Abstract
In resting-state functional magnetic resonance imaging (fMRI), the temporal correlation between spontaneous fluctuations of the blood oxygenation level dependent (BOLD) signal from different brain regions is used to assess functional connectivity. However, because the BOLD signal is an indirect measure of neuronal activity, its complex hemodynamic nature can complicate the interpretation of differences in connectivity that are observed across conditions or subjects. For example, prior studies have shown that caffeine leads to widespread reductions in BOLD connectivity but were not able to determine if neural or vascular factors were primarily responsible for the observed decrease. In this study, we used source-localized magnetoencephalography (MEG) in conjunction with fMRI to further examine the origins of the caffeine-induced changes in BOLD connectivity. We observed widespread and significant (p < 0.01) reductions in both MEG and fMRI connectivity measures, suggesting that decreases in the connectivity of resting-state neuro-electric power fluctuations were primarily responsible for the observed BOLD connectivity changes. The MEG connectivity decreases were most pronounced in the beta band. By demonstrating the similarity in MEG and fMRI based connectivity changes, these results provide evidence for the neural basis of resting-state fMRI networks and further support the potential of MEG as a tool to characterize resting-state connectivity.
Highlights
The temporal correlation between spontaneous low-frequency fluctuations in the blood oxygenation level dependent (BOLD) signal measured using functional magnetic resonance imaging is being increasingly used to characterize functional connectivity (FC) in the brain
A similar qualitative assessment can be made about the functional magnetic resonance imaging (fMRI) data, where the connectivity in the post-dose section of the caffeine session shows a widespread decrease as compared to the pre-dose condition
We found that caffeine led to a significant and widespread reduction in both fMRI and MEG measures of resting-state connectivity in the eyes closed (EC) condition
Summary
The temporal correlation between spontaneous low-frequency fluctuations in the blood oxygenation level dependent (BOLD) signal measured using functional magnetic resonance imaging (fMRI) is being increasingly used to characterize functional connectivity (FC) in the brain. As the BOLD signal reflects both vascular and neural factors, the interpretation of resting-state FC observations can be challenging. The BOLD response is a complex function (known as the hemodynamic response) of changes in oxygen metabolism (CMRO2), cerebral blood flow (CBF) and blood volume, and provides an indirect measure of the underlying neuro-electrical activity (Buxton et al, 2004). Other non-neuronal confounds, such as metabolic and vascular factors rising from differences in age, diet, medications, and pathology, can alter the neurovascular coupling linking neural activity to the observed hemodynamic changes (Cohen et al, 2002; D’Esposito et al, 2003; Liu et al, 2004; Behzadi and Liu, 2005; Liau et al, 2008) and affect the BOLD signal. Changes in metabolic and vascular factors can give rise to changes in FC measures even when there is no underlying change in neural connectivity
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