|Mechanisms of BOLD Contrast|
Post-Stimulus FMRI Changes in Cerebral Blood Flow,
Volume and Oxygenation Following Visual Stimulation and Breath-Hold
Provide Evidence for the Hemodynamic Response Being
Manus Joseph Donahue1, 2, Robert D. Stevens1, Michiel de Boorder3, James J. Pekar1, 2, Peter van Zijl1, 2
1The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; 2The Kennedy Krieger Institute, Baltimore, Maryland, USA; 3University Medical Center Utrecht, Utrecht, Netherlands
CMRO2, CBF and CBV all increase in gray matter parenchyma during visual stimulation, yet only CBF and CBV increase during breath-hold. Here, the relationship between neuronal activity and the hemodynamic response is investigated by performing BOLD fMRI (~CMRO2, CBF and CBV) concurrently with ASL fMRI (~CBF), and vascular-space-occupancy (VASO) fMRI at long repetition time (~CBV), during both visual stimulation and breath-hold. Results show that the BOLD post-stimulus undershoot is only present in the visual experiments, which suggests that this response is due to persisting CMRO2. These results provide additional evidence for an uncoupling of CMRO2 to CBF and CBV.
|Origins of the BOLD Post-Stimulus Undershoot
J. Jean Chen1, G. Bruce Pike1
1McGill University, Montreal, Canada
The BOLD post-stimulus undershoot has been attributed to either biomechanical venous ballooning or to sustained post-stimulus oxygen metabolism. Furthermore, a contribution from cerebral blood flow (CBF) undershoots has been demonstrated. We performed human in vivo fMRI measurements of the transient venous blood volume δ CBVv), δ CBF and δ BOLD under graded visual and sensorimotor stimulation using the QUIPSS II and VERVE (venous refocusing for volume estimation) techniques. We demonstrate a slow post-stimulus return of CBVv to baseline, which supports the existence of a passive “ballooning” effect. We also confirm the role of CBF undershoots in producing the BOLD undershoots.
The Post-Stimulation Undershoot in BOLD
FMRI of Human Brain is Not Caused by Elevated Cerebral Blood Volume
Jens Frahm1, Juergen Baudewig, Kai Kallenberg, Andreas Kastrup, Dietmar Merboldt1, Peter Dechent
1Biomedizinische NMR Forschungs GmbH am MPI fuer biophysikalische Chemie, Goettingen, Germany
The post-stimulation undershoot in BOLD fMRI, that is increased deoxyhemoglobin, has been suggested to originate from a delayed recovery of elevated CBV or CMRO2 to baseline. Here we performed bolus-tracking fMRI (Gd-DTPA, 8 subjects) at 3 T to evaluate the relative CBV (rCBV) during both visual stimulation and the post-stimulation undershoot. The results confirm a pronounced rCBV increase during stimulation (31.4 ± 8.6 %), but reveal no change in rCBV in the post-stimulation phase (0.7 ± 7.2 %). Assuming a rapid post-stimulation return of CBF to baseline this finding supports the idea of a prolonged elevation of oxidative metabolism.
Differentiating Sensitivity of Post-Stimulus
Undershoot Under Diffusion Weighting: Implication of Signal Origins
Todd B. Harshbarger1, Allen W. Song1
1Duke University, Durham, North Carolina, USA
The post-stimulus BOLD undershoot is generally observed in fMRI experiments. Recent studies have indicated the spatial localization of the undershoot may provide means for improved spatial localization to neuronal activities. In the present study, we applied diffusion weighting to eliminate intravascular spins of varying speeds in order to determine if the undershoot would be differentially affected based on the signal source. We show that areas in which the BOLD undershoot is reduced with increasing diffusion weighting are separable from areas which show no such effect. ADC values within affected areas are higher than unaffected regions, indicating their separate vascular origins.
Intravascular vs. Extravascular Contributions to FMRI
Signal Change for Visual Stimuli and Hypercapnia
Hannah Devlin1, Egill Rostrup2, Daniel P. Bulte1, Karla Louise Miller1, Peter Jezzard1
1FMRIB Centre, Oxford, UK; 2Copenhagen University, Copenhagen, Denmark
Hypercapnic fMRI calibration has the potential to further the ultimate goal of quantitative fMRI. However, the technique makes the assumption that the spatial origins of the signal are equivalent for metabolic and hypercapnia-induced activation. We tested this assumption using a diffusion-weighted fMRI paradigm to investigate the relative intravascular (IV) and extravascular (EV) contributions to the BOLD signal for a visual stimulus and for hypercapnia. Our results imply that the relative intravascular and extravascular contributions may not be comparable for functional and hypercapnic stimuli suggesting that it may not be fully appropriate to calibrate functional BOLD data with hypercapnia.
Dissociation of CBF Responses Corresponding to
Negative BOLD Activity
Yi-Ching Lynn Ho1, 2, Esben Thade Petersen1, 2, Xavier Golay1, 3
1National Neuroscience Institute, Singapore, Singapore; 2University of Aarhus, Denmark; 3A*STAR, Singapore
The sustained negative BOLD signal could be a useful marker of neuronal inhibition/deactivation or simply a result of vascular draining. CBF activity could be differentiated between the two. A novel motor task elicited both positive (PBR) and negative (NBR) BOLD responses in the sensorimotor cortex. CBF changes were coupled with the contralateral PBR and ipsilateral NBR (thought to be due to neuronal inhibition). However, for the contralateral NBR, which surrounded the PBR in a pattern suggestive of the vascular steal effect, no significant CBF changes were seen.
Is the Negative BOLD Response a Gain Control
Alex Robert Wade1
1SKERI, San Francisco, California , USA
We examined whether the magnitude of the negative BOLD response in visual cortex was a function of the ongoing neural activity in the suppressed region. We present data for the relationship between NBR magnitude and background contrast level in multiple retinotopic visual areas.
The Negative BOLD Effect in the Rodent Barrel Cortex
Model: Investigation Using Multimodal Imaging and Electrophysiology
Aneurin James Kennerley1, Luke Boorman1, David Johnston1, Ying Zheng1, Peter Redgrave1, John Edward Mayhew1, Jason Berwick1
1University of Sheffield, Sheffield, UK
Using fMRI at 7T we observed a prolonged negative BOLD signal surrounding a region in rat somatosensory cortex activated by electrical stimulation of the whiskers. The origin of the negative BOLD signal is not well understood. We therefore used intrinsic optical imaging and electrophysiology to investigate neurovascular coupling of this negative BOLD signal. Sensory-induced increases in neural activity were found to extend into the negative BOLD region. This suggests that the negative BOLD response does not reflect a corresponding decrease in underlying neural activity. Data were used to parameterize a forward biophysical model of neural activity.
A Temporal Comparison of Diffusion-Weighted FMRI,
NIRS and BOLD Responses to Visual Stimuli in Adult Humans
Satoru Kohno1, 2, Nobukatsu Sawamoto1, Shinichi Urayama1, Toshihiko Aso1, 3, Akitoshi Seiyama1, Denis Le Bihan3, Hidenao Fukuyama1
1Kyoto University Graduate School of Medicine, Kyoto, Japan; 2Shimadzu Corporation, Kyoto, Japan; 3NeuroSpin, Saclay, France
Functional response of diffusion-weighted magnetic resonance imaging (DfMRI) at high b-value precedes that of blood oxygenation level dependent (BOLD) fMRI by several seconds. The evidence suggests a direct link of DfMRI signal to neuronal activation, such as cell swelling. However, it was reported that total hemoglobin response measured with near-infrared spectroscopy (NIRS) also precedes BOLD response. Here, we compared temporal dynamics of DfMRI, NIRS and BOLD response, by conducting simultaneous acquisition of those signals during visual stimulation.
Caffeine's Effects on Neurovascular Coupling
Yufen Chen1, 2, Todd B. Parrish1
1Northwestern University, Chicago, Illinois, USA
Caffeine is a widely consumed methylxanthine that binds nonspecifically to adenosine receptors leading to a reduction in resting blood flow while improving attention and cognitive function. In this study we investigate its effects on neurovascular coupling using the calibrated BOLD model. Subjects were scanned before and after an injection of 2.5mg/kg body weight of caffeine. Our results demonstrate that caffeine increases the CMRO2:CBF ratio in both motor and visual cortices.