fMRI studies, which measure blood oxygenation-dependent (BOLD) signal, do report brain activations.

It seems obvious, but it’s been subject to debate.  Why? – well, largely because validations of the technique have tended to involve stimulating neurons using electrodes and measuring the resulting BOLD response using fMRI.  Unfortunately, whenever you stick an electrode into the brain to stimulate a region, that electrical stimulation tends to have extremely non-specific effects.  It’s like testing whether the energy-saving light bulbs (and not the tube fluorescents or the traditional filament bulbs) in the Dobbins Lab explode at high currents by sending a power surge to the whole university and checking to see if the fire department is called to the Psychology building.  There are any number of other, related events associated with the power surge that could have caused the fire-department to be called out.

But now we have some more solid evidence for fMRI doing what we think it does.  Using a pretty cool technique called optogenetic stimulation, mouse neurons can be modified (by a locally-injected virus) to fire when exposed to light, and very specific neuronal firing can be non-invasively stimulated using ‘optical stimulation’.  Resultant changes in local BOLD signal can be assessed using high field-strength fMRI to see whether there is a BOLD activation that corresponds directly to the neuronal firing.  Thankfully, as reported by Lee et al. in Nature, excitatory neuronal firing does lead to the sort of BOLD activation we typically see in fMRI studies.

So, excitatory neurons firing causes an elevated BOLD response.  But wait, there’s more:

“Evoked BOLD was dominated by positive signals while driving these excitatory CaMKIIα-positive cells; in contrast, optically driving inhibitory parvalbumin-positive cells10, which may have unique connectivity with local neuronal circuitry or vasculature, additionally gave rise to a zone of negative BOLD, consistent with the GABAergic phenotype, surrounding the local positive BOLD signal (Supplementary Fig. 4).”

The suggestion there is that the firing of inhibitory neurons leads to negative BOLD signal.  The justification for this statement is hidden away in the supplementary materials, but if it’s well-supported (and replicated,  of course) then fMRI may start being the intuitively plausible brain interrogation tool that we’ve also shied away from allowing it to be.  It doesn’t get too much simpler than: more excitation = more activation = more blood; more inhibition = less activation = less blo0d, does it?

It’s good to know I may not be in the snake-oil business.

Here’s a link to the article:

One thought on “What a Relief!

  1. Let’s not get carried away, Akira… we are still in the snake-oil business; just maybe not for that reason. ;)

    Also, I’m enjoying the blog, and thanks for the link!


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