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bioRxiv · 10.1101/2022.02.15.480629

Mechanistic model for human brain metabolism and the neurovascular coupling.

Sundqvist, N.·Sten, S.·Engström, M.·Cedersund, G.
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Abstract

The neurovascular and neurometabolic couplings (NVC and NMC) connects cerebral activity, blood flow, and metabolism. This interconnection is used in for instance functional imaging, which analyses the blood-oxygen-dependent (BOLD) signal. The mechanisms underlying the NVC are complex, which warrants a model-based analysis of data. We have previously developed a mechanistically detailed model for the NVC, and others have proposed detailed models for cerebral metabolism. However, existing metabolic models are still not fully utilizing available magnetic resonance spectroscopy (MRS) data and are not connected to detailed models for NVC. Therefore, we herein present a new model that integrates mechanistic modelling of both MRS and BOLD data. The metabolic model covers central metabolism, using a minimal set of interactions, and can describe time-series data for glucose, lactate, aspartate, and glutamate, measured after visual stimuli. Statistical tests confirm that the model can describe both estimation data and predict independent validation data, not used for model training. The interconnected NVC model can simultaneously describe BOLD data and can be used to predict expected metabolic responses in experiments where metabolism has not been measured. This model is a step towards a useful and mechanistically detailed model for cerebral blood flow and metabolism, with potential applications in both basic research and clinical applications. Author summaryThe 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 describes the balancing between increased metabolic demand and blood flow, and which involves 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.

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Sundqvist, N., Sten, S., Engström, M., Cedersund, G.. 2022-02-19. Mechanistic model for human brain metabolism and the neurovascular coupling.. https://doi.org/10.1101/2022.02.15.480629

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