Origin of the signal undershoot in BOLD studies of the visual cortex

The nature of the signal undershoot observed in the inter‐stimulation intervals in fMRI studies using a block paradigm consisting of alternating periods of visual stimulation and rest was investigated using the following single shot EPI sequences: gradient echo (GRE), spin echo (SE), spin echo with additional flow dephasing gradients and inversion recovery (IR) prepared SE. Both the GRE and SE sequences showed a significant signal undershoot during the inter‐stimulation intervals. ΔR2*/ΔR2 ratios of 3.7 ± 0.9 and 3.1 ± 0.7 were measured in the stimulation and inter‐stimulation periods, respectively, with the latter being lower than that which would be consistent with a pure extra‐vascular effect arising from an elevated venous blood volume and a normal deoxyhaemoglobin content post‐stimulation. The addition of dephasing gradients to the SE sequence in order to attenuate the signal from spins flowing within larger vessels produced a four‐fold reduction in the number of activated pixels but had little effect on the time intensity profile. Our interpretation of these results is that both extra‐ and intra‐vascular BOLD effects are present in the inter‐stimulation intervals and the lack of any effect of the dephasing gradient on the time–intensity profile indicates that the intra‐vascular component probably occurs mainly in smaller vessels, such as venules, which are affected relatively little by the relatively weak dephasing gradient (b = 29 s/mm2) used in this study. For the IR–SE sequence the ΔR2 measured during the inter‐stimulation intervals was similar to that seen with the SE BOLD sequence and thus was consistent with a residual BOLD effect, implying that perfusion changes in the capillary vessels did not contribute significantly to the signal undershoot. Copyright © 1999 John Wiley & Sons, Ltd.