Let us consider the specific findings individually. Figure 1 shows a schematic summary of the results. The first result of the paper—that regions showing positive BOLD responses correlate with increases in CBV and CBF—is arguably the most straightforward and easiest to understand. It is well known that, with activation, CBV and CBF increase. Second, they show that adjacent regions associated with a negative BOLD response correspond to a decrease in CBF but an increase in CBV. This result is slightly puzzling. This could be explained Apoptosis Compound Library ic50 if the CBV response, being larger than BOLD, might result

in significant amount of hemodynamic “spillover” from the truly active regions. However, this explanation seems likely to be wrong since multiple papers have shown that CBV, if anything, has a smaller point-spread function www.selleckchem.com/Bcl-2.html than BOLD, and further, the results here show an exquisite layer specificity of CBV. Goense et al. (2012) also show that with regard to layer specificity, for positive BOLD responses, CBF and CBV both increased in the central layers. This is also an interesting but yet not easily explained finding. It is thought that the center layers, which have the greatest concentration of microvessels, would be most active (and it is heartening to see that both CBF and CBV show selective increases in the center layers). The

most surprising of the study’s findings is their last result, that for negative BOLD responses, CBF decreased near the surface but CBV increased in the central layers. Why and how would only surface CBF decrease and why would only middle-layer CBV increase in these areas of negative BOLD? The CBF decrease at the surface layers appears to be what determines the decrease in BOLD, but is this something that reflects a decrease in neuronal activity? Surface (larger) vessels are presumably less directly controlled by neuronal activity. Why would the middle layers

not show any decrease in CBF with less neuronal activity? Lastly, the increase second in CBV in the middle layers might even suggest a local increase in neuronal activity (increased activity of inhibitory neurons?) in these negative regions. The authors suggest that interneuron inhibitory activity often eludes electrophysiological measures, thus explaining the failure to detect this effect in previous experiments. Other hypotheses to explain this apparently perplexing result invoke more “plumbing”-related autoregulatory or redistribution effects, mechanisms which would be extremely difficult fully unravel. For instance, it is suggested that there might be a decrease in perfusion pressure in center layers (without a decrease in perfusion itself), causing a reduction of flow in superficial vessels and an therefore an increase in venous backpressure, leading to an increase in center layer CBV.