Abstract
As high-resolution functional magnetic resonance imaging (fMRI) and fMRI of cortical layers become more widely used, the question how well high-resolution fMRI signals reflect the underlying neural processing, and how to interpret laminar fMRI data becomes more and more relevant. High-resolution fMRI has shown laminar differences in cerebral blood flow (CBF), volume (CBV), and neurovascular coupling. Features and processes that were previously lumped into a single voxel become spatially distinct at high resolution. These features can be vascular compartments such as veins, arteries, and capillaries, or cortical layers and columns, which can have differences in metabolism. Mesoscopic models of the blood oxygenation level dependent (BOLD) response therefore need to be expanded, for instance, to incorporate laminar differences in the coupling between neural activity, metabolism and the hemodynamic response. Here we discuss biological and methodological factors that affect the modeling and interpretation of high-resolution fMRI data. We also illustrate with examples from neuropharmacology and the negative BOLD response how combining BOLD with CBF- and CBV-based fMRI methods can provide additional information about neurovascular coupling, and can aid modeling and interpretation of high-resolution fMRI.
Highlights
COMBINING blood oxygenation level dependent (BOLD) WITH CBV AND CBV METHODS TO INVESTIGATE NEUROVASCULAR COUPLINGcerebral blood flow (CBF) and CBV usually co-vary and are related to the cerebral metabolic rate of oxygen consumption (CMRO2)
The question we aim to address here is: what additional compartments and terms should be included in mesoscopic functional magnetic resonance imaging (fMRI) models to explain or predict high-resolution fMRI data? Additional terms can describe anatomical or biological features such as differences in neurovascular coupling in the cortical layers, while other terms may be needed to describe the spatial scale of blood flow regulation, or to take technical properties into account such as the differential sensitivity of various fMRI techniques to arteries, veins and parenchyma, or the effect of increasing field strength
In this paper we discussed the properties of high-resolution fMRI and factors that need to be taken into account when extending current macroscopic fMRI models to the mesoscopic scale that becomes accessible with high-resolution fMRI
Summary
CBF and CBV usually co-vary and are related to the cerebral metabolic rate of oxygen consumption (CMRO2). In some cases, for instance in disease, development, or after pharmacological intervention, CBV, CBF, and CMRO2 do not increase or decrease simultaneously (Kozberg et al, 2013; Hillman, 2014) This is important since it has been shown that neurovascular coupling and capillary function are impaired in a number of diseases, for instance Alzheimer’s disease or small vessel disease, while for other diseases it is not known if and how neurovascular coupling is affected (Fleisher et al, 2009; Troprés et al, 2015; Østergaard et al, 2016). This demonstrates the potential of high-resolution fMRI to separate different laminar and/or vascular compartments, and to determine laminar differences in neurovascular coupling, demonstrating the utility of high-resolution fMRI for improving our understanding of neurovascular coupling
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