Modeling the Relationship Between Neuronal Activity and the BOLD Signal: Contributions from Astrocyte Calcium Dynamics

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.