Hemodynamic changes after visual stimulation and breath holding provide evidence for an uncoupling of cerebral blood flow and volume from oxygen metabolism

Abstract

Functional neuroimaging is most commonly performed using the blood-oxygenation-level-dependent (BOLD) approach, which is sensitive to changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the cerebral metabolic rate of oxygen (CMRO(2)). However, the precise mechanism by which neuronal activity elicits a hemodynamic response remains controversial. Here, visual stimulation (14 secs flashing checkerboard) and breath-hold (4 secs exhale+14 secs breath hold) experiments were performed in alternating sequence on healthy volunteers using BOLD, CBV-weighted, and CBF-weighted fMRI. After visual stimulation, the BOLD signal persisted for 33+/-5 secs (n=9) and was biphasic with a negative component (undershoot), whereas CBV and CBF returned to baseline without an undershoot at 20+/-5 and 20+/-3 secs, respectively. After breath hold, the BOLD signal returned to baseline (23+/-7 secs) at the same time (P>0.05) as CBV (21+/-6 secs) and CBF (18+/-3 secs), without a poststimulus undershoot. These data suggest that the BOLD undershoot after visual activation reflects a persistent increase in CMRO(2). These observations support the view that CBV and CBF responses elicited by neuronal activation are not necessarily coupled to local tissue metabolism.

Figure 1

Visual (black) and breath-hold (gray) time courses for voxels analyzed according to Method 1 voxel selection. On the left, the subject-averaged (n=9) time courses are shown for all four task periods; on the right, the block-averaged time courses are shown. (a,b) The BOLD time course shows a clear post-stimulus undershoot following visual stimulation, but not post-stimulus undershoot following breath-holding. In addition, the BOLD response during visual stimulation is larger than during breath-holding. (c,d) The CBVw time course (negative of the VASO signal change) shows no undershoot and a larger signal change during breath-hold than during visual stimulation. (e,f) The CBFw time course shows no post-stimulus undershoot in either task and comparable signal changes, within error, between task periods.

Figure 2

BOLD, CBVw and CBFw time courses for voxels analyzed according to Method 2 voxel selection. Here, the four-block stimulus paradigm has been averaged to make direct comparison between modalities clearer. The dark gray box shows the duration of the exhale period, the light gray box shows the duration of the stimulus (visual or breath-hold) and the gray-lined box demarcates the location of the BOLD visual post-stimulus undershoot. (a) The visual time course shows a clear BOLD post-stimulus undershoot which persists during a period when the CBVw and CBFw signal have returned to baseline. (b) The visual time course normalized with respect to the maximum signal change. (c) The breath-hold time course shows that the BOLD, CBVw and CBFw responses return to baseline in the absence of any detectable undershoot. (d) The normalized breath-hold time courses.