Long‐term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA‐type glutamate receptors (AMPARs). A combination of AMPAR structural data, super‐resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever‐clearer picture of how AMPARs are (...) recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse. (shrink)

Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults from the DZNE-Longitudinal Cognitive Impairment and Dementia Study study. Participants reporting having played a musical instrument across three life periods were compared to controls without a history of musical instrument playing, well-matched for reserve proxies of education, (...) intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion. (shrink)

Background: Although convolutional neural networks (CNNs) achieve high diagnostic accuracy for detecting Alzheimer’s disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap as they allow the visualization of key input image features that drive the decision of the model. We investigated whether models with higher accuracy (...) also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N = 663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including in total N = 1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps, thereby allowing intuitive model inspection. Results: Across the three independent datasets, group separation showed high accuracy for AD dementia versus controls (AUC ≥ 0.91) and moderate accuracy for amnestic MCI versus controls (AUC ≈ 0.74). Relevance maps indicated that hippocampal atrophy was considered the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson’s r ≈ −0.86, p < 0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels. The high hippocampus relevance scores as well as the high performance achieved in independent samples support the validity of the CNN models in the detection of AD-related MRI abnormalities. The presented data-driven and hypothesis-free CNN modeling approach might provide a useful tool to automatically derive discriminative features for complex diagnostic tasks where clear clinical criteria are still missing, for instance for the differential diagnosis between various types of dementia. (shrink)

A number of biologists and philosophers have noted the diversity of interpretations of evolvability in contemporary evolutionary research. Different clusters of research defined by co-citation patterns or shared methodological orientation sometimes concentrate on distinct conceptions of evolvability. We examine five different activities where the notion of evolvability plays conceptual roles in evolutionary biological investigation: setting a research agenda, characterization, explanation, prediction, and control. Our analysis of representative examples demonstrates how different conceptual roles of evolvability are quasi-independent and yet exhibit important (...) relationships across scientific activities. It also provides us with the resources to detail two distinct strategies for how evolvability can help to synthesize disparate areas of research and thereby potentially serve as a unifying concept in evolutionary biology. (shrink)

In several works on modality, G. H. von Wright presents tree structures to explain possible worlds. Worlds that might have developed from an earlier world are possible relative to it. Actually possible worlds are possible relative to the world as it actually was at some point. Many logically consistent worlds are not actually possible. Transitions from node to node in a tree structure are probabilistic. Probabilities are often more useful than similarities between worlds in treating counterfactual conditionals.

The Travail of Nature shows that the theological tradition in the West is neither ecologically bankrupt, as some of its popular and scholarly critics have maintained, nor replete with immediately accessible, albeit long-forgotten, ecological riches hidden everywhere in its deeper vaults, as some contemporary Christians, who are profoundly troubled by the environmental crisis and other related concerns, might wistfully hope to find. This is why it is appropriate to speak of the ambiguous ecological promises of Christian theology.

Islamic philosophy; Hanbalites; doctrines; creation (Islam); early works to 1800.

Descartes, René, 1596-1650; Modern philosophy.

Studying Mesilat Yesharim with Hadar Goldin.