kg) both scopolamine and physostigmine, or saline. Physostigmine given with scopolamine was able to reverse the scopolamine-induced reduction of accuracy on working memory trials. In neither study did scopolamine promote accelerated forgetting as the delay interval was increased. These results indicate that manipulation of central cholinergic neurotransmitter systems influences working memory processes in the pigeon, but these effects occur without alterations in the ability of the birds to actively maintain information during the retention interval.

Animals↗

PubMed2002

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed.

Amygdala↗

PubMed2003

In-hospital cardiac arrest leads to chronic memory impairment.

OBJECTIVE: To assess the prevalence and severity of memory deficits in a group of patients who survived an in-hospital cardiac arrest (IHCA) in comparison with patients resuscitated after cardiac arrest outside hospital (OHCA) and patients with acute myocardial infarction (MI). SUBJECTS: Thirty-five IHCA survivors, 35 OHCA survivors, and 35 patients who had suffered MI uncomplicated by cardiac arrest. PROCEDURE: Participants were assessed 8.2 (4.5) months after the event for current affective state (Hospital anxiety and depression scale (HADS)), pre-morbid intelligence (National adult reading test (NART)), short-term memory (digit span test) and long-term episodic memory (Rivermead behavioural memory test-RBMT). RESULTS: IHCA patients scored lower on the RBMT than MI controls but did not score significantly differently OHCA patients. Moderate or severe memory impairment was found in 26% of the IHCA group and 38% of the OHCA group. None of the MI group was found to have this degree of impairment. This difference in prevalence of memory impairment between the two cardiac arrest groups was not statistically significant. However, both arrest groups had significantly greater memory impairment than the MI control group. CONCLUSIONS: Clinically important memory impairment was found in one in four patients surviving IHCA. The shorter arrest durations that are thought to be associated with IHCA may not be sufficient to protect patients from memory impairment associated with cerebral hypoxia.

Adolescent↗

PubMed2003

Aging specifically impairs amnesiac-dependent memory in Drosophila.

Age-related memory impairment (AMI) is observed in many species. However, it is uncertain whether AMI results from a specific or a nonspecific decay in memory processing. In Drosophila, memory acquired after a single olfactory conditioning paradigm has three distinct phases: short-term memory (STM), middle-term memory (MTM), and longer-lasting anesthesia-resistant memory (ARM). Here, we demonstrate that age-related defects in olfactory memory are identical to those of the MTM mutant amnesiac (amn). Furthermore, amn flies do not exhibit an age-dependent decrease in memory, in contrast to other memory mutants. The absence of AMI in amn flies is restored by expression of an amn transgene predominantly in DPM cells. Thus, we propose that AMI in flies results from a specific decrease in amn-dependent MTM.

Aging↗

PubMed1989

Distinct memory impairments following electroconvulsive therapy and imipramine.

Memory functioning was assessed in 26 unmedicated patients with major depressive disorder (DSM-III) who were then administered either bilateral electroconvulsive therapy (ECT) (N = 16) or imipramine 200 mg per day (N = 10). The subjects were retested following seven ECT administrations or 21 days of imipramine treatment respectively. The retrograde memory tasks included recall of public and autobiographic events. The anterograde memory tasks included an immediate memory task, a verbal paired-associates recall task, and a non-verbal figure reproduction task. Depression was significantly improved in the ECT-treated subjects but not in those administered imipramine. Both ECT- and imipramine-treated patients showed a deficit in recent anterograde memory relative to their pretreatment performance, but no deficit in immediate memory. ECT-treated patients also had a significant and well-characterized impairment in retrograde remote memory. By contrast, imipramine-treated patients did not show a retrograde memory impairment which could be explained by treatment. The results suggest qualitatively different memory deficits produced by ECT and imipramine.

Depressive Disorder↗

PubMed1999

A naturalistic study comparing the efficacy of a memory enhancement course to a general academic course.

OBJECTIVE: The goal of this study was to compare the effectiveness of a memory improvement course to a course in general psychology. METHODS: Thirty-four healthy elderly persons enrolled in a college memory improvement course for senior citizens, and 33 who enrolled in a parallel course, Introduction to Psychology, were tested on verbal and visual memory prior to and after completing the course. Before they took the course, they were also assessed on subjective memory (self-assessment scale of memory efficacy) and psychological distress (General Health Questionnaire). Changes within and between groups were examined using multivariate analysis of covariance to control for baseline scores. RESULTS: Both groups had similar improvements on all cognitive measures. The memory improvement course group showed very significant correlations between objective and subjective memory. CONCLUSIONS: It appears that participation in academic courses is associated with improvement in certain aspects of cognitive functioning. Awareness of objective memory functioning may be a natural selection factor or a significant motivating factor for healthy elderly to enroll in memory enhancement courses.

Aged↗

PubMedDate not supplied

Memory impairment in Parkinson's disease.

A total of 52 patients with Parkinson's disease (PD), 11 with presumptive Alzheimer's disease (AD), and 20 healthy subjects were studied; subjects were aged 55-74 years. Neurological symptoms were assessed quantitatively, and the state of higher mental processes were evaluated using the Luriya method. A number of memory tests were also used. These studies showed that PD was almost always accompanied by memory impairment exceeding the age norm. The major mechanism for memory impairment in PD without dementia was inadequate independent organization of memory-related activity at the memorizing and retrieval stages. In PD with dementia, there was also a primary impairment. Differences in memory impairments were found in PD with dementia (deeper derangements of involuntary memory and of information processing during memorizing). Impairments of consolidation of traces were more dependent on the age at onset of PD, while inadequacy of independent organization of memory-related activity was more dependent on disease duration. Most memory parameters in PD correlated with the severity of disturbances in gait and postural reflexes. It is suggested that memory impairment in PD is a manifestation of the major pathological process, which shows a number of differences from other neurogeriatric diseases.

Adult↗