Commentary on a comment

If you want to see a masterclass in dissecting a paper, go read Tal Yarkoni’s discussion of “The dACC is selective for pain“:

That conclusion rests almost entirely on inspection of meta-analytic results produced by Neurosynth, an automated framework for large-scale synthesis of results from thousands of published fMRI studies. And while I’ll be the first to admit that I know very little about the anterior cingulate cortex, I am probably the world’s foremost expert on Neurosynth*—because I created it.

…The basic argument L&E make is simple, and largely hangs on the following observation about Neurosynth data: when we look for activation in the dorsal ACC (dACC) in various “reverse inference” brain maps on Neurosynth, the dominant associate is the term “pain”…The blue outline in panel A is the anatomical boundary of dACC; the colorful stuff in B is the Neurosynth map for ‘dACC’…As you can see, the two don’t converge all that closely. Much of the Neurosynth map sits squarely inside preSMA territory rather than in dACC proper…That said, L&E should also have known better, because they were among the first authors to ascribe a strong functional role to a region of dorsal ACC that wasn’t really dACC at all… Much of the ongoing debate over what the putative role of dACC is traces back directly to this paper.

…Localization issues aside, L&E clearly do have a point when they note that there appears to be a relatively strong association between the posterior dACC and pain. Of course, it’s not a novel point…Of course, L&E go beyond the claims made in Yarkoni et al (2011)—and what the Neurosynth page for pain reveals—in that they claim not only that pain is preferentially associated with dACC, but that “the clearest account of dACC function is that it is selectively involved in pain-related processes.”…Perhaps the most obvious problem with the claim is that it’s largely based on comparison of pain with just three other groups of terms, reflecting executive function, cognitive conflict, and salience**. This is, on its face, puzzling evidence for the claim that the dACC is pain-selective.

etc. etc. Traditionally, this type of critique would slowly be drafted as a short rebuttal to PNAS. But isn’t this better? Look how deep the critique is, look how well everything is defined and explained. And what is stopping the authors from directly interacting with the author of the critique to really get at the problem? The only thing left is some way for pubmed or Google Scholar to link these directly to the paper.

Go read the whole thing and be learned.

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What should we be allowed to forget?

Should we be dampening the emotional aspect of memory?

Two decades ago, scientists began to wonder if they could weaken traumatic memories by suppressing the hormonal rush that accompanies their formation. They turned to propranolol, which was already on the market as a treatment for hypertension and blocks the activity of hormones like epinephrine and norepinephrine….Next, in 2002, neuroscientists reported that emergency room patients who took propranolol within 6 hours of a traumatic event were less likely to experience the heightened emotions and arousal associated with PTSD one month later, compared with people who took placebos.

The hitch was that in order to interfere with memory consolidation, propranolol needed to be given within hours of a trauma, long before doctors knew whether someone would go on to develop PTSD. But around the same time, studies began to show that memories can once again become fragile when they are recalled…Perhaps, researchers hypothesized, propranolol could weaken emotional memories if PTSD patients took the drug after they conjured up the details of a painful experience. By blocking the effects of norepinephrine and epinephrine upon recall, propranolol might dampen down activity in the amygdala and disrupt reconsolidation.

I liked this comment someone left on the article:

If the memory of my trauma were to be removed, I would make no sense to myself.

If we could edit our memories, what is important to who we are? Is there a threshold of pain beyond which we should not be forced to endure our entire lives? What was adaptive one hundred thousand years ago may not be adaptive in modern society.

Study: Men smell and that will stress you out

ferret-specific neurons

A study in Nature Methods has kicked up a bit of a fuss:

In 2007, his lab observed that mice spend less time licking a painful injection—a sign that they’re hurting—when a person is nearby, even if that “person” is a cardboard cutout of Paris Hilton. Other scientists began to wonder if their own data were biased by the same effect. “There were whisperings at meetings that this was confounding research results,” Mogil says.

—–

Male, but not female, experimenters induce intense stress in rodents that can dampen pain responses, according to a paper published today in Nature Methods. Such reactions affect the rodents’ behaviour and potentially confound the results of animal studies, the study suggests.

Yup, the paper says that the stench of men is just plain stressful to rodents. And it’s just human males, but males from many (most?) species.

It is pretty well-established that many animals have neurons that have an innate response to the odor of other animal species. Look at the percent of neurons in the vomeronasal organ (VNO) of the mouse that detect the scent of specific other animals:

Conspecific cells

 

I suppose that means it shouldn’t be surprising that there would be a way to detect males across species. And the data from this paper kinda-sorta points to that: bedding from male guinea pigs, rats, cats, and dogs induced stress-related behaviors but not when the bedding came from castrated males (poor guys). Overall, the affect of the stress was stronger on the female than the male mice.

There are three interesting take-aways from this paper. First, obviously, is that males stress out mice they handle more than females do – and they stress out female mice more than male mice. Second, certain male-specific effects seem to require both an odor and the physical presence of the (male/female) handler. Third, the odor isn’t likely to be a pheromone but rather a complex mix of odors. Three of the stress-inducing odors that they identify are 300 μM (E)-3-methyl-2-hexenoic acid (3M2H), 0.75–3 mM androstenone and 0.75–3 mM androstadienone (4,16-androstadien-3-one), which I’m sure everyone is familiar with! The first is a fatty acid that contributes to “Caucasian male underarm odor” (yum), the second is a steroid found in sweat and urine (and celery), and the third is a metabolite of testosterone.

Also, let’s take a moment to pity the poor grad students who had to take “repeated rectal measurement of core [mouse] body temperature”.

References

Isogai Y, Si S, Pont-Lezica L, Tan T, Kapoor V, Murthy VN, & Dulac C (2011). Molecular organization of vomeronasal chemoreception. Nature, 478 (7368), 241-5 PMID: 21937988

Sorge, R., Martin, L., Isbester, K., Sotocinal, S., Rosen, S., Tuttle, A., Wieskopf, J., Acland, E., Dokova, A., Kadoura, B., Leger, P., Mapplebeck, J., McPhail, M., Delaney, A., Wigerblad, G., Schumann, A., Quinn, T., Frasnelli, J., Svensson, C., Sternberg, W., & Mogil, J. (2014). Olfactory exposure to males, including men, causes stress and related analgesia in rodents Nature Methods DOI: 10.1038/nmeth.2935