Biology subjects

Braun, U.

Publications and source records attributed to Braun, U..

5 recordsLinked to original sources

bioRxiv2024

Exploring the role of the rich club in network control of neurocognitive states

We present a systematic analysis of the rich club as a possible control center of brain dynamics. Contrary to research stressing control properties of the rich club, our results indicate that the rich club and high-degree regions were not involved in optimally controlling the human connectome for a set of data-driven and task-evoked patterns of activity. Indeed, low-degree peripheral regions were more suited towards this. Findings were stable across group-level and individual-level rich club definitions, various cognitively meaningful brain state transitions, and different parameter settings. A regions contribution to optimal control processes was associated with its affiliation with certain intrinsic connectivity networks and its position on the secondary, but not primary, cortical gradient. These results do not negate an integratory role of the rich club, but merely question its proposed role as a driver of control. Indeed, if it would inhabit such a role, we would have expected opposite results. Our findings fit with a position describing the rich club as a passive "data-highway" which, by means of its high connectivity, can be easily controlled by peripheral regions and thus facilitate relevant communication channels between them. We call for methodological expansions of the control theoretical toolbox allowing for elaborations on the temporal dynamics of control processes.

neuroscience↗

bioRxiv2024

GSK3 inhibition ameliorates the abnormal contractility of Newfoundland ACM patient iPSC-cardiomyocytes

Arrhythmogenic Cardiomyopathy (ACM) is clinically characterized by ventricular arrhythmias causing sudden cardiac death and fibrofatty replacement of the myocardium leading to heart failure. One form of ACM is highly prevalent in the Canadian Province of Newfoundland and Labrador (NL) and has earned the moniker, The "Newfoundland Curse". This ACM in NL patients is often caused by a fully penetrant heterozygous missense pathogenic variant in the TMEM43 gene (TMEM43 c.1073C>T; TMEM43 p.S358L). Although the causative variant has been identified, little is known about the function of the TMEM43 protein in cardiomyocytes, how the TMEM43 p.S358L mutation contributes to the development of arrhythmias, or why the disease is more severe in males than females. To explore the role of TMEM43 in cardiomyocyte function, we generated induced pluripotent stem cells (iPSCs) from 2 severely affected male Newfoundland ACM (TMEM43 p.S358L) patients. CRISPR-Cas9 was used to genetically "repair" the heterozygous TMEM43 variant in ACM patient iPSCs or for TMEM43 gene knockout. ACM patient iPSC-cardiomyocytes with the TMEM43 p.S358L variant display pro-arrhythmogenic phenotypes in vitro with significantly elevated contraction rates and altered calcium handling, although no obvious gross abnormalities were observed across several major intracellular organelles. GSK3 inhibition significantly increased protein expression of {beta}-catenin as well as Lamin A/C and ameliorated the pro-arrhythmic tendencies of ACM patient iPSC-CMs.

cell biology↗

bioRxiv2019

Brain state stability during working memory is explained by network control theory, modulated by dopamine D1/D2 receptor function, and diminished in schizophrenia

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brain-wide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations.

neuroscience↗

bioRxiv2019

Generative network models identify biological mechanisms of altered structural brain connectivity in schizophrenia

BackgroundAlterations in the structural connectome of schizophrenia patients have been widely characterized, but the mechanisms leading to those alterations remain largely unknown. Generative network models have recently been introduced as a tool to test the biological underpinnings of the formation of altered structural brain networks.\n\nMethodsWe evaluated different generative network models to investigate the formation of structural brain networks in healthy controls (n=152), schizophrenia patients (n=66) and their unaffected first-degree relatives (n=32), and we identified spatial and topological factors contributing to network formation. We further investigated the association of these factors to cognition and to polygenic risk for schizophrenia.\n\nResultsStructural brain networks can be best accounted for by a two-factor model combining spatial constraints and topological neighborhood structure. The same wiring model explained brain network formation for all groups analyzed. However, relatives and schizophrenia patients exhibited significantly lower spatial constraints and lower topological facilitation compared to healthy controls. The model parameter for spatial constraint was correlated with the polygenic risk for schizophrenia and predicted reduced cognitive performance.\n\nConclusionsOur results identify spatial constraints and local topological structure as two interrelated mechanisms contributing to normal brain development as well as altered connectomes in schizophrenia. Spatial constraints were linked to the genetic risk for schizophrenia and general cognitive functioning, thereby providing insights into their biological basis and behavioral relevance.

neuroscience↗

bioRxiv2019

Neural network-based alterations during repeated heat pain stimulation in major depression

The current study aimed to identify alterations in brain activation and connectivity related to nociceptive processing and pain sensitization in major depressive disorder (MDD), using repeated heat pain stimulation during functional magnetic resonance imaging (fMRI) in 37 MDD patients and 33 healthy controls. Regional activation did not differ between groups, but functional connectivity was significantly decreased in MDD in a neural network connecting frontal, temporal and occipital areas (family-wise error (FWE)-corrected pFWE = 0.045). Supplemental analyses suggested a significant association between network connectivity and trait neuroticism (p = 0.007) but not with the clinical state or familiar risk of MDD (all p values > 0.13). Our data relate a network-based phenotype for altered pain processing and antinociceptive control to MDD and encourage future studies on the shared intermediate neural psychological risk architecture of MDD and chronic pain.

neuroscience↗