Blog Image

The ISBGroup Blog

About the blog

Here you can read about everything that's happening in the ISB Group.

Celebrating 2023 with new a publication in PLOS Computational Biology

Uncategorised Posted by ISB GroupPosted on Tue, January 03, 2023 11:32:57

We are pleased to announce that our manuscript entitled “Mechanistic model for human brain metabolism and its connection to the neurovascular coupling” have recently been accepted for publication in PLoS Computational Biology. In this manuscript we present a mechanistic model for the human cerebral metabolism based on magnetic resonance spectroscopy data. We have also connected this model to our previously published model for the neurovascular coupling. Below follows a slightly more detailed summary of the manuscript. 

The neurovascular and neurometabolic couplings are highly central for several clinical imaging techniques since these frequently use blood oxygenation (the BOLD signal) as a proxy for neuronal activity. This relationship is described by the highly complex neurovascular and neurometabolic couplings, which describe the balancing between increased metabolic demand and blood flow, and which involve several cell types and regulatory systems, which all change dynamically over time. While there are previous works that describe the neurovascular coupling in detail, neither we nor others have developed connections to corresponding mechanistic models for the third aspect, the metabolic aspect. Furthermore, magnetic resonance spectroscopy (MRS) data for such modelling readily is available. In this paper we present a minimal mechanistic model that can describe the metabolic response to visual stimuli. The model is trained to describe experimental data for the relative change in metabolic concentrations of several metabolites in the visual cortex during stimulation. The model is also validated against independent validation data, that was not used for model training. Finally, we also connect this metabolic model to a detailed mechanistic model of the neurovascular coupling. Showing that the model can describe both the metabolic response and a neurovascular response simultaneously. 

You can find the article HERE!

Overview of the modelling work presented A. A table summary of different models and what aspects of the neurovascular coupling they cover. B. A schematic overview of how this work connects pre-existing models for the neurovascular coupling with a description for the cerebral metabolism and how this new interconnected model can be used for informative simulations. C: A detailed illustration of the metabolism model precented in this work. Neuronal activity triggers increased consumption of glucose, which triggers downstream signaling cascades of different metabolites, which can be captured using Magnetic Resonance Spectroscopy (MRS). D. A schematic illustration of the modelling cycle used to develop a minimal model.


ICSB 2022

Uncategorised Posted by ISB GroupPosted on Mon, October 10, 2022 09:59:46

The 21st International Conference on Systems Biology (ICSB 2022) was held in Berlin, Germany, these past few days. We had a great time there and had the opportunity to meet great people, take part in interesting discussions, and see some of Berlin. During the conference, we presented several posters and gave some talks (summarized below). We would like to extend our thanks to the ICSB committee for a well-organized conference. Until next time, from the ISB group.

The full program can be found here: https://www.icsb2022.berlin/, and down below is a summary of our contributions.

M4-health: digital twins that follow you throughout your health journey, Gunnar Cedersund

Authors: Gunnar Cedersund

An interconnected multi-level mechanistic model of the human brain, Nicolas Sundqvist

Authors: Nicolas Sundqvist, Henrik Podéus, Malin Ejneby Silverå, Sebastian Sten, Salvador Dura-Bernal, Soroush Safaei, Maria Engström and Gunnar Cedersund

Digital twins and hybrid modelling for simulation of physiological variables and stroke risk, Tilda Herrgårdh

Authors: Tilda Herrgårdh, Elizabeth Hunter, Kajsa Tunedal, John D. Kelleher and Gunnar Cedersund

Insights on hemodynamic changes in hypertension and T2D through non-invasive cardiovascular modeling, Kajsa Tunedal

Authors: Kajsa Tunedal, Carl-Johan Carlhäll, Federica Viola, Tino Ebbers and Gunnar Cedersund

Mathematical modeling of cytokine interplay in human monocytes during LPS stimulation, Niloofar Nikaein

Authors: Niloofar Nikaein, Kedeye Tuerxun, Daniel Eklund, Alexander Persson, Robert Kruse, Eva Särndahl, Eewa Nånberg, Antje Thonig, Gunnar Cedersund, Elin Nyman, Dirk Repsilber and On Behalf Of The X-Hide Consortium

Connecting the Neurovascular coupling and Electrophysiological signaling – a modeling approach, Henrik Podéus

Authors: Henrik Podéus, Gunnar Cedersund and Salvador Dura-Bernal

An in silico resection to estimate global and regional hepatobiliary function in patients undergoing hepatectomy, Christian Simonsson

Authors: Christian Simonsson, Wolf Claus Bartholomä, Anna Lindhoff Larsson, Markus Karlsson, Bengt Norén, Gunnar Cedersund, Nils Dahlström, Per Sandström and Peter Lundberg

A comprehensive mechanistic model of adipocyte signaling with layers of confidence, William Lövfors

Authors: William Lövfors, Cecilia Jönsson, Charlotta S. Olofsson, Gunnar Cedersund and Elin Nyman



A multi-data based quantitative model for the neurovascular coupling in the brain

Uncategorised Posted by ISB GroupPosted on Thu, September 08, 2022 20:06:18

A while back we made our expanded brain model, capable of describing and predicting various multi-species data, available on bioRxiv (https://doi.org/10.1101/2021.03.25.437053). After some further work we are aiming to submit our work, In the meanwhile feel free to take part of the currently available version.

Abstract: The neurovascular coupling (NVC) forms the foundation for functional imaging techniques of the brain, since NVC connects neural activity with observable hemodynamic changes. Many aspects of the NVC have been studied both experimentally and with mathematical models: various combinations of blood volume and flow, electrical activity, oxygen saturation measures, blood oxygenation level-dependent (BOLD) response, and optogenetics have been measured and modeled in rodents, primates, or humans. We now present a first inter-connected mathematical model that describes all such data types simultaneously. The model can predict independent validation data not used for training. Using simulations, we show for example how complex bimodal behaviors appear upon stimulation. These simulations thus demonstrate how our new quantitative model, incorporating most of the core aspects of the NVC, can be used to mechanistically explain each of its constituent datasets.

Overview of the presented study: A: Cellular pathways underlying the neurovascular coupling (NVC). B. Overview of commonly used experimental techniques C. Overview of the study D. Comparison of different published models describing the NVC with regards to different mechanisms


Upcoming Ph.D. defense, Sebastian Sten, “Mathematical modelling of neurovascular coupling”

Events, News Posted by Gunnar CedersundPosted on Sat, September 05, 2020 01:59:22

https://www.youtube.com/watch?v=OTvhkYVhq5Y&feature=youtu.be

On Friday, this coming week, September 11, 2020, at 9AM CET, our Ph.D. student Sebastian Sten will defend his Ph.D. thesis, entitled “Mathematical modelling of neurovascular coupling”.

Sebastian has been co-supervised between Gunnar Cedersund (who leads this group), Fredrik Elinder (BKV and electrophysiological expert), and Maria Engström (who was the main supervisor, and who is an expert on fMRI). In the thesis, Sebastian presents four papers which incrementally unravels more and more mechanistic details of how the main signal in fMRI – the BOLD signal – is generated. In Paper 1, he demonstrates that the main part of the BOLD signal response can not be caused by a negative feedback, as was first believed, but by a combination of a fast positive and a slow negative feedforward arm. In Paper 2, the model from paper 1 is extended with GABA, which makes it able to describe the negative BOLD response. In Paper 3, he unravels more mechanistic details of the two arms, and finds out that there are in fact at least three arms: the fastest positive is the NO-arm from interneurons, the slightly slower positive arm is the PGE2 arm from pyramidal cells, and the slowest negative arm is caused by NPY interneurons. In the final paper 4 (still in ms), these mechanistic details for the signalling and the control of the arteriolar diameter is embedded in a larger model, which also contains the biomechanical flow to capillariies and venules, and the creation of the actual BOLD signal. The final model is – to the best of our knowledge – the most complete and comprehensive model for the BOLD signal, and it simultaneously describes data and extracts information from informative optogenetic stimulation experiments in mice, from unique BOLD and Local Field Potential (LFP) experiments in monkeys, and from advanced MRI measurements of BOLD, volumes and flows, in humans.

Front page of the thesis, illustration done by our other group member Christian Simonsson, who wanted to capture not only the brain, but that experiments, analysis, and mathematical modelling has come together.

Overview of the main processes studied in the thesis.

After the defense, Sebastian will work for two more weeks, wrapping up the final paper. Thereafter, other people in the group will continue to work on these models, e.g. by connecting them to more detailed models for metabolism, electrophysiology, and – eventually – to clinical practice, e.g. by allowing for more measurements to come together into a more comprehensive and complete analysis of fMRI data. However, Sebastian himself will thereafter start a position at AstraZeneca, in the group we have the most contact with there: their metabolic and cardiovascular preclinical modelling group.

A link to the Ph.D. thesis is found here, and a link to the youtube event where the defense is broadcasted is found here.

Sebastian about to do the final formal step before the actual defense: nailing his thesis to the “thesis tree” of the medical faculty.