initial publication

2. Quiet changes in initial publication, and pathology questions.

As preamble to the interview said “They are called BigBrain, Julich-Brain or EBRAINS – laypeople may quickly lose track. All these projects, however, link together for one common goal: decoding the brain. HIBALL, a German-Canadian research collaboration, now adds another piece to the puzzle.”

As it is shown below (part 3), it took 10 years to produce the first paper describing the project: “BigBrain: An Ultrahigh-Resolution 3D Human Brain Model”, 21 June 2013, Science 340, 1472 (2013) [1]. So it seems authors had enough time to “consider all the angles” of this challenging project. Still, this paper leave strange impression: too many details show a rather sloppy job.

For instance: is it possible to have a sex-change operation after death? Surprisingly, BigBrain project proved that it is possible. This quiet but important operation could become the most significant achievement of modern science. Here we have two fragments of the same page:

Fig. 1. Male or female? That is the question.

As we can see, left image is downloaded recently, but the right-one was downloaded almost immediately after publication of the paper. Somewhere between these time points the gender of the brain’s donor quietly changed. Moreover, it changed twice: the second time the same information had to be corrected in “Supplementary Materials” (Fig.2, B and C).

Fig.2. A (top): Supplementary materials, title page. B (left): page 1, “male”, C(right): page 1, “female”

Considering what we can read here, “male-female” mix-up was not just a typo: it is difficult to make the same typo twice, on two completely separate pages. If this is not strange enough, consider more: is it OK to limit description of the donor by short sentence: “without any neurological or psychiatric diseases in clinical records”? Compare this description with rather more meticulous statements describing clinical diagnosis, cause of death, other pathological finding present in other papers from the same group, where donors brains were used:

K.Amunts et al, 2000: age, gender, postmortem delay, cause of death, weight, fixation procedure
F.Scheperjans et al., 2008: gender, age, cause of death, postmortem delay, fixation
M.Kujovic, et al, 2013: gender, age, cause of death, postmortem delay, fixation.
S.Bludau et al, 2013: gender, age, cause of death, postmortem delay, fixation
S.Lorenz, et al, 2015: age, gender, cause of death, fresh weight, shrinkage factor.

So, in this paper the cause of death or clinical diagnosis is missing. Instead, if we look closer, despite the statement “no known neurological or psychiatric pathology”, we see gross pathology: big thalamic stroke in the right hemisphere. The size of this stroke can be approximated as 10 x 10 x 15 mm. Additional pathology can be noticed as well: middle fissure is slanted and moved to the left, which creates clear asymmetry between left and right hemispheres. Actually, MRI-image marked “B” in Science publication shows it even better. Such changes usually indicate significant brain edema, mainly of the right hemisphere in this case (Fig. 3, source source: https://www.youtube.com/watch?v=vUSp-P42k2o&t=864s)

Fig.3: Big stroke of the BigBrain.

With respect to this pathology, many questions arise. In particular, is it reasonable not to disclose it in writing? Is it possible to use this particular brain, possibly distorted by edema, and some neuro-degenerative changes, caused by this stroke, as a reference brain all over the World? Thalamic projections are very important for cortical development, so the stroke could lead to degeneration, and have a significant impact on neuronal densities, cortical thicknesses and other parameters of the brain. Should this issue at least be discussed, not hidden in “supplementary materials”?

Finally, another strange detail emerged during donor’s brain evaluation: that is clearly visible damage of the surface of the temporal lobe of the brain, which in my mind could have only one explanation: sloppy job of pathologist, who performed brain extraction during autopsy (Fig.4). This detail might be considered as minor, but all described problems and discrepancies together amount to inevitable conclusion:  there is a clear discrepancy between importance to make high-quality decision regarding selection of this unique brain and the real brain, selected for this project. This brain has too many problems to be considered an “ideal” example for use as a model by the whole world. Strange, is it not?

 

 

 

 

 

 

 

Fig. 4: Brain damage (source: https://bigbrainproject.org/about.html). Looks like surgical saw damage, most likely inflicted during sawing of the scalp before brain extraction.

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