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Several studies have demonstrated age-related regional differences in the magnitude of the BOLD signal using task-based fMRI. It has been suggested that functional changes reflect either compensatory or de-differentiation mechanisms, both of which assume response to a specific stimulus. Here, we have tested whether ageing affects both task-based and resting brain function, and the extent to which functional changes are mediated by reductions in grey matter (GM) volume. Two groups, of 22 healthy younger and 22 older volunteers, underwent an imaging protocol involving structural and functional MRI, both during a memory task and at rest. The two groups had similar socio-demographical characteristics and cognitive performance. Image analysis revealed both structural and functional differences. Increased BOLD signal in older relative to younger volunteers was mainly observed in the frontal lobes, both during the task and at rest. Functional changes in the frontal lobes were largely located in brain regions spared from GM loss, and adding GM covariates to the fMRI analysis did not significantly alter the group differences. Our results are consistent with the suggestion that, during normal ageing, the brain responds to neuronal loss by fine-tuning connections between spared neurons. Longitudinal studies will be necessary to fully test this hypothesis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Increasing age and carrying an APOE ε4 allele are well established risk factors for Alzheimer's disease (AD). The earlier age of onset of AD observed in ε4-carriers may reflect an accelerated aging process. We recently reported that APOE genotype modulates brain function decades before the appearance of any cognitive or clinical symptoms. Here we test the hypothesis that APOE influences brain aging by comparing healthy ε4-carriers and non-carriers, using the same imaging protocol in distinct groups of younger and older healthy volunteers. A cross-sectional factorial design was used to examine the effects of age and APOE genotype, and their interaction, on fMRI activation during an encoding memory task. The younger (N=36; age range 20-35; 18 ε4-carriers) and older (35 middle-age/elderly; age range 50-78 years; 15 ε4-carriers) healthy volunteers taking part in the study were cognitively normal. We found a significant interaction between age and ε4-status in the hippocampi, frontal pole, subcortical nuclei, middle temporal gyri and cerebellum, such that aging was associated with decreased activity in e4-carriers and increased activity in non-carriers. Reduced cerebral blood flow was found in the older ε4-carriers relative to older non-carriers despite preserved grey matter volume. Overactivity of brain function in young ε4-carriers is disproportionately reduced with advancing age even before the onset of measurable memory impairment. The APOE genotype determines age-related changes in brain function that may reflect the increased vulnerability of ε4-carriers to late-life pathology or cognitive decline., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This study investigated the use of event-related brain potentials (ERPs) as a neurophysiological measure of eyewitness identification accuracy during a lineup task (ERP-lineup). Time delay between viewing the crime and completing the ERP-lineup (no-delay, 1-h delay and 1-week delay conditions) and culprit presence or absence were also manipulated. Results demonstrated that a P300 provided a reliable index of recognition of the culprit relative to the other lineup members across all time delay conditions. Although participants' accuracy decreased at the 1-week time delay compared to no delay and the 1-h time delay, the P300 effect remained strong for participants that made correct identifications irrespective of the time delay. In addition, the P300 was attenuated or was not elicited when the culprit was absent from the lineup.

Cued recall of categorized lists was used to examine effects of category structure on the creation of false memories. In three experiments, category members that had not been presented on studied categorized lists were nonetheless recalled by participants. Delaying the category cued recall test (Experiment 1) and priming category members that had been omitted from target lists (Experiment 3) increased the frequency of false recall. All three experiments showed that nonpresented category members that were higher in output dominance were more frequent intrusions. The typicality of category members, however, did not uniquely contribute to the predictability of false recall (or accurate recall) once the contribution of output dominance was taken into account, suggesting that item accessibility (related to output dominance) may be more instrumental than item distinctiveness (related to typicality) in causing certain types of false recall. The results show that created memories in category cued recall are strongly biased by prior category knowledge and can be predicted by the graded structure of categories, particularly in terms of the output dominance of category instances.

Activation of cAMP synthesis by intracellular Ca2+ is thought to be the main mode of cAMP generation in the brain. Accordingly, the Ca2+-activated adenylyl cyclases I and VIII are expressed prominently in forebrain neurons. The present study shows that the novel adenylyl cyclase type IX is inhibited by Ca2+ and that this effect is blocked selectively by inhibitors of calcineurin such as FK506 and cyclosporin A. Moreover, adenylyl cyclase IX is inhibited by the same range of intracellular free Ca2+ concentrations that stimulate adenylyl cyclase I. Adenylyl cyclase IX is expressed prominently in the forebrain. Substantial arrays of neurons positive for AC9 mRNA were found in the olfactory lobe, in limbic and neocortical areas, in the striatum, and in the cerebellar system. These data show that the initiation of the cAMP signal by adenylyl cyclase may be controlled by Ca2+/calcineurin and thus provide evidence for a novel mode of tuning the cAMP signal by protein phosphorylation/dephosphorylation cascades.

Tip-of-the-tongue (TOT) states were examined in relation to acquisition manipulations, using named imaginary animals (TOTimals) as targets. High levels of TOT states were found in three experiments. In the first experiment an increase in the duration of initial exposure to target material improved recall and recognition, and reduced the number of unrecalled items not in TOT states (NTOTs), but did not affect TOT levels. In Experiment 2 practice at writing target names, as compared with only reading them, improved recall performance and decreased TOT levels, but did not reduce NTOTs. Experiment 3 replicated the finding that writing during practice reduced TOT states, but did not reduce NTOTs, and also found that more frequent practice trials increased recall without affecting TOT levels. The results suggest that practice writing target names prevents TOT states by strengthening otherwise deficient phonological connections in memory, a deficiency that can cause TOT states when visual-to-lexical connections give only partial access to a target in memory. The results also demonstrate the usefulness of the TOTimal technique for testing effects of acquisition variables on TOT experiences.

Reminiscence, the recall of material that was not successfully recalled on a previous attempt, was examined in three experiments as a function of the interest (incubation) interval. Incubation intervals inserted between successive recall tests resulted in increased reminiscence, but the effect was seen primarily in the first retested minute. Neither the duration of the initial test (1-4 min), nor the incubation activity (maze problems vs. rest) affected this incubated reminiscence effect. The results support models in which recall tests cause output interference, but incubation intervals reduce it.

Two experiments provided evidence of environmental context-dependent memory using a homophone spelling test (e.g., Jacoby & Witherspoon, 1982), an implicit, indirect measure of memory (Richardson-Klavehn & Bjork, 1988). Context reinstatement significantly increased priming in both experiments. The finding of environmental context reinstatement effects with this implicit memory test and others (Garberg & Radtke, 1986; Graf, 1988) indicates that the effect can be found reliably using a test that does not encourage subjects to generate their own context cues from memory.

Examines the association between symbols and their meanings in the context of analytical psychology. Evidence of collective unconscious memory; Relationship between morphic resonance and collective unconscious; Development of archetypal symbol inventory.