Sabine Schaefer

A theoretical framework for the study of adult cognitive plasticity

Does plasticity contribute to adult cognitive development, and if so, in what ways? The vague and overused concept of plasticity makes these controversial questions difficult to answer. In this article, we refine the notion of adult cognitive plasticity and sharpen its conceptual distinctiveness. According to our framework, adult cognitive plasticity is driven by a prolonged mismatch between functional organismic supplies and environmental demands and denotes the brains capacity for anatomically implementing reactive changes in behavioral flexibility (i.e., the possible range of performance and function). We distinguish between 2 interconnected but distinct cognitive outcomes of adult cognitive plasticity: alterations in processing efficiency and alterations in representations. We demonstrate the usefulness of our framework in evaluating and interpreting (a) increments in frontal brain activations in the course of normal aging and (b) the effects of cognitive training in adulthood and old age. Finally, we outline new research questions and predictions generated by the present framework and recommend design features for future cognitive-training studies.

Identification of the initiation sequence for viral-strand DNA synthesis of wheat dwarf virus.

The intergenic region of the circular single‐stranded DNA genome of geminiviruses contains a sequence potentially able to fold into a stem‐loop structure. This sequence has been reported to be involved in viral replication by serving as the origin for rolling‐circle replication. However, in wheat dwarf virus (WDV) a deletion of 128 bp, removing this sequence, surprisingly does not prevent de novo viral DNA synthesis, but instead abrogates the processing of replicative intermediates into monomeric genomes. This deletion mutant permitted us to study the initiation of viral‐strand DNA synthesis independently from its termination and also to identify the sequence within which rolling‐circle DNA replication of WDV begins. We have mapped the initiation site of replication to a pentanucleotide, TACCC, a sequence that occurs twice in the large intergenic region of WDV: it is found in the right half of the stem‐loop sequence and again 170 bases upstream where it is part of a 15 nucleotide sequence highly homologous to the right half of the stem‐loop sequence. Here we show that viral‐strand DNA synthesis efficiently initiates at both sequences.

Spatial navigation training protects the hippocampus against age-related changes during early and late adulthood

It is unknown whether lifestyle, including mental stimulation, and appropriate training interventions, may directly improve spatial navigation performance and its underlying neural substrates. Here we report that healthy younger and older men performing a cognitively demanding spatial navigation task every other day over 4 months display navigation-related gains in performance and stable hippocampal volumes that were maintained 4 months after termination of training. In contrast, control groups displayed volume decrements consistent with longitudinal estimates of age-related decline. Hippocampal barrier density, as indicated by mean diffusivity estimated from diffusion tensor imaging, showed a quadratic shape of increased density after training followed by a return to baseline in the right hippocampus, but declined in the control groups and in the left hippocampus. We conclude that sustained experiential demands on spatial ability protect hippocampal integrity against age-related decline. These results provide the first longitudinal evidence indicating that spatial navigation experience modifies hippocampal volumes in humans, and confirm epidemiological results suggesting that mental stimulation may have direct effects on neural integrity.

Comparing Manual and Automatic Segmentation of Hippocampal Volumes: Reliability and Validity Issues in Younger and Older Brains

We compared hippocampal volume measures obtained by manual tracing to automatic segmentation with FreeSurfer in 44 younger (20–30 years) and 47 older (60–70 years) adults, each measured with magnetic resonance imaging (MRI) over three successive time points, separated by four months. Retest correlations over time were very high for both manual and FreeSurfer segmentations. With FreeSurfer, correlations over time were significantly lower in the older than in the younger age group, which was not the case with manual segmentation. Pearson correlations between manual and FreeSurfer estimates were sufficiently high, numerically even higher in the younger group, whereas intra‐class correlation coefficient (ICC) estimates were lower in the younger than in the older group. FreeSurfer yielded higher volume estimates than manual segmentation, particularly in the younger age group. Importantly, FreeSurfer consistently overestimated hippocampal volumes independently of manually assessed volume in the younger age group, but overestimated larger volumes in the older age group to a less extent, introducing a systematic age bias in the data. Age differences in hippocampal volumes were significant with FreeSurfer, but not with manual tracing. Manual tracing resulted in a significant difference between left and right hippocampus (right > left), whereas this asymmetry effect was considerably smaller with FreeSurfer estimates. We conclude that FreeSurfer constitutes a feasible method to assess differences in hippocampal volume in young adults. FreeSurfer estimates in older age groups should, however, be interpreted with care until the automatic segmentation pipeline has been further optimized to increase validity and reliability in this age group. Hum Brain Mapp 35:4236–4248, 2014.

The Interplay between Cognitive and Motor Functioning in Healthy Older Adults: Findings from Dual-Task Studies and Suggestions for Intervention

Reaching late adulthood is accompanied by losses in physical and mental resources, but lifestyle choices seem to have a considerable influence on the aging trajectory. This review deals with the interplay between cognitive and motor functioning in old age, focusing on two different lines of research, namely (a) dual-task studies requiring participants to perform a cognitive and a motor task simultaneously, and (b) intervention studies investigating whether increases in physical fitness also lead to improvements in cognitive performance. Dual-task studies indicate that healthy older adults show greater performance reductions in both domains than young adults when performing a cognitive and a motor task simultaneously. In addition, older adults often tend to protect their motor functioning at the expense of the cognitive task when the situation involves a threat to balance. This can be considered an adaptive behavior since fall-related injuries can have severe consequences. Fitness intervention studies which increased the aerobic fitness of previously sedentary older adults have demonstrated impressive performance improvements in the cognitive domain, especially for tasks involving executive control processes. These findings are interesting in light of cognitive intervention studies, which often fail to find significant transfer effects to tasks that have not been trained directly. The authors argue that future research should compare the effects of cognitive and aerobic fitness interventions in older adults, and they present a study design in which cognition and fitness are trained sequentially as well as simultaneously. Finally, methodological issues involved in this type of research and potential applications to applied settings are discussed.

Wheat dwarf virus vectors replicate and express foreign genes in cells of monocotyledonous plants.

Wheat dwarf virus (WDV) is a geminivirus that infects monocotyledonous plants. To exploit the potential of WDV as a replicative gene vector, we developed a transient replication and expression system based on the transfection of protoplasts derived from Triticum monococcum suspension culture cells. Cloned genomic copies of various WDV isolates as well as mutants constructed in vitro were introduced into the protoplasts and assayed for their ability to replicate. As a result, regions of the WDV genome necessary or dispensable for the viral DNA replication could be defined. In addition, the gene encoding the viral capsid protein was replaced by three different bacterial marker genes, neomycin phosphotransferase, chloramphenicol acetyltransferase, and beta-galactosidase. The beta-galactosidase gene doubled the size of the WDV genome. The replication of the recombinant WDV genomes and the expression of these genes were monitored in suspension culture cells of T. monococcum. The potential of replicative expression vectors based on the WDV genome is discussed.

Cortical thickness changes following spatial navigation training in adulthood and aging

A widespread network involving cortical and subcortical brain structures forms the neural substrate of human spatial navigation. Most studies investigating plasticity of this network have focused on the hippocampus. Here, we investigate age differences in cortical thickness changes evoked by four months of spatial navigation training in 91 men aged 20-30 or 60-70 years. Cortical thickness was automatically measured before, immediately after, and four months after termination of training. Younger as well as older navigators evidenced large improvements in navigation performance that were partly maintained after termination of training. Importantly, training-related cortical thickening in left precuneus and paracentral lobule were observed in young navigators only. Thus, spatial navigation training appears to affect cortical brain structure of young adults, but there is reduced potential for experience-dependent cortical alterations in old age.

Age Differences between Children and Young Adults in the Dynamics of Dual-Task Prioritization: Body (Balance) versus Mind (Memory).

Task prioritization can lead to trade-off patterns in dual-task situations. The authors compared dual-task performances in 9- and 11-year-old children and young adults performing a cognitive task and a motor task concurrently. The motor task required balancing on an ankle-disc board. Two cognitive tasks measured working memory and episodic memory at difficulty levels individually adjusted during the course of extensive training. Adults showed performance decrements in both task domains under dual-task conditions. In contrast, children showed decrements only in the cognitive tasks but actually swayed less under dual-task than under single-task conditions and continued to reduce their body sway even when instructed to focus on the cognitive task. The authors argue that children perform closer to their stability boundaries in the balance task and therefore prioritize protection of their balance under dual-task conditions.

Interacting Effects of Cognitive Load and Adult Age on the Regularity of Whole-Body Motion During Treadmill Walking

We investigated effects of concurrent cognitive task difficulty (n-back) on the regularity of whole-body movements during treadmill walking in women and men from 3 age groups (20-30, 60-70, and 70-80 years old). Using principal component analysis of individual gait patterns, we separated main (regular) from residual (irregular) components of whole-body motion. Proportion of residual variance (RV) was used as an index of gait irregularity. The gait in all age groups became more regular (reduced RV) upon introduction of a simple cognitive task (1-back), relative to walking without a concurrent cognitive task. In contrast, parametrically increasing working memory load from 1-back to 4-back led to age-differential effects, with gait patterns becoming more regular in those 20-30 years old, becoming less regular in those 70-80 years old, and showing no significant effects in those 60-70 years old. Our results support the dual-process account of sensorimotor-cognitive interactions (O. Huxhold, S.-C. Li, F. Schmiedek, and U. Lindenberger, 2006), with age-general effects of internal versus external attentional focus and age-specific effects of resource competition with increasing cognitive task difficulty.

The conserved nonanucleotide motif of the geminivirus stem-loop sequence promotes replicational release of virus molecules from redundant copies

Recombinant plasmids containing head-to-tail copies of different coat-protein replacement genomes of wheat dwarf virus (WDV) were used to study the mechanism leading to the release of replicating unit-length molecules in suspension culture cells of Triticum monococcum. For plasmids bearing two complete genomes, the viral unit bracketed by the two large intergenic regions (LIR) becomes preferentially released. Addition of a third copy of the LIR on the inoculum plasmid is necessary for release of both WDV genomes with the same efficiency. Using plasmids containing a single viral genome flanked by two different hybrid LIRs, we show that the sequence TAATATTA, which is part of the conserved geminivirus nonanucleotide motif of the potential hairpin structure, is the region of the LIR within which the release of unit-length molecules occurs. Moreover, the data suggest that this release results primarily from rolling-circle replication, also in situations where intramolecular homologous recombination is simultaneously possible.