Modification of the biophysical model of the neuro-glia-vascular unit to improve the characteristics of the BOLD signal

Loshkarev R.I., Postnov D.E.
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Functional magnetic resonance imaging (fMRI) based on the blood-oxygen-level-dependent (BOLD) signal is the leading method for non-invasive mapping of human brain activity. Quantitative interpretation of fMRI data requires biophysical models that trace the multi-stage signaling chain from neuronal electrical activity to the measured hemodynamic response. The biophysical model of the neurogliovascular unit (NGVU), which describes neuronal dynamics based on the Hodgkin –Huxley formalism, calcium signaling in astrocytes, smooth muscle electrophysiology, and a balloon model of hemodynamics, is a promising tool for predictive modeling of BOLD signal dynamics in fMRI. However, calculation results using the existing version of the NGVU model show several discrepancies with experimental data. In this study, we identify the reasons for this discrepancy, including the absence of a mechanism for sustained vasodilation via epoxyeicosatrienoic acids (EET) in the model. To address this issue, the NGVU model is supplemented with a description of the EET pathway linking astrocytic calcium to smooth muscle calcium, and metabolic inertia of oxygen consumption is added. Together with refinement of the model parameter values, this made it possible to eliminate the non-physiological decrease in the BOLD signal during long-term neuron stimulation and reproduce a stable BOLD plateau of +5% with a poststimulus decrease of about −1.5%. A systematic computational study (30 experiments, ∼ 165 computational cases) of the initial overshoot of the hemodynamic response was performed. It was found that acceleration of cross-bridge dynamics alone provides canonical BOLD peak timing; strengthening KIR is not required for this, but brings the late-stimulus level to the observed value and thereby determines the overshoot ratio. A sweep over 16 stimulation conditions (32 simulation runs for two model configurations) showed that the response shape is preserved for stimulus durations of 10–30 s at I = 0.018–0.022 mA/cm2, and delineated the limits of the model’s applicability. The contribution of the studied signaling pathways to the BOLD signal characteristics was revealed: the fast K+/KIR pathway generates the initial overshoot, while the slow EET pathway maintains the plateau, consistent with the biphasic (fast and slow) dynamics of functional hyperemia.

Keywords: neurogliovascular unit, neurovascular coupling, BOLD signal, smooth muscle cells, KIR channels, EET pathway, cross-bridge dynamics
Citation in English: Loshkarev R.I., Postnov D.E. Modification of the biophysical model of the neuro-glia-vascular unit to improve the characteristics of the BOLD signal // Computer Research and Modeling, 2026, vol. 18, no. 5, pp. 1379-1400
Citation in English: Loshkarev R.I., Postnov D.E. Modification of the biophysical model of the neuro-glia-vascular unit to improve the characteristics of the BOLD signal // Computer Research and Modeling, 2026, vol. 18, no. 5, pp. 1379-1400
DOI: 10.20537/2076-7633-2026-18-5-1379-1400
URL: http://crm-en.ics.org.ru/journal/article/3786/

 

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Copyright © 2026 Loshkarev R.I., Postnov D.E.

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