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β-amyloid (Aβ) and tau aggregation as well as neuronal injury and atrophy (ATN) are the major hallmarks of Alzheimer’s disease (AD), and biomarkers for these hallmarks have been linked to neuroinflammation. However, the detailed regional associations of these biomarkers with microglial activation in individual patients remain to be elucidated.We investigated a cohort of 55 patients with AD and primary tauopathies and 10 healthy controls that underwent TSPO-, A-, tau-, and perfusion-surrogate-PET, as well as structural MRI. Z-score deviations for 246 brain regions were calculated and biomarker contributions of Aβ (A), tau (T), perfusion (N1) and gray matter atrophy (N2) to microglial activation (TSPO, I) were calculated for each individual subject. Individual ATN-related microglial activation was correlated with clinical performance and CSF soluble TREM2 (sTREM2) concentrations.In typical and atypical AD, regional tau was stronger and more frequently associated with microglial activation when compared to regional A (AD: βT= 0.412±0.196 vs. βA= 0.142±0.123, p < 0.001; AD-CBS: βT= 0.385±0.176 vs. βA= 0.131±0.186, p = 0.031). The strong association between regional tau and microglia reproduced well in primary tauopathies (βT= 0.418±0.154). Stronger individual associations between tau and microglial activation were associated with poorer clinical performance. In patients with 4RT, sTREM2 levels showed a positive association with tau-related microglial activation.Tau pathology has strong regional associations with microglial activation in primary and secondary tauopathies. An index of tau- and Aβ-associated microglia activation accounts for regional heterogeneity and allows for clinical and biomarker correlations with ATN-specific neuroinflammation.

Sleep complaints are the most prevalent syndromes in older adults, particularly in women. Moreover, they are frequently accompanied with a high level of depression and stress. Although several diffusion tensor imaging (DTI) studies reported associations between sleep quality and brain white matter (WM) microstructure, it is still unclear whether gender impacts the effect of sleep quality on structural alterations, and whether these alterations mediate the effects of sleep quality on emotional regulation. We included 389 older participants (176 females, age = 65.5 ± 5.5 years) from the 1000BRAINS project. Neuropsychological examinations covered the assessments of sleep quality, depressive symptomatology, current stress level, visual working memory, and selective attention ability. Based on the DTI dataset, the diffusion parameter maps, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were calculated and normalized to a population-specific FA template. According to the global Pittsburgh Sleep Quality Index (PSQI), 119 poor sleepers (PSQI: 10∼17) and 120 good sleepers (PSQI: 3∼6) were identified. We conducted a two by two (good sleepers/poor sleepers) × (males/females) analysis of variance by using tract-based spatial statistics (TBSS) and JHU-ICBM WM atlas-based comparisons. Moreover, we performed a voxel-wise correlation analysis of brain WM microstructure with the neuropsychological tests. Finally, we applied a mediation analysis to explore if the brain WM microstructure mediates the relationship between sleep quality and emotional regulation. No significant differences in brain WM microstructure were detected on the main effect of sleep quality. However, the MD, AD, and RD of pontine crossing tract and bilateral inferior cerebellar peduncle were significant lower in the males than females. Voxel-wise correlation analysis revealed that FA and RD values in the corpus callosum were positively related with depressive symptomatology and negatively related with current stress levels. Additionally, we found a significantly positive association between higher FA values in visual-related WM tracts and better outcomes in a visual pattern recognition test. Furthermore, a mediation analysis suggested that diffusion metrics within the corpus callosum partially mediated the associations between poor sleep quality/high stress and depressive symptomatology.

Corticobasal syndrome (CBS) is a rare neurodegenerative condition characterized by four-repeat tau aggregation in the cortical and subcortical brain regions and accompanied by severe atrophy. The aim of this study was to evaluate partial volume effect correction (PVEC) in patients with CBS compared to a control cohort imaged with the 18-kDa translocator protein (TSPO) positron emission tomography (PET) tracer [

TSPO-PET tracers are sensitive to a single-nucleotide polymorphism (rs6971-SNP), resulting in low-, medium- and high-affinity binders (LABs, MABs and HABS), but the clinical relevance of [18F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [18F]GE-180 binding in a healthy brain and in pseudo-reference tissue in neuro-oncological and neurodegenerative diseases. Standardized uptake values (SUVs) of [18F]GE-180-PET were assessed using a manually drawn region of interest in the frontoparietal and cerebellar hemispheres. The SUVs were compared between the LABs, MABs and HABs in control, glioma, four-repeat tauopathy (4RT) and Alzheimer’s disease (AD) subjects. Second, the SUVs were compared between the patients and controls within their rs6971-subgroups. After excluding patients with prior therapy, 24 LABs (7 control, 5 glioma, 6 4RT and 6 AD) were analyzed. Age- and sex-matched MABs (n = 38) and HABs (n = 50) were selected. The LABs had lower frontoparietal and cerebellar SUVs when compared with the MABs and HABs, but no significant difference was observed between the MABs and HABs. Within each rs6971 group, no SUV difference between the patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [18F]GE-180 quantification, revealing lower binding in the LABs when compared to the MABs and HABs. The frontoparietal and cerebellar ROIs were successfully validated as pseudo-reference regions.

ObjectiveThe aim of this cross-sectional single center study was to investigate 18kDa translocator protein (TSPO)-PET as a biomarker for microglial activation in the 4-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy (PSP).MethodsSpecific binding of the TSPO tracer 18F-GE-180 was determined by serial PET during pharmacological depletion of microglia in a 4-repeat tau mouse model. TSPO-PET was performed in 30 patients with corticobasal syndrome (CBS, 68±9 years, 16 female) and 14 patients with PSP (69±9 years, 8 female), and 13 control subjects (70±7 years, 7 female). Group comparisons and associations with parameters of disease progression and sTREM2 were assessed by region-based and voxel-wise analyses.ResultsTracer binding was significantly reduced after pharmacological depletion of microglia in 4-repeat tau mice. Elevated TSPO labeling (standardized-uptake-value-ratios) was observed in subcortical brain areas of CBS and PSP patients when compared to controls, most pronounced in the globus pallidus internus (CBS: 1.039 [95%CI 1.000–1.078, pInterpretationOur data indicate a potential of 18F-GE-180 PET to detect microglial activation in the brain of 4-repeat tauopathy patients, fitting to predilection sites of the phenotype. TSPO-PET may serve as a sensitive early disease stage biomarker in 4-repeat tauopathies.

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In this paper, we present a methodology to conduct content analyses on character depiction in 3D animated children's movies. Using this methodology, we analyzed the depictions and emotive expressions of female characters by conducting a content analysis in two popular contemporary 3D animations. We studied the design of feminine coded appearance and movement using simplified drawings. Based on this study, we observe that female characters and their emotive expressions are still designed to fit stereotypes in contemporary 3D animated children's movies. Our findings are the following: 1. The percentage of female characters in contemporary 3D animated children's movies is the same as the percentage of females in human society; 2. On the other hand, those female characters did not demonstrate human diversity; and 3. Moreover, the expressions did not demonstrate the diversity of human emotions in terms of how female characters visually express their emotions.

The article analyzes a rare German science fiction film produced at the end of the Weimar period, with special attention to its complex use of sound in the presentation of telecommunications and other new audio media in the context of a shifting geo-political climate. Produced just before Hitler assumed the chancellorship of Germany, Hartl's film, F.P. 1 antwortet nicht [F.P. 1 Doesn't Answer] draws on the military-industrial complex, public media practices, and advances in telecommunications and cinematic technologies to present the nation as a networked, "sonic" space. The film's portrayal of the design and construction of a landing platform in the Atlantic, told through a series of telephone calls, telegrams, telegraphs, and wireless transmissions, underscores linkages between geo-politics and telecommunications, while exploiting advances in cinematic sound recording, including the musical soundtrack. Although wireless communications (especially radio) may render physical frontiers obsolete and thereby serve to oppose national coherence, they simultaneously serve to reinforce the unity of national culture. Hartl's film likewise underscores the conflict between instability, impermanence, and unpredictability, on the one hand, and constancy, endurance, and prescription, on the other, between deterritorialization and normativity. These dual impulses are further embodied in the clash between the film's leading men: the pilot and the engineer. In the near-future of the film, the concept of Heimat or "home" is not a physical but an aural construction. Dominated by sound transmissions, the film neglects the visual spectacle of most science fiction, but thereby emphasizes the role of audio technologies in the construction of the nation.

If Alexander Kluge's prose and films are populated with figures looking for escape, his programmatic statements on the media are no less concerned with how various narrative strategies provide more or less possibility for a way out from dominant discursive practices. This idea of Auswege—at the level of both the experience as well as the representation and the conceptualization of historical events—is at the core of Kluge's multi-media project and is the focus of this article. Auswege describe processes of representation/depiction that serve as the reader's point of departure to re-imagine the present, and potentially, offer a Rettung from the repetition of catastrophe. The article traces the evolution of this concept in examples of Kluge's work from the 1970s (Luftangriff auf Halberstadt and Verschrottung durch Arbeit) and in prose texts composed in the context of the end of the GDR and the unification of Germany in 1989/90 (Verfallserscheinungen der Macht).

WG. Sebald's Die Ausgewanderten begins at the end, with a photograph of a cemetery in the shadow of an enormous tree.' Encountering this image, the reader may initially assume that the photograph perhaps presents the location in which the narrative will unfold, and this assumption appears to be reinforced when within the first ten lines of the work, the narrator refers to "einem Rasenfriedhof" (A 8) and its trees.2 However, one soon finds that the graveyard is only peripheral in fixing the location of the narrator's eventual destination. No scene will be explicitly set in the graveyard, thus leaving us to wonder at its inclusion. As we continue to read, we may conclude retrospectively that the photograph had provisionally announced the subject matter pursued thematically in the book-namely, the deaths of the four men whose biographies will follow, and more broadly those of all who perished in the Holocaust. The photograph would thus serve to prepare us for the text, to underscore pertinent themes, and to illustrate abstract ideas. Examining the picture more closely, we note the visual details: the tombstones are askew and the grass is overgrown, presenting a scene of neglect, of a cemetery that has been forgotten. This quality of neglect certainly resonates throughout the pages of the text, for example in the descriptions of the run-down English estate in the first section or the accumulating debris and disintegration of the city of Manchester found in the fourth section. Further, the photograph is later doubled in the images of an overgrown Jewish cemetery that the narrator visits toward the end of the work (A 334-36). In a work that includes so many photographic imagesseventy-eight in the German edition-we must ask, however, do they merely serve to illustrate the narrative?3 Alternatively, is their function only that of introducing a mode of factuality into a narrative that might otherwise be read as fiction? Or is there something in the nature of photography, in the temporal and spatial frame of the photographic image, that presents a particular relationship to death and to memry that exceeds the symbolic mode of the linguistic text in which the images are embedded? Sebald will include visual images not because they underscore the written narrative but because they present the reader with that which the text alone cannot. In a recent interview, Sebald addresses the question concerning the difficult classification of his books by saying: "Facts are troublesome. The idea is to make it seem factual, though some of it might be invented" (Atlas 282). Here, Sebald seems to acknowledge the problematic position of aesthetics in relationship to the representation of the Holocaust introduced at least since Adorno. Seen in this light, one could conclude that Sebald employs photographs in his works not for their pictorial value but only their referential character-in other words, the photographs verify something in the world, or to borrow from Roland Barthes, they are the "certificate of presence" for the thing that has been there