Biology subjects

Winkler, A.

Publications and source records attributed to Winkler, A..

16 recordsLinked to original sources

bioRxiv2026

Quantitative and sensitive neuroblastoma minimal residual disease detection using extrachromosomal DNA (ecDNA) breakpoints

Sensitive detection of minimal residual disease (MRD) remains a major unmet need in high-risk neuroblastoma. MYCN amplification, a hallmark of high-risk disease, typically occurs on extrachromosomal DNA (ecDNA), but the potential of ecDNA-associated genomic rearrangements for individualized MRD monitoring has not been fully exploited. Here, we applied neuroblastoma-specific hybrid capture-based panel sequencing to identify patient-unique breakpoints within MYCN amplicons, and used Circle-seq and Nanopore sequencing to resolve the extrachromosomal amplicon structure in representative samples. Analysis of 8 neuroblastoma cell lines and 22 primary tumors identified 69 tumor-specific breakpoints. Those selected for assay development were validated by breakpoint-specific PCR and Sanger sequencing. Breakpoints detected in primary tumors remained detectable at relapse, supporting their stability as MRD markers. Breakpoint-specific real-time quantitative PCR and droplet digital PCR detected these junctions in bone marrow aspirates with high specificity and reached sensitivities down to a tumor DNA fraction of 10^-6. We applied this approach to 53 serial bone marrow aspirates from 14 patients with high-risk neuroblastoma to monitor MRD dynamics, resolving treatment response and molecular persistence. In six samples, breakpoint-positive DNA was detected in bone marrow that was negative by conventional cytology and immunocytology, highlighting the added value of molecular monitoring. Together, these findings establish ecDNA breakpoint-based detection as a strategy for MRD assessment in neuroblastoma, that is, in principle, applicable to any ecDNA-amplified oncogene.

cancer biology↗

bioRxiv2026

Lung microvascular rarefaction impairs pulmonary gas exchange and exacerbates heart failure with preserved ejection fraction

BackgroundDyspnea and exercise intolerance are the primary clinical symptoms of heart failure. Heart failure patients experience frequent hypoxemic episodes, yet underlying mechanisms and relevance remain poorly understood. In a cohort of heart failure patients and multiple animal models, we identify pulmonary capillary rarefaction driven by excessive autophagy in endothelial cells as a novel mechanism of hypoxemia and cardiac disease progression. MethodsA cohort of heart failure with preserved ejection fraction (HFpEF) patients was analyzed for parameters of left ventricular (LV) dysfunction and pulmonary gas exchange. Morphological and cellular mechanisms of impaired pulmonary oxygenation were assessed in three animal models of heart failure, namely two HFpEF models, SU5416-treated ZSF1 obese rats and high fat diet/L-NAME treated mice, and in rats subjected to aortic banding. Lung microvascular rarefaction was quantified by micro-computed tomography, stereology, flow cytometry and dye efflux. Cellular mechanisms of capillary loss were analyzed by single-cell transcriptomics, electron microscopy and immunofluorescence, and in mice with endothelial-specific deletion of the autophagy gene Atg7 (Atg7EN-KO). ResultsIn 234 HFpEF patients, advancing NYHA class was associated with progressive worsening of arterial oxygen saturation at rest and during exercise and a reduced lung diffusing capacity. Impaired gas diffusion correlated with indices of LV diastolic dysfunction. Impaired oxygenation and reduced exercise capacity were similarly evident in animal models of left heart disease, which showed a distinct loss of pulmonary microvessels and capillaries. Lung microvascular endothelial cells in HFpEF showed characteristics of increased autophagic flux and apoptosis. Relative to their wild type HFpEF controls, Atg7EN-KO mice had less capillary loss, restored normoxemia, improved exercise tolerance, and mitigated LV diastolic dysfunction. Additional studies in HFpEF mice corroborated the functional relevance of impaired gas exchange for the progression of left heart disease by demonstrating that additional hypoxia aggravated, whereas moderate hyperoxia improved LV function. ConclusionOur findings identify pulmonary microvascular rarefaction as a novel pathomechanism in heart failure that i) contributes to dyspnea and exercise intolerance, ii) impairs pulmonary gas exchange and iii) accelerates LV disease progression. Strategies targeting this axis such as moderate oxygen therapy may mitigate cardiopulmonary morbidity in heart failure. Clinical Trial RegistrationRegistered in the DRKS (Deutsches Register fur klinische Studien) as trial# DRKS00032974 at https://drks.de/search/en/trial/DRKS00032974.

physiology↗

bioRxiv2026

A new humanized TCR transgenic mouse model to study citrullinated tenascin C reactive T cells relevant to rheumatoid arthritis

ObjectivesAutoreactive T cells recognizing citrullinated antigens, although rare and difficult to study, are implicated in rheumatoid arthritis (RA). To allow functional studies and manipulation of such T cells, we have generated and characterized transgenic mice expressing a TCR cloned from an RA patient and reactive with a prominent target, citrullinated tenascin C (citTNC). MethodsA humanized TCR transgenic (hTCR-tg) mouse recognizing the citrullinated TNC22 (citTNC22) antigen in an HLA-DRB1*04:01 (HLA-DR4) restricted manner was developed by genetically engineering a chimeric TCR expressing murine constant domains and human V(D)J sequences. hTCR-tg mice were immune phenotyped in murine H-2b and humanized HLA-DR4 backgrounds using full spectrum flow cytometry, cytokine ELISAs and fluorospot assays at steady-state and after antigen challenge. Additionally, we investigated the presence of antibodies to citTNC and arthritis following citTNC protein immunization. ResultsThymic selection of hTCR T cells differed between the two MHC-II alleles, with a normal CD4+ T cell development observed solely under HLA-DR4 restriction. The chimeric hTCR maintained its citTNC22 specificity in vitro and ex vivo, without cross-reactivity to native TNC22 or other citrullinated autoantigens. hTCR-tg CD4+ T cells responded to antigen challenge in vivo and provided support to IgG class-switch and antigen-specific antibody production. Moreover, protein immunized hTCR-tg mice developed arthritis after periarticular challenge with citTNC. ConclusionshTCR-tg mice expressing an RA patient-derived autoreactive TCR develop functional antigen-specific and HLA-restricted CD4+ T cells. The combination of humanized HLA-DR4 and TNC22 mice will be a valuable tool in the development of antigen-specific therapies translatable to human disease.

immunology↗

bioRxiv2026

Molecular logics in dual sensor regulation of enzyme activity: Phosphorylation OR blue-light activation of cyanobacterial diguanylate cyclases

Bacterial cells use multiple environmental cues to regulate levels of the second messenger cyclic dimeric GMP. This compound influences key lifestyle decisions such as motility, biofilm formation, or virulence. Although many diguanylate cyclases (DGCs) combined with various sensory domains have been studied previously, how distinct inputs are integrated within a single enzyme remains incompletely understood. Here, we investigate a cyanobacterial family of dual-sensor DGCs that combine an N-terminal receiver (Rec) domain followed by a light-oxygen-voltage (LOV) domain upstream of a diguanylate cyclase (GGDEF) domain. Using in vivo activity screening and in vitro characterisation, we determined how phosphorylation and blue light, individually and jointly, regulate enzyme activity. By measuring kinetic parameters across four defined functional states, unphosphorylated or phosphorylated, in combination with dark or light states, we reveal logic gate-like behaviours. One representative, LaRldC, integrates both signals with pronounced fold-changes in activity-, consistent with overall OR-type logic and with light acting as the dominant input. Our results demonstrate its function as a molecular gate coupling phosphorylation and illumination sensing to cyclic-di-GMP formation. These findings provide valuable insights into multi-signal decision-making in cyanobacteria and establish further understanding of how modular sensory domains are wired to control bacterial second-messenger signalling.

biochemistry↗

bioRxiv2025

Myeloid cell recruitment propels right ventricular dysfunction in HFpEF via sterile inflammation.

BackgroundIn contrast to what has already been shown in HFpEF associated left ventricular (LV) diastolic dysfunction, leukocytes role in frequently occurring right ventricular dysfunction (RVD) secondary to HFpEF are so far missing, partially due to the lack of suitable small animal models. Here, we follow a translational research approach by establishing a murine HFpEF model developing manifest RVD and analyzed human HFpEF cohorts to study the mechanistic link between leukocytes and RVD in HFpEF. Methods8-week-old male and female C57BL/6J or Cx3cr1CreER/+R26tdTomato/+ mice were divided into four experimental groups: i) chow, ii) HFpEF (N[{omega}]-nitro-l-arginine methyl ester (L-NAME), 60% high-fat diet), iii) chronic hypoxia (10% O2) and iv) HFpEF and hypoxia (RV-HFpEF) to assess bi-ventricular function and myeloid cell dynamics. To test whether myeloid cells are causally involved in the development of RV remodeling in HFpEF, we additionally treated RV-HFpEF mice with the colony stimulating factor 1 receptor inhibitor PLX-5622 (PLX) to deplete myeloid cells. After 12 weeks, all experimental groups were subjected to transthoracic echocardiography, invasive hemodynamics or flow cytometry. ResultsRV-HFpEF resulted in LV diastolic dysfunction indicated by increased E/E ratio, reduced global longitudinal peak strain, smaller end-diastolic diameters and increased isovolumetric relaxation time compared to chow. RV-HFpEF animals developed RV hypertrophy and RVD evident as increased Fultons index and collagen content as well as elevated RV systolic pressures (RVSPs) and reduced tricuspid annular plane systolic excursion, respectively. Flow cytometric analyses revealed elevated total leukocyte, monocyte, and macrophage counts in RV tissue of RV-HFpEF compared to chow or LV tissue from RV-HFpEF animals. These data were confirmed by unbiased proteomic analyses of RV tissue from RV-HFpEF mice, demonstrating increased abundance of proteins involved in activation of the innate immune system, macrophage chemotaxis, cell adhesion and extracellular matrix organization when compared to LV tissue or other experimental groups. Fate mapping experiments revealed that recruited monocyte-derived macrophages became the main source of total cardiac macrophages in RV tissue from RV-HFpEF mice. Depletion of myeloid cells was associated with rescued RVSP profiles compared to RV-HFpEF control mice. In HFpEF patients, RV dilation was associated with an increased percentage of circulating monocytes. In RV biopsies from HFpEF patients, we found increased expression of adhesion molecules, fibrotic markers and inflammatory transcripts. ConclusionWe demonstrate that dysregulated myeloid cell dynamics are associated with, and directly contribute to, the pathogenesis of HFpEF-associated RVD in humans and mice. Clinical PerspectiveWhat is new: O_LIWe explore myeloid cell dynamics in a novel three-hit experimental HFpEF mouse model with RV hypertrophy, RV end-systolic pressure and RV dysfunction. C_LIO_LIIn this model, RV dysfunction was associated with macrophage expansion, monocyte recruitment and extracellular matrix deposition, whilst macrophage depletion partly reversed these changes and rescued RV hemodynamics. C_LIO_LIHFpEF patients with RV dilation or RV dysfunction exhibit unique leukocyte dynamics and inflammatory profiles when compared to HFpEF patients with normal RV function or diameters. C_LI Clinical implications: O_LIThere exists a major clinical discrepancy between high incidence of RV dysfunction associated to HFpEF and a lack of targeted treatment strategies. C_LIO_LIOur novel three-hit mouse model recapitulates many features of the clinical scenario of HFpEF patients with RV dysfunction, therefore representing an important step towards systematic testing and development of targeted treatment options. C_LIO_LISterile inflammation and dysregulation of innate immune cells may be suitable targets for therapeutic interventions against RV dysfunction in HFpEF. C_LI

physiology↗

bioRxiv2025

Crosstalk between the Methyl-Cytosine Dioxygenase TET3 and the Methyl-CpG-binding protein MECP2 Controls Neuronal Maturation

Active DNA demethylation depends on Ten-Eleven-Translocation (TET) enzymes, which oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC) and further derivatives. Mutations in TET3, encoding the predominant neuronal isoform, lead to Beck-Fahrner syndrome, a neurodevelopmental disorder. Using human iPSC-derived neurons, we show that TET3 is dispensable for neuronal specification but critical for subsequent maturation. Differentiating TET3-deficient neurons exhibit delayed transcriptional and proteomic transitions, altered synaptic signatures, and impaired network activity, indicating delayed functional maturation. Mechanistically, we identified an interaction between TET3 and the mC/hmC-binding protein MECP2, pathogenic variants of which cause Rett syndrome. MECP2 negatively regulates TET3 activity, as demonstrated in functional assays and by inverse hmC patterns in MECP2- and TET3-deficient neurons. Despite this, MECP2- and TET3-deficient neurons exhibit highly similar phenotypes later in differentiation. Our findings uncover a functional interplay between TET3 and MECP2 that coordinates DNA methylation and chromatin dynamics during neuronal maturation, suggesting a shared pathogenic mechanism in Beck-Fahrner and Rett syndromes.

neuroscience↗

bioRxiv2025

Scalable TCR synthesis and screening enables antigen reactivity mapping in vitiligo

T cell receptors (TCRs) mediate antigen recognition in adaptive immunity, yet large-scale mapping of TCR-antigen interactions remains a major challenge. Current approaches to synthesize and functionally screen TCRs remain technically complex and limited in throughput. We introduce a modular strategy, TCRAFT, to rapidly construct tens of thousands of TCRs for <$1 each while maintaining TCR-{beta} pairing with >99% accuracy. We integrate this approach with a high-throughput antigen discovery platform to enable library-on-library TCR-antigen screening. We reconstruct and screen 3,808 TCRs from vitiligo lesions, linking TCR specificity to transcriptional phenotypes for antigen-reactive T cells. To demonstrate scalability, we synthesize and screen 30,810 TCRs from donors with pancreatic ductal adenocarcinoma to capture antigen-specific TCRs. This workflow reduces the cost and complexity of large-scale TCR screening, enabling the expansion of the known landscape of antigen-specific TCRs in vitiligo with a method that can be readily extended to other immunological applications.

immunology↗

bioRxiv2024

Tracing active bugs in microbial communities by BONCAT and click chemistry-based enrichment of newly synthesised proteins

A comprehensive understanding of microbial community dynamics is fundamental to the advancement of environmental microbiology, human health, and biotechnology. Metaproteomics, i.e. the analysis of all proteins in a microbial community, provides insights into these complex systems. Microbial adaptation and activity depend to an important extent on newly synthesized proteins (nP), however, the distinction between nP and bulk proteins is challenging. The application of bioorthogonal non-canonical amino acid tagging (BONCAT) with click chemistry has demonstrated efficacy in the enrichment of nP in pure cultures. However, the transfer of this technique to microbial communities has proven challenging and has therefore not been used on microbial communities before. To address this, a new workflow with efficient and specific nP enrichment was developed using a laboratory-scale mixture of labelled E. coli and unlabelled yeast. This workflow was successfully applied to an anaerobic microbial community with initially low BONCAT efficiency. A substrate shift from glucose to ethanol selectively enriched nP with minimal background. The identification of bifunctional alcohol dehydrogenase and a syntrophic interaction between an ethanol-utilizing bacterium and two methanogens (hydrogenotrophic and acetoclastic) demonstrates the potential of metaproteomics targeting nP to trace microbial activity in complex microbial communities.

microbiology↗

bioRxiv2024

Fast and robust objective EEG audiometry

The current gold standard of audiometry relies on subjective behavioral responses, which is impractical and unreliable for certain groups such as children, individuals with severe disabilities, or the disabled elderly. This study presents a novel electroencephalography (EEG) system that is easy to setup and estimates audiometric thresholds quickly. Air-conduction audiometric thresholds at 250, 500, 1000, 2000, 4000, and 8000 Hz and 5 dB resolution were estimated from ten elderly patients with asymmetric sensorineural hearing loss and five normal hearing young adults using three different systems: the novel EEG system, conventional pure-tone audiometry (PTA), and an automated behavioral test with the same stimulus properties as in the EEG test. EEG data was collected for 15 minutes from 32 semi-dry EEG electrodes. Later, the EEG system was trimmed to 8 electrodes and 7.5 minutes of data with satisfactory results. Correlation and regression analysis validated the hearing thresholds derived from both EEG configurations relative to the behavioral hearing thresholds-Pearsons correlation of 0.82 between PTA and 8-electrode 7.5-minute EEG data. The results of this study open the door to fast and objective hearing threshold estimation with EEG.

neuroscience↗

bioRxiv2023

ESM-Scan - a tool to guide amino acid substitutions

Protein structure prediction and (re)design have gone through a revolution in the last three years. The tremendous progress in these fields has been almost exclusively driven by readily available machine-learning algorithms applied to protein folding and sequence design problems. Despite these advancements, predicting site-specific mutational effects on protein stability and function remains an unsolved problem. This is a persistent challenge mainly because the free energy of large systems is very difficult to compute with absolute accuracy and subtle changes to protein structures are also hard to capture with computational models. Here, we describe the implementation and use of ESM-Scan, which uses the ESM zero-shot predictor to scan entire protein sequences for preferential amino acid changes, thus enabling in-silico deep mutational scanning experiments. We benchmark ESM-Scan on its predictive capabilities for stability and functionality of sequence changes using three publicly available datasets and proceed by experimentally evaluating the tools performance on a challenging test case of a blue-light-activated diguanylate cyclase from Methylotenera species (MsLadC). We used ESM-Scan to predict conservative sequence changes in a highly conserved region of this enzyme responsible for allosteric product inhibition. Our experimental results show that the ESM-zero shot model emerges as a robust method for inferring the impact of amino acid substitutions, especially when evolutionary and functional insights are intertwined. ESM-Scan is publicly available at https://huggingface.co/spaces/thaidaev/zsp

biochemistry↗

bioRxiv2020

Heterogeneous relationships between white matter and behaviour

Several studies have established specific relationships between White Matter (WM) and behaviour. However, these studies have typically focussed on fractional anisotropy (FA), a neuroimaging metric that is sensitive to multiple tissue properties, making it difficult to identify what biological aspects of WM may drive such relationships. Here, we carry out a pre-registered assessment of WM-behaviour relationships in 50 healthy individuals across multiple behavioural and anatomical domains, and complementing FA with myelin-sensitive quantitative MR modalities (MT, R1, R2*). Surprisingly, we only find support for predicted relationships between FA and behaviour in one of three pre-registered tests. For one behavioural domain, where we failed to detect an FA-behaviour correlation, we instead find evidence for a correlation between behaviour and R1. This hints that multimodal approaches are able to identify a wider range of WM-behaviour relationships than focusing on FA alone. To test whether a common biological substrate such as myelin underlies WM-behaviour relationships, we then ran joint multimodal analyses, combining across all MRI parameters considered. No significant multimodal signatures were found and power analyses suggested that sample sizes of 40 to 200 may be required to detect such joint multimodal effects, depending on the task being considered. These results demonstrate that FA-behaviour relationships from the literature can be replicated, but may not be easily generalisable across domains. Instead, multimodal microstructural imaging may be best placed to detect a wider range of WM-behaviour relationships, as different MRI modalities provide distinct biological sensitivities. Our findings highlight a broad heterogeneity in WMs relationship with behaviour, suggesting that variable biological effects may be shaping their interaction. HighlightsO_LIPre-registered testing of microstructural imaging across modalities (FA, MT, R1, R2*) to test WM-behaviour relationships. C_LIO_LIPartial support for FA-behaviour relationships hypothesised based on previous literature. C_LIO_LIMultimodal approaches can help detect WM-behaviour relationships that are not detected with FA alone. C_LIO_LISample sizes of 40 to 200 may be needed to detect myelin-behaviour relationships in joint multimodal analyses. C_LIO_LIVariable biological effects may be shaping WM-behaviour relationships. C_LI

neuroscience↗

bioRxiv2020

Chronic Pain Patients Exhibit Individually Unique Cortical Signatures of Pain

We investigated how the trajectory of pain patients ongoing and fluctuating pain is encoded in the brain. In repeated fMRI sessions, 20 chronic back pain patients and 20 chronic migraineurs were asked to continuously rate the intensity of their endogenous pain. Linear mixed effects models were used to disentangle cortical processes related to pain intensity and to pain intensity changes. We found that the intensity of pain in chronic back pain patients is encoded in the anterior insula, the frontal operculum, and the pons; the change of pain of chronic back pain and chronic migraine patients is mainly encoded in the anterior insula. At the individual level, we identified a more complex picture where each patient exhibited their own signature of endogenous pain encoding. The diversity of the individual cortical signatures of chronic pain encoding results adds to the understanding of chronic pain as a complex and multifaceted disease.

neuroscience↗

bioRxiv2020

Metric and chronological time in human episodic memory

The relative contributions of metric and chronological time in the encoding of episodic memories are unknown. One hundred one healthy young adults viewed 48 unique episodes of visual events and were later tested on recall of the order of events (chronological time) and the precise timing of events (metric time). The behavioral results show that metric recall accuracy correlates with chronological accuracy for events within episodes, but does not play a role on larger time-scales across episodes. Functional magnetic resonance imaging during encoding and recall showed that metric time was represented in the posterior medial entorhinal cortex, as well as the temporal pole and the cerebellum, whereas chronological time was represented in a widespread brain network including the anterior lateral entorhinal cortex, hippocampus, parahippocampal cortex and the prefrontal cortex. We conclude that metric time has a role in episodic memory on short time-scales and is mainly subserved by medial temporal lobe structures.

neuroscience↗

bioRxiv2019

Experience-related alterations in white matter structure and gene expression in adult rats

White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI). However, it remains unclear which mechanisms drive or underlie WM plasticity in adulthood. Here, we combined DTI and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. Somatosensory experience resulted in differences in WM and grey matter structure. C-FOS mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the structural WM measures, suggesting that WM plasticity is activity-dependent. Analysis of myelin-related genes revealed higher myelin basic protein expression in WM, while genome-wide RNA sequencing analysis identified 134 differentially-expressed genes regulating proteins involved in functions related to cell proliferation and differentiation, neuronal activity modulation and regulation of myelination. In conclusion, the macroscale measures of WM differences identified in response to somatosensory experience are supported by molecular evidence, which strongly suggest myelination as, at least, one of the underlying mechanisms.

neuroscience↗

bioRxiv2018

The ‘zoo’ accompanying Botryococcus braunii: Unraveling the fundamentals of algae-bacteria biocoenosis

Bacteria occupy all major ecosystems and maintain an intensive relationship to the eukaryotes, developing together into complex biomes (i.e., phycosphere and rhizosphere). Interactions between eukaryotes and bacteria range from cooperative to competitive, with the associated microorganisms affecting their hosts development, growth, health and disease. Since the advent of non-culture dependent analytical techniques such as metagenome sequencing, consortia have been described but owing to the complex interactions rarely functionally dissected. Multifaceted analysis of the microbial consortium of the ancient phytoplankton Botryococcus as an attractive model food web revealed that its all abundant bacterial members belong to a distinct niche of biotin auxotrophs, essentially depending on the microalga. In addition, hydrocarbonoclastic bacteria without vitamin auxotrophies, which adversely affect the algal cell morphology, appear evidently decimated. Synthetic rearrangement of a minimal community consisting of alga, mutualistic and parasitic bacteria underpins the model of a eukaryote that domesticates its own mutualistic bacterial "zoo" to manipulate and control its surrounding biosphere. This model of domestication of mutualistic bacteria for the defense against destruents by a eukaryotic host could represent ecologically relevant interactions that cross species boundaries. Metabolic and system reconstruction disentangles the relationships and provide a blueprint for the construction of mutually beneficial synthetic ecosystems.

microbiology↗

bioRxiv2017

Schizophrenia Exhibits Bi-Directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits

Distributed neural dysconnectivity is considered a hallmark feature of schizophrenia, yet a tension exists between studies pinpointing focal disruptions versus those implicating brain-wide disturbances. The cerebellum and the striatum communicate reciprocally with the thalamus and cortex through monosynaptic and polysynaptic connections, forming cortico-striatal-thalamic-cerebellar (CSTC) functional pathways that may be sensitive to brain-wide dysconnectivity in schizophrenia. It remains unknown if the same pattern of alterations persists across CSTC systems, or if specific alterations exist along key functional elements of these networks. We characterized connectivity along major functional CSTC subdivisions using resting-state functional magnetic resonance imaging in 159 chronic patients and 162 matched controls. Associative CSTC subdivisions revealed consistent brain-wide bi-directional alterations in patients, marked by hyper-connectivity with sensory-motor cortices and hypo-connectivity with association cortex. Focusing on the cerebellar and striatal components, we validate the effects using data-driven k-means clustering of voxel-wise dysconnectivity and support vector machine classifiers. We replicate these results in an independent sample of 202 controls and 145 patients, additionally demonstrating that these neural effects relate to cognitive performance across subjects. Taken together, these results from complementary approaches implicate a consistent motif of brain-wide alterations in CSTC systems in schizophrenia, calling into question accounts of exclusively focal functional disturbances.

neuroscience↗