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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.

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 CBV_v), 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 CBV_v to baseline, which supports the existence of a passive “ballooning” effect. We also confirm the role of CBF undershoots in producing the BOLD undershoots.

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.

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.

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.

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.

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.

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.

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.

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.