Relationship between respiration, end-tidal CO2, and BOLD signals in resting-state fMRI

Abstract

A significant component of BOLD fMRI physiological noise is caused by variations in the depth and rate of respiration. It has previously been demonstrated that a breath-to-breath metric of respiratory variation (respiratory volume per time; RVT), computed from pneumatic belt measurements of chest expansion, has a strong linear relationship with resting-state BOLD signals across the brain. RVT is believed to capture breathing-induced changes in arterial CO(2), which is a cerebral vasodilator; indeed, separate studies have found that spontaneous fluctuations in end-tidal CO(2) (PETCO(2)) are correlated with BOLD signal time series. The present study quantifies the degree to which RVT and PETCO(2) measurements relate to one another and explain common aspects of the resting-state BOLD signal. It is found that RVT (particularly when convolved with a particular impulse response, the "respiration response function") is highly correlated with PETCO(2), and that both explain remarkably similar spatial and temporal BOLD signal variance across the brain. In addition, end-tidal O(2) is shown to be largely redundant with PETCO(2). Finally, the latency at which PETCO(2) and respiration belt measures are correlated with the time series of individual voxels is found to vary across the brain and may reveal properties of intrinsic vascular response delays.

Figure 1

The respiration response function (Birn et al., 2008).

Figure 2

(A) (−)PETO₂, PETCO₂, RVT, and RVTRRF for one subject, and (B) RVTRRF and PETCO₂ for the same subject. In (B), PETCO₂ has been shifted to the right by 10 s, which is the time lag yielding the maximum cross-correlation between the 2 signals. For display, all signals have been normalized to have unit standard deviation and zero mean, and PETO₂ has been negated.

Figure 3

Correlations between end-tidal gas and respiratory belt measurements for all subjects. The y-axis represents the maximum magnitude of the cross-correlation between the indicated pair of signals. The maximum cross-correlations between RVT and PETCO₂, and between RVTRRF and PETO₂, are negative; the absolute value is shown for ease of comparison.

Figure 4

Percentage of variance explained by the maximum cross-correlation with each vox el in the brain for (A) PETCO₂ and (B) RVTRRF. Maps are thresholded at the percentage variance explained corresponding to Z>5.3. (C) The percentage of variance explained by the model containing both PETCO₂ and RVTRRF, thresholded at the same values as (A) and (B).

Figure 4

Percentage of variance explained by the maximum cross-correlation with each vox el in the brain for (A) PETCO₂ and (B) RVTRRF. Maps are thresholded at the percentage variance explained corresponding to Z>5.3. (C) The percentage of variance explained by the model containing both PETCO₂ and RVTRRF, thresholded at the same values as (A) and (B).

Figure 5

Comparison between the effects of 4 respiratory measures (PETCO₂, PETCO₂-GAM, PETO₂, RVTRRF) in the brain. For each respiratory measure, the sum of Z-scores across voxels for which Z>5.3, normalized by the total number of voxels in the brain, is plotted.

Figure 6

Voxel-wise comparison between the cross-correlation magnitudes of PETCO ₂ and RVTRRF for one subject (Subject 4).

Figure 7

Group-level (n=7) random-effects analysis of the BOLD signal changes explained by the model containing both PETCO₂ and RVTRRF (shown at p<0.01 uncorrected).

Figure 8

Latency maps. For each voxel, the time delay maximizing its cross-correlation with PETCO₂ (left) and RVTRRF (right) is displayed. Maps are thresholded at a cross-correlation magnitude of Z>5.3. The range of latency values displayed for each subject is the mean ± SD [sec] of a Gaussian function fit to the latency histogram (except for Subject 2, whose latency distribution was bimodal).

Figure 9

Group average (n=6) latency map, for cross-correlation with PETCO ₂. Latency maps of individual subjects were mean-centered and spatially normalized to an EPI template prior to averaging. Map is shown thresholded to include only voxels for which 3 or more subjects had a cross-correlation magnitude of Z>5.3.

Figure 10

Comparison between PETCO₂ and BH latency maps for one subject. (A) PETCO₂ and BH latency maps [sec]. (B) Correlation between the PETCO₂ and BH latency maps was significant (r=0.75).