Hua J, Stevens RD, Huang AJ, Pekar JJ, van Zijl PCPhysiological origin for the BOLD poststimulus undershoot in human brain: vascular compliance versus oxygen metabolism. J Cereb Blood Flow Metab 31:1599-1611

Russell H Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism (Impact Factor: 5.41). 04/2011; 31(7):1599-611. DOI: 10.1038/jcbfm.2011.35
Source: PubMed


The poststimulus blood oxygenation level-dependent (BOLD) undershoot has been attributed to two main plausible origins: delayed vascular compliance based on delayed cerebral blood volume (CBV) recovery and a sustained increased oxygen metabolism after stimulus cessation. To investigate these contributions, multimodal functional magnetic resonance imaging was employed to monitor responses of BOLD, cerebral blood flow (CBF), total CBV, and arterial CBV (CBV(a)) in human visual cortex after brief breath hold and visual stimulation. In visual experiments, after stimulus cessation, CBV(a) was restored to baseline in 7.9±3.4 seconds, and CBF and CBV in 14.8±5.0 seconds and 16.1±5.8 seconds, respectively, all significantly faster than BOLD signal recovery after undershoot (28.1±5.5 seconds). During the BOLD undershoot, postarterial CBV (CBV(pa), capillaries and venules) was slightly elevated (2.4±1.8%), and cerebral metabolic rate of oxygen (CMRO(2)) was above baseline (10.6±7.4%). Following breath hold, however, CBF, CBV, CBV(a) and BOLD signals all returned to baseline in ∼20 seconds. No significant BOLD undershoot, and residual CBV(pa) dilation were observed, and CMRO(2) did not substantially differ from baseline. These data suggest that both delayed CBV(pa) recovery and enduring increased oxidative metabolism impact the BOLD undershoot. Using a biophysical model, their relative contributions were estimated to be 19.7±15.9% and 78.7±18.6%, respectively.

Download full-text


Available from: Robert D. Stevens
  • Source
    • "The mechanism of the undershoot is debated, but likely a result of a sustained increase in high oxygen consumption after the stimulus has subsided (van Zijl et al., 2012). Vascular compliance also contributes to the undershoot (Hua et al., 2011; Zong and Huang, 2011) and may be important in our study since cocaine and amphetamine have known vasoactive properties (Chen et al., 2011; Gottschalk and Kosten, 2002). Recent work also suggests that the undershoot reflects inhibitory neural activity (Mullinger et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Substance dependence is associated with impaired decision-making and altered fronto-striatal-limbic activity. Both greater and lesser brain activity have been reported in drug users compared to controls during decision-making. Inconsistent results might be explained by group differences in the temporal profile of the functional magnetic resonance imaging (fMRI) response. While most previous studies model a canonical hemodynamic response, a finite impulse response (FIR) model measures fMRI signal at discrete time points without assuming a temporal profile. We compared brain activity during decision-making and feedback in substance users and controls using two models: a canonical hemodynamic response function (HRF) and a FIR model. Methods 37 substance-dependent individuals (SDI) and 43 controls performed event-related decision-making during fMRI scanning. Brain activity was compared across group using canonical HRF and FIR models. Results Compared to controls, SDI were impaired at decision-making. The canonical HRF model showed that SDI had significantly greater fronto-striatal-limbic activity during decisions and less activity during feedback than controls. The FIR model confirmed greater activity in SDI during decisions. However, lower activity in SDI during feedback corresponded to a lower post-stimulus undershoot of the hemodynamic response. Conclusions Greater activity in fronto-striatal-limbic pathways in SDI compared to controls is consistent with prior work, further supporting the hypothesis that abnormalities in these circuits underlie impaired decision-making. We demonstrate for the first time using FIR analysis that lower activity during feedback may simply reflect the tail end of the hemodynamic response to decision, the post-stimulus undershoot, rather than an actual difference in feedback response.
    Full-text · Article · Mar 2014 · Drug and alcohol dependence
  • Source
    • "CVR can be assessed by increasing the blood concentration of CO 2 , a potent vasodilator, while monitoring vascular responses using MRI. While MRI techniques to measure CBF and CBV changes have been utilized (Davis et al., 1998; Donahue et al., 2009a; Donahue et al., 2009b; Hoge et al., 1999; Hua et al., 2011; Mandell et al., 2008b), the BOLD sequence is by far the most widely used acquisition "
    [Show abstract] [Hide abstract]
    ABSTRACT: With a growing need for specific biomarkers in vascular diseases, there has been a surging interest in mapping cerebrovascular reactivity (CVR) of the brain. This index can be measured by conducting a hypercapnia challenge while acquiring Blood-oxygenation-level-dependent (BOLD) signals. A BOLD signal increase with hypercapnia is the expected outcome and represents the majority of literature reports; in this work we report an intriguing observation of an apparently negative BOLD CVR response at 3 Tesla, during inhalation of 5% CO2 with balance medical air. These "negative-CVR" clusters were specifically located in the ventricular regions of the brain, where CSF is abundant and results in an intense baseline signal. The amplitude of the CVR response was -0.51±0.44% (N=14, age 26±4years). We hypothesized that this observation might not be due to a decrease in oxygenation but rather a volume effect in which bright CSF signal is replaced by a less intensive blood signal as a result of vasodilation. To test this, we performed an inversion-recovery (IR) experiment to suppress the CSF signal (N=10, age 27±5years). This maneuver in imaging sequence reversed the sign of the signal response (to 0.66±0.25%), suggesting that the volume change was the predominant reason for the apparently negative CVR in the BOLD experiment. Further support of this hypothesis was provided by a BOLD hyperoxia experiment, in which no voxels showed a negative response, presumably because vasodilation is not usually associated with this challenge. Absolute CBF response to hypercapnia was measured in a new group of subjects (N=8, age 29±7years) and it was found that CBF in ventricular regions increased by 48% upon CO2 inhalation, suggesting that blood oxygenation most likely increased rather than decreased. The findings from this study suggest that CO2 inhalation results in the dilation of ventricular vessels accompanied by shrinkage in CSF space, which is responsible for the apparently negative CVR in brain ventricles.
    Full-text · Article · Jul 2013 · NeuroImage
  • Source
    • "In the context of established biomechanical models such as the Balloon Model, a deep post-stimulus undershoot can be explained by an initially stiff post-capillary-bed venous compartment which becomes compliant after prolonged expansion , leading to the volume outflow of the system resembling a hysteresis loop (Buxton et al., 1998, 2004). Alternatively, there is also recent evidence to suggest that transient decoupling between the CBF and a sustained post-stimulus increase in the local cerebral metabolic rate of oxygen (CMRO 2 ) results in deoxygenated Hb accumulation and therefore a decrease in BOLD signal (Dechent et al., 2011; Hua et al., 2011). In the neonatal brain, the latter effect may predominate as marked increases in neuronal density and integration occur in the late preterm to term infant period, and these changes are associated with a significant maturational rise in CMRO 2 (Altman et al., 1988; Chugani and Phelps, 1986; Roche-Labarbe et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the Blood Oxygen Level Dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41+1weeks), and 10 preterm infants (median PMA 34+4weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond.
    Full-text · Article · Jul 2012 · NeuroImage
Show more