Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling

Abstract

Modern neuroimaging techniques rely on neurovascular coupling to show regions of increased brain activation. However, little is known of the neurovascular coupling relationships that exist for inhibitory signals. To address this issue directly we developed a preparation to investigate the signal sources of one of these proposed inhibitory neurovascular signals, the negative blood oxygen level-dependent (BOLD) response (NBR), in rat somatosensory cortex. We found a reliable NBR measured in rat somatosensory cortex in response to unilateral electrical whisker stimulation, which was located in deeper cortical layers relative to the positive BOLD response. Separate optical measurements (two-dimensional optical imaging spectroscopy and laser Doppler flowmetry) revealed that the NBR was a result of decreased blood volume and flow and increased levels of deoxyhemoglobin. Neural activity in the NBR region, measured by multichannel electrodes, varied considerably as a function of cortical depth. There was a decrease in neuronal activity in deep cortical laminae. After cessation of whisker stimulation there was a large increase in neural activity above baseline. Both the decrease in neuronal activity and increase above baseline after stimulation cessation correlated well with the simultaneous measurement of blood flow suggesting that the NBR is related to decreases in neural activity in deep cortical layers. Interestingly, the magnitude of the neural decrease was largest in regions showing stimulus-evoked positive BOLD responses. Since a similar type of neural suppression in surround regions was associated with a negative BOLD signal, the increased levels of suppression in positive BOLD regions could importantly moderate the size of the observed BOLD response.

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

“…During inhibitory tasks, NBR amplitude was larger (p < 0.05) in deeper laminae (Fig. 3B), as observed previously (Boorman et al, 2010;Goense et al, 2012).…”

“…The occurrence of vasoconstriction with negative BOLD response is consistent with the majority of animal studies (Boorman et al, 2010;Harel et al, 2002;Kennerley et al, 2012b). The fast temporal CBV response shown in Figs.…”

“…Further studies (Kennerley et al, 2012b;Pasley et al, 2007) leave no room for non-neurally driven CBF contributions to NBR, and suggest that neurovascular coupling is conserved for both the positive and negative BOLD responses. There is now a general consensus that the NBR is accompanied by decreases in CBF and CMRO 2 , as shown with fMRI in human visual and motor cortex (Pasley et al, 2007;Shmuel et al, 2002;Stefanovic et al, 2004), with fMRI in monkey visual cortex (Shmuel et al, 2006), and with fMRI and optical imaging spectroscopy (OIS) in rat somatosensory cortex (Boorman et al, 2010;Kennerley et al, 2012b). …”

“…More refined layer-dependent studies of NBR in sensory motor cortex of rats and visual cortex of monkeys suggest that the NBR peaks in deeper cortical layers, while the positive gradient echo (GE) BOLD response (PBR) peaks at the cortical surface (Boorman et al, 2010;Goense et al, 2012). The role of cerebral blood volume (CBV) in NBR has remained elusive.…”

“…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.…”