Dynamic models of BOLD contrast

Abstract

This personal recollection looks at the evolution of ideas about the dynamics of the blood oxygenation level dependent (BOLD) signal, with an emphasis on the balloon model. From the first detection of the BOLD response it has been clear that the signal exhibits interesting dynamics, such as a pronounced and long-lasting post-stimulus undershoot. The BOLD response, reflecting a change in local deoxyhemoglobin, is a combination of a hemodynamic response, related to changes in blood flow and venous blood volume, and a metabolic response related to oxygen metabolism. Modeling is potentially a way to understand the complex path from changes in neural activity to the BOLD signal. In the early days of fMRI it was hoped that the hemodynamic/metabolic response could be modeled in a unitary way, with blood flow, oxygen metabolism, and venous blood volume-the physiological factors that affect local deoxyhemoglobin-all tightly linked. The balloon model was an attempt to do this, based on the physiological ideas of limited oxygen delivery at baseline and a slow recovery of venous blood volume after the stimulus (the balloon effect), and this simple model of the physiology worked well to simulate the BOLD response. However, subsequent experiments suggest a more complicated picture of the underlying physiology, with blood flow and oxygen metabolism driven in parallel, possibly by different aspects of neural activity. In addition, it is still not clear whether the post-stimulus undershoot is a hemodynamic or a metabolic phenomenon, although the original venous balloon effect is unlikely to be the full explanation, and a flow undershoot is likely to be important. Although our understanding of the physics of the BOLD response is now reasonably solid, our understanding of the underlying physiological relationships is still relatively poor, and this is the primary hurdle for future models of BOLD dynamics.

Figure 1

A) Schematic view of the BOLD response as a ‘neural response’ filtered through a ‘hemodynamic response’. B) The balloon model was an attempt to describe the hemodynamic response as a deterministic function of the dynamic CBF change with three components: 1) a model for slow recovery of venous CBV after the stimulus (the balloon effect); 2) a model for the oxygen extraction fraction E based on limited oxygen delivery in the baseline state; and 3) a model for the conversion of dynamic changes in total deoxyhemoglobin and venous CBV into the BOLD response.

Figure 2

/B> Measured CBF (red) and BOLD (blue, x50 for display) responses to a visual stimulus redrawn from the calibrated BOLD study reported in (Griffeth et al., 2011). For each subject, the CMRO₂ response curve was estimated by analyzing the measured responses at each time point by applying the BOLD signal model with the calibration factor determined from the hypercapnia experiment. All curves are the average of 9 subjects. These data illustrate that the BOLD signal model predicts that a weak CBF undershoot can produce a much larger BOLD signal undershoot without elevated CMRO₂. (Figure courtesy of Valerie Griffeth).

Figure 3

The current view of the physiological basis of the BOLD response is more complex than what was modeled with the balloon model. The key difference is that current studies support a picture of CBF and CMRO₂ responses driven in parallel by different aspects of neural activity, so that we must think of a hemodynamic response and a metabolic response as independent effects. The origin of the post-stimulus undershoot is still uncertain, although the original assumption of a pure CBV effect cannot explain all of the current experimental data. Instead, a useful focus now is between a hemodynamic hypothesis, including elements of both a CBF undershoot and a slow venous CBV recovery (as shown) or a metabolic hypothesis related to slow recovery of CMRO₂.