Arterial impulse model for the BOLD response to brief neural activation

Abstract

The blood oxygen level dependent (BOLD) signal evoked by brief neural stimulation, the hemodynamic response function (HRF), is a critical feature of neurovascular coupling. The HRF is directly related to local transient changes in oxygen supplied by cerebral blood flow (CBF) and oxygen demand, the cerebral metabolic rate of oxygen (CMRO2). Previous efforts to explain the HRF have relied upon the hypothesis that CBF produces a non-linear venous dilation within the cortical parenchyma. Instead, the observed dynamics correspond to prompt arterial dilation without venous volume change. This work develops an alternative biomechanical model for the BOLD response based on the hypothesis that prompt upstream dilation creates an arterial flow impulse amenable to linear description. This flow model is coupled to a continuum description of oxygen transport. Measurements using high-resolution fMRI demonstrate the efficacy of the model. The model predicts substantial spatial variations of the oxygen saturation along the length of capillaries and veins, and fits the varied gamut of measured HRFs by the combined effects of corresponding CBF and CMRO2 responses. Three interesting relationships among the hemodynamic parameters are predicted. First, there is an offset linear correlation with approximately unity slope between CBF and CMRO2 responses. Second, the HRF undershoot is strongly correlated to the corresponding CBF undershoot. Third, late-time-CMRO2 response can contribute to a slow recovery to baseline, lengthening the HRF undershoot. The model provides a powerful mathematical framework to understand the dynamics of neurovascular and neurometabolic responses that form the BOLD HRF.

Reliability of the depth-dependent high-resolution BOLD hemodynamic response in human visual cortex and vicinity

“…In our data, we observed that the WM HRF rose more quickly to a peak than in the GM. The early period of the HRF corresponds primarily to a competition between inflowing oxygenated blood and local cerebral metabolic rate of oxygen (CMRO 2 ) [54–57]. Because WM is more distant from vascular sources at the pial surface, convective flow delays should be similar or even longer, suggesting that local metabolism in the WM is lower than in GM, arguing against a metabolic-demand linkage for the observed WM HRF.…”

“…The greater reliability in this trailing edge of the hyperoxic peak may be the consequence of its more purely vascular character. The leading edge of the hyperoxic peak is likely affected by both blood flow and oxygen metabolism [60–62], but most models of the BOLD HRF would postulate a more purely vascular mechanism for the trailing edge of the response [54, 56, 57, 63, 64]. The weaker depth trends for time-to-peak and FWHM may be a consequence of the nonlinear competition between oxygen demand (CMRO 2 response) and blood supply (CBF response) that occurs early in the HRF [56, 57].…”

Whole brain measurements of the positive BOLD response variability during a finger tapping task at 7 T show regional differences in its profiles

“…Several studies have shown that short stimulations, like those used in this study, do not lead to observable changes in venous cerebral blood volume . In this case, the undershoot amplitude is modulated by both the decrease in CBF and the time needed for CMRO 2 to return to baseline . Alternatively, the poststimulus undershoot can be caused, at least partially, by poststimulus inhibitory neuronal modulation .…”

“…[38][39][40] In this case, the undershoot amplitude is modulated by both the decrease in CBF and the time needed for CMRO 2 to return to baseline. 41 Alternatively, the poststimulus undershoot can be caused, at least partially, by poststimulus inhibitory neuronal modulation. [42][43][44] Interestingly, triggering both inhibitive GABAergic activity and excitatory glutamatergic activity in the cerebellum increases the local field potential and CBF to a greater extent than glutamatergic activity alone, 45,46 which, in case of a GABAergic origin of the undershoot in the forebrain, could explain the negligible undershoot in the cerebellum.…”

Axial variation of deoxyhemoglobin density as a source of the low-frequency time lag structure in blood oxygenation level-dependent signals

“…56 Importantly, there is no clear physiological distinction between these 2 phenomena as each 57 involves multiple pathways (Willie et al, 2014). Their traces in the fMRI signal are also 58 uniformly postulated to reflect the increased cerebral blood flow and eventual dilution of 59 deoxy-hemoglobin (Hb) in the postcapillary part of the vasculature, with the additional 60 effect of a local blood volume increase (Kim & Ress, 2016). 61…”