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Kuehn, S.

Publications and source records attributed to Kuehn, S..

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3-D navigation: A core driver of brain plasticity in video game interventions

Recent evidence has repeatedly shown that 3D platform video game training leads to substantial brain structural plasticity in hippocampus, prefrontal cortex and cerebellum. However, a great disadvantage of using complex video game interventions is the difficulty to attribute the observed effects to specific game mechanics.\n\nIn order to address this caveat, we conducted a longitudinal training study in which 40 participants were randomly assigned to train with a 3D platformer game or a 2D platformer game. The main difference between the two games lies within their affordance for spatial exploration. After a training phase of two months, we observed extended brain structural increases in the 3D in comparison to the 2D condition in bilateral prefrontal areas, hippocampus/ entorhinal cortex as well as precuneus and the temporal lobe. In the reverse contrast an increase in bilateral caudate nucleus was observed.\n\nThe results demonstrate a crucial role of 3D spatial navigation for widespread brain plasticity effects within a two-months training setup. Given the vast complexity of video games, spatial navigation seems to play an outstanding role in structural plasticity. Since prefrontal, temporal and hippocampal volume deficits are prominent risk factors for several psychiatric disorders, daily navigation habits (outdoor movement, using GPS devices etc.) have to be considered in future mental disorders prevention research.

neuroscience

Influence of nutritional tyrosine on cognition and functional connectivity in healthy old humans

Tyrosine is precursor for monoamine neurotransmitters such as dopamine (DA), which is one of the key neurotransmitters in the frontostriatal network and of crucial relevance for mental disorders. Recent research reported that high dose tyrosine application resulted in increased brain DA synthesis, which is consistent with the observation of positive associations between daily tyrosine intake and cognitive test performance. In the present study, we investigated the associations between working memory (WM) dependent tasks and self-reported nutritional tyrosine intake within a large group of healthy elderly humans (286 subjects) by additionally including brain functional data. We observed a negative correlation between tyrosine intake and resting-state functional connectivity (rsFC) between the striatum (putamen) and the prefrontal cortex. That is to say, we found higher rsFC in individuals consuming less tyrosine per day. At the same time, this increased rsFC or hyperconnectivity was associated with lower WM performance. These findings suggest that lower or insufficient supply of tyrosine might result in dysfunctional connectivity between striatal and frontal regions leading to lower WM capacity in healthy elderly humans.

neuroscience

I know that I don’t know: Structural and functional connectivity underlying meta-ignorance in pre-schoolers

Research Highlights[1] Children develop the ability to report that they do not know something at around five years of age.\n\n[2] Children who could correctly report their own ignorance in a partial-knowledge task showed thicker cortices within medial orbitofrontal cortex.\n\n[3] This region was functionally connected to parts of the default-mode network.\n\n[4] The default-mode network might support the development of correct metacognitive monitoring.\n\nAbstractMetacognition plays a pivotal role in human development. The ability to realize that we do not know something, or meta-ignorance, emerges after approximately five years of age. We aimed at identifying the brain systems that underlie the developmental emergence of this ability in a preschool sample.\n\nTwenty-four children aged between five and six years answered questions under three conditions of a meta-ignorance task twice. In the critical partial knowledge condition, an experimenter first showed two toys to a child, then announced that she would place one of them in a box behind a screen, out of sight from the child. The experimenter then asked the child whether or not she knew which toy was in the box.\n\nChildren who answered correctly both times to the metacognitive question in the partial knowledge condition (n=9) showed greater cortical thickness in a cluster within left medial orbitofrontal cortex than children who did not (n=15). Further, seed-based functional connectivity analyses of the brain during resting state revealed that this region is functionally connected to the medial orbitofrontal gyrus, posterior cingulate gyrus and precuneus, and mid- and inferior temporal gyri.\n\nThis finding suggests that the default mode network, critically through its prefrontal regions, supports introspective processing. It leads to the emergence of metacognitive monitoring allowing children to explicitly report their own ignorance.

neuroscience

Hitchhiking, collapse and contingency in phage infections of migrating bacterial populations

Natural bacterial populations are subject to constant predation pressure by phages. Bacteria use a variety of well-studied molecular mechanisms to defend themselves from phage predation. However, since phage are non-motile, perhaps the simplest defense against phage would be for bacteria to outrun their predators. In particular, chemotaxis, the active migration of bacteria up attractant gradients, may help the bacteria escape slowly diffusing phages. Here we study phage infection dynamics in migrating bacterial populations driven by chemotaxis through low viscosity agar plates. We find that expanding phage-bacteria populations support two migrating fronts, an outermost \"bacterial\" front driven by nutrient uptake and chemotaxis and an inner \"phage\" front at which bacterial population collapses due to phage predation. We show that with increasing adsorption rate and initial phage population, the rate of migration of the phage front increases, eventually overtaking the bacterial front and driving the system across a \"phage transition\" from a regime where bacteria outrun a phage infection to one where they must evolve phage resistance to survive. We confirm experimentally that this process requires phages to \"surf\" the bacterial front by repeatedly reinfecting the fastest moving bacteria. A deterministic model recapitulates the transition. Macroscopic fluctuations in bacterial densities at the phage front suggest that a feedback mechanism, possibly due to growth rate dependent phage infection rates, drives millimeter scale spatial structure in phage-bacteria populations. Our work opens a new, spatiotemporal, line of investigation into the eco-evolutionary struggle between bacteria and their phage predators.\n\nSignificance StatementThe infection of bacteria by phage requires physical contact. This fact means that motile bacteria may avoid non-motile phage by simply running away. By this mechanism bacterial chemotaxis may help bacteria to escape phages. Here we show that when phage infect bacteria moving in soft agar plates, high phage populations or infectivity rates result in phages stopping and killing all bacteria. Conversely, when initial phage numbers or infectivity rates are low, bacteria are able to migrate away from phage successfully, despite phage ability to \"surf\" bacterial fronts for more than 24 hours. Between these regimes we document a \"phage transition\" where bacterial physiology and contingency in phage infection manifest through large-scale fluctuations in spatio-temporal dynamics.

ecology

Locus coeruleus integrity preserves memory performance across the adult life span

For decades, research into memory decline in human cognitive aging has focused on neocortical regions, the hippocampus, and dopaminergic neuromodulation. Recent findings indicate that the locus coeruleus (LC) and noradrenergic neuromodulation may also play an important role in shaping memory development in later life. However, technical challenges in quantifying LC integrity have hindered the study of LC-cognition associations in humans. Using high-resolution neuromelanin-sensitive magnetic resonance imaging, we found that individual differences in learning and memory were positively associated with LC integrity across a variety of memory tasks in younger (n = 66), and older adults (n = 228). Moreover, we observed functionally relevant age differences confined to rostral LC. Older adults with a more youth-like rostral LC also showed higher memory performance. These findings link non-invasive, in vivo indices of LC integrity to memory in aging and highlight the role of the LC norepinephrine system in the decline of cognition.

neuroscience

Subject- and behavior-specific signatures extracted from fMRI data using whole-brain effective connectivity

The study of brain communication based on fMRI data is often limited because such measurements are a mixture of session-to-session variability with subject- and condition-related information. Disentangling these contributions is crucial for real-life applications, in particular when only a few recording sessions are available. The present study aims to define a reliable standard for the extraction of multiple signatures from fMRI data, while verifying that they do not mix information about the different modalities. In particular, condition-specific signature should not be contaminated by subject-related information. Practically, signatures correspond to subnetworks of directed interactions between brain regions (typically 100 covering the whole brain) supporting the subject and condition identification for single fMRI sessions. The key for robust prediction is using effective connectivity instead of functional connectivity. Our method demonstrates excellent generalization capabilities for subject identification in two datasets, using only a few sessions per subject as reference. Using another dataset with resting state and movie viewing, we show that the two signatures related to subjects and tasks correspond to distinct subnetworks, which are thus topologically orthogonal. Our results set solid foundations for applications tailored to individual subjects, such as clinical diagnostic.

neuroscience

Environment determines evolutionary trajectory in a constrained phenotypic space

Constraints on phenotypic variation limit the capacity of organisms to adapt to the multiple selection pressures encountered in natural environments. To better understand evolutionary dynamics in this context, we select Escherichia coli for faster migration through a porous environment, a process which depends on both motility and growth. We find that a trade-off between swimming speed and growth rate constrains the evolution of faster migration. Evolving faster migration in rich medium results in slow growth and fast swimming, while evolution in minimal medium results in fast growth and slow swimming. In each condition parallel genomic evolution drives adaptation through different mutations. We show that the trade-off is mediated by antagonistic pleiotropy through mutations that affect negative regulation. A model of the evolutionary process shows that the genetic capacity of an organism to vary traits can qualitatively alter the evolutionary trajectory when selection pressures are complex.

evolutionary biology

Resting-state fMRI correlations: from link-wiseunreliability to whole brain stability

The functional architecture of spontaneous BOLD fluctuations has been characterized in detail by numerous studies, demonstrating its potential relevance as a biomarker. However, the systematic investigation of its consistency is still in its infancy. Here, we analyze both the within- and between-subject variability as well as the test-retest reliability of resting-state functional connectivity (FC) estimates in a unique data set comprising multiple fMRI scans (42) from 5 subjects, and 50 single scans from 50 subjects. To this aim we adopted a statistical framework enabling us to disentangle the contribution of different sources of variability and their dependence on scan duration, and showed that the low reliability of single links can be largely improved using multiple scans per subject. Moreover, we show that practically all observed inter-region variability (at the link-level) is not significant and due to the statistical uncertainty of the estimator itself rather than to genuine variability among areas. Finally, we use the proposed statistical framework to demonstrate that, despite the poor consistency of single links, the information carried by the whole-brain spontaneous correlation structure is indeed robust, and can in fact be used as a functional fingerprint.

neuroscience