Mild cognitive impairment as a clinical entity and treatment target.
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Cognition Disorders↗
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Results for “memory differentiation”
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Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease.
The hippocampal formation is composed of separate anatomical regions interconnected to form a circuit, and investigating abnormal hippocampal function is most revealing at the level of these regions. Until recently, regional analysis of the hippocampal formation could be performed only in animals or in human postmortem tissue. Here, we report a method using functional magnetic resonance imaging that evaluates the hippocampal regions in vivo, and we use this method to study elderly with normal memory, with isolated memory decline, and with probable Alzheimer's disease (AD). Although age-related memory decline occurs commonly, the cause of this decline remains unknown, with disagreement as to whether this decline represents one or more etiologies. Analysis revealed two distinct patterns of regional dysfunction among elderly with isolated memory decline--one pattern similar to that found in elders with AD, involving all hippocampal regions, and a second pattern with dysfunction restricted to only one hippocampal region, the subiculum. These results offer direct evidence of hippocampal dysfunction associated with memory decline in the elderly, and implicate both predementia AD and non-AD processes as possible underlying causes.
Aged↗
Is dissociation a multidimensional construct? Data from the Multiscale Dissociation Inventory.
The dimensionality of dissociation was examined in a combined sample of 1,326 general population, clinical, and university participants who completed the Multiscale Dissociation Inventory (MDI). Principal components analysis identified five moderately intercorrelated factors (mean r = .39): Disengagement, Identity Dissociation, Emotional Constriction, Memory Disturbance, and Depersonalization/Derealization. Differential relationships were found between individual MDI factors and demographics, trauma history, clinical status, posttraumatic stress, and scores on other dissociation measures. Surprisingly, after controlling for sex and age, trauma exposure accounted for only 3 to 7% of the variance in MDI factors. The notion of dissociation as a general trait was not supported. Instead, dissociation may represent a variety of phenomenologically distinct and only moderately related symptom clusters whose ultimate commonality is more theoretical than empirical.
Adolescent↗
Inversion and contrast polarity reversal affect both encoding and recognition processes of unfamiliar faces: a repetition study using ERPs.
Using ERPs in a face recognition task, we investigated whether inversion and contrast reversal, which seem to disrupt different aspects of face configuration, differentially affected encoding and memory for faces. Upright, inverted, and negative (contrast-reversed) unknown faces were either immediately repeated (0-lag) or repeated after 1 intervening face (1-lag). The encoding condition (new) consisted of the first presentation of items correctly recognized in the two repeated conditions. 0-lag faces were recognized better and faster than 1-lag faces. Inverted and negative pictures elicited longer reaction times, lower hit rates, and higher false alarm rates than upright faces. ERP analyses revealed that negative and inverted faces affected both early (encoding) and late (recognition) stages of face processing. Early components (N170, VPP) were delayed and enhanced by both inversion and contrast reversal which also affected P1 and P2 components. Amplitudes were higher for inverted faces at frontal and parietal sites from 350 to 600 ms. Priming effects were seen at encoding stages, revealed by shorter latencies and smaller amplitudes of N170 for repeated stimuli, which did not differ depending on face type. Repeated faces yielded more positive amplitudes than new faces from 250 to 450 ms frontally and from 400 to 600 ms parietally. However, ERP differences revealed that the magnitude of this repetition effect was smaller for negative and inverted than upright faces at 0-lag but not at 1-lag condition. Thus, face encoding and recognition processes were affected by inversion and contrast-reversal differently.
Brain↗
Fetal alcohol-exposed rats exhibit differential response to cholinergic drugs on a delay-dependent memory task.
Fetal alcohol exposure in human and rodents produces a number of cognitive deficits including impairments in learning and memory. Recent evidence in our laboratory has shown that fetal alcohol-exposed (FAE) rats respond differently to systemic administration of cholinergic drugs when tested for vigilance and locomotor activity. The present study examined the effects of muscarinic and nicotinic agonists and antagonists on memory performance in a delayed alternation task. Subjects were male offspring of Sprague-Dawley rats fed a 35% ethanol-derived caloric diet, pair-fed with sucrose, or chow-fed with lab chow during the last 2 weeks of gestation. Rats (3 months old) were food-deprived prior to training in the T-maze. Rats were first trained in the alternation task at no delay for five sessions. Rats were then trained at longer delays (20, 60, 180 s) until all groups showed similar performance for two consecutive sessions. Each animal was then tested following systemic injections of the cholinergic antagonists scopolamine and mecamylamine (60-s delay) and the cholinergic agonists pilocarpine and nicotine (180-s delay). Rats received saline injections on alternate days of testing. The results revealed that FAE rats exhibited no impairments in alternation performance at the no delay and 20-s delay, but showed impairments on both the 60- and 180-s delays during the initial sessions. However, with additional training, FAE rats showed performance similar to that of control groups at these delays. Following both pilocarpine and nicotine injections, control groups, but not the FAE group, showed significant memory enhancement in the alternation task. Following scopolamine injections, the FAE rats showed a significant impairment, while control groups showed a nonsignificant decrease in performance. All three groups showed impairments in the alternation task following administration of mecamylamine compared to saline treatment. These findings suggest that alterations in the cholinergic system in FAE rats may underlie some of the cognitive deficits observed with prenatal alcohol exposure.
Animals↗
A comparison of the effects of scopolamine and diazepam on working memory.
Two drug models of memory dysfunction, namely the benzodiazepine and the cholinergic models, have emerged from the considerable number of studies which have examined drug effects on information processing. The reported impairments produced by administration of compounds from these two families appear to be more similar than dissimilar, and to date, direct comparisons on traditional memory tasks have failed to differentiate the models. This study compared the effects of diazepam and scopolamine on tasks associated with separable components of working memory. The results indicate that this model also fails to discriminate between the drug models; both compounds selectively impaired tasks associated with the central executive mechanism and failed to disrupt tasks associated with the articulatory loop or the visuospatial scratchpad.
Adolescent↗
Early family mealtime experiences and eating attitudes in normal weight, underweight and overweight females.
The aim of this study was to examine young women's recollections of family mealtimes in order to determine whether these memories may serve to differentiate those of normal weight from those who were underweight or overweight. A sample of 340 women selected on the basis of their enrollment in a college course completed the Childhood Family Mealtimes Questionnaire and the short form of the Eating Attitudes Test (EAT). The women were divided into under, normal and overweight groups on the basis of their body mass index (BMI). Two factors (appearance-weight control and emphasis on mother's weight) were significantly higher among the overweight than the underweight women, and mealtime communication-based stress was highest among the underweight women. The use of family mealtimes as a window for understanding the development of eating disorders (ED) is discussed.
Adult↗
Differentiating the effects of centrally acting drugs on arousal and memory: an event-related potential study of scopolamine, lorazepam and diphenhydramine.
The degree to which apparent amnesic effects of various centrally acting drugs are secondary to their effects on arousal remains a contentious issue. The present study uses two methods to dissociate memory and arousal effects of the cholinergic antagonist, scopolamine (SP), and the GABA-A/benzodiazepine receptor agonist, lorazepam (LZ). First, it compared their effects to those of an antihistamine, diphenhydramine (DPh), to provide an active control for arousal reduction. Second, it used the same measure--event-related potentials (ERPs)--as as a parallel index of both the arousal and cognitive effects of the drugs. Fifty participants were allocated to one of five parallel treatment groups (0.6 mg SP; 2 mg LZ; 25, 50 mg DPh; placebo). ERPs were recorded during a continuous word recognition task as well as during an "oddball" task. SP, LZ and 50 mg DPh produced a similar profile of effects on certain indices of arousal and on early components of ERPs. However, SP and LZ (but not DPh) produced marked impairments of episodic memory, and this pattern was similar to that on later components of ERPs. Memory impairments by SP and LZ were highly significant on retention in the continuous recognition task and further, no drug effects were found on response bias. Subsequent free recall was similarly very impaired by SP and LOR but not by the antihistamine. We conclude that benzodiazepines and anticholinergic drugs both reduce arousal and induce amnesia, but these effects are not interdependent. Our findings provide strong evidence for a dissociation between the effects on episodic memory and on arousal of these centrally acting compounds.
Adult↗
Differential contribution of some cortical sites to the formation of memory traces supporting fear conditioning.
The aim of the present work was to assess the role of some cortical sites of the rat (the prefrontal, PFC, frontal, FC, parietal, PAC, and perirhinal, PC, cortices) in the acquisition of classical fear conditioning (CS and context conditioned freezing). Using the reversible ablation technique the sites were inactivated with lidocaine (LIDO), administered before the one-trial training session. The freezing response, taken as memorization index, was measured in conditions of full functional recovery after the short reversible LIDO inactivation either 3 h ("short-term" memory) and/or 72 h ("long-term" memory) later, so as to follow the temporal dimension of mnemonic elaboration. The results of the inactivations performed during the training session show that PFC, FC, PAC and PC play contemporaneous but distinct roles in the memorization of aversive responses to CS and context. PC inactivation weakened the retention of both mnemonic traces at the 3-h delay. At the same delay FC and PAC inactivation weakened only freezing to acoustic CS while PFC inactivation improved the retention of both traces. Inactivation of all four sites was followed by significant amnesia for both traces at the 72-h after-acquisition delay. The present findings show that PFC, FC, PAC and PC reversible inactivation during the acquisition training session diversely interferes with the memorization of conditioned freezing to acoustic CS and context. Moreover, the different results obtained at the two different retention intervals support the hypothesis that "short-term" and "long-term" memories are not necessarily linked, the earlier one not always influencing the subsequent one.
Acoustic Stimulation↗
The differential expression of homing and adhesion molecules on virgin and memory T cells in the mouse.
We have used an anti-CD45R mAb to identify virgin and memory CD4+ T cells. In this report, we demonstrate that in mice, as in humans, virgin and memory T cells express different levels of adhesion molecules. Splenic CD45Rlo memory T cells express higher levels of PgP-1, Lyt-1, and LFA-1 than do CD45Rhi virgin cells. In contrast, CD45Rlo memory cells express lower levels of antigens identified by the mAbs. Mel-14 (leukocyte homing receptor) and SM3G11. These observations are in agreement with work in humans and rats which suggests that differences in the levels of adhesion molecules and homing receptors might be related to the efficiency of activation and patterns of recirculation among virgin and memory T cells.
Animals↗
The case for reverse translation.
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Antibody Formation↗
Differential effect of right and left hemispheric lesions on two memory tasks: free recall and frequency judgement.
We investigated the relationship between lateralized cerebral damage and two memory tasks; free recall and frequency judgement. Free recall is considered to be processed effortfully while frequency judgement is considered to be processed automatically (Hasher and Zacks). Nine right brain-damaged patients (RBD), nine left brain-damaged patients (LBD) and nine control subjects participated in this study. It was hypothesized that RBD would show an advantage over LBD on the free-recall task, whereas LBD would show an advantage over RBD on the frequency-judgement task. In accordance with our hypothesis, free-recall was more impaired in LBD than in RBD. In the frequency-judgement task, an effect of laterality of lesion was found in high (4-6) and low (0-1) frequencies, but not in the medium (2-3) frequencies. The anticipated LBD advantage was shown in judgement of the high frequencies, but unexpectedly RBD performed better than LBD in low frequencies. The results are discussed in terms of the relationship between effortful and automatic memory processes and cerebral lateralization.
Aged↗
Differential effects of scopolamine and mecamylamine on working and reference memory in the rat.
The effects of the muscarinic antagonist scopolamine (0.1-0.6 mg/kg, IP) and the nicotinic antagonist mecamylamine (1-10 mg/kg) were compared in T-maze alternation and discrimination tasks in the rat. Scopolamine dose dependently disrupted performance on the alternation task and potentiated the increase in errors made in controls when the delay between forced and choice runs was increased from 0 to 30 s. Mecamylamine disrupted performance at the 10-mg/kg dose only and dose dependently inhibited the increase in errors made in controls when the delay between forced and choice runs was increased to 30 s. In simple T-maze discrimination, only the 0.6-mg/kg dose of scopolamine disrupted performance of the task, while mecamylamine at both 5 and 10 mg/kg disrupted task performance. These results confirm that working memory tasks are more sensitive to central muscarinic blockade than reference memory tasks. They also demonstrate that in delay conditions working memory performance is enhanced following central nicotinic blockade while reference memory performance is disrupted. This suggests that centrally active muscarinic and nicotinic antagonists have dissociable effects on memory processes in the rat.
Animals↗
Differential effects of dentate kindling on working and reference spatial memory in the rat.
An 8-arm radial maze was used to examine the effects of dentate kindling on the performance of a task which requires both working (short-term) and reference (long-term) memory. During the 4-week post-operative training period, control and experimental rats performed both components of the task equally well. Performance of the reference memory component, but not the working memory component of the task was significantly impaired during kindling stimulation. The impairment in reference memory appeared to be primarily due to the elicitation of afterdischarges, since the disruption in maze performance was evident in the pre-convulsive stages of kindling. Following the cessation of kindling stimulation, a gradual recovery in reference memory performance was observed. Dentate kindling may provide a useful model for the study of long-term memory deficits associated with temporal lobe epilepsy.
Animals↗
Differential involvement of hippocampal G-protein subtypes in the memory process of rats.
Inactivation of Gi and G(o) proteins in the dentate gyrus of the hippocampus by pertussis toxin did not affect memory retention of a one-way passive avoidance learning task in rats. Interference of normal Gs activity in the dentate gyrus by cholera toxin impaired retention performance dose-dependently. Cholera toxin also antagonized the memory-enhancing effect of corticotropin-releasing factor in the hippocampus. However, although Gi and G(o) proteins are probably not involved in the memory consolidation process per se, in animals showing a full retention score there was a significant and long-lasting increase of G(o) concentration in the dentate gyrus. Results of ADP-ribosylation experiments have shown that there was a dose-dependent decrease of ADP-ribosylation in vitro as the concentration of in vivo pertussis toxin and cholera toxin increased. These results together suggest that Gs protein is probably involved in the initiation of the memory consolidation process, while enhanced G(o) expression is the ultimate result upon memory formation. These results provide the first in vivo evidence relating the functions of hippocampal G proteins to the memory process of mammals.
Animals↗
The screening of cognitive impairment in the elderly: a critical review of current methods.
The continued appearance of new screening tests for dementia suggests both the continuing need for a valid measure of pathological cognitive change and dissatisfaction with what is currently available. A brief review of current tests is presented which focuses on the major theoretical and methodological issues which have impeded the development of adequate screening instruments. Strategies for the management of such difficulties are also indicated, with a view to guiding prospective researchers in this field and increasing the critical perspective of those currently using these instruments.
Aged↗
Differential cerebellar activation on functional magnetic resonance imaging during working memory performance in persons with multiple sclerosis.
OBJECTIVE: To explore the potential role of the cerebellum in working memory dysfunction in multiple sclerosis (MS). DESIGN: Blood oxygen level dependent functional magnetic resonance imaging (fMRI) was used to examine cerebellar activation during a working memory task. SETTING: University-affiliated medical rehabilitation facility. PARTICIPANTS: Eight persons with MS and 5 healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Change in hemodynamic response. fMRI data were acquired and subsequently analyzed by using Statistical Parametric Mapping. RESULTS: Both the control and MS groups showed significantly greater activations in the right cerebellar hemisphere as compared with the left side. Persons with MS, however, showed no detectable activations in 4 cerebellar substructures that were significantly active in controls (ie, right vermis, right dentate nucleus, right tonsil, cerebellar peduncle). CONCLUSIONS: The significantly decreased cerebellar activation in the MS group suggests that the cerebellum may play a role in the working memory impairment observed in MS.
Adolescent↗
T cell receptor crossreactivity as a general property of T cell recognition.
TCR recognition of MHC/peptide complexes directs many aspects of T cell biology, including thymic selection, survival of naïve T cells and differentiation into effector and memory T cells. It was widely thought that TCR recognition is highly specific, with an individual T cell being capable of only recognizing a particular peptide and closely related sequence variants. By considering the structural requirements for peptide binding to MHC molecules and TCR recognition of MHC/peptide complexes, we demonstrated that T cell clones could recognize a number of peptides from different organisms that are remarkably distinct in their primary sequence. These peptides are particularly diverse at those sequence positions buried in pockets of the MHC binding site, while a higher degree of similarity is present at a limited number of peptide residues that create the interface with the TCR. Many examples have now been documented for human and murine T cells, indicating that TCR crossreactivity represents a general feature of TCR recognition.
Animals↗