fMRI of the Amygdala: All In Vein?

By Neuroskeptic | May 24, 2015 5:44 am

Neuroscientists might need to rethink much of what’s known about the amygdala, a small brain region that’s been the focus of a lot of research. That’s according to a new paper just published in Scientific Reports: fMRI measurements of amygdala activation are confounded by stimulus correlated signal fluctuation in nearby veins draining distant brain regions.

The amygdala is believed to be involved in emotion, especially negative emotions such as fear. Much of the evidence for this comes from fMRI studies showing that the amygdala activates in response to stimuli such as images of scared faces.

However, according to the authors of the new paper, Austrian neuroscientists Roland N. Boubela and colleagues, there’s a flaw in these fMRI studies. The problem, they say, is that the amygdala happens to be located next to a large vein, called the basal vein of Rosenthal (BVR).

fMRI works by detecting blood oxygenation, so changes in the oxygen level in the blood within the BVR could produce signal changes that could be mistaken for activation in the amygdala. Because the BVR drains blood from several brain regions, some of which are themselves involved in emotion processing, the BVR could act as a proxy for emotion-related neural activation elsewhere in the brain, which is then projected onto the amygdala.

Neuroscientists have long been aware of potential large vein contributions to the fMRI signal, but it hasn’t generally been seen as a serious concern. According to Boubela et al., however, the problem is serious, when it comes to the amygdala. In a series of MRI scanning experiments using high resolution fMRI alongside susceptibility weighted imaging (SWI), a method that reveals the structure of blood vessels, Boubela et al. say that they’ve shown that

Major signal changes measured in the amygdala region in a typical emotional task is not, in fact, located in the amygdala itself. Rather, these signal changes occur in the adjacent BVR that drains large regions of the medial temporal lobe and has confluences from other large veins in the amygdala region, and are therefore largely unrelated to neuronal activity in the amygdala itself.

The key result can be seen in this image, showing the fMRI neural activation in response to images of fearful faces compared to neutral stimuli. The large red blob at the bottom is the visual cortex. Above this can be seen two long, thin, S-shaped blobs which, Boubela et al. say, is the BVR on the left and right sides of the brain. The white arrows represent the emotion processing hotspot of the amygdala, according to a published meta-analysis of brain activation to emotional stimuli. This location is right next to the BVR.

faces_amygdala

Boubela et al. conclude that

This discovery has rather wide-ranging implications. Most immediately, it casts doubt on previous findings on amygdala function that rely solely on fMRI as evidence… [we do not] want to dispute the role of the amygdala in the processing of emotions per se, as this is established well enough even when completely disregarding all fMRI evidence. [But] one should be wary of fMRI signal changes in this region…

And they say, the problem might not be limited to the amygdala: “It is plausible that such effects might also occur in other areas of the brain characterized by the presence of large vessels”, and they cite the parahippocampal gyrus and the insula as other potential trouble-spots.

ResearchBlogging.orgBoubela RN, Kalcher K, Huf W, Seidel EM, Derntl B, Pezawas L, Našel C, & Moser E (2015). fMRI measurements of amygdala activation are confounded by stimulus correlated signal fluctuation in nearby veins draining distant brain regions. Scientific Reports, 5 PMID: 25994551

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  • http://brain4biz.wordpress.com/ Brain Molecule Marketing

    Oops! Gee, wonder what Joe LeDoux and all the “cognitive”/affective n-scientists will handle this hot potato!? The above research identifies the fusiform gryus as a key processing area. Gee, that’s a very primitive neural system to handle such “advanced and (human) exceptional things like emotions!? duh…

    The whole paper is worth reading. It debunks a whole lot…

    I have blogged a long excerpt on this and spread all over Linked In…heh, heh…http://goo.gl/Z4qtz2

    • Defenestrator

      Joe LeDoux built his career on rodent research, not human fMRI.

      • http://brain4biz.wordpress.com/ Brain Molecule Marketing

        True and he has done direct electrode placement. Wonder if venous system is similar. Still, lots of “cognitive” theories built on “blobism” and fMRI.

        • Defenestrator

          Luckily the amygdala is very well-studied in animal models, and there’s been a nice convergence between that literature and human fMRI findings in some paradigms, for example fear conditioning. Much harder to make animal models of other emotional experiences, but that convergence tells me that the fMRI-amygdala literature is not as debunked as some are claiming.

          I’d be interested to see if/how the basal vein of Rosenthal story affects interpretation of PET scan rCBF studies or FDG studies. My guess is that it’s not particularly important for FDG studies. Another argument for multiple modality replications. For example:
          http://www.ncbi.nlm.nih.gov/pubmed/19232481

          • http://brain4biz.wordpress.com/ Brain Molecule Marketing

            My read is that understanding brain function is MUCH more complicated than the fMRI pictures suggest. If you look at LaDoux’s work with different amy- cortices, etc The best and brightest n-sci grad students I know scorn “imaging.” Fortunately, the tech gets better.

            My understanding is also that brain processes are massively parallel and thus “blobology” is flawed. I was intrigued by the articles mention the fusiform gyri. My money is on the basal ganglia as determining most behavior.

            What the heck is an “emotion” other than anthropomorphizing a cultural concept?

  • practiCalfMRI

    Time for ASL-based fMRI, or spin echo BOLD, perhaps. But both may have insufficient sensitivity at 3 T. Something for people to try!

    • practiCalfMRI

      Also, temporal information in T2* BOLD might be useful. Veins draining distant brain tissue regions tends to have time-to-peak (TTP) response 5-6 sec after a brief stimulus whereas closer regions may have TTP around 4-5 sec. See e.g. http://www.ncbi.nlm.nih.gov/pubmed/15652302.

      • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

        Interesting! I wonder if the “initial dip” in the BOLD response might be more localized, and less vein-based, than the subsequent increase in oxygenation?

        • D Samuel Schwarzkopf

          It ought to be at least in optical imaging it clearly is. The question is if you can really get this signal in fMRI. This seems to remain controversial.

          • practiCalfMRI

            A big issue is potential aliasing of the post-stim undershoot if the inter-trial interval is less than tens of seconds, as shown by Frahm’s group a decade or more ago. I also take my cue from Seong-Gi Kim, who has tested in cat cortex at 9.4 T probably all we can ever hope to see with human fMRI, that is, down to laminar specificity. His conclusion is that CBF localization is about as good as one can do, and that it’s approximately the same as CBV localization. BOLD-based contrasts tend to bias towards the cortical surface.

          • http://brain4biz.wordpress.com/ Brain Molecule Marketing

            So BOLD will make cortical events more prominent – as an artifact?

          • practiCalfMRI

            Sorry, don’t follow your question. But in case it helps, think of the superior sagittal sinus. Many regions of the brain drain to it. (Just don’t ask me which ones.) If the sum of differences between two tasks is such that there is a net difference in oxygenation in SSS blood, one could easily interpret that part of the brain adjacent to the SSS as being involved in the task unless one knows better. This is a well-known issue of using draining vasculature as a proxy for neural activity. Using microvasculature closer to the cellular level, such as CBV-weighted fMRI, which reflects arterioles-capillaries-venuoles, is more specific than BOLD.

  • Martin Hebart

    I quickly created an animated gif of the veins (using MRIcroGL and an atlas from here: http://tinyurl.com/p4jgcvj). Looks a lot like the striatum and the ACC are also affected.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Fascinating, thanks very much!

      Veins per se may not be the problem, the problem (according to Boubela et al.) is when a brain area is located next to a vein that drains blood from other, different brain areas. Because then activation in one area can get “transferred downstream”.

      • D Samuel Schwarzkopf

        That’s the worst case scenario I guess but there can be other problems. There was a nice paper by Winnawer et al few years ago suggesting that visual area V4 in humans is often masked my a draining vein which explains why it can often be hard to map (although I haven’t had many problems with this in my 3T data – in 1.5T it seems to be much trickier which could well be due to the blood vessel artifact).

    • http://brain4biz.wordpress.com/ Brain Molecule Marketing

      Oops….gee, all those high powered machines and, apparently, low power theories….is that the sound of circling a drain?

  • http://www.postlinearity.com gregorylent

    locationism will be gently smiled at in recollection as the subtlety of neuroscience grows and takes it out into the field, where consciousness is more accurately doing its dance … until then, phrenology 2.0

  • poniesinjudah

    This is pretty entertaining. But I’m sure the fMRI fetishizing scientists won’t be moved by this. One point, they know veins carry the de-oxygenated blood, right?

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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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