Toward an integrative neurovascular framework for studying brain networks.

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.

Movement correction method for laser speckle contrast imaging of cerebral blood flow in cranial windows in rodents.

Laser speckle contrast imaging (LSCI) is used in clinical research to dynamically image blood flow. One drawback is its susceptibility to movement artifacts. We demonstrate a new, simple method to correct motion artifacts in LSCI signals measured in awake mice with cranial windows during sensory stimulation. The principle is to identify a region in the image in which speckle contrast (SC) is independent of blood flow and only varies with animal movement, then to regress out this signal from the data. We show that (1) the regressed signal correlates well with mouse head movement, (2) the corrected signal correlates better with independently measured blood volume and (3) it has a (59 ± 6)% higher signal-to-noise ratio. Compared to three alternative correction methods, ours has the best performance. Regressing out flow-independent global variations in SC is a simple and accessible way to improve the quality of LSCI measurements.

Structural and Functional Features of Developing Brain Capillaries, and Their Alteration in Schizophrenia.

Schizophrenia affects more than 1% of the world's population and shows very high heterogeneity in the positive, negative, and cognitive symptoms experienced by patients. The pathogenic mechanisms underlying this neurodevelopmental disorder are largely unknown, although it is proposed to emerge from multiple genetic and environmental risk factors. In this work, we explore the potential alterations in the developing blood vessel network which could contribute to the development of schizophrenia. Specifically, we discuss how the vascular network evolves during early postnatal life and how genetic and environmental risk factors can lead to detrimental changes. Blood vessels, capillaries in particular, constitute a dynamic and complex infrastructure distributing oxygen and nutrients to the brain. During postnatal development, capillaries undergo many structural and anatomical changes in order to form a fully functional, mature vascular network. Advanced technologies like magnetic resonance imaging and near infrared spectroscopy are now enabling to study how the brain vasculature and its supporting features are established in humans from birth until adulthood. Furthermore, the contribution of the different neurovascular unit elements, including pericytes, endothelial cells, astrocytes and microglia, to proper brain function and behavior, can be dissected. This investigation conducted among different brain regions altered in schizophrenia, such as the prefrontal cortex, may provide further evidence that schizophrenia can be considered a neurovascular disorder.