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. DeltaR(2)*/DeltaR(2) 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/mm(2)) used in this study. For the IR-SE sequence the DeltaR(2) 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.