A real space renormalization group approach to spin glass dynamics

The slow non-equilibrium dynamics of the Edwards-Anderson spin glass model on a hierarchical lattice is studied by means of a coarse-grained description based on renormalization concepts. We evaluate the isothermal aging properties and show how the occurrence of temperature chaos is connected to a gradual loss of memory when approaching the overlap length. This leads to rejuvenation effects in temperature shift protocols and to rejuvenation--memory effects in temperature cycling procedures with a pattern of behavior parallel to experimental observations.Comment: 4 pages, 4 figure

Constitutivism

A brief explanation and overview of constitutivism

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Single-value brain activity scores reflect both severity and risk across the Alzheimer’s continuum

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer’s disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD).To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants’ whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype.Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel.Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients

An unsupervised XAI framework for dementia detection with context enrichment

Explainable Artificial Intelligence (XAI) methods enhance the diagnostic efficiency of clinical decision support systems by making the predictions of a convolutional neural network's (CNN) on brain imaging more transparent and trustworthy. However, their clinical adoption is limited due to limited validation of the explanation quality. Our study introduces a framework that evaluates XAI methods by integrating neuroanatomical morphological features with CNN-generated relevance maps for disease classification. We trained a CNN using brain MRI scans from six cohorts: ADNI, AIBL, DELCODE, DESCRIBE, EDSD, and NIFD (N = 3253), including participants that were cognitively normal, with amnestic mild cognitive impairment, dementia due to Alzheimer's disease and frontotemporal dementia. Clustering analysis benchmarked different explanation space configurations by using morphological features as proxy-ground truth. We implemented three post-hoc explanations methods: (i) by simplifying model decisions, (ii) explanation-by-example, and (iii) textual explanations. A qualitative evaluation by clinicians (N = 6) was performed to assess their clinical validity. Clustering performance improved in morphology enriched explanation spaces, improving both homogeneity and completeness of the clusters. Post hoc explanations by model simplification largely delineated converters and stable participants, while explanation-by-example presented possible cognition trajectories. Textual explanations gave rule-based summarization of pathological findings. Clinicians' qualitative evaluation highlighted challenges and opportunities of XAI for different clinical applications. Our study refines XAI explanation spaces and applies various approaches for generating explanations. Within the context of AI-based decision support system in dementia research we found the explanations methods to be promising towards enhancing diagnostic efficiency, backed up by the clinical assessments.</p

Perivascular space enlargement accelerates in ageing and Alzheimer’s disease pathology: evidence from a three-year longitudinal multicentre study

Abstract Background Perivascular space (PVS) enlargement in ageing and Alzheimer’s disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD. Methods We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; meanage = 70.78 ± 5.78) of the ongoing observational multicentre “DZNE Longitudinal Cognitive Impairment and Dementia Study” (DELCODE) cohort. We analysed data from subjects who were cognitively unimpaired (n = 401), had amnestic mild cognitive impairment (n = 71), or had AD (n = 31). We used linear mixed-effects modelling to test for changes of PVS volumes in relation to cross-sectional and longitudinal age, as well as sex, years of education, hypertension, white matter hyperintensities, AD diagnosis, and cerebrospinal-fluid-derived amyloid (A) and tau (T) status (available for 46.71%; A-T-/A + T-/A + T + n = 143/48/39). Results PVS volumes increased significantly over follow-ups (CSO: B = 0.03 [0.02, 0.05], p &lt; 0.001; BG: B = 0.05 [0.03, 0.07], p &lt; 0.001). PVS enlargement rates varied substantially across subjects and depended on the participant’s age, white matter hyperintensities volumes, and amyloid and tau status. PVS volumes were higher across elderly participants, regardless of region of interest (CSO: B = 0.12 [0.02, 0.21], p = 0.017; BG: B = 0.19 [0.09, 0.28], p &lt; 0.001). Faster BG-PVS enlargement related to lower baseline white matter hyperintensities volumes (ρspearman = -0.17, pFDR = 0.001) and was more pronounced in individuals who presented with combined amyloid and tau positivity versus negativity (A + T +  &gt; A-T-, pFDR = 0.004) or who were amyloid positive but tau negative (A + T +  &gt; A + T-, pFDR = 0.07). CSO-PVS volumes increased at a faster rate with amyloid positivity as compared to amyloid negativity (A + T-/A + T +  &gt; A-T-, pFDR = 0.021). Conclusion Our longitudinal evidence supports the relevance of PVS enlargement in presumably healthy ageing as well as in AD pathology. We further discuss the region-specific involvement of white matter hyperintensities and neurotoxic waste accumulation in PVS enlargement and the possibility of additional factors contributing to PVS progression. A comprehensive understanding of PVS dynamics could facilitate the understanding of pathological cascades and might inform targeted treatment strategies. Trial registration German Clinical Trials Register DRKS00007966. Registered 04.05.2015 – retrospectively registered, https://drks.de/search/en/trial/DRKS00007966

Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks

Background Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. Objective This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. Methods We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. Results Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. Conclusion We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. Trial registration German Clinical Trials Register (DRKS00007966, 04/05/2015)

Philosophy of action

The philosophical study of human action begins with Plato and Aristotle. Their influence in late antiquity and the Middle Ages yielded sophisticated theories of action and motivation, notably in the works of Augustine and Aquinas.1 But the ideas that were dominant in 1945 have their roots in the early modern period, when advances in physics and mathematics reshaped philosophy