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Biology subjects

Mueller, N.

Publications and source records attributed to Mueller, N..

17 recordsLinked to original sources

Image-grounded encoding models reveal distinct temporal profiles of naturalistic object and scene processing in the human brain

In real-world vision, the human brain needs to process large amounts of information to effectively interact with its environment. It is well established that our visual system has specialized regions to process information efficiently, such as scene-, face-, and object-selective areas, which can be uncovered using functional magnetic resonance imaging (fMRI). However, functional localizers typically use artificially separated stimuli (e.g. scene backgrounds vs. object cutouts), and fMRI signals are insensitive to potential temporal processing differences. Here, we identify temporal signatures of object and scene processing in natural visual environments by building image-grounded brain-predictive encoding models of human electroencephalography (EEG) responses. In a large set of high-resolution natural images, we first separate object from scene information on a per-image basis, and then feed this information to train separate deep neural network-based encoding models to predict EEG responses to the full, intact images. We find that encoding models that receive only object information consistently exhibit a delayed temporal encoding profile compared to models that only receive scene information. Control analyses confirm the robustness of this delayed object encoding, showing that consistent selection of object or scene information is needed to achieve high encoding performance. Using these distinct encoding profiles as processing templates, we reveal which image parts are seen by the brain as an object, versus a background scene element. These findings demonstrate that object and scene processing in the human brain unfold differentially over time and indicate that image-grounded encoding models are powerful tools for isolating components of naturalistic perception. SignificanceThe neural mechanisms underlying visual perception are typically studied by experimentally separating different kinds of information, for example presenting either isolated objects or scene backgrounds. Since information naturally co-occurs in the world -- objects are typically embedded within scenes -- this artificial separation reduces ecological validity. We leverage image-computable neural encoding models to identify distinct visual processing profiles within ecologically valid, natural images. Models that receive stimuli in which only objects are visible and scene information is masked predict EEG responses at later time points than models receiving the inverse, "scene-only" stimuli. By quantifying how items such as buildings, trees or the ground are encoded in EEG signals, we reveal which elements of visual environments drive neural responses to intact, real-world images.

neuroscience↗

Spatial sampling of deep neural network features improves encoding models of foveal and peripheral visual processing in humans

Deep Neural Networks (DNNs) are increasingly being used to build encoding models to predict neural data recorded during visual stimulation. Their ability to process natural images makes them a prime candidate for studying the neural profile underlying real-world visual perception. However, there are still prominent discrepancies in how DNNs and humans process visual information. One discrepancy lies in the spatial sampling of visual input: while DNNs uniformly sample from their input at every spatial location, the human visual system samples differentially from central and peripheral regions. Here, we implement multiple spatial sampling strategies on feature maps of DNNs into encoding models that predict human EEG responses to a novel stimulus set consisting of large, high-quality natural scene images. By applying differential spatial sampling of DNN feature maps, we reveal distinct temporal profiles for encoding of peripheral vs. central information in EEG signals. Moreover, we show that a differential spatial sampling derived from the density of retinal ganglion cells yields the best performing encoding model when using DNN feature maps. We experimentally confirm this pattern by separately stimulating peripheral and central visual field regions, and demonstrate that the distinct temporal profiles for central and peripheral information are only revealed when using large-field stimuli. Together, these results show that aligning the spatial sampling of humans and DNN encoding models can improve predictions of neural data. The distinct temporal profiles for encoding of peripheral vs. central information support a global-to-local processing hierarchy of real-world vision.

neuroscience↗

Shape-Biased Learning by Thinking Inside the Box

Convolutional Neural Networks (CNNs) surpass human-level performance on visual object recognition and detection, but their behavior still differs from human behavior in important ways. One prominent example is that CNNs trained on ImageNet exhibit an image texture bias, while humans exhibit a strong bias toward object shape. Although CNN shape bias can be increased in various ways, e.g., using data augmentation or additional training techniques, it remains unclear what causes the strong discrepancy between human and CNN object recognition strategies. Developmental research suggests that one factor driving human shape bias is that during early childhood, toddlers tend to fill their field-of-view with close-up objects. Here, we operationalize this close-up as a zoom-in on objects during CNN training which we show increases shape bias without any additional training or data augmentation. We provide further evidence for the advantage of closeup object vision by systematically manipulating the background-object ratio during CNN training, and demonstrate a strong (inverse) correlation with shape bias. Moreover, zooming-in on objects, thereby more closely emulating child vision, not only increases shape bias but also concurrently aligns classification accuracy and shape bias between humans and CNNs. Finally, we achieve a near human-like shape bias when using a developmentally-inspired background-object ratio for training and shape bias assessment. In sum, from a simple adjustment to common image datasets - zooming-in on objects - human-like shape bias can emerge. These results suggest that taking inspiration from human learning strategies is a promising avenue for building human-aligned, efficient, and more robust vision CNNs.

neuroscience↗

Inter-individual and inter-regional variability of breast milk antibody reactivity to bacterial lipopolysaccharides

Breast milk is a vital source of nutrients, prebiotics, and protective factors, including antibodies and antimicrobial proteins. Using bacterial lipopolysaccharide arrays, we investigated the reactivity and specificity of breast milk antibodies towards microbial antigens, comparing samples from rural Kenya and urban Switzerland. Results showed considerable variability in antibody reactivity both within and between these locations. Kenyan breast milk demonstrated broad reactivity to bacterial lipopolysaccharides, likely due to increased microbial exposure. Antibodies primarily recognized the O-antigens of lipopolysaccharides and showed strong binding to specific carbohydrate motifs. Notably, antibodies against specific Escherichia coli O-antigens showed cross-reactivity with parasitic pathogens like Leishmania major and Plasmodium falciparum, thus showing that antibodies reacting against lipopolysaccharide O-antigens can recognize a wide range of antigens beyond bacteria. The observed diversity in antigen recognition highlights the significance of breast milk in safeguarding infants from infections, particularly those prevalent in specific geographic regions. The findings also offer insights for potential immunobiotic strategies to augment natural antibody-mediated defense against diverse pathogens.

microbiology↗

Online stimulation of the prefrontal cortex during practice increases motor variability and modulates later cognitive transfer: a randomized, double-blinded and sham-controlled tDCS study

BackgroundThe benefits of learning a motor skill extend to improved task-specific cognitive abilities. The mechanistic underpinnings of this motor-cognition relationship potentially rely on overlapping neural resources involved in both processes, an assumption lacking causal evidence. ObjectivesWe hypothesize that interfering with prefrontal networks would affect concurrent motor skill performance, long-term learning and associated cognitive functions dependent on similar networks (transfer). MethodsWe conducted a randomized, double-blinded, sham-controlled brain stimulation study using transcranial direct current stimulation (tDCS) in young adults spanning over three weeks to assess the role of the prefrontal regions in learning a complex balance task and long-term cognitive performance. ResultsBalance training combined with active tDCS led to higher performance variability in the trained task as compared to the sham group, without affecting the learning rate. Furthermore, active tDCS also positively impacted performance in untrained motor and cognitive tasks. ConclusionThe findings of this study help ascertaining the networks directly involved in learning a complex motor task and its implications on cognitive function. Hence, opening up the possibility of harnessing the observed frontal networks involved in resource mobilization in instances of aging, brain lesion/injury or dysfunction.

neuroscience↗

Validation and Establishment of a SARS-CoV-2 Lentivirus Surrogate Neutralization Assay as a pre-screening tool for the Plaque Reduction Neutralization Test

Neutralization assays are important in understanding and quantifying neutralizing antibody responses towards SARS-CoV-2. The SARS-CoV-2 Lentivirus Surrogate Neutralization Assay (SCLSNA) can be used in biosafety level 2 (BSL-2) laboratories and has been shown to be a reliable, alternative approach to the plaque reduction neutralization test (PRNT). In this study, we optimized and validated the SCLSNA to assess its ability as a comparator and pre-screening method to support the PRNT. Comparability between the PRNT and SCLSNA was determined through clinical sensitivity and specificity evaluations. Clinical sensitivity and specificity produced acceptable results with 100% (95% CI: 94-100) specificity and 100% (95% CI: 94-100) sensitivity against ancestral Wuhan spike pseudotyped lentivirus. The sensitivity and specificity against B.1.1.7 spike pseudotyped lentivirus resulted in 88.3% (95% CI: 77.8 to 94.2) and 100% (95% CI: 94-100), respectively. Assay precision measuring intra-assay variability produced acceptable results for High (1:[≥] 640 PRNT50), Mid (1:160 PRNT50) and Low (1:40 PRNT50) antibody titer concentration ranges based on the PRNT50, with %CV of 14.21, 12.47, and 13.28 respectively. Intermediate precision indicated acceptable ranges for the High and Mid concentrations, with %CV of 15.52 and 16.09, respectively. However, the Low concentration did not meet the acceptance criteria with a %CV of 26.42. Acceptable ranges were found in the robustness evaluation for both intra-assay and inter-assay variability. In summary, the validation parameters tested met the acceptance criteria, making the SCLSNA method fit for its intended purpose, which can be used to support the PRNT.

scientific communication and education↗

LGR5 targeting molecules as therapeutic agents for multiple cancer types

Leucine-rich repeat-containing G-protein receptor 5 (LGR5) has been characterised as a stem cell and cancer stem cell marker. Previous analyses of LGR5 transcript levels indicate high level expression discriminates malignancies such as colorectal cancer (CRC) and pre-B acute lymphoblastic leukaemia (pre-B ALL) from healthy tissues suggesting LGR5 protein expression may provide a molecular handle for prognosis and treatment. We have developed highly specific, high affinity antibodies to the extracellular domain of human LGR5 (-LGR5) that detect high LGR5 protein levels in colorectal cancer (CRC), hepatocellular carcinoma (HCC), and pre-B ALL. In contrast, there is low to undetectable levels of LGR5 protein in normal colon and rectal epithelia, liver, ovarian tissues, brain and immune cell types. LGR5 is rapidly internalised from the plasma membrane and trafficked to intracellular vesicular compartments including lysosomes. Treatment of high LGR5-expressing CRC and pre-B ALL cancer cell lines with an antibody-drug conjugate version of -LGR5 (-LGR5-ADC) lead to effective cell killing at nanomolar concentrations. Interventional treatment of pre-B ALL tumours with -LGR5-ADC in vivo led to rapid tumour attrition. We further demonstrated the therapeutic utility of humanised -LGR5 by using the corresponding scFv fragment for the generation of -LGR5 chimeric antigen receptors (CARs) and a Bispecific T cell Engager (BiTE). -LGR5-CAR-NK cells were effective at killing LGR5-expressing cells while -LGR5/-CD3 BiTEs induce T cell activation and killing of NALM6 cells by cytotoxic CD8+ T cells. Taken together, this study establishes -LGR5-based therapeutic modalities that effectively discriminate and target CRC, HCC and pre-B ALL tumour cells. One Sentence SummaryWe generated novel antibodies against the cancer cell marker LGR5, validated diagnostic use in prioritizing specific cancer types for targeting, and developed antibody-based therapeutics.

cell biology↗

ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow calculating temporal biodiversity change at the community scale and reach back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century.

ecology↗

Repeated toxic injuries of murine liver are tolerated through microsteatosis and mild inflammation

The liver has a remarkable capacity to regenerate and thus compensates for repeated injuries through toxic chemicals, drugs, alcohol or malnutrition for decades. However, largely unknown is how and when alterations in the liver occur due to tolerable damaging insults. To that end, we induced repeated liver injuries over ten weeks in a mouse model injecting carbon tetrachloride (CCl4) twice a week. We lost 10% of the study animals within the first six weeks, which was accompanied by a steady deposition of extracellular matrix (ECM) regardless of metabolic activity of the liver. From week six onwards, all mice survived, and in these mice ECM deposition was rather reduced, suggesting ECM remodeling as a liver response contributing to better coping with repeated injuries. The data of time-resolved paired transcriptome and proteome profiling of 18 mice was subjected to multi-level network inference, using Knowledge guided Multi-Omics Network inference (KiMONo), identified multi-level key markers exclusively associated with the injury-tolerant liver response. Interestingly, pathways of cancer and inflammation were lighting up and were validated using independent data sets compiled of 1034 samples from publicly available human cohorts. A yet undescribed link to lipid metabolism in this damage-tolerant phase was identified. Immunostaining revealed an unexpected accumulation of small lipid droplets (microvesicular steatosis) in parallel to a recovery of catabolic processes of the liver to pre-injury levels. Further, mild inflammation was experimentally validated. Taken together, we identified week six as a critical time point to switch the liver response program from an acute response that fosters ECM accumulation to a tolerant "survival" phase with pronounced deposition of small lipid droplets in hepatocytes potentially protecting against the repetitive injury with toxic chemicals. Our data suggest that microsteatosis formation plus a mild inflammatory state represent biomarkers and probably functional liver requirements to resist chronic damage. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=163 HEIGHT=200 SRC="FIGDIR/small/476054v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@11ecc7aorg.highwire.dtl.DTLVardef@1027df5org.highwire.dtl.DTLVardef@9ba0f7org.highwire.dtl.DTLVardef@164f80a_HPS_FORMAT_FIGEXP M_FIG C_FIG The datasets generated via transcriptomics, proteomics as well as blood, histopathological and biochemical analysis were analyzed in an independent and integrative manner. The independent analysis was performed via state-of-the-art statistical approaches i.e. differential and consistently regulated genes and proteins. Combining the results identified three fibrosis phases. Using the KiMONo algorithm, a fibrosis specific multi-omic network was inferred. Within this network we identified several nodes connecting phase III specific features forming 13 distinct multi-omic modules suggesting a tolerance scheme. Some of these modules were experimentally validated and compared to 11 independent human studies of various liver diseases.

systems biology↗

Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome

Strong evidence suggests that human human RNA-binding proteins (RBPs) are critical factors for viral infection, yet there is no feasible experimental approach to map exact binding sites of RBPs across the SARS-CoV-2 genome systematically at a large scale. We investigated the role of RBPs in the context of SARS-CoV-2 by constructing the first in silico map of human RBP / viral RNA interactions at nucleotide-resolution using two deep learning methods (pysster and DeepRiPe) trained on data from CLIP-seq experiments. We evaluated conservation of RBP binding between 6 other human pathogenic coronaviruses and identified sites of conserved and differential binding in the UTRs of SARS-CoV-1, SARS-CoV-2 and MERS. We scored the impact of variants from 11 viral strains on protein-RNA interaction, identifying a set of gain-and loss of binding events. Lastly, we linked RBPs to functional data and OMICs from other studies, and identified MBNL1, FTO and FXR2 as potential clinical biomarkers. Our results contribute towards a deeper understanding of how viruses hijack host cellular pathways and are available through a comprehensive online resource (https://sc2rbpmap.helmholtz-muenchen.de).

bioinformatics↗

Inhibiting BCKDK in triple-negative breast cancer suppress protein translation, impair mitochondrial function, and potentiate doxorubicin cytotoxicity

Triple-negative breast cancers (TNBCs) are characterized by poor survival, prognosis and gradual resistance to cytotoxic chemotherapeutics, like doxorubicin (DOX), which is limited by its cardiotoxic and chemoresistant effects that manifest over time. TNBC growth and survival are fuelled by reprogramming branched-chain amino acids (BCAAs) metabolism, which rewires oncogenic gene expression and cell signaling pathways. A regulatory kinase of the rate-limiting enzyme of the BCAA catabolic pathway, branched-chain ketoacid dehydrogenase kinase (BCKDK), have recently been implicated in driving tumor cell proliferation and conferring drug resistance by activating RAS/RAF/MEK/ERK signaling. However it remains unexplored if BCKDK remodels TNBC proliferation, survival and susceptibility to DOX-induced genotoxic stress. TNBC cell lines exhibited reduced BCKDK expression in response to DOX. Genetic and pharmacological inhibition of BCKDK in TNBC cell lines displayed reduced intracellular and secreted BCKAs. Moreover, BCKDK inhibition with concurrent DOX treatment exacerbated apoptosis, caspase activity and loss of TNBC proliferation. Transcriptome analysis of BCKDK silenced cells confirmed a marked upregulation of the apoptotic signaling pathway with increased protein ubiquitylation and compromised mitochondrial metabolism. BCKDK silencing in TNBC downregulated mitochondrial metabolism genes, reduced electron complex protein expression, oxygen consumption and ATP production. Silencing BCKDK in TNBC upregulated sestrin 2 and concurrently decreased protein synthesis and mTORC1 signaling. Inhibiting BCKDK in TNBC remodel BCAA flux, reduces protein translation triggering cell death, ATP insufficiency and susceptibility to genotoxic stress. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/444634v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@19d375eorg.highwire.dtl.DTLVardef@9dfe2corg.highwire.dtl.DTLVardef@9a1eecorg.highwire.dtl.DTLVardef@642fdb_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

Genotype and age influence cortical-FKBP5 at multiple regulatory and single-cell-type levels in severe psychiatric disorders

Identification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with decades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a therapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell-types and sub-anatomical areas of the human brain this occurs. This knowledge is critical to propel FKBP5/1-targeted treatment development. Here, we performed an extensive, large-scale postmortem study (n=1024) of FKBP5/1 examining prefrontal cortex (BA9, BA11, BA24) derived from subjects that lived with schizophrenia, major depression or bipolar disorder. With an extensive battery of RNA (bulk RNA sequencing, single-nucleus RNA sequencing, microarray, qPCR, RNAscope) and protein (immunoblot, immunohistochemistry) analysis approaches, we thoroughly investigated the effects of disease-state, aging and genotype on cortical FKBP5/1 expression including in a cell-type specific manner. We identified consistently heightened FKBP5/1 levels in psychopathology and with age, but not genotype, with these effects strongest in schizophrenia. Using single-nucleus RNA sequencing (snRNAseq) and targeted histology, we established that these disease- and aging-effects on FKBP5/1 expression were most pronounced in excitatory supragranular neurons. We then found that this increase in FKBP5 levels likely impacts on synaptic plasticity, as FKBP5 gex levels strongly and inversely correlated with dendritic mushroom spine density and brain-derived neurotrophic factor (BDNF) levels in supragranular neurons. These findings pinpoint a novel cellular and molecular mechanism that has significant potential to open a new avenue of FKBP51 drug development to treat cognitive symptoms in psychiatric disorders.

neuroscience↗

Identifying hidden drivers of heterogeneous inflammatory diseases

Chronic inflammatory diseases are characterized by complex interactions between genetic predisposition and tissue-specific immune responses. This heterogeneity complicates diagnoses and the ability to exploit omics approaches to improve disease management, develop more effective therapeutics, and apply precision medicine. Using skin inflammation as a model, we developed a method that integrates deep clinical phenotyping information (phenomics) with transcriptome data of lesional and non-lesional skin (564 samples) to identify clinically-relevant gene signatures. It led us to discover so-far unexplored factors, including CCAAT Enhancer-Binding Protein Beta (CEBPB) in neutrophil invasion, and Pituitary Tumor-Transforming 2 (PTTG2) in the pathogenic epithelial response to inflammation. These factors were validated using genetically-modified human skin equivalents, migration assays, and in situ imaging. Thus, by meaningful integration of deep clinical phenotyping and omics data we reveal hidden drivers of clinically-relevant biological processes.

immunology↗

A comparative 'omics approach to candidate pathogenicity factor discovery in the brain-eating amoeba Naegleria fowleri

Of the 40 described Naegleria species, only N. fowleri can establish infection in humans, killing almost invariably within two weeks. In the brain, the amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing massive inflammation. Conversely, its close relative Naegleria gruberi, which is used as a laboratory model organism, is non-pathogenic. The exact pathogenicity factors distinguishing N. fowleri from its harmless relatives are unclear. We have here taken an -omics approach to understanding N. fowleri biology and infection at the system level. We provide the first analysis of genomic diversity between strains, finding little conservation in synteny but high conservation in protein complement. We also demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in N. gruberi. Our comparative genomic analysis, together with a transcriptomic analysis of low versus high pathogenicity N. fowleri cultured in a mouse infection model, allowed us to construct a model of cellular systems involved in pathogenicity and furthermore provides ~500 novel candidate pathogenicity factors in this currently rare but highly fatal pathogen.

microbiology↗

Regulation of Hepatic MicroRNAs in Response to Early Stage Echinococcus multilocularis Egg Infection in C57BL/6 mice

In this study, we present a comprehensive analysis of the hepatic miRNA transcriptome in mice suffering from experimental primary alveolar echinococcosis (AE), a parasitic infection caused upon ingestion of Echinococcus multilocularis (E. multilocularis) eggs. At one month post-infection, infected C57BL/6 mice, along with non-infected control mice, were euthanized. Subsequently livers were collected and used for small RNA library preparation and next-generation sequencing (NGS). The most significantly dysregulated hepatic miRNAs were validated by Stem-loop RT-qPCR. We identified 28 miRNAs with significantly altered expression levels upon infection with E. multilocularis. Of these, 9 were up-regulated (fold change (FC) [≥] 1.5) and 19 were down-regulated (FC [≤] 0.66) as compared to the non-infected controls. In infected liver tissues, mmu-miR-148a-3p and mmu-miR-101b-3p were 8- and 6-fold down-regulated, respectively, and the expression of mmu-miR-22-3p was reduced by 50%, compared to non-infected liver tissue. Conversely, significantly higher hepatic levels were noted for Mus musculus (mmu)-miR-21a-5p (FC = 2.3) and mmu-miR-122-5p (FC = 1.8). Down-regulated miRNAs were highly enriched in Reactome and KEGG pathways of angiogenesis and fatty acids biosynthesis. Moreover, relative mRNA expression levels of three pro-angiogenic (VEGFA, MTOR and HIF1-) and two lipogenic (FASN and ACSL1) genes were significantly higher in livers of E. multilocularis infected mice. Lastly, we studied the issue related to functionally mature arm selection preference (5p and/or 3p) from the miRNA precursor and showed that 9 pre-miRNAs exhibited different arm selection preferences in normal versus infected liver tissues. Our study provides first evidence of miRNA involvement in liver pathogenesis during AE. Our future research will focus on the characterization of miRNA transcriptome patterns in more advanced AE-stages towards the assessment of microRNA therapy for AE, and experimentally address functional characteristics of selected features presently found.\n\nAuthor SummaryVarious infectious diseases in humans have been associated with altered expression patterns of microRNAs (miRNAs), a class of small non-coding RNAs involved in negative regulation of gene expression. Herein, we revealed that significant alterations of miRNA expression occurred in murine liver subsequently to experimental infection with Echinococcus multilocularis (E. multilocularis) eggs when compared to non-infected controls. At the early stage of murine AE, hepatic miRNAs were mainly downregulated. Respective target genes of the most extensively downregulated miRNAs were involved in angiogenesis and fatty acid synthesis. Indeed, angiogenic and lipogenic genes were found to be significantly higher expressed in E. multilocularis infected livers relative to non-infected controls. These boosted cellular pathways are advantageous for development of the E. multilocularis metacestodes, since this larval stage is not able to undertake de novo fatty acid synthesis, and angiogenesis allows the larvae to be periparasitically supplied by oxygen and nutrients and to get rid of waste products. More research on the miRNA transcriptome at more advanced infection-stages, and on the role of angiogenesis in E. multilocularis larval growth and metastasis, is required to assess the usefulness of microRNA- and anti-angiogenic therapies against E. multilocularis infection.

microbiology↗

Differences in strategic abilities but not associative processes explain memory development

Childrens learning capabilities change while growing up. One framework that describes the cognitive and neural development of childrens growing learning abilities is the two-component model. It distinguishes processes that integrate separate features into a coherent memory representation (associative component) and executive abilities, such as elaboration, evaluation and monitoring, that support memory processing (strategic component). In an fMRI study using an object-location association paradigm, we investigated how the two components influence memory performance across development. We tested children (10-12 yrs., n=31), late adolescents (18 yrs., n=29) and adults (25+ yrs., n=30) of either sex. For studying the associative component, we also probed how the utilisation of prior knowledge (schemas) facilitates memory across age groups. Children had overall lower retrieval performance, while adolescents and adults did not differ from each other. All groups benefitted from schemas, but this effect did not differ between groups. Performance differences between groups were associated with deactivation of the dorsal medial prefrontal cortex (dmPFC), which in turn was linked to executive functioning. These patterns were stronger in adolescents and adults and seemed absent in children. This pattern of results suggests the childrens executive system, the strategic component, is not as mature and thus cannot facilitate memory performance in the same way as in adolescents/adults. In contrast, we did not find age-related differences in the associative component; with activity in the angular gyrus predicting memory performance systematically across groups. Overall our results suggest that differences of executive rather than associative abilities explain memory differences between children, adolescents and adults.

neuroscience↗

Pre-stimulus feedback connectivity biases the content of visual experiences

Ongoing, spontaneous fluctuations in neural excitability and in network-wide activity patterns before stimulus onset have been proposed to underlie variability in near-threshold stimulus detection paradigms, i.e. whether an object is perceived or not. Here, we investigated the impact of pre-stimulus neural fluctuations on the content of perception, i.e. whether one or another object is perceived. We recorded neural activity with magnetoencephalography before and while participants briefly viewed a bi-stable image, the Rubin face/vase illusion, and required them to report their perceived interpretation on each trial. Using multi-variate pattern analysis, we showed robust decoding of the perceptual report during the post-stimulus period. Applying source localization to the classifier weights suggested early recruitment of V1 and ~160 ms recruitment of category-sensitive FFA. These post-stimulus effects were driven by stronger oscillatory power in the gamma frequency band for face vs vase reports. In pre-stimulus intervals, we found no differences in oscillatory power between face vs. vase reports in V1 nor in FFA, indicating similar levels of neural excitability. Despite this, we found stronger connectivity between V1 and FFA prior to face reports for low-frequency oscillations. Specifically, the strength of pre-stimulus feedback connectivity (i.e. Granger causality) from FFA to V1 predicted not only the category of the upcoming percept, but also the strength of post-stimulus neural activity associated with the percept. Our work identifies pre-stimulus network states that shape future processing in category-sensitive brain regions and in this way determine the content of visual experiences.

neuroscience↗