A combined DTI-fMRI approach for optimizing the delineation of posteromedial versus anterolateral entorhinal cortex.

In the entorhinal cortex (EC), attempts have been made to identify the human homologue regions of the medial (MEC) and lateral (LEC) subregions using either functional magnetic resonance imaging (fMRI) or diffusion tensor imaging (DTI). However, there are still discrepancies between entorhinal subdivisions depending on the choice of connectivity seed regions and the imaging modality used. While DTI can be used to follow the white matter tracts of the brain, fMRI can identify functionally connected brain regions. In this study, we used both DTI and resting-state fMRI in 103 healthy adults to investigate both structural and functional connectivity between the EC and associated cortical brain regions. Differential connectivity with these regions was then used to predict the locations of the human homologues of MEC and LEC. Our results from combining DTI and fMRI support a subdivision into posteromedial (pmEC) and anterolateral (alEC) EC and reveal a confined border between the pmEC and alEC. Furthermore, the EC subregions obtained by either imaging modality showed similar distinct whole-brain connectivity profiles. Optimizing the delineation of the human homologues of MEC and LEC with a combined, cross-validated DTI-fMRI approach allows to define a likely border between the two subdivisions and has implications for both cognitive and translational neuroscience research.

Disruption of Social Orders in Societal Transitions as Affective Control of Uncertainty.

Bayesian affect control theory is a model of affect-driven social interaction under conditions of uncertainty. In this paper, we investigate how the operationalization of uncertainty in the model can be related to the disruption of social orders-societal pressures to adapt to ongoing environmental and technological change. First, we study the theoretical tradeoffs between three kinds of uncertainty as groups navigate external problems: validity (the predictability of the environment, including of other agents), coherence (the predictability of interpersonal affective dynamics), and dependence (the predictability of affective meanings). Second, we discuss how these uncertainty tradeoffs are related to contemporary political conflict and polarization in the context of societal transitions. To illustrate the potential of our model to analyze the socio-emotional consequences of uncertainty, we present a simulation of diverging individual affective meanings of occupational identities under uncertainty in a climate change mitigation scenario based on events in Germany. Finally, we sketch a possible research agenda to substantiate the novel, but yet mostly conjectural, ideas put forward in this paper.

Structural connectivity-based segmentation of the human entorhinal cortex.

The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posteromedial (pmEC) and anterolateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected with presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected with distal CA1 and proximal subiculum (dCA1pSub) and lateral orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in the previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC.

Functional parcellation using time courses of instantaneous connectivity.

Functional neuroimaging studies have led to understanding the brain as a collection of spatially segregated functional networks. It is thought that each of these networks is in turn composed of a set of distinct sub-regions that together support each network's function. Considering the sub-regions to be an essential part of the brain's functional architecture, several strategies have been put forward that aim at identifying the functional sub-units of the brain by means of functional parcellations. Current parcellation strategies typically employ a bottom-up strategy, creating a parcellation by clustering smaller units. We propose a novel top-down parcellation strategy, using time courses of instantaneous connectivity to subdivide an initial region of interest into sub-regions. We use split-half reproducibility to choose the optimal number of sub-regions. We apply our Instantaneous Connectivity Parcellation (ICP) strategy on high-quality resting-state FMRI data, and demonstrate the ability to generate parcellations for thalamus, entorhinal cortex, motor cortex, and subcortex including brainstem and striatum. We evaluate the subdivisions against available cytoarchitecture maps to show that our parcellation strategy recovers biologically valid subdivisions that adhere to known cytoarchitectural features.

Radiosensitive Hematopoietic Cells Determine the Extent of Skin Inflammation in Experimental Epidermolysis Bullosa Acquisita.

Animal models have enhanced our understanding of the pathogenesis of autoimmune diseases. For these models, genetically identical, inbred mice have commonly been used. Different inbred mouse strains, however, show a high variability in disease manifestation. Identifying the factors that influence this disease variability could provide unrecognized insights into pathogenesis. We established a novel Ab transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune disease characterized by (muco)-cutaneous blistering caused by anti-type VII collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against the von Willebrand factor A-like domain 2) transfer showed clear variability among inbred mouse strains, that is, severe cutaneous blistering and inflammation in C57BL/6J and absence of skin lesions in MRL/MpJ mice. The transfer of anti-COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex activation of neutrophils from C57BL/6J or MRL/MpJ mice showed an impaired reactive oxygen species release from the latter, whereas no differences were observed after PMA activation. This finding was paralleled by divergent expression profiles of immune complex-activated neutrophils from either C57BL/6J or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine the varying extent of skin inflammation and blistering in the end-stage effector phase of EBA.

Consensus and stratification in the affective meaning of human sociality.

We investigate intrasocietal consensus and variation in affective meanings of concepts related to authority and community, two elementary forms of human sociality. Survey participants (n = 2,849) from different socioeconomic status (SES) groups in German society provided ratings of 909 social concepts along three basic dimensions of affective meaning. Results show widespread consensus on these meanings within society and demonstrate that a meaningful structure of socially shared knowledge emerges from organizing concepts according to their affective similarity. The consensus finding is further qualified by evidence for subtle systematic variation along SES differences. In relation to affectively neutral words, high-status individuals evaluate intimacy-related and socially desirable concepts as less positive and powerful than middle- or low-status individuals, while perceiving antisocial concepts as relatively more threatening. This systematic variation across SES groups suggests that the affective meaning of sociality is to some degree a function of social stratification.

Emotional connotations of words related to authority and community.

We present a database of 858 German words from the semantic fields of authority and community, which represent core dimensions of human sociality. The words were selected on the basis of co-occurrence profiles of representative keywords for these semantic fields. All words were rated along five dimensions, each measured by a bipolar semantic-differential scale: Besides the classic dimensions of affective meaning (valence, arousal, and potency), we collected ratings of authority and community with newly developed scales. The results from cluster, correlational, and multiple regression analyses on the rating data suggest a robust negativity bias for authority valuation among German raters recruited via university mailing lists, whereas community ratings appear to be rather unrelated to the well-established affective dimensions. Furthermore, our data involve a strong overall negative correlation-rather than the classical U-shaped distribution-between valence and arousal for socially relevant concepts. Our database provides a valuable resource for research questions at the intersection of cognitive neuroscience and social psychology. It can be downloaded as supplemental materials with this article.

ANGST: affective norms for German sentiment terms, derived from the affective norms for English words.

We present the German adaptation of the Affective Norms for English Words (ANEW; Bradley & Lang in Technical Report No. C-1. Gainsville: University of Florida, Center for Research in Psychophysiology). A total of 1,003 Words-German translations of the ANEW material-were rated on a total of six dimensions: The classic ratings of valence, arousal, and dominance (as in the ANEW corpus) were extended with additional arousal ratings using a slightly different scale (see BAWL: Võ et al. in Behavior Research Methods 41: 531-538, 2009; Võ, Jacobs, & Conrad in Behavior Research Methods 38: 606-609, 2006), along with ratings of imageability and potency. Measures of several objective psycholinguistic variables (different types of word frequency counts, grammatical class, number of letters, number of syllables, and number of orthographic neighbors) for the words were also added, so as to further facilitate the use of this new database in psycholinguistic research. These norms can be downloaded as supplemental materials with this article.

Effects of estrogen on spatial navigation and memory.

RATIONALE: Animal studies suggest that the so-called "female" hormone estrogen enhances spatial navigation and memory. This contradicts the observation that males generally out-perform females in spatial navigation and tasks involving spatial memory. A closer look at the vast number of studies actually reveals that performance differences are not so clear. OBJECTIVES: To help clarify the unclear performance differences between men and women and the role of estrogen, we attempted to isolate organizational from activational effects of estrogen on spatial navigation and memory. METHODS: In a double-blind, placebo-controlled study, we tested the effects of orally administered estradiol valerate (E2V) in healthy, young women in their low-hormone menstrual cycle phase, compared to healthy, young men. Participants performed several first-person, environmentally rich, 3-D computer games inspired by spatial navigation and memory paradigms in animal research. RESULTS: We found navigation behavior suggesting that sex effects dominated any E2 effects with men performing better with allocentric strategies and women with egocentric strategies. Increased E2 levels did not lead to general improvements in spatial ability in either sex but to behavioral changes reflecting navigation flexibility. CONCLUSION: Estrogen-driven differences in spatial cognition might be better characterized on a spectrum of navigation flexibility rather than by categorical performance measures or skills.

Sonographic Aeration Scoring Indicates Disease Severity in Critically Ill Patients with COVID-19.

AIMS AND METHODS: We evaluated an ultrasound score from 0 to 32 points in eight pulmonary regions to monitor critically ill COVID-19 patients. The score was correlated to surrogate parameters of disease severity, i.e., the oxygenation index, respiratory support, mortality, plasma interleukin-6, and WHO and ARDS classifications. RESULTS: A total of 27 patients were repeatedly examined, and 71 examinations were evaluated. Patients with severe COVID-19 scored higher (median 17) than those with moderate disease (median 11, p < 0.01). The score did not differentiate between stages of ARDS as defined by the Berlin criteria (p = 0.1) but could discern ARDS according to the revised ESICM definition (p = 0.002). Non-survivors had higher ultrasound scores than survivors (median 18.5 vs. 14, p = 0.04). The score correlated to the oxygenation index (ρ = -0.56, p = 0.03), and changes in the score between examinations correlated to changes in oxygenation (ρ = -0.41, p = 0.16). The correlation between the score and interleukin-6 was ρ = 0.35 (p < 0.001). The interrater reliability for the score was ICC = 0.87 (p < 0.001). CONCLUSIONS: The ultrasound score is a reliable tool that might help monitor disease severity and may help stratify the risk of mortality.

Molecular capsules derived from resorcin[4]arenes by metal-coordination.

A short introduction to the fundamental features and recent developments of supramolecular chemistry is presented besides defining scope and limitation of this review article. A brief overview about calix[n]arenes and especially resorcin[4]arenes and their conformationally rigid cavitands is given. Selected examples are presented to demonstrate the dependence of self-assembly of cavitands exhibiting different flexibility either due to their basic macrocycle or due to flexible receptor units commonly located at the o,o'-position of the resorcinarene ring. In addition, the process of self-assembly is also controlled by metal coordination geometry as shown by one example. The receptor units may also be connected at the methylene group of the cavitand as shown by one example. Examples of supramolecular architectures are presented utilizing the special features of 2,2':6',2″-terpyridine (terpy) metal-binding ligand. The synthesis and characterization of a metallo-supramolecular Zn-coordination cage with a diameter of 4-5 nm based on a cavitand-terpy building block is presented in detail.

Insights into the quantification and reporting of model-related uncertainty across different disciplines.

Quantifying uncertainty associated with our models is the only way we can express how much we know about any phenomenon. Incomplete consideration of model-based uncertainties can lead to overstated conclusions with real-world impacts in diverse spheres, including conservation, epidemiology, climate science, and policy. Despite these potentially damaging consequences, we still know little about how different fields quantify and report uncertainty. We introduce the "sources of uncertainty" framework, using it to conduct a systematic audit of model-related uncertainty quantification from seven scientific fields, spanning the biological, physical, and political sciences. Our interdisciplinary audit shows no field fully considers all possible sources of uncertainty, but each has its own best practices alongside shared outstanding challenges. We make ten easy-to-implement recommendations to improve the consistency, completeness, and clarity of reporting on model-related uncertainty. These recommendations serve as a guide to best practices across scientific fields and expand our toolbox for high-quality research.

Individual attitude change and societal dynamics: Computational experiments with psychological theories.

We present an agent-based model for studying the societal implications of attitude change theories. Various psychological theories of persuasive communication at the individual level are implemented as simulation experiments. The model allows us to investigate the effects of contagion and assimilation, motivated cognition, polarity, source credibility, and idiosyncratic attitude formation. Simulations show that different theories produce different characteristic macrolevel patterns. Contagion and assimilation are central mechanisms for generating consensus, however, contagion generates a radicalized consensus. Motivated cognition causes societal polarization or the fragmentation of attitudes. Polarity and source credibility have comparatively little effect on the societal distribution of attitudes. We discuss how the simulations provide a bridge between microlevel psychological theories and the aggregated macrolevel studied by sociology. This approach enables new types of evidence for evaluating psychological theory to complement experimental approaches, thus answering calls to enhance the role of coherent and formalized theory in psychological science. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Single-molecule force spectroscopy of supramolecular heterodimeric capsules.

The specific interaction of a supramolecular binding motif was quantitatively evaluated by dynamic single-molecule force spectroscopy (SMFS) using an atomic force microscope (AFM). The supramolecular capsule forms by two different cavitands stitched together by four hydrogen bonds between carboxylic acid and pyridyl groups. The tetra(carboxyl)cavitand is monofunctionalized at the lower rim with a flexible poly(ethylene glycol) linker and attached to the AFM sensor tip. Single-molecule association experiments are accomplished using a diluted self-assembled monolayer (SAM) of the tetra(pyridyl)cavitand on a gold substrate. The measured single-molecule dissociation forces of the heterodimeric capsule represent the mechanical stability of the supramolecular system and allow a quantitative evaluation of the interaction according to the Bell-Evans model yielding dissociation rate constant k(off) = (0.14 +/- 0.14) s(-1), reaction length x(beta) = (0.56 +/- 0.076) nm and an estimated value of DeltaG(0) = -27 kJ mol(-1).

Behavior-dependent directional tuning in the human visual-navigation network.

The brain derives cognitive maps from sensory experience that guide memory formation and behavior. Despite extensive efforts, it still remains unclear how the underlying population activity unfolds during spatial navigation and how it relates to memory performance. To examine these processes, we combined 7T-fMRI with a kernel-based encoding model of virtual navigation to map world-centered directional tuning across the human cortex. First, we present an in-depth analysis of directional tuning in visual, retrosplenial, parahippocampal and medial temporal cortices. Second, we show that tuning strength, width and topology of this directional code during memory-guided navigation depend on successful encoding of the environment. Finally, we show that participants' locomotory state influences this tuning in sensory and mnemonic regions such as the hippocampus. We demonstrate a direct link between neural population tuning and human cognition, where high-level memory processing interacts with network-wide visuospatial coding in the service of behavior.

Making sense of social interaction: Emotional coherence drives semantic integration as assessed by event-related potentials.

We compared event-related potentials during sentence reading, using impression formation equations of a model of affective coherence, to investigate the role of affective content processing during meaning making. The model of Affect Control Theory (ACT; Heise, 1979, 2007) predicts and quantifies the degree to which social interactions deflect from prevailing social norms and values - based on the affective meanings of involved concepts. We tested whether this model can predict the amplitude of brain waves traditionally associated with semantic processing. To this end, we visually presented sentences describing basic subject-verb-object social interactions and measured event-related potentials for final words of sentences from three different conditions of affective deflection (low, medium, high) as computed by a variant of the ACT model (Schröder, 2011). Sentence stimuli were closely controlled across conditions for alternate semantic dimensions such as contextual constraints, cloze probabilities, co-occurrences of subject-object and verb-object relations. Personality characteristics (schizotypy, Big Five) were assessed to account for individual differences, assumed to influence emotion-language interactions in information processing. Affective deflection provoked increased negativity of ERP waves during the P2/N2 and N400 components. Our data suggest that affective incoherence is perceived as conflicting information interfering with early semantic processing and that increased respective processing demands - in particular in the case of medium violations of social norms - linger on until the N400 time window classically associated with the integration of concepts into embedding context. We conclude from these results that affective meanings influence basic stages of meaning making.

Hippocampal theta phases organize the reactivation of large-scale electrophysiological representations during goal-directed navigation.

Humans are adept in simultaneously following multiple goals, but the neural mechanisms for maintaining specific goals and distinguishing them from other goals are incompletely understood. For short time scales, working memory studies suggest that multiple mental contents are maintained by theta-coupled reactivation, but evidence for similar mechanisms during complex behaviors such as goal-directed navigation is scarce. We examined intracranial electroencephalography recordings of epilepsy patients performing an object-location memory task in a virtual environment. We report that large-scale electrophysiological representations of objects that cue for specific goal locations are dynamically reactivated during goal-directed navigation. Reactivation of different cue representations occurred at stimulus-specific hippocampal theta phases. Locking to more distinct theta phases predicted better memory performance, identifying hippocampal theta phase coding as a mechanism for separating competing goals. Our findings suggest shared neural mechanisms between working memory and goal-directed navigation and provide new insights into the functions of the hippocampal theta rhythm.

Hexadirectional coding of visual space in human entorhinal cortex.

Entorhinal grid cells map the local environment, but their involvement beyond spatial navigation remains elusive. We examined human functional MRI responses during a highly controlled visual tracking task and show that entorhinal cortex exhibited a sixfold rotationally symmetric signal encoding gaze direction. Our results provide evidence for a grid-like entorhinal code for visual space and suggest a more general role of the entorhinal grid system in coding information along continuous dimensions.

Alzheimer's disease.

The German psychiatrist and neuropathologist Alois Alzheimer was fascinated by the symptoms of Auguste D., a 50-year-old woman admitted to the Frankfurt Psychiatric Hospital in 1901 who suffered from memory disturbances, paranoia and progressive confusion. After her death and autopsy, Alzheimer described histological alterations in her brain that later came to be known as amyloid plaques and neurofibrillary tangles (Figure 1). The case report was published in a psychiatric textbook some years later, and this peculiar and (at the time) seemingly rare illness was later named Alzheimer's disease.

Resting-state gamma-band power alterations in schizophrenia reveal E/I-balance abnormalities across illness-stages.

We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64-90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ.