Many fMRI studies of brain activity could be biased by the effect of large blood vessels, according to an interesting new report: Origins of intersubject variability of BOLD and arterial spin labeling fMRI.

fMRImeasures BOLD, the Blood Oxygenation Level Dependent response. As the name says, BOLD is when a bit of the brain becomes more active, it uses more oxygen, and the oxygenation level of the blood in the area drops - although it then increases to compensate, and it's the increase that most fMRI picks up.

There's a catch though: blood flows. Specifically, it flows from arteries, into tissues - the brain, in this case - and then into veins. Blood leaving the brain tends to end up in the larger veins and, being large, these exert a large effect on BOLD - even though they're some distance from the true site of neural activation.

So, the worry is that BOLD blobs may be shifted towards the nearest large vein, reducing the accuracy of fMRI. It's a well-recognized issue, but it's not clear just how serious it is... or what we can do about it.

Enter Canadian researchers Ismael Gaxiola-Valdez and Bradley Goodyear. By comparing BOLD to the alternative method of ASL - They show that the large vessel effect does happen to BOLD signals, shifting the activation blobs nearer to the surface of the brain (where veins are.) However, the effect is more pronounced when the blobs represent absolute BOLD changes. When blobs represent the z score - which they usually do - the difference is smaller.

That's somewhat reassuring... but here's the bad news. Some peoples' brains show larger BOLD changes than others. Gaxiola-Valdez and Goodyear show that these individual differences in BOLD magnitude are probably driven by large vessel effects because as the pic at the top shows, BOLD was most variable (between people) at the surface, i.e. near the veins, while ASL, less subject to the vein bias, was most variable deep in the brain, as you'd expect.

Worse, the size of people's BOLD and ASL signal changes (to the same task) were not correlated (or only weakly) when the BOLD study used short task blocks. This calls into question short-block or event-related fMRI experiments that measure differences between people or between groups: the differences might be in the veins, not the brain. With longer task blocks, however, there was a good correlation with the ASL.

Overall, it's an important paper and a reminder that, although neuroscientists sometimes treat the brain as separate from the rest of the body, it's not.

Gaxiola-Valdez I, and Goodyear BG (2012). Origins of intersubject variability of blood oxygenation level dependent and arterial spin labeling fMRI: implications for quantification of brain activity. Magnetic resonance imaging PMID: 22795932