Physiological origin for the BOLD poststimulus undershoot in human brain: vascular compliance versus oxygen metabolism

The poststimulus blood oxygenation level-dependent (BOLD) undershoot has been attributed to two main plausible origins: delayed vascular compliance based on delayed cerebral blood volume (CBV) recovery and a sustained increased oxygen metabolism after stimulus cessation. To investigate these contributions, multimodal functional magnetic resonance imaging was employed to monitor responses of BOLD, cerebral blood flow (CBF), total CBV, and arterial CBV (CBV(a)) in human visual cortex after brief breath hold and visual stimulation. In visual experiments, after stimulus cessation, CBV(a) was restored to baseline in 7.9 +/- 3.4 seconds, and CBF and CBV in 14.8 +/- 5.0 seconds and 16.1 +/- 5.8 seconds, respectively, all significantly faster than BOLD signal recovery after undershoot (28.1 +/- 5.5 seconds). During the BOLD undershoot, postarterial CBV (CBV(pa), capillaries and venules) was slightly elevated (2.4 +/- 1.8%), and cerebral metabolic rate of oxygen (CMRO(2)) was above baseline (10.6 +/- 7.4%). Following breath hold, however, CBF, CBV, CBVa and BOLD signals all returned to baseline in similar to 20 seconds. No significant BOLD undershoot, and residual CBVpa dilation were observed, and CMRO(2) did not substantially differ from baseline. These data suggest that both delayed CBV(pa) recovery and enduring increased oxidative metabolism impact the BOLD undershoot. Using a biophysical model, their relative contributions were estimated to be 19.7 +/- 15.9% and 78.7 +/- 18.6%, respectively. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 1599-1611; doi: 10.1038/jcbfm.2011.35; published online 6 April 2011