Integrated models of neurovascular coupling and BOLD signals: Responses for varying neural activations

Mathias, E. J.; Kenny, Allanah; Plank, Michael J.; Todem, David

doi:10.1016/j.neuroimage.2018.03.010

Cited by 33 publications

(33 citation statements)

References 63 publications

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“…Mathias et al 83 model that extended Kenny et al, 2018 82 model as explained in Table 3. For comparison of the model responses, the models were simulated using the 'ode23tb' solver in Simulink (MathWorks, Inc., USA), and the normalized vessel radius change was considered during a neuronal stimulus between 30 to 70 sec as shown in Fig.…”

Section: (B) Detailed Physiological Model Selectionmentioning

confidence: 95%

Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans

Arora

Walia

Hayashibe

et al. 2021

Preprint

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Transcranial direct current stimulation (tDCS) has been shown to evoke hemodynamics response; however, the mechanisms have not been investigated systematically using systems biology approaches. We postulate that such a mechanistic understanding of the hemodynamics response, called cerebrovascular reactivity (CVR) to tDCS, can facilitate adequate delivery of the tDCS current density to the neurovascular tissue in cerebrovascular diseases. Our study presents a systems biology approach to evaluate CVR during high-definition (HD) tDCS using a physiologically constrained grey-box linear model. Our grey-box linear model was developed for the multi-compartmental neurovascular unit consisting of the vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. The physiologically detailed model generated vessel oscillations in the frequency range of 0.05–0.2 Hz driven mainly by non-linear calcium dynamics. Then, model linearization was performed to develop a grey-box linear model for evaluating the acute effects during the first 150 seconds of anodal HD-tDCS in eleven healthy humans using functional near-infrared spectroscopy (fNIRS) based measure of blood volume. The grey-box linear model was fitted to the total hemoglobin concentration (tHb) changes with optodes in the vicinity of 4x1 HD-tDCS electrodes. We found that the grey-box model pathway from perivascular potassium to the vessel circumference (Pathway 3) presented the best fit to fNIRS tHb time series with the least mean square error (MSE, median < 2.5%). Then, minimal realization transfer function with reduced-order approximations of the grey-box model pathways was fitted to the average tHb time series. Pathway 3, with nine poles and two zeros (all free parameters), provided the best Chi-Square Goodness of Fit of 0.0078. Therefore, our study provided a sound systems biology approach to investigate the hemodynamic response to tDCS that needs further investigation in health, aging, and disease. Future studies can leverage transcranial alternating current stimulation for frequency-dependent physiological entrainment of relevant pathways, e.g., oscillations driven by nonlinear calcium dynamics, that can provide additional insights based on our grey-box modeling approach.

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Section: (B) Detailed Physiological Model Selectionmentioning

confidence: 95%

Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans

Arora

Walia

Hayashibe

et al. 2021

Preprint

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“…Nevertheless, mechanistic models based on the current understanding of the molecular underpinnings of the NVC are lacking. Some models exist, such as models proposed by Yücel et al [49] and Mathias et al [50,51]. However, these models have rarely been trained to time-resolved experimental data, and are typically connected to the 'Balloon' model in order to simulate the hemodynamic responses.…”

Section: Models Of the Nvcmentioning

confidence: 99%

Mathematical modeling of neurovascular coupling

Sten

2020

Linköping University Medical Dissertations

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“…Previous work [30] has provided the construction of an experimentally validated numerical (in silico) model based on experimental data to simulate the functional magnetic resonance imaging (fMRI) bloodoxygen-level dependent (BOLD) signal associated with NVC along with the associated metabolic and blood volume responses. An existing neuron model [28,29] has been extended to include an additional transient sodium (Na + ) ion channel (NaT) expressed in the neuron, and integrated into a complex NVC model [7,8,19].…”

Section: Physiological Model: Neurovascular Couplingmentioning

confidence: 99%

Global Sensitivity Analysis of High-Dimensional Neuroscience Models: An Example of Neurovascular Coupling

2019

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The complexity and size of state-of-the-art cell models have significantly increased in part due to the requirement that these models possess complex cellular functions which are thought-but not necessarily proven-to be important. Modern cell models often involve hundreds of parameters; the values of these parameters come, more often than not, from animal experiments whose relationship to the human physiology is weak with very little information on the errors in these measurements. The concomitant uncertainties in parameter values result in uncertainties in the model outputs or Quantities of Interest (QoIs). Global Sensitivity Analysis (GSA) aims at apportioning to individual parameters (or sets of parameters) their relative contribution to output uncertainty thereby introducing a measure of influence or importance of said parameters. New GSA approaches are required to deal with increased model size and complexity; a three stage methodology consisting of screening (dimension reduction), surrogate modeling, and computing Sobol' indices, is presented. The methodology is used to analyze a physiologically validated numerical model of neurovascular coupling which possess 160 uncertain parameters. The sensitivity analysis investigates three quantities of interest (QoIs), the average value of K + in the extracellular space, the average volumetric flow rate through the perfusing vessel, and the minimum value of the J.actin/myosin complex in the smooth muscle cell. GSA provides a measure of the influence of each parameter, for each of the three QoIs, giving insight into areas of possible physiological dysfunction and areas of further investigation.

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Integrated models of neurovascular coupling and BOLD signals: Responses for varying neural activations

Cited by 33 publications

References 63 publications

Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans

Grey-box modeling and hypothesis testing of functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal high-definition tDCS in healthy humans

Mathematical modeling of neurovascular coupling

Global Sensitivity Analysis of High-Dimensional Neuroscience Models: An Example of Neurovascular Coupling

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