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PubMed2005

Orexin-saporin lesions of the medial septum impair spatial memory.

The medial septum and diagonal band of Broca (MSDB) provide a major input to the hippocampus and are important for spatial learning and memory. Although electrolytic MSDB lesions have prominent memory impairing effects, selective lesions of either cholinergic or GABAergic MSDB neurons do not or only mildly impair spatial memory. MSDB neurons are targets of orexin-containing neurons from the hypothalamus. At present, the functional significance of orexin afferents to MSDB is unclear, and the present study investigated a possible involvement of orexin innervation of the MSDB in spatial memory. Orexin-saporin, a toxin that damages neurons containing the hypocretin-2 receptor, was administered into the MSDB of rats. Rats were subsequently tested on a water maze to assess spatial reference memory and a plus maze to assess spatial working memory. At 100 ng/microl, orexin-saporin destroyed primarily GABAergic septohippocampal neurons, sparing the majority of cholinergic neurons. At 200 ng/microl, orexin-saporin almost totally eliminated GABAergic septohippocampal neurons and destroyed many cholinergic neurons. Spatial reference memory was impaired at both concentrations of orexin-saporin with a dramatic impairment observed for 24-h retention. Short-term reference memory was also impaired at both concentrations. Rats treated with 200 ng/microl, but not 100 ng/microl, of orexin-saporin were also impaired on a spontaneous alternation task, showing a deficit in spatial working memory. Our results, together with previous studies, suggest that orexin innervation of the MSDB may modulate spatial memory by acting on both GABAergic and cholinergic septohippocampal neurons.

Animals↗

PubMed2004

Accelerated senescence prone mouse-8 shows early onset of deficits in spatial learning and memory in the radial six-arm water maze.

Available data indicate that the senescence-accelerated prone mouse 8 (SAMP8) is an appropriate model of brain aging, with impairments in nonspatial learning and memory beginning as early as 2 months of age, and spatial learning and memory deficiencies not becoming apparent until after 4 months of age. However, with other strains (e.g., C57BL mice), the impairment in spatial memory was found earlier than that in nonspatial memory. We considered the possibility that the observed differences could be due to strain-specific differences in the training equipment. In the present study, a new optimized testing apparatus-the radial six-arm water maze (RAWM)-for detecting spatial learning and memory in mice, was employed, to determine whether there is impairment of spatial learning and memory in young SAMP8. The relationship between the spatial learning measures observed with the RAWM and the Morris maze, a classic spatial learning and memory testing apparatus, was also explored. It was found that, in the RAWM, rather than in the Morris maze, the impairment in spatial learning could be measured in SAMP8 mice as early as 3 months old, and the impairment in spatial memory in SAMP8 mice aged 5 months. These results suggested that the spatial learning and memory deficiencies could be found in early life of SAMP8 mice, and that RAWM and Morris maze each detect different aspects of spatial learning and memory.

Aging↗

PubMed2004

Depressed mood and memory impairment in temporal lobe epilepsy as a function of focus lateralization and localization.

OBJECTIVE: Memory disorders and depressed mood are prominent psychological symptoms of temporal lobe epilepsies (TLEs). We examined the interaction of depressive mood and memory as a function of focus localization. METHODS: One hundred fifty-two TLE patients with right mesial (n=37, RTLE-AHS), right lateral (n=31, RTLE-LAT), left mesial (n=42, LTLE-AHS), and left lateral (n=42, LTLE-LAT) lesions and epilepsies underwent comprehensive presurgical evaluation and neuropsychological assessment of mood and memory. Univariate and multivariate analyses of covariance (ANCOVAs) and partial correlation analyses were performed to reveal interactions of depression and memory as a function of focus localization. RESULTS: No differences between the study groups were revealed for depression, indicating a general risk of 30% for depressed mood (BDI>12) in patients with TLE. ANCOVAs revealed significant main effects of focus side (left: verbal learning deficits; right: figural learning deficits) and site (mesial at disadvantage) on learning and memory scores. Correlation analyses revealed interactions between memory and mood only in LTLE-LAT patients. CONCLUSIONS: Although the data provide evidence that side and site of the epileptogenic region differentially affect material specific memory performance, there was no evidence of a specific temporal target region for depressive mood. In the majority of the patients, depressed mood and memory impairment appeared as independent rather than as related symptoms of TLE. In LTLE-LAT, however, mood was significantly related to verbal and figural memory performance. Epilepsy-driven pathological left temporofrontal circuits are discussed as a prerequisite for the coupling of mood disorders and memory impairment in this specific patient subgroup which is also known from the psychiatric major depression syndrome.

Adult↗

PubMedDate not supplied

Contributions of thalamic nuclei to declarative memory functioning.

In spite of the acknowledged role that the thalamus plays in declarative memory, details about the precise memory processes it is involved in and which are the structures of the thalamus that contribute to these processes remain unknown. An overview is presented of human clinical and animal experimental findings showing the involvement of the thalamus, at the level of white matter tracts and separate nuclei, in aspects of memory functioning. The region in the thalamus that contributes to declarative memory is the anterior and medial division, containing the anterior nuclei, the medial dorsal nucleus and the intralaminar and midline nuclei. A lesion to the anterior nuclei or their afferent white matter tract, the mammillothalamic tract, results in deficits of encoding of new stimuli. Lesions to the medial dorsal nucleus affect executive processes pertaining to declarative memory, such as the use of memory strategies for retrieval; damage to the intralaminar and midline nuclei results in decreased arousal and thus affects the declarative memory process. Based on anatomical and functional data, a theory is proposed of how the thalamus might play a role at different levels of declarative memory functioning. Firstly, the anterior and mediodorsal nucleus are involved in processing the contents of the stimuli for storage and recall. The anterior nuclei influence the selection of material to be stored and remembered, whereas the mediodorsal nucleus is involved in the coordination and selection of the strategies used to retrieve material. Secondly, the intralaminar and midline nuclei and specifically the lateral and ventral components, maintain a necessary state of the cortical regions involved in the ongoing memory processes. The two types of function subserved by these groups of thalamic nuclei, focussing on contents vs. state, need to work in parallel to mediate and allow memory functioning, respectively.

Animals↗

PubMed1999

Estrogen improves working but not reference memory and prevents amnestic effects of scopolamine of a radial-arm maze.

This study investigated the effect of estrogen treatment on working memory and reference memory of female rats. In addition, the impact of estrogen on the sensitivity of these two types of memory to the cholinergic antagonist scopolamine was investigated. At 35 days of ages, rats were ovariectomized and implanted chronically with Silastic capsules containing either 25% crystalline estradiol or 100% cholesterol. Thirty days after surgery, animals were trained on an eight-arm radial maze with four arms baited to assess both working and reference memory performance. Following training, females were given scopolamine hydrobromide (0.2 mg/kg i.p.) prior to retesting on the task. Results indicated that estrogen treatment improved working memory performance during maze acquisition but did not affect reference memory performance. Scopolamine treatment impaired performance on the working memory component, but not the reference memory component, while estrogen prevented the impairment of working memory by scopolamine. Results support previous evidence that estrogen selectively enhances performance on tasks that depend on working memory.

Amnesia↗

PubMed2002

Effects of glucose and 2-deoxyglucose on memory formation in the chick: interaction with beta(3)-adrenoceptor agonists.

Consolidation of a weakly reinforced memory that would otherwise fade after 30 min can be achieved by central or peripheral injection of the selective beta(3)-adrenoceptor agonist CL316243 as well as the beta(2)-adrenoceptor agonist zinterol and the alpha(1)-adrenoceptor antagonist prazosin in the day-old chick. The effect of the beta(3)-adrenoceptor agonist is mimicked by peripheral or central injection of glucose that is effective in enhancing memory from 25 min before to 25 min after training. Glucose uptake into various cell types has been described following activation of beta(3)-adrenoceptors and in this paper we demonstrate that activation of beta(3)-adrenoceptors by CL316243 facilitates the effect of a dose of glucose that does not normally enhance memory, whereas a beta(2)-adrenoceptor agonist and an alpha(1)-adrenoceptor antagonist have no effect. Administration of the glucose uptake inhibitor 2-deoxyglucose prevented the consolidation of strongly reinforced training. The beta(3)-adrenoceptor agonist facilitated the effect of a non-amnestic dose of 2-deoxyglucose to inhibit memory. There are two time periods relative to the learning trial where memory is vulnerable to interference by centrally administered 2-deoxyglucose: one related to short-term memory and one at the time of consolidation into long-term memory. Peripheral injection of 2-deoxyglucose is only effective at the time of consolidation. The action of the beta(3)-adrenoceptor agonist to facilitate the action of 2-deoxyglucose only occurs at the time of consolidation. We suggest that a noradrenergic agonist acting at beta(3)-adrenoceptors enhances memory formation by facilitation of glucose uptake at the time of memory consolidation. This may represent a novel mechanism that would be beneficial for developing compounds for the facilitation of memory in diseases with cognitive deficits.

Adrenergic beta-3 Receptor Agonists↗

PubMed2002

Brain imaging of human memory systems: between-systems similarities and within-system differences.

There is much evidence for the existence of multiple memory systems. However, it has been argued that tasks assumed to reflect different memory systems share basic processing components and are mediated by overlapping neural systems. Here we used multivariate analysis of PET-data to analyze similarities and differences in brain activity for multiple tests of working memory, semantic memory, and episodic memory. The results from two experiments revealed between-systems differences, but also between-systems similarities and within-system differences. Specifically, support was obtained for a task-general working-memory network that may underlie active maintenance. Premotor and parietal regions were salient components of this network. A common network was also identified for two episodic tasks, cued recall and recognition, but not for a test of autobiographical memory. This network involved regions in right inferior and polar frontal cortex, and lateral and medial parietal cortex. Several of these regions were also engaged during the working-memory tasks, indicating shared processing for episodic and working memory. Fact retrieval and synonym generation were associated with increased activity in left inferior frontal and middle temporal regions and right cerebellum. This network was also associated with the autobiographical task, but not with living/non-living classification, and may reflect elaborate retrieval of semantic information. Implications of the present results for the classification of memory tasks with respect to systems and/or processes are discussed.

Adult↗

PubMed2000

Remediation of memory disorders in schizophrenia.

BACKGROUND: Memory deficits are commonly experienced by patients with schizophrenia, often persist even after effective psychotropic treatment of psychotic symptoms and have been demonstrated to interfere with many aspects of successful psychiatric rehabilitation. Because of significant impact on functional outcome, effective remediation of cognitive deficits has been increasingly cited as an essential component of comprehensive treatment. Efforts to remediate memory deficits have met with circumscribed success, leaving uncertain whether schizophrenia patients can be taught, without experimental induction, independently to employ semantic encoding or a range of other mnemonic techniques. METHOD: We examined the feasibility of using memory and problem solving teaching techniques developed within educational psychology--techniques which promote intrinsic motivation and task engagement through contextualization and personalization of learning activities--to remediate memory deficits in a group of in-patients with chronic schizophrenia spectrum disorders. RESULTS: Although our memory remediation group significantly improved on the memory remediation task, they did not make greater gains on measures of immediate paragraph recall or list learning than the control groups. CONCLUSIONS: Targeted remediation of memory appears to yield task specific improvement but the gains do not generalize to other memory tasks. Subjects receiving memory remediation failed to independently activate mnemonic encoding strategies learned and used successfully within training tasks to other general measures of verbal learning and memory.

Adult↗

PubMed1999

Verbal working memory and sentence comprehension.

This target article discusses the verbal working memory system used in sentence comprehension. We review the concept of working memory as a short-duration system in which small amounts of information are simultaneously stored and manipulated in the service of accomplishing a task. We summarize the argument that syntactic processing in sentence comprehension requires such a storage and computational system. We then ask whether the working memory system used in syntactic processing is the same as that used in verbally mediated tasks that involve conscious controlled processing. Evidence is brought to bear from various sources: the relationship between individual differences in working memory and individual differences in the efficiency of syntactic processing; the effect of concurrent verbal memory load on syntactic processing; and syntactic processing in patients with poor short-term memory, patients with poor working memory, and patients with aphasia. Experimental results from these normal subjects and patients with various brain lesions converge on the conclusion that there is a specialization in the verbal working memory system for assigning the syntactic structure of a sentence and using that structure in determining sentence meaning that is separate from the working memory system underlying the use of sentence meaning to accomplish other functions. We present a theory of the divisions of the verbal working memory system and suggestions regarding its neural basis.

Cognition↗

PubMed2000

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.

Aged↗

PubMed2005

Fluoxetine disrupts the integration of anxiety and aversive memories.

Anxiety disorders may result from an overexpression of aversive memories. Evidence suggests that the hippocampal cholinergic system could be the point of convergence of anxiety and memory. We propose that clinically effective anxiolytics may exert their effect by interfering with this integration mechanism. To assess anxiety and aversive memory, we used the shock-probe burying test. A reduction in anxiety in this test is indicated by decreased burying, whereas impaired cognition is reflected by an increased number of probe-contacts and/or reduced retention latency. Both an aversive stimulus and the memory of that stimulus significantly increased hippocampal acetylcholine (ACh) levels (Experiment 1). In fact, the memory of the event seemed to be more important than the event itself since the aversive memory induced a greater increase in hippocampal ACh. Injections (i.p.) of fluoxetine (Prozac) reduced burying behavior, while not affecting probe contacts or retention latency (Experiment 2). Although injections of fluoxetine did not affect basal hippocampal ACh efflux (Experiment 3), fluoxetine abolished the increase in ACh induced by the aversive stimulus and the memory of that stimulus (Experiment 4), emphasizing the significance of aversive memories in anxiety disorders. These actions may be mediated by a decrease in the event-related enhancement in cholinergic neurotransmission through M1 cholinergic receptors (Experiment 5). Therefore, anxiety disorders may stem from an unopposed formation of aversive memories and clinically effective anxiolytics hinder the association between emotional and cognitive processing. This reduces the emotional impact of aversive memories, thereby opposing consequent anxiety.

Acetylcholine↗

PubMed2001

The perception of memory failures in patients with epilepsy.

The aim of the study is to evaluate the correlation between subjective memory complaints and neuropsychological tests in the epilepsy population. We administered a Self Report Memory Questionnaire, based on possible everyday memory failures, two questionnaires on anxiety and depression and a battery of cognitive tests to 150 patients with epilepsy (n=100 with partial epilepsy, n=50 with idiopathic generalized epilepsy) and a control group (n=50). A discrepancy between the results of the memory questionnaire and the cognitive tests was found in the epilepsy patients: the Self Report Memory Questionnaire did not show any correlation with the psychological tests. The same discrepancy was not seen in the controls, where the memory questionnaire was related to two verbal memory tests. Furthermore, patients with epilepsy reported greater difficulties on the Self Report Memory Questionnaire than the controls (P < 0.05). It appeared that the tendency to overstate memory problems was mainly related to anxiety and depression, but was not connected with the type of epilepsy, nor with its duration (in years). Seizure frequency, on the other hand, seemed to greatly influence mood, which in turn is probably affect subjective memory perception.

Adult↗

PubMed1998

Olfactory memory: the long and short of it.

It has been proposed that memory for odors does not have a short-term (or working) memory system. The distinction between short- and long-term memory in other sensory modalities has been generally supported by three main lines of evidence: capacity differences between the proposed systems, evidence of differential coding, and differential memory losses in neuropsychological patients. The present paper examines these issues in an effort to establish a similar distinction for the memory of olfactory stimuli. Each of these lines of evidence is examined in relation to the literature on olfactory memory. Based on this examination, it seems that there is at least preliminary support from each of these lines of evidence to advocate a distinction between a long- and short-term memory for olfactory stimuli. Emphasis is placed upon the qualitative similarity of olfactory memory to other memory systems. This similarity is further highlighted through an examination of the literature pertinent to serial position effects in memory for olfactory stimuli.

Humans↗

PubMed2005

Dissociable memory effects after medial thalamus lesions in the rat.

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.

Animals↗

PubMed2003

Patterns of drug use and the influence of gender on self-reports of memory ability in ecstasy users: a web-based study.

Research indicates that the use of recreational drugs, including MDMA ('ecstasy') can result in impairments in cognitive functioning. Recent evidence, based on accounts of 'on drug' effects and cortical binding ratios suggests that women may be more susceptible to the effects of MDMA; however, no research has explored whether there are differences in the long-term behavioural sequelae of the drug between men and women. In addition, little is known about the profile of functioning of the 'typical' user. The present investigation accessed a large sample of recreational drug users, using the Internet, to obtain self-reports of memory functioning with a view to exploring any differences in self-reported ability amongst male and female users, and the level of difficulty reported by the 'typical' ecstasy user. A web site (www.drugresearch.org.uk) was developed and used for data collection. Prospective memory ability was assessed using the Prospective Memory Questionnaire. Self-report of day-to-day memory performance was investigated using the Everyday Memory Questionnaire. The UEL Drug Questionnaire assessed the use of other substances. The number of mistakes made while completing the questionnaires was also taken as an objective measure of performance errors. Findings, based on datasets submitted from 763 respondents, indicate no differences in self-reports of functioning between male and female participants. An overall dissociation between the effects of cannabis and ecstasy on self-reported memory functioning and on the likelihood of making an error during the completion of the questionnaire was found. Typical ecstasy users were found to report significantly more difficulties in long-term prospective memory and to make more completion errors than users of other substances and drug naive controls. Whilst taking into account the fact that participants were recruited via the World Wide Web and that a number of stringent exclusion criteria were applied to the data, a number of conclusions can be drawn. Recreational drug users perceive their memory ability to be impaired compared to non-users. The type of memory difficulties reported varies depending upon the drug of choice. These difficulties are exacerbated in ecstasy users. Individuals reporting average levels of use of ecstasy are more likely to report memory problems than non-ecstasy drug users or drug free individuals. The deleterious effects of ecstasy are therefore not restricted to heavy or chronic users. No gender differences were detected, suggesting that there may be a dissociation between cognitive impairment and cortical binding worthy of further exploration.

Amphetamine-Related Disorders↗

PubMed2025

The effect of scopolamine on memory and attention: a systematic review and meta-analysis.

BACKGROUND: Scopolamine is a muscarinic receptor antagonist and is widely utilized as a "memory-loss model." However, its impact across different memory and attention tasks and using different modes of administration has yet to be clearly evaluated. This systematic review and meta-analysis investigates the effect of scopolamine, across all routes of administration and across different dosages, on memory and attention performance in healthy humans (PROSPERO ID: CRD42024531634). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched (on 20 April 2024) for studies that utilized scopolamine and assessed memory and/or attention. Random-effects meta-analyses were conducted across a range of memory and attention tasks using "Comprehensive Meta-Analysis," Version 3, to evaluate differential pharmacological effects on cognitive tasks between the scopolamine and placebo groups. RESULTS: Forty-six studies fulfilled the inclusion and exclusion criteria. Scopolamine negatively impaired performance on all memory tasks (immediate memory, delayed recall, digit span, Buschke selective reminding task, and recognition memory) and led to slower reaction times for three of the five attention tasks examined (choice reaction time, simple reaction time, and rapid visual information processing) compared to placebo. Scopolamine's negative effect on memory and attention was greater with injectable (e.g., intramuscular, intravenous, and subcutaneous) compared to non-injectable routes of administration (e.g., intranasal, oral, and transdermal). CONCLUSION: This study supports the use of scopolamine as a "memory-loss model," particularly when given by an injectable route of administration. Future clinical trials should evaluate the bioavailability of scopolamine across different routes of administration to ensure therapeutic benefits outweigh any potential adverse cognitive effects.

Humans↗

PubMed1999

Subjective versus objective memory change after temporal lobe epilepsy surgery.

OBJECTIVE: To examine subjective versus objective memory change after anterior temporal lobectomy (ATL). METHODS: A prospective, controlled study. Controls included 39 unoperated patients with intractable temporal lobe epilepsy (TLE) who were administered a series of cognitive and health-related quality of life measures at baseline and at 12-month follow-up intervals. The surgery sample included 65 patients with intractable, focal TLE who had undergone either a right or left ATL. These patients were tested preoperatively and at 6-month follow-up intervals. Subjective and objective memory change was quantified using a newly developed methodology to control for practice effect and regression to the mean. RESULTS: Measures of subjective and objective memory change were not significantly related in the surgery sample. Prevalence of significant subjective memory decline 1 year after surgery ranged from 3 to 7%, whereas prevalence of significant objective memory decline ranged from 26 to 55%. Postoperative levels of emotional distress significantly predicted self-reported memory decline 1 year after ATL. Postoperative medication side effect and seizure outcome were also related significantly to subjective memory change in patients who had undergone left ATL. CONCLUSIONS: Subjective and objective memory change after temporal lobectomy are not related. Complaints of significant memory decline after ATL are infrequent and may serve as a marker for depression or other mood disorder rather than organically based memory decline.

Adult↗

PubMed2005

Drosophila as a novel animal model for studying the genetics of age-related memory impairment.

Understanding the molecular mechanisms underlying age-related memory impairment (AMI) is important not only from a scientific viewpoint but also for the development of therapeutics that may eventually lead to the development of drugs to combat memory loss. AMI has been generally considered to be an overall or nonspecific decay of memory processes that results from dysfunction of neural networks. However, behavioral genetics to test this hypothesis have not been performed previously, due, in part, to the long lifespan of animal models. Using Drosophila, the first extensive behavioral-genetic characterization of AMI has been carried out. 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). Significantly, AMI results from the specific decay of only one memory component, amnesiac-dependent MTM, and not other components. Since amnesiac encodes peptides that enhance adenylyl cyclase activity, these studies suggest the importance of the cAMP signaling pathway in AMI in Drosophila, a finding consistent with several models of AMI in mammals. Although many advances have been made in the study of pathways involved in aging, much remains to be elucidated on how these pathways affect memory formation to cause AMI. Due to its short lifespan, powerful genetics, and well-characterized and conserved pathways involved in memory and lifespan, Drosophila will be a useful model system for studying the molecular mechanisms underlying this process.

Aging↗