APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach to modeling a CNS disorder

Animal models are considered essential in research ensuing elucidation of human disease processes and subsequently, testing of potential therapeutic strategies. This is especially true for neurodegenerative disorders, in which the first steps in pathogenesis are often not accessible in human patients. Alzheimer's disease is vastly becoming a major medical and socioeconomic problem in our aging society. Valid animal models for this uniquely human condition should exhibit histopathological, biochemical, cognitive, and behavioral alterations observed in Alzheimer's disease patients. Major progress has been made since the understanding of the genetic basis of Alzheimer's disease and the development and improvement of transgenic mouse models. All present Alzheimer's disease models developed are partial but nevertheless essential in further unraveling the nature and spatial and temporal development of the complex molecular pathology underlying this condition. One of the more recent transgenic attempts to model Alzheimer's disease is the APP23 transgenic mouse. This article describes the development and assessment of this human amyloid precursor protein overexpression model. We summarize histopathological and biochemical, cognitive and behavioral observations made in heterozygous APP23 mice, thereby emphasizing the model's contribution to clarification of neurodegenerative disease mechanisms. In addition, the first therapeutic interventions in the APP23 model are included.     

Mood-congruent attentional bias in dysphoria: maintained attention to and impaired disengagement from negative information

Attentional bias to negative information has been proposed to be a cognitive vulnerability factor for the development of depression. In 2 experiments, the authors examined mood-congruent attentional bias in dysphoria. In both experiments, dysphoric and nondysphoric participants performed an attentional task with negative, positive, and neutral word cues preceding a target. Targets appeared either at the same or at the opposite location of the cue. Overall, results indicate that dysphoric participants show maintained attention for negative words at longer stimulus presentations, which is probably caused by impaired attentional disengagement from negative words. Furthermore, nondysphoric participants maintain their attention more strongly to positive words. These results are discussed in relation to recent developments in the pathogenesis and treatment of depression.     

Structural brain variation,age, and response time

Response time (RT) generally slows with aging, but the contribution of structural brain changes to this slowing is unknown. We used voxel-based morphometry (VBM) to determine gray matter (GM) and white matter (WM) brain volumes in 9 middle-aged adults (38–58 years old) and 9 seniors (66–82 years old). We correlated brain volumes with RT assessed in both a simple visual stimulus-response task and a visual continuous recognition memory task. No GM correlations with simple RT were significant; there was one WM correlation in the right fusiform gyrus. In the memory task, faster RT was correlated (p<.05, corrected) with less GM in the globus pallidus, the parahippocampus, and the thalamus for both groups. Several Brodmann areas (BA) differed between the groups such that in each area, less GM was correlated with slower RTs in the middle-aged group but with faster RTs in the senior group (BAs 19, 37, 46, 9, 8, 6, 13, 10, 41, and 7). The results suggest that individual differences in specific brain structure volumes should be considered as potential moderating factors in cognitive brain imaging studies.     

The odd-even effect in addition: an analysis per problem type

The odd-even effect is a well documented finding in the literature on mental arithmetic, at least for multiplication. It implies that false answers with the same parity as the correct answer are rejected more slowly than false answers with a different parity. For addition, this effect is not so well documented. The study by Krueger and Hallford (1984) is the only one that investigated odd-even effects for addition. However, they did not investigate odd-even effects per problem, even though there are indications that problem type can modulate odd-even effects for multiplication (Lemaire & Reder, 1999). Therefore, we wanted to get more insight into odd-even effects for addition by investigating odd-even effects per problem type. Our results extended the findings of Krueger and Hallford. First of all, we found an interaction between split and problem type. The most important and new result of present study, however, was a strong parity effect for E + E problems. We discuss our results in terms of two alternative explanations for odd-even effects, namely use of a parity rule on the one hand and familiarity with even outcomes on the other.     

Automatic processing of dominance and submissiveness

We investigated whether people are able to detect in a relatively automatic manner the dominant or submissive status of persons engaged in social interactions. We used a nonaffective variant of the affective Simon paradigm of De Houwer and Eelen (1998) in which participants responded by saying either "dominant" or "submissive" depending on the right or left spatial position of a target person who was engaged as either the dominant or the submissive agent in a social interaction. We observed that responses were facilitated when the status connotation of the target person and the correct response corresponded. These results provide new information about the automatic nature of information related to emotion-antecedent appraisals.     

Decline in working memory updating through ageing: intrusion error analyses

The present research examines the decline in working memory updating through age. Two experiments compared groups of participants in different age ranges (young-old, 55-65 years, old, 66-75 years and old-old, more than 75 years and, in Experiment 2 only, young, 20-30 years). Memory updating tasks were administered, which required participants to remember the smallest items in each list. To perform the task correctly, participants had to update information efficiently, reducing interference from items no longer relevant. Intrusion errors were computed and in the first experiment these were described as "intrusions of irrelevant items" (immediate exclusion) and "intrusions of once relevant items" (delayed exclusion). The oldest adults performed worse in memory updating and made a greater number of intrusion errors of once relevant information. In the second experiment results showed that increases in memory load (number of items that had to be remembered) and updating demand (number of potentially relevant items) impaired performance. The oldest adults had greater difficulty when the task demand was increased. Furthermore, they produced a higher number of intrusion errors, particularly when the updating demand was increased. It therefore appears that elderly people have specific difficulty in updating information in working memory by excluding irrelevant information.     

The closer we are,the more we are alike: The effect of self-other merging on depersonalized self-perception

The present study examined whether or not the extent to which people include other group members in the self, influences depersonalized self-perception (i.e., perceiving self and others as similar in terms of group characteristics). The results revealed that self-other merging positively influenced feelings of belongingness and identification with the in-group. Furthermore, a strong experience of self-other merging was shown to lead to depersonalized self-perception as measured by a self-assimilation and an in-group homogeneity index. Finally, results also revealed that feelings of belongingness and group identification mediated, at least partly, the effect of self-other merging on depersonalized self-perception. The findings are discussed in light of the literature on self-expansion.     

Extinction-induced immobility in the water maze and its neurochemical concomitants in aged and adult rats: a possible model for depression?

Extinction of escape behavior in the water maze due to the removal of the platform, was hypothesized to induce a negative state, including the development of immobility, which is held to reflect a state of "despair" when measured in the forced swimming test. 27 aged and 8 adult animals (26 and 3 months old Wistar rats, respectively) were tested in the water maze during nine days with a platform hidden, followed by 7 days of extinction trials with the platform absent. As expected, both age groups developed immobility over the extinction trials, with the aged showing more than the adults. To examine whether the age difference in immobility was related to performance differences during acquisition, the aged were subdivided into superior, intermediate and inferior learners (n = 9 per group) on the basis of overall times to platform during acquisition, and compared with each other and the adults. Results showed that the aged inferior learners displayed the highest levels of immobility among the aged. Immobility scores were then correlated with post-mortem neurotransmitter contents in the hippocampus and ventral striatum. In the ventral striatum, levels of immobility were correlated with levels of acetylcholine, dopamine and the metabolite dihydroxyphenylacetic acid in the aged, and with norepinephrine in the adults. The data support the hypothesis that multiple extinction trials in the water maze result in immobility that may indicate "behavioral despair," and that striatal neurotransmitter systems correlate with the degree of its expression. The concept of extinction-induced despair is held to provide the promise of a conceptual and empirical model of human depression that is the consequence of loss of reinforcers.     

The Five-factor Personality Inventory as a measure of the Five-factor Model: Belgian, American, and Hungarian comparisons with the NEO-PI-R

The lexically based Five-Factor Personality Inventory (FFPI) was correlated with the factors and facets of the Revised NEO Personality Inventory (NEO-PI-R) in Belgian (N = 265), American (N = 116), and Hungarian (N = 320) samples. Results were similar across the three cultures. Analysis of orthogonalized FFPI factors showed that three of them--emotional stability, extraversion, and agreeableness--showed a direct correspondence to their NEO-PI-R counterparts. Autonomy, however, was not clearly related to openness, and facet analysis suggested that it might be interpreted as a dominance factor Better matches to NEO-PI-R conscientiousness and openness could be obtained by using vectors rotated 30 degrees from the FFPI positions. Raw scale scores showed similar results. Researchers should not assume that all measures of the Five-Factor Model are qualitatively similar     

Does imminent threat capture and hold attention?

According to models of attention and emotion, threat captures and holds attention. In behavioral tasks, robust evidence has been found for attentional holding but not for attentional capture by threat. An important explanation for the absence of attentional capture effects is that the visual stimuli used posed no genuine threat. The present study investigated whether visual cues that signal an aversive white noise can elicit attentional capture and holding effects. Cues presented in an attentional task were simultaneously provided with a threat value through an aversive conditioning procedure. Response latencies showed that threatening cues captured and held attention. These results support recent views on attention to threat, proposing that imminent threat captures attention in everyone.