Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal

Abstract

Changes in neuronal activity are accompanied by the release of vasoactive mediators that cause microscopic dilation and constriction of the cerebral microvasculature and are manifested in macroscopic blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signals. We used two-photon microscopy to measure the diameters of single arterioles and capillaries at different depths within the rat primary somatosensory cortex. These measurements were compared with cortical depth-resolved fMRI signal changes. Our microscopic results demonstrate a spatial gradient of dilation onset and peak times consistent with "upstream" propagation of vasodilation toward the cortical surface along the diving arterioles and "downstream" propagation into local capillary beds. The observed BOLD response exhibited the fastest onset in deep layers, and the "initial dip" was most pronounced in layer I. The present results indicate that both the onset of the BOLD response and the initial dip depend on cortical depth and can be explained, at least in part, by the spatial gradient of delays in microvascular dilation, the fastest response being in the deep layers and the most delayed response in the capillary bed of layer I.blood flow | cortical layer | hemodynamic | imaging | somatosensory N euroglial activation is accompanied by release of vasoactive mediators that dilate and constrict the surrounding arterioles (1, 2) and capillaries (3, 4). These changes in diameter in turn lead to changes in blood flow throughout the vascular matrix and can be detected on the macroscopic level as a positive blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal when blood flow response exceeds oxygen consumption (5-7). Under the assumption of local neurovascular coupling, the onset of the changes in diameter is determined by the following three factors, any of which may differ as a function of the cortical depth and branching order within the vascular tree: (i) the onset and peak time of the neuronal activity evoking the response; (ii) the time needed to release a vascular messenger [e.g., prostaglandin or NO (8)]; and (iii) the time needed for the target vessel to respond. However, in addition to local neurovascular coupling, vascular responses can propagate within the arteriolar/capillary networks (3, 9, 10). Indeed, propagation of dilation and constriction has been observed on the cortical surface (11-15), in excised cerebral vessels, and in noncerebral preparations (16,17).Previous studies with single-vessel resolution in vivo have been limited to the cortical surface, but recent improvements in twophoton microscopy technology allow direct imaging of singlevessel diameters and flow velocities within a 3D geometry of vascular trees (1,2,18,19). In the present study, we used this technology to examine microvascular responses to sensory stimulation down to 550 μm below the cortical surface in the rat primary somatosensory cortex (SI). We then compared the results with highresolution BOLD fMRI to investigate the extent to which laminar ...

Cortical Depth-Dependent Temporal Dynamics of the BOLD Response in the Human Brain

“…Differences in the BOLD onset could also be due to the varying delays in microvascular (arterial) dilation across the cortical depth (Tian et al, 2010). Our results for the visual cortex showed a significant increase in onset time for the upper gray matter (0 to 1 mm) as compared with the deeper gray matter compartments (1 to 2 and 2 to 3 mm).…”

“…It is likely that at our imaging resolution may not be high enough to sample directly from specific layers; at 1.5 mm voxel size we most likely averaged across layers, thereby reducing any potential onset time variation across layers. However, Tian et al (2010) did not find any significant onset time differences in the deeper gray matter (cortical layers IV to VI), although they used a lower spatial and temporal resolution than Silva and Koretsky (2002). Furthermore, the shape of the BOLD response has been shown to change with stimulus duration due to nonlinearities in the seconds range (Boynton et al, 1996;Wager et al, 2005; Figure 2 displays onsets) and in the subsecond range (Birn et al, 2001).…”

“…Even more, BOLD fMRI signal models predict an increased contrast-to-noise ratio for the microvasculature at 7 T due to increasing extravascular effects (Ogawa et al, 1993;Uludag et al, 2009). Recent animal studies at high field strength (X7 T) have shown that BOLD can be specific to the laminar vascular architecture of the cortex, by differences in temporal dynamics of the BOLD signal in reference to cortical depth (Jin and Kim, 2008;Silva and Koretsky, 2002;Tian et al, 2010). The onset times and time-to-peak (TTP) of the BOLD signal were found to be shorter in the deeper gray matter layers as compared with the pial surface.…”

Columnar Specificity of Microvascular Oxygenation and Blood Flow Response in Primary Visual Cortex: Evaluation by Local Field Potential and Spiking Activity

“…The functional significance of this arrangement in nature still is largely unknown (Tian et al, 2010;Zheng et al, 1991;see Attwell et al, 2010 for review). Both the arterial supply and the capillary network in the cortex contain various flow-control structures sensitive to the fluctuation of energy demands (Iadecola, 2004), in a way that spatially 'filters' (or blurs) neuronal activity patterns.…”

“…Based on the notion that increased flow leads to increased cerebral blood volume (CBV), columnar specificity of blood volume responses have been demonstrated on rat barrel cortex and striate cortex of cats and monkeys with the intrinsic optical imaging (IOI) technique (Sheth et al, 2004;Vanzetta et al, 2004), as well as with contrast agent-enhanced CBV fMRI methods (Fukuda et al, 2006). Spatially specific regulation of CBF has been also observed in the vertical dimension of cortex in which laminarspecific regulation of CBF in deep cortical layers was independent of dilation of large surface vessels (Caesar et al, 2003;Fabricius et al, 1997;Tian et al, 2010). Thus, there are indications that blood flow can be regulated at a local scale.…”