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PubMed1989

Comparison of the effects of four cholinomimetic agents on cognition in primates following disruption by scopolamine or by lists of objects.

The ability of four central cholinomimetics to reverse a scopolamine-induced spatial memory impairment or to improve visual recognition memory in primates was examined. Physostigmine (0.04-0.08 mg/kg IM) fully reversed the effects of scopolamine (0.03 mg/kg). Coadministration of pilocarpine (3.0-5.0 mg/kg) caused partial reversal of the scopolamine impairment after intermediate or long retention intervals (10 or 20 s). Treatment with arecoline (0.1-1.8 mg/kg) or nicotine (1.0-2.0 mg/kg) generally did not reverse the effects of scopolamine. A task in which memory could be taxed by increasing the number of visual stimuli presented appeared more sensitive to the effects of cholinomimetics on cognition than the scopolamine reversal model. In this paradigm treatment with physostigmine (0.001, 0.01 or 0.03 mg/kg) increased choice accuracy from about 55 to 70% correct. Arecoline improved performance at one dose only (0.1 mg/kg) which also induced marked adverse side-effects (salivation and tremor). Pilocarpine improved performance in the dose range 0.125-0.35 mg/kg, but not at higher doses which also induced marked salivation. Treatment with nicotine (0.001-2.0 mg/kg tended to improve performance but this did not reach statistical significance. The relevance of these findings for studies in man and for animal models of dementia is discussed.

Animals↗
PubMed1998

The effect of pain on memory for affective words.

Memory is a key cognitive variable in pain management, but lacks extensive research. This study is a replication and extension of Seltzer and Yarczower's investigation of pain's influence on memory for affective words, which found fewer positive words and more negative words recalled if subjects were in acute pain (versus no pain). In the present study, two experiments were conducted: one with a recall memory test and one with a recognition memory test. One hundred sixty undergraduate subjects were randomly placed in one of four groups: two groups had the same condition (pain or no pain) for both the encoding task and memory test, and two groups had mixed conditions (pain at encoding-no pain at memory test or no pain at encoding-pain at memory test). Pain was induced by 0 degrees-2 degrees C water immersion. At encoding, subjects categorized words by judging them as either positive or negative. Results of both experiments show that pain impairs memory. In neither experiment were differences found on memory for positive and negative words. These results do not support Seltzer and Yarczower's discriminative effects of pain on word category, but they are consistent with other research using acute pain manipulations and chronic pain populations, suggesting that pain interferes with memory. It is hypothesized that pain depletes scarce attentional resources, thereby interfering with concurrent cognitive tasks such as thinking, reasoning, and remembering.

Adult↗
PubMed2006

Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior.

Coffin-Lowry Syndrome (CLS) is an X-linked syndromic form of mental retardation associated with skeletal abnormalities. It is caused by mutations of the Rsk2 gene, which encodes a growth factor regulated kinase. Gene deletion studies in mice have shown an essential role for the Rsk2 gene in osteoblast differentiation and function, establishing a causal link between Rsk2 deficiency and skeletal abnormalities of CLS. Although analyses in mice have revealed prominent expression of Rsk2 in brain structures that are essential for learning and memory, evidence at the behavioral level for an involvement of Rsk2 in cognitive function is still lacking. Here, we have examined Rsk2-deficient mice in two extensive batteries of behavioral tests, which were conducted independently in two laboratories in Zurich (Switzerland) and Orsay (France). Despite the known reduction of bone mass, all parameters of motor function were normal, confirming the suitability of Rsk2-deficient mice for behavioral testing. Rsk2-deficient mice showed a mild impairment of spatial working memory, delayed acquisition of a spatial reference memory task and long-term spatial memory deficits. In contrast, associative and recognition memory, as well as the habituation of exploratory activity were normal. Our studies also revealed mild signs of disinhibition in exploratory activity, as well as a difficulty to adapt to new test environments, which likely contributed to the learning impairments displayed by Rsk2-deficient mice. The observed behavioral changes are in line with observations made in other mouse models of human mental retardation and support a role of Rsk2 in cognitive functions.

Abnormalities, Multiple↗
PubMed1996

Memory impairment in schizophrenia: its' relationship to executive function.

The presence of memory impairment in schizophrenia has frequently been documented but much less attention has been given to the qualitative aspects of this impairment and its association to executive function. Using a cognitive-process approach, we examined memory and executive function in 25 patients who met DSM-III-R criteria for schizophrenia. Patients were matched with 25 healthy volunteers. The schizophrenic group was found to have a significant impairment in immediate memory, with relatively spared long-delay memory. Performance on verbal learning and recognition memory was similar to that of controls. Memory deficits were present irrespective of the encoding strategies used and were unrelated to chronicity. In addition, the schizophrenics performed worse than controls on tests of executive function, but the degree of impairment was greater on tests of response initiation and suppression. This pattern of performance resembled that found in patients with subcortical or frontal lesions which was supported by some significant correlations between aspects of memory and executive function. Our results suggest that in schizophrenia, specific executive functions may make a selective contribution to the pattern of memory performance in schizophrenia which is subserved by frontal and to a lesser extent hippocampal/diencephalic systems.

Adult↗
PubMed2004

Nitrous oxide impairs selective stages of working memory in rats.

Working memory impairment under narcosis has never been investigated. Furthermore, mechanisms by which narcosis disturbs working memory processes remain relatively unknown. The present work was aimed at answering to these two questions using a well-known normobaric narcotic gas, nitrous oxide (N2O), and a classical working memory task (a two-trial recognition memory task). Ten Long-Evans rats were tested in this behavioral task under nitrous oxide exposure. The results showed (i) a dose-related impairment of working memory, (ii) a selective effect of N2O on two out of three mnemonic processes: acquisition, and retention, and (iii) a compensatory effect of increasing the acquisition phase duration on these impairments. These results, as previously suggested for long-term memory, agree with the fact that nitrous oxide disrupts in a dose-related manner working memory by notably slowing down acquisition processes.

Analgesics, Non-Narcotic↗
PubMed2005

Less is more: how reduced activity reflects stronger recognition.

The mechanisms of recognition involve reductions of activity in the medial temporal lobe. This preview discusses recent fMRI and MEG data from Gonsalves et al. (this issue of Neuron) that provide some of the strongest evidence to date demonstrating that reduced medial temporal activity is correlated with stronger recognition of items in humans. This result provides an important test of theories of recognition memory function based on previous neuroimaging and unit recording data.

Brain Mapping↗
PubMed2006

Human memory development and its dysfunction after early hippocampal injury.

Cognitive memory involves long-term memories for facts (semantic memory) and personal experiences (episodic memory) that can be brought to mind. There is consensus that the hippocampus and related medial temporal lobe (MTL) structures are crucial for adult cognitive memory, but much less is known about their contribution to memory during infancy and childhood. We argue that the MTL is involved in memory from early in life, supporting recognition memory within the first postnatal months and recall memory within the first year. We propose that normal development involves a sequence in which a form of semantic-like memory emerges first, whereas the characteristics of episodic memory develop only later with progressive development of the hippocampus. Early bilateral injury to the hippocampus disrupts this normal pattern such that memory skills cannot develop beyond the stage of semantic memories. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Brain Injuries↗
PubMed1998

Effects of "isolated" transcutaneous electrical nerve stimulation on memory and affective behavior in patients with probable Alzheimer's disease.

BACKGROUND: In previous studies, transcutaneous electrical nerve stimulation (TENS), tactile stimulation, and a combination of the two resulted in cognitive and affective improvements in patients with Alzheimer's disease (AD). As in those studies the therapist was present during the treatment of the experimental and control group (sham stimulation), a positive effect of the combination of TENS with interpersonal communication could not be excluded. Therefore, the effects of "isolated" TENS, i.e., in the absence of the therapist, on memory and affective disturbances in AD patients were examined. METHODS: Eighteen subjects (78-92 years old) met the NINCDS-ADRDA criteria for the clinical diagnosis of probable AD. To evaluate treatment effects, the experimental group (9) and the control group (9) underwent a number of neuropsychological tests and two observation scales. RESULTS: Treatment effects were observed for nonverbal short-term (Visual Memory) and long-term (Face Recognition) memory, word fluency (Verbal Fluency), and need of help, whereas patients' affective behavior did not improve. CONCLUSIONS: The results of the present study show that isolated TENS has a positive effect on patients' cognitive and independent functioning; however, isolated TENS appeared not to have a therapeutic effect on patients' affective behavior.

Affect↗
PubMed2003

Development of face-sensitive event-related potentials during infancy: a review.

Event-related potential (ERP) studies in adults have identified a number of components related to encoding and recognition memory of faces. Although behavioural studies indicate that even very young infants are able to detect faces and recognise familiar individuals, very few ERP studies document the neural correlates of these early abilities. In this article, we review four components (P1, N290, P400, Nc) and slow wave activity that are elicited while infants view faces. Where possible we draw links between these components and their possible equivalents to those observed in children and adults, and we highlight areas where further investigation is required. The theoretical importance of ERP studies of face processing in infants for debates about the origins and domain specificity of the adult cortical face processing system are discussed.

Child, Preschool↗
PubMed2002

Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation.

Local protein translation in dendrites could be a means for delivering synaptic proteins to their sites of action, perhaps in a spatially regulated fashion that could contribute to plasticity. To directly test the functional role of dendritic translation of calcium/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) in vivo, we mutated the endogenous gene to disrupt the dendritic localization signal in the mRNA. In this mutant mouse, the protein-coding region of CaMKIIalpha is intact, but mRNA is restricted to the soma. Removal of dendritic mRNA produced a dramatic reduction of CaMKIIalpha in postsynaptic densities (PSDs), a reduction in late-phase long-term potentiation (LTP), and impairments in spatial memory, associative fear conditioning, and object recognition memory. These results demonstrate that local translation is important for synaptic delivery of the kinase and that local translation contributes to synaptic and behavioral plasticity.

Animals↗
PubMed2003

Sexually selective cognition: beauty captures the mind of the beholder.

Across 5 experimental studies, the authors explore selective processing biases for physically attractive others. The findings suggest that (a). both male and female observers selectively attend to physically attractive female targets, (b). limiting the attentional capacity of either gender results in biased frequency estimates of attractive females, (c). although females selectively attend to attractive males, limiting females' attentional capacity does not lead to biased estimates of attractive males, (d). observers of both genders exhibit enhanced recognition memory for attractive females but attenuated recognition for attractive males. Results suggest that different mating-related motives may guide the selective processing of attractive men and women.

Adolescent↗
PubMed1998

Dissociation of the neural correlates of implicit and explicit memory.

One presentation of a word to a subject is enough to change the way in which the word is processed subsequently, even when there is no conscious (explicit) memory of the original presentation. This phenomenon is known as implicit memory. The neural correlates of implicit memory have been studied previously, but they have never been compared with the correlates of explicit memory while holding task conditions constant or while using a procedure that ensured that the neural correlates were not 'contaminated' by explicit memory. Here we use scalp-recorded event-related brain potentials to identify neural activity associated with implicit and explicit memory during the performance of a recognition memory task. Relative to new words, recently studied words produced activity in three neuroanatomically and functionally dissociable neural populations. One of these populations was activated whether or not the word was consciously recognized, and its activity therefore represents a neural correlate of implicit memory. Thus, when task and memory contamination effects are eliminated, the neural correlates of explicit and implicit memory differ qualitatively.

Adult↗
PubMed1999

Differential neuronal responsiveness in primate perirhinal cortex and hippocampal formation during performance of a conditional visual discrimination task.

Neuronal responses in the hippocampal formation, including the entorhinal cortex, have been compared with those in the inferior temporal cortex, including the perirhinal cortex, during performance by monkeys of a visual conditional discrimination task. In the task, the arrangement of three geometric shapes determined the correctness of either a left or right behavioural response according to a conditional rule. Neurons that responded differently to different types of trial were common (50% of the visually responsive neurons) in the entorhinal cortex, perirhinal cortex and area TE of the inferior temporal cortex, but significantly less common in the hippocampus (13%). This differential incidence suggests a more important role for the rhinal cortices and area TE than for the hippocampus in this task. Based on the neuronal responses, arguments are advanced that the animals probably solved the task by a strategy that did not require spatial or hippocampal processing. Thus, of the differential responses, those that would allow the animals to solve the task by using a conditional rule and so avoid spatial processing were twice as common (37%) as those allowing solution to be by selection of a particular spatially directed response to each arrangement of shapes (19%). Moreover, the differential latencies of responses that allowed the task to be solved by a conditional rule were shorter (< approximately 165 ms), and hence processing was faster, than those that provided information about particular individual types of trial ( approximately 195 ms). Even so, hippocampal responsiveness in the conditional task was differentially enhanced when compared with that during a recognition memory task, and the neuronal responses potentially allow the animal to employ a second, alternative strategy that might be expected to depend on hippocampal processing.

Animals↗
PubMed2004

Memory conjunction errors for autobiographical events: more than just familiarity.

Two diary studies investigated the prevalence of memory conjunction errors for real-life events. In both studies, participants completed detailed diary pages over the course of several weeks. Participants in both diary studies committed memory conjunction errors on a later recognition memory test. In the second diary study participants also made remember/know judgements. For a large proportion of their memory conjunction errors participants indicated that they "remembered" the event occurring in that context. These diary studies demonstrate that memory conjunction errors do occur for autobiographical memories, and these errors can seem compelling.

Analysis of Variance↗
PubMed2004

Simulating episodic memory deficits in semantic dementia with the TraceLink model.

Although semantic dementia is primarily characterised by deficits in semantic memory, episodic memory is also impaired. Patients show poor recall of old autobiographical and semantic memories, with better retrieval of recent experiences; they can form new memories, and normal performance on pictorial recognition memory has been demonstrated. As these abnormalities in episodic memory are virtually a mirror image of those seen in the amnesic syndromes, semantic dementia poses a challenge to extant models of remote memory and amnesia. Here, we show that one such model, TraceLink, can reproduce some of the principal findings on episodic memory in semantic dementia. A loss of nodes and connections within the trace system, which can be identified with the temporal neocortical memory storage sites implicated in semantic dementia, simulates without further assumptions the findings reported above.

Amnesia↗
PubMedDate not supplied

The effects of tibolone on mood and libido.

OBJECTIVE: To review published data pertaining to the effects of tibolone on sexual parameters, mood, and cognitive function in postmenopausal women. DESIGN: A review of all relevant published, peer-reviewed studies. RESULTS: Tibolone is a compound that can be selectively metabolized by individual tissues to its estrogenic, progestogenic, or androgenic metabolites and hence exhibits tissue-specific hormonal effects. Tibolone also lowers sex hormone binding globulin, thus increasing free estradiol and testosterone levels. Tibolone alleviates climacteric vasomotor symptoms and displays a dominant progestogenic effect on the endometrium. Tibolone normalizes the vaginal karyopyknotic and maturation indexes and alleviates symptomatic atrophic vaginitis. Women treated with tibolone report significant reductions in vaginal dryness and dyspareunia, effects that may be secondary to both estrogenic and androgenic actions. Randomized studies indicate tibolone has positive effects on mood compared with placebo and alleviates several adverse mood parameters to a similar extent as conventional hormone replacement therapy. Improved mood is associated with increased plasma beta-endorphin. With respect to cognition, tibolone seems to improve semantic memory but does not significantly improve recognition memory. Tibolone is associated with improvements in sexual function that seem to be greater than those achieved with standard hormone replacement therapy. CONCLUSION: Published studies indicate beneficial effects of tibolone on both libido and mood, which otherwise significantly compromise physical, psychological, and social well-being. Hence, tibolone provides another option for menopausal women experiencing loss of libido as part of their symptomatology or who have persistent low libido despite adequate estrogen/progestin replacement therapy.

Affect↗
PubMed2002

Evidence concerning how neurons of the perirhinal cortex may effect familiarity discrimination.

Many studies indicate that recognition memory involves at least two separable processes, familiarity discrimination and recollection. Aspects of what is known of potential neuronal substrates of familiarity discrimination are reviewed. Lesion studies have established that familiarity discrimination for individual visual stimuli is effected by a system centred on the perirhinal cortex of the temporal lobe. The fundamental change that encodes prior occurrence of such stimuli appears to be a reduction in the response of neurons in anterior inferior temporal (including perirhinal) cortex when a stimulus is repeated. The neuronal responses rapidly signal the presence of a novel stimulus, and are evidence of long-lasting learning after a single exposure. Computational modelling indicates that a neuronal network based on such a change in responsiveness is potentially highly efficient in information theoretic terms. Processes that occur in long-term depression within the perirhinal cortex provide candidate synaptic plastic mechanisms for that underlying the change, but such linkage remains to be experimentally established.

Animals↗