Fig 1.
Illustration of the combined BOLD-CVR and task-evoked BOLD-fMRI study protocol in one subject.
Top: Fig 1A and 1B show the CO2 (grey dotted line) and mean BOLD signal time course (black line) during a BOLD-CVR study at CO2 baseline (A) versus hypercapnia (B), respectively. Note that the BOLD signal follows the CO2 increase from normocapnia and quickly returns to baseline levels. However, during hypercapnia, the mean BOLD signal increase with CO2 rise is less than in normocapnia. Bottom: Fig 1C and 1D show the CO2 time course during a task-evoked BOLD-fMRI block protocol. The black short lines represent the task phase of the protocol. The ability of precise CO2 control with the MPET method produced a constant CO2 level at CO2 baseline (C) versus hypercapnia (D), respectively.
Fig 2.
Schematic overview of the analysis pipeline.
1) Representation of the raw BOLD-fMRI data obtained from the MRI system. 2) From the raw BOLD-fMRI images t-value maps are then calculatedusing a mass-univariate general linear model within SPM12. 3) By using a predetermined t-value threshold of 3.43, all significant voxels of each t-value map are combined into a significant-t-value binary mask, i.e. a combined T-map. 4)This map is then overlaid onto the predefined ROIsto determine the significant t-values within each ROI. 5)The BOLD-CVR and fMRI Δ%signal maps for the normocapnic condition are calculated and the values of the combined significant t-value voxels for each region of interest are scatter-plotted. 6)The BOLD-CVR and fMRI Δ%signal maps for the hypercapnic condition are calculated and the values of the combined significant t-value voxels for each region of interest are scatter-plotted. Abbreviations: Blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR, defined as %signal change/mmHg CO2 change). Functional MRI (fMRI, defined as %signal change).
Table 1.
Regional CVR and fMRI signal activation and t-values.
Table 2.
Number of significantly activated voxels (t>3.43) during task-evoked fMRI.
Fig 3.
Upper row: Scatterplot of the t-values obtained from the BOLD-CVR and the fMRI finger tapping data.
Lower row: Scatterplot of BOLD-CVR % signal change and %fMRI signal change for each ROI and subject. Each red and blue point represents the average value of a ROI of a single subject during either normocpanie (blue) or hypercapnia (red). Black line: least square error linear fit of each scatterplot. Abbreviations: BOLD: blood oxygenation-level dependent; -CVR: cerebrovascular reactivity, CO2: carbon dioxide, %fMRI: mean percent BOLD signal changes, ROI: Region of Interest.
Fig 4.
The fMRI t-values are represented as a function of the BOLD-CVR (relative BOLD fMRI signal change per mmHg CO2).
Each red and blue point represents the average value of a ROI of a single subject during either normocpanie (blue) or hypercapnia (red). Black line: least square error linear fit of each scatterplot. Abbreviations: BOLD: blood oxygenation-level dependent; -CVR: cerebrovascular reactivity, CO2: carbon dioxide, %fMRI: mean percent BOLD signal changes, ROI: Region of Interest.
Fig 5.
Scatterplot of the voxel-wise t-value of the task-evoked fMRI (y-axis) and BOLD CVR data (x-axis) for an illustrative subject.
For each ROI, only the voxels which were significantly activated in at least one of the two finger-tapping fMRI data are plotted. The drop in t-values from normo- to hyper-capnia below the threshold (here 3.43) is clearly visible. This is known as false negative activation, implying the limitation of the task-evoked fMRI by the remaining BOLD-CVR, especially with a fixed threshold.