Memory Encoding and Dopamine in the Aging Brain: A Psychopharmacological Neuroimaging Study

Normal aging brings with it changes in dopaminergic and memory functions. However, little is known about how these 2 changes are related. In this study, we identify a link between dopamine, episodic memory networks, and aging, using pharmacological functional magnetic resonance imaging. Young and older adults received a D2-like agonist (Bromocriptine, 1.25 mg), a D2-like antagonist (Sulpiride, 400 mg), and Placebo, in a double-blind crossover procedure. We observed group differences, during memory encoding, in medial temporal, frontal, and striatal regions and moreover, these regions were differentially sensitive across groups to dopaminergic perturbation. These findings suggest that brain systems underlying memory show age-related changes and that dopaminergic function may be key in understanding these changes. That these changes have behavioral consequences was suggested by the observation that drug modulations were most pronounced in older subjects with poorer recognition memory. Our findings provide direct evidence linking ageing, memory, and dopaminergic change

A theoretical study of the structural phases of Group 5B - 6B metals and their transport properties

In order to predict the stable and metastable phases of the bcc metals in the block of the Periodic Table defined by groups 5B to 6B and periods 4 to 6, as well as the structure dependence of their transport properties, we have performed full potential computations of the total energies per unit cell as a function of the c/a ratio at constant experimental volume. In all cases, a metastable body centered tetragonal (bct) phase was predicted from the calculations. The total energy differences between the calculated stable and metastable phases ranged from 0.09 eV/cell (vanadium) to 0.39 eV/cell (tungsten). The trends in resistivity as a function of structure and atomic number are discussed in terms of a model of electron transport in metals. Theoretical calculations of the electrical resistivity and other transport properties show that bct phases derived from group 5B elements are more conductive than the corresponding bcc phases, while bct phases formed from group 6B elements are less conductive than the corresponding bcc phases. Special attention is paid to the phases of tantalum where we show that the frequently observed beta phase is not a simple tetragonal distortion of bcc tantalum

Evidence for adult age-invariance in associative false recognition

Older people are more prone to memory distortions and errors than young people, but do not always show greater false recognition in the Deese-Roediger-McDermott (DRM) task. We report two preregistered experiments investigating whether recent findings of age-invariant false recognition extend to designs in which studied items are blocked. According to Tun, Wingfield, Rosen, & Blanchard (1998), age effects on false recognition in the DRM task are due to a greater reliance on gist processing which is enhanced under blocked study conditions. Experiment 1 assessed false recognition in an online variant of the DRM task where words were presented visually, with incidental encoding. The results showed Bayesian evidence against greater false recognition by older adults, whether lures were semantically associated with studied lists, or perceptually related (presented in the same distinctive font as studied lists) or both. Experiment 2 used a typical DRM procedure with auditory lists and intentional encoding, closely reproducing Tun et al.’s (1998) Experiment 2 but omitting an initial test of recall. The results showed evidence against an age-related increase in critical lure false recognition under these conditions. Together, the data suggest that older people do not make more associative memory errors in recognition tests than young people

Aging, working memory capacity and the proactive control of recollection:An event-related potential study

The present study investigated the role of working memory capacity (WMC) in the control of recollection in young and older adults. We used electroencephalographic event-related potentials (ERPs) to examine the effects of age and of individual differences in WMC on the ability to prioritize recollection according to current goals. Targets in a recognition exclusion task were words encoded using two alternative decisions. The left parietal ERP old/new effect was used as an electrophysiological index of recollection, and the selectivity of recollection measured in terms of the difference in its magnitude according to whether recognized items were targets or non-targets. Young adults with higher WMC showed greater recollection selectivity than those with lower WMC, while older adults showed nonselective recollection which did not vary with WMC. The data suggest that aging impairs the ability to engage cognitive control effectively to prioritize what will be recollected

Decoding information in the human hippocampus: a user's guide

Multi-voxel pattern analysis (MVPA), or 'decoding', of fMRI activity has gained popularity in the neuroimaging community in recent years. MVPA differs from standard fMRI analyses by focusing on whether information relating to specific stimuli is encoded in patterns of activity across multiple voxels. If a stimulus can be predicted, or decoded, solely from the pattern of fMRI activity, it must mean there is information about that stimulus represented in the brain region where the pattern across voxels was identified. This ability to examine the representation of information relating to specific stimuli (e.g., memories) in particular brain areas makes MVPA an especially suitable method for investigating memory representations in brain structures such as the hippocampus. This approach could open up new opportunities to examine hippocampal representations in terms of their content, and how they might change over time, with aging, and pathology. Here we consider published MVPA studies that specifically focused on the hippocampus, and use them to illustrate the kinds of novel questions that can be addressed using MVPA. We then discuss some of the conceptual and methodological challenges that can arise when implementing MVPA in this context. Overall, we hope to highlight the potential utility of MVPA, when appropriately deployed, and provide some initial guidance to those considering MVPA as a means to investigate the hippocampus

Retrieval orientation and the control of recollection: An FMRI study

The present study used event-related fMRI to examine the impact of the adoption of different retrieval orientations on the neural correlates of recollection. In each of two study-test blocks, subjects encoded a mixed list of words and pictures, and then performed a recognition memory task with words as the test items. In one block, the requirement was to respond positively to test items corresponding to studied words, and to reject both new items and items corresponding to the studied pictures. In the other block, positive responses were made to test items corresponding to pictures, and items corresponding to words were classified along with the new items. Based on previous event-related potential (ERP) findings, we predicted that in the word task, recollection-related effects would be found for target information only. This prediction was fulfilled. In both tasks, targets elicited the characteristic pattern of recollection-related activity. By contrast, non-targets elicited this pattern in the picture task, but not in the word task. Importantly, the left angular gyrus was among the regions demonstrating this dissociation of non-target recollection effects according to retrieval orientation. The findings for the angular gyrus parallel prior findings for the `left-parietal' ERP old/new effect, and add to the evidence that the effect reflects recollection-related neural activity originating in left ventral parietal cortex. Thus, the results converge with the previous ERP findings to suggest that the processing of retrieval cues can be constrained to prevent the retrieval of goal-irrelevant information

Recruitment of lateral rostral prefrontal cortex in spontaneous and task-related thoughts

Behavioural and neuroimaging studies suggest that spontaneous and task-related thought processes share common cognitive mechanisms and neural bases. Lateral rostral prefrontal cortex (RPFC) is a brain region that has been implicated both in spontaneous thought and in high-level cognitive control processes, such as goal/subgoal integration and the manipulation of self-generated thoughts. We therefore propose that the recruitment of lateral RPFC may follow a U-shaped function of cognitive demand: relatively high in low-demand situations conducive to the emergence of spontaneous thought, and in high-demand situations depending on processes supported by this brain region. We used functional magnetic resonance imaging to investigate brain activity while healthy participants performed two tasks, each with three levels of cognitive demands, in a block design. The frequency of task-unrelated thoughts, measured by questionnaire, was highest in the low cognitive demand condition. Low and high cognitive demand conditions were each compared to the intermediate level. Lateral RPFC and superior parietal cortex were recruited in both comparisons, with additional activations specific to each contrast. These results suggest that RPFC is involved both when (a) task demands are low, and the mind wanders, and (b) the task requires goal/subgoal integration and manipulation of self-generated thoughts

The Dopamine Augmenter L-DOPA Does Not Affect Positive Mood in Healthy Human Volunteers

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans

Impaired Resting-State Functional Integrations within Default Mode Network of Generalized Tonic-Clonic Seizures Epilepsy

Generalized tonic-clonic seizures (GTCS) are characterized by unresponsiveness and convulsions, which cause complete loss of consciousness. Many recent studies have found that the ictal alterations in brain activity of the GTCS epilepsy patients are focally involved in some brain regions, including thalamus, upper brainstem, medial prefrontal cortex, posterior midbrain regions, and lateral parietal cortex. Notably, many of these affected brain regions are the same and overlap considerably with the components of the so-called default mode network (DMN). Here, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients are different from normal controls, even in the resting state. To test this hypothesis, we compared the DMN of the GTCS epilepsy patients and the controls using the resting state functional magnetic resonance imaging. Thirteen brain areas in the DMN were extracted, and a complete undirected weighted graph was used to model the DMN for each participant. When directly comparing the edges of the graph, we found significant decreased functional connectivities within the DMN of the GTCS epilepsy patients comparing to the controls. As for the nodes of the graph, we found that the degree of some brain areas within the DMN was significantly reduced in the GTCS epilepsy patients, including the anterior medial prefrontal cortex, the bilateral superior frontal cortex, and the posterior cingulate cortex. Then we investigated into possible mechanisms of how GTCS epilepsy could cause the reduction of the functional integrations of DMN. We suggested the damaged functional integrations of the DMN in the GTCS epilepsy patients even during the resting state, which could help to understand the neural correlations of the impaired consciousness of GTCS epilepsy patients