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      Agreement and repeatability of vascular reactivity estimates based on a breath-hold task and a resting state scan

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          Abstract

          FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan.

          This study aimed to compare three breath-hold based analysis approaches (block design, sine–cosine regressor and CO 2 regressor) and a resting state approach (CO 2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO 2 being recorded during both. Vascular reactivity was defined as CO 2-related BOLD percent signal change/mm Hg change in CO 2.

          Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO 2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity.

          We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment.

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          Influence of heart rate on the BOLD signal: the cardiac response function.

          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.
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            Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal.

            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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              The effect of resting condition on resting-state fMRI reliability and consistency: a comparison between resting with eyes open, closed, and fixated.

              Resting-state fMRI (rs-fMRI) has been demonstrated to have moderate to high reliability and produces consistent patterns of connectivity across a wide variety of subjects, sites, and scanners. However, there is no one agreed upon method to acquire rs-fMRI data. Some sites instruct their subjects, or patients, to lie still with their eyes closed, while other sites instruct their subjects to keep their eyes open or even fixating on a cross during scanning. Several studies have compared those three resting conditions based on connectivity strength. In our study, we assess differences in metrics of test-retest reliability (using an intraclass correlation coefficient), and consistency of the rank-order of connections within a subject and the ranks of subjects for a particular connection from one session to another (using Kendall's W tests). Twenty-five healthy subjects were scanned at three different time points for each resting condition, twice the same day and another time two to three months later. Resting-state functional connectivity measures were evaluated in motor, visual, auditory, attention, and default-mode networks, and compared between the different resting conditions. Of the networks examined, only the auditory network resulted in significantly higher connectivity in the eyes closed condition compared to the other two conditions. No significant between-condition differences in connectivity strength were found in default mode, attention, visual, and motor networks. Overall, the differences in reliability and consistency between different resting conditions were relatively small in effect size but results were found to be significant. Across all within-network connections, and within default-mode, attention, and auditory networks statistically significant greater reliability was found when the subjects were lying with their eyes fixated on a cross. In contrast, primary visual network connectivity was most reliable when subjects had their eyes open (and not fixating on a cross). Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Neuroimage
                Neuroimage
                Neuroimage
                Academic Press
                1053-8119
                1095-9572
                1 June 2015
                June 2015
                : 113
                : 387-396
                Affiliations
                [a ]Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, UK
                [b ]MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK
                Author notes
                [* ]Corresponding author. wiserg@ 123456cardiff.ac.uk
                Article
                S1053-8119(15)00178-0
                10.1016/j.neuroimage.2015.03.004
                4441043
                25795342
                8accfbd0-1e9d-433a-88f2-51a19cc2eed7
                © 2015 The Authors. Published by Elsevier Inc.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 15 July 2014
                : 3 March 2015
                Categories
                Article

                Neurosciences
                vascular reactivity,breath-hold,resting state,rsfa,repeatability
                Neurosciences
                vascular reactivity, breath-hold, resting state, rsfa, repeatability

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