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It has previously been shown that low-frequency fluctuations in both respiratory volume and cardiac rate can induce changes in the blood-oxygen level dependent (BOLD) signal. Such physiological noise can obscure the detection of neural activation using fMRI, and it is therefore important to model and remove the effects of this noise. While a hemodynamic response function relating respiratory variation (RV) and the BOLD signal has been described [Birn, R.M., Smith, M.A., Jones, T.B., Bandettini, P.A., 2008b. The respiration response function: The temporal dynamics of fMRI signal fluctuations related to changes in respiration. Neuroimage 40, 644-654.], no such mapping for heart rate (HR) has been proposed. In the current study, the effects of RV and HR are simultaneously deconvolved from resting state fMRI. It is demonstrated that a convolution model including RV and HR can explain significantly more variance in gray matter BOLD signal than a model that includes RV alone, and an average HR response function is proposed that well characterizes our subject population. It is observed that the voxel-wise morphology of the deconvolved RV responses is preserved when HR is included in the model, and that its form is adequately modeled by Birn et al.'s previously-described respiration response function. Furthermore, it is shown that modeling out RV and HR can significantly alter functional connectivity maps of the default-mode network.
Carbon dioxide is a potent cerebral vasodilator. We have identified a significant source of low-frequency variation in blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal at 3 T arising from spontaneous fluctuations in arterial carbon dioxide level in volunteers at rest. Fluctuations in the partial pressure of end-tidal carbon dioxide (Pet(CO(2))) of +/-1.1 mm Hg in the frequency range 0-0.05 Hz were observed in a cohort of nine volunteers. Correlating with these fluctuations were significant generalized grey and white matter BOLD signal fluctuations. We observed a mean (+/-standard error) regression coefficient across the group of 0.110 +/- 0.033% BOLD signal change per mm Hg CO(2) for grey matter and 0.049 +/- 0.022% per mm Hg in white matter. Pet(CO(2))-related BOLD signal fluctuations showed regional differences across the grey matter, suggesting variability of the responsiveness to carbon dioxide at rest. Functional magnetic resonance imaging (fMRI) results were corroborated by transcranial Doppler (TCD) ultrasound measurements of the middle cerebral artery (MCA) blood velocity in a cohort of four volunteers. Significant Pet(CO(2))-correlated fluctuations in MCA blood velocity were observed with a lag of 6.3 +/- 1.2 s (mean +/- standard error) with respect to Pet(CO(2)) changes. This haemodynamic lag was adopted in the analysis of the BOLD signal. Doppler ultrasound suggests that a component of low-frequency BOLD signal fluctuations is mediated by CO(2)-induced changes in cerebral blood flow (CBF). These fluctuations are a source of physiological noise and a potentially important confounding factor in fMRI paradigms that modify breathing. However, they can also be used for mapping regional vascular responsiveness to CO(2).
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