Modeling the relationship between neuronal activity and the BOLD signal: contributions from astrocyte calcium dynamics

Abstract

Functional magnetic resonance imaging relies on the coupling between neuronal and vascular activity, but the mechanisms behind this coupling are still under discussion. Recent experimental evidence suggests that calcium signaling may play a significant role in neurovascular coupling. However, it is still controversial where this calcium signal is located (in neurons or elsewhere), how it operates and how relevant is its role. In this paper we introduce a biologically plausible model of the neurovascular coupling and we show that calcium signaling in astrocytes can explain main aspects of the dynamics of the coupling. We find that calcium signaling can explain so-far unrelated features such as the linear and non-linear regimes, the negative vascular response (undershoot) and the emergence of a (calcium-driven) Hemodynamic Response Function. These features are reproduced here for the first time by a single model of the detailed neuronal-astrocyte-vascular pathway. Furthermore, we analyze how information is coded and transmitted from the neuronal to the vascular system and we predict that frequency modulation of astrocytic calcium dynamics plays a key role in this process. Finally, our work provides a framework to link neuronal activity to the BOLD signal, and vice-versa, where neuronal activity can be inferred from the BOLD signal. This opens new ways to link known alterations of astrocytic calcium signaling in neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s diseases) with detectable changes in the neurovascular coupling.

Multiscale modelling of neuronal dynamics in hippocampus CA1

“…In addition, the framework developed here is suitable to be included in whole-brain simulation platforms [4], which extends the importance and utility of our study. Furthermore, methods to estimate brain signals (LFP, EEG, MEG, fMRI) from the type of mean-field used here have already been developed [28, 29], which will also allow the comparison with experimental results on whole-brain activity. In combination, these developments provide an efficient solution to the complicated task of modeling the brain at different scales and open new perspectives for future studies.…”

Medial temporal lobe hyperconnectivity is key to Alzheimer’s disease: Insight from physiological aging to dementia

“…44 Yet, further insight will be required to accurately determine the causal relationships underlying this circuit dysfunction. Since abnormal calcium signalling in astrocytes is known to affect neurovascular coupling and could lead to neuronal hyperactivity, 45,46 astrocytic deficiency or inflammation might be further explored as possible explanations for aberrant AT activity in AD. Prognostically, we deliver compelling evidence that AT hyperconnectivity indicates hastened disease advancement, as increased AT functional connectivity was associated with faster dementia onset in MCI patients who progressed to AD-dementia.…”

A mean-field to capture asynchronous irregular dynamics of conductance-based networks of adaptive quadratic integrate-and-fire neuron models

“…The next step within our semi-analytic approach is to fit the output firing rate of the single neuron with the template transfer function given in Equation (12), where erf c is the Gauss error function.…”

“…Mean-field or neural-mass models are appropriate to model clinically recorded signals such as fMRI, EEG, or MEG [11,12] because they provide a simplified representation of the complex electrical and synaptic activity of large populations of neurons. These models are based on the idea that the activity of a large group of neurons can be described by the average electrical activity of the group, without having to consider the individual activity of each neuron.…”