Origin of Negative Blood Oxygenation Level—Dependent fMRI Signals

Abstract

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in spike activity are accompanied by modulation in the blood oxygenation level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed and are thought to reflect a decrease in neural activity. In this study, the source of the negative BOLD signal was investigated using T2*-weighted BOLD and cerebral blood volume (CBV) techniques in isoflurane-anesthetized cats. A positive BOLD signal change was observed in the primary visual cortex (area 18) during visual stimulation, while a prolonged negative BOLD change was detected in the adjacent suprasylvian gyrus containing higher-order visual areas. However, in both regions neurons are known to increase spike activity during visual stimulation. The positive and negative BOLD amplitudes obtained at six spatial-frequency stimuli were highly correlated, and negative BOLD percent changes were approximately one third of the positive changes. Area 18 with positive BOLD signals experienced an increase in CBV, while regions exhibiting the prolonged negative BOLD signal underwent a decrease in CBV. The CBV changes in area 18 were faster than the BOLD signals from the same corresponding region and the CBV changes in the suprasylvian gyrus. The results support the notion that reallocation of cortical blood resources could overcome a local demand for increased cerebral blood flow induced by increased neural activity. The findings of this study imply that caution should be taken when interpreting the negative BOLD signals as a decrease in neuronal activity.

Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T

“…For this reason, and due to the potential of the negative signal to shed further light on neurovascular coupling, NBR is in the focus of current research (Hutchison et al, 2013;Mullinger et al, 2014;Schäfer et al, 2012;Smith et al, 2004;Tajima et al, 2010;Vafaee and Gjedde, 2004). Early work suggested that the NBR was a result of non-neurally driven hemodynamic mechanisms, such as vascular steal (Harel et al, 2002;Woolsey et al, 1996). However, recent work obtaining electrophysiological recordings simultaneously with BOLD-based functional magnetic resonance imaging (fMRI), in anesthetized macaque monkeys, suggests that decreases in the CMRO2 and neural activity are the major contributors (>60%) to NBR (Shmuel et al, 2006).…”

“…The role of cerebral blood volume (CBV) in NBR has remained elusive. Measurements with OIS and monocrystalline iron oxide nanoparticles (MION) reveal vasoconstriction in regions of NBR in rat somatosensory cortex (Boorman et al, 2010;Kennerley et al, 2012b) and cat extrastriate cortex (Harel et al, 2002). Goense et al (2012), on the other hand, investigated CBV changes in regions of NBR with vascular space occupancy (VASO) (Lu et al, 2003;Yang et al, 2004) and MION in visual cortex of monkeys.…”

Common deactivation patterns during working memory and visual attention tasks: An intra‐subject fMRI study at 4 Tesla

“…fMRI studies of visual stimulation in cats (Harel, et al 2002) and humans (Shmuel, et al 2002) demonstrated negative blood oxygenation level dependent (BOLD) responses (NBR) in non-stimulated areas of the visual cortex. Similarly, fMRI studies using cross-modal stimuli showed deactivation of the auditory cortices during visual stimulation, while deactivation of the visual cortices occurred during auditory stimulation (Laurienti, et al 2002;Lewis, et al 2000).…”

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

“…In fact, it is still uncertain whether these changes are sufficiently localized in the actual areas of elevated neuronal activity to resolve submillimeter functional units of the cortex, such as cortical orientation columns ). In addition, emerging spatial patterns such as the vascular steal phenomenon (or surround negativity) Boas et al, 2008;Harel et al, 2002;Woolsey et al, 1996;Cox et al, 1993;Kennerley et al, 2007) will be investigated. …”