Nonlinear coupling between evoked rCBF and BOLD signals: A simulation study of hemodynamic responses

The aim of this work was to investigate the dependence of BOLD responses on different patterns of stimulus input/neuronal changes. In an earlier repor t, we described an input-state-output model that combined (i) the Balloon/W indkessel model of nonlinear coupling between rCBF and BOLD signals, and (i i) a linear model of how regional flow changes with synaptic activity. In t he present investigation, the input-state-output model was used to explore the dependence of simulated PET (rCBF) and fMRI (BOLD) signals on various p arameters pertaining to experimental design. Biophysical simulations were u sed to estimate rCBF and BOLD responses as functions of (a) a prior stimulu s, (b) epoch length (for a fixed SOA), (c) SOA (for a fixed number of event s), and (d) stimulus amplitude. We also addressed the notion that a single neuronal response may differ, in terms of the relative contributions of ear ly and late neural components, and investigated the effect of (e) the relat ive size of the, late or "endogenous" neural component. We were interested in the estimated average rCBF and BOLD responses per stimulus or event, not in the statistical efficiency with which these responses are detected. The BOLD response was underestimated relative to rCBF with a preceding stimulu s, increasing epoch length, and increasing SOA. Furthermore, the BOLD respo nse showed some highly nonlinear behaviour when varying stimulus amplitude, suggesting some form of hemodynamic "rectification." Finally, the BOLD res ponse was underestimated in the context of large late neuronal components. The difference between rCBF and BOLD is attributed to the nonlinear transdu ction of rCBF to BOLD signal. Our simulations support the idea that varying parameters that specify the experimental design may have differential effe cts in PET and fMRI. Moreover, they show that fMRI can be asymmetric in its ability to detect deactivations relative to activations when an absolute b aseline is stipulated. Finally, our simulations suggest that relative insen sitivity to BOLD signal in specific regions, such as the temporal lobe, may be partly explained by higher cognitive functions eliciting a relatively l arge late endogenous neuronal component. (C) 2001 Academic Press.