Exploring the post-stimulus undershoot with spin-echo fMRI: Implications for models of neurovascular response

As a consequence of neural stimulation the blood oxygenation-level dependent (BOLD) contrast in gradient-echo echo-planar imaging (GE-EPI) based functional MRI (fMRI) leads to an increased MR signal in activated brain regions. Following this, a BOLD signal undershoot below baseline is generally observed with GE-EPI. The origin of this undershoot has been the focus of many investigations using fMRI and optical modalities, but the underlying mechanisms remain disputed. Here, we investigate the BOLD undershoot following visual stimulation by using a purely T2-weighted fMRI sequence at 1.5 and 3 T. By taking advantage of the field strength dependency of the T2 BOLD contrast and complete absence of static dephasing effects due to the pure spin echoes, one can draw conclusions about the origin of the BOLD undershoot and test the hypotheses in the literature. We observe a significant undershoot at both field strengths, with constant undershoot-to-main response ratio. This provides strong evidence that the undershoot is caused by BOLD changes due to elevated post-stimulus deoxyhaemoglobin concentration in the small vessels. ‘Delayed vascular compliance’ as suggested by the well-known Balloon and Windkessel models does not appear capable of explaining the undershoot. Our results also suggest that blood volume changes in arterioles and capillaries, for which there is consistent evidence from optical imaging studies, cannot alone cause the undershoot. This has important implications for models of neurovascular response and provides further support for the decoupling of changes in the rate of oxygen metabolism and blood flow. In addition, we found that an ‘arteriolar balloon’ (delayed arterial compliance) may provide a plausible explanation for the temporal characteristics of the BOLD undershoot. Hum Brain Mapp, 2010.