Toward an integrative neurovascular framework for studying brain networks

Abstract

. Brain functional connectivity based on the measure of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals has become one of the most widely used measurements in human neuroimaging. However, the nature of the functional networks revealed by BOLD fMRI can be ambiguous, as highlighted by a recent series of experiments that have suggested that typical resting-state networks can be replicated from purely vascular or physiologically driven BOLD signals. After going through a brief review of the key concepts of brain network analysis, we explore how the vascular and neuronal systems interact to give rise to the brain functional networks measured with BOLD fMRI. This leads us to emphasize a view of the vascular network not only as a confounding element in fMRI but also as a functionally relevant system that is entangled with the neuronal network. To study the vascular and neuronal underpinnings of BOLD functional connectivity, we consider a combination of methodological avenues based on multiscale and multimodal optical imaging in mice, used in combination with computational models that allow the integration of vascular information to explain functional connectivity.

Microvascular structure variability explains variance in fMRI functional connectivity

“…Both cell types are important in neurovascular coupling, as nNOS is known to impact blood flow through its vasodilatory effects [51][52][53] and it also has been shown that pericytes have a role in the regulation of blood flow [54,55]. Here, the amplitude of the BOLD signal is related to the measured FC as it influences the Signal-to-Noise Ratio (SNR) and a reduced SNR can diminish the correlation between two time series, potentially leading to lower predictions of FC [56][57][58].…”

“…One approach to ascertain whether vasculature variability is intricately linked to neuronal FC or if it primarily affects the magnitude of the BOLD signal, subsequently impacting measured FC, is to explore the correlation between non-BOLD FC and VS. This kind of functional connectivity can be measured using genetically encoded calcium indicators (such as GCaMP) [59][60][61] in combination with fluorescence imaging techniques such as wide-field imaging as summarized in Guilbert et al (2022) [58]. The combination of these techniques has been used in the mouse to image cortical functional connectivity [62,63] and even simultaneously with BOLD FC [64].…”

Systemic physiology augmented functional near-infrared spectroscopy: a powerful approach to study the embodied human brain

“…SPA-fNIRS has also a great potential to understand if the fNIRS-derived functional resting-state and task-positive networks represents more resting-state physiological networks or genuine NVC-associated neuronal networks. Since the interplay between these two types of networks is currently an open research question, 140 SPA-fNIRS could possible provide novel answers to this question. In addition, the extension of the fNIRS hyperscanning approach 133 to SPA-fNIRS hyperscanning, as recently demonstrated, 135 , 136 will allow one to explore the physiological functional coupling between interacting subjects in a new way.…”

Special Section Guest Editorial: Hybrid Photonic/X Neurointerfaces

“…Guilbert et al. 4 provide a thorough review to cover the vascular and neural network interaction underlying the functional connectivity detected by resting-state fMRI. Cleppien et al.…”

“…Ioanas et al 3 provide a focused review on the capabilities and limitations of optical/fMRI method to study neurovascular coupling (NVC) and neuronal network mapping. Guilbert et al 4 provide a thorough review to cover the vascular and neural network interaction underlying the functional connectivity detected by resting-state fMRI. Cleppien et al 5 provide a comprehensive review to introduce the OPTO-MAgnetic Integration Concept (OPTOMAIC) to extract the temporal characteristics of the BOLD response based on optically recorded neuronal signals.…”