I am blind, but my other personality can see

58depression-388872_960_720This is a truly bizarre report.

A woman named BT suffered an accident when she was 20 years old and she became blind. Thirteen year later she was referred to Bruno Waldvogel (one of the two authors of the paper) for psychotherapy by a psychiatry clinic who diagnosed her with dissociative identity disorder, formerly known as multiple personality disorder.

The cortical blindness diagnosis has been established after extensive ophtalmologic tests in which she appeared blind but not because of damage to the eyes. So, by inference, it had to be damage to the brain. Remarkably (we shall see later why), she had no oculomotor reflexes in response to glare. Moreover, visual evoked potentials (VEP is an EEG in the occipital region) showed no activity in the primary visual area of the brain (V1).

During the four years of psychotherapy, BT showed more than 10 distinct personalities. One of them, a teenage male, started to see words on a magazine and pretty soon could see everything. With the help of hypnotherapeutic techniques, more and more personalities started to see.

“Sighted and blind states could alternate within seconds” (Strasburger & Waldvogel, 2015).

The VEP showed no or very little activity when the blind personality was “on” and showed normal activity when the sighted personality was “on”. Which is extremely curious, because similar studies in people with psychogenic blindness or anesthetized showed intact VEPs.

There are a couple of conclusions from this: 1) BT was misdiagnosed, as is unlikely to be any brain damage because some personalities could see, and 2) Multiple personalities – or dissociate identities, as they are now called – are real in the sense that they can be separated at in biological way.

The visual pathway that mediates conscious visual perception. a) A side view of the human brain with the retinogeniculocortical pathway shown inside (blue). b) A horizontal section through the brain exposing the same pathway.

Fascinating! The next question is, obviously, what’s the mechanism behind this? The authors say that it’s very likely the LGN (the lateral geniculate nucleus of the thalamus) which is the only relay between retina and V1 (see pic). It can be. Surely is possible. Unfortunately, so are other putative mechanisms, as 10% of the neurons in the retina also go to the superior colliculus, and some others go directly to the hypothalamus, completely bypassing the thalamus. Also, because it is impossible to have a precise timing on the switching between personalities, even if you MRI the woman it would be difficult to establish if the switching to blindness mode is the result of a bottom-up or a top-down modulation (i.e. the visual information never reaches V1, it reaches V1 and is suppressed there, or some signal form other brain areas inhibits V1 completely, so is unresponsive when the visual information arrives).

Despite the limitations, I would certainly try to get the woman into an fMRI. C’mon, people, this is an extraordinary subject and if she gave permission for the case study report, surely she would not object to the scanning.

Reference: Strasburger H & Waldvogel B (Epub 15 Oct 2015). Sight and blindness in the same person: Gating in the visual system. PsyCh Journal. doi: 10.1002/pchj.109.  Article | FULLTEXT PDF | Washington Post cover

By Neuronicus, 29 November 2015


The runner’s euphoria and opioids

The runner’s high is most likely due to release of the endorphins binding to the opioid receptors according to Boecker et al. (2008, doi: 10.1093/cercor/bhn013). Image courtesy of Pixabay.

We all know that exercise is good for you: it keeps you fit, it reduces stress and improves your mood. And also, sometimes, particularly after endurance running, it gets you high. The mechanism of euphoria reported by some runners after resistance training is unknown. Here is a nice paper trying to figure it out.

Boecker et al. (2008) scanned 10 trained male athletes at rest and after 2 hour worth of endurance running. By “trained athletes” they mean people that ran for 4-10 hours weekly for the past 2 years. The scanning was done using a positron emission tomograph (PET). The PET looks for a particular chemical that has been injected into the bloodstream of the subjects, in this case non-selective opioidergic ligand (it binds to all opioid receptors in the brain; morphine, for example, binds only to a subclass of the opioid receptors).

The rationale is as follows: if we see an increase in ligand binding, then the receptors were free, unoccupied, showing a reduction in the endogenous neurotransmitter, that is the substance that the brain produces for those receptors; if we see a decrease in the ligand binding it was because the receptors were occupied, meaning that there was an increase in the production of the endogenous neurotransmitter. The endogenous neurotransmitters for the opioid receptors are the endorphins (don’t confuse them with epinephrine a.k.a. adrenaline; different systems entirely).

After running, the subjects reported that they are euphoric and happy, but no change in other feelings (confusion, anger, sadness, fear etc.; there was a reduction in fear, but it was not significant). The scanning showed that it was less binding of the opioidergic ligand in many places in the brain (for the specialist, here you go: prefrontal/orbitofrontal cortices, dorsolateral prefrontal cortex, anterior and posterior cingulate cortex, insula and parahippocampal gyrus, sensorimotor/parietal regions, cerebellum and basal ganglia).

Regression analysis showed that there was a link between the euphoria feeling and the receptor occupancy: the more euphoric the people said they were, the more endorphines (i.e. endogenous opioids) they had bound in the brain. This study is the first to show this kind of link.

Reference: Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, & Tolle TR. (Nov 2008, Epub 21 Feb 2008). The Runner’s High: Opioidergic Mechanisms in the Human Brain. Cerebral Cortex, 18:2523–2531. doi:10.1093/cercor/bhn013. Article | FREE FULLTEXT PDF

By Neuronicus, 28 November 2015


The FIRSTS: the isolation of tryptophan (1901)

The post-Thanksgiving dinner drowsiness is due to the very carbohydrates-rich meal and not to the amounts of tryptophan in the turkey meat, which are not higher that those in chicken.

There is a myth that says the post-Thanksgiving dinner drowsiness is due to high amounts of tryptophan found in the turkey meat. Nothing farther from the truth; in fact, it is due to the high amounts of carbohydrates in the Thanksgiving dinner which trigger massive insulin production. Anyway, the myth still goes on, despite evidence that the turkey has about the same amount of tryptophan as the chicken. That being said, what’s this tryptophan business?

Tryptophan is an amino acid necessary for many things in the body, including the production of serotonin, a brain neurotransmitter. You cannot live without it and your body cannot make it. Thus, you need to eat it. There are many sources of tryptophan, like eggs, soybeans, cheeses, various meats and so on.

Tryptophan was first isolated by Hopkins & Cole (1901) through hydrolysis of casein, a protein found in milk. And there were no two ways about it: “there is indeed not the smallest doubt that our substance is the much-sought tryptophane” (p. 427). No “we’re confident that…”, “we’re suggesting this…”, no maybe, possibly, probably, and most likely’s that one finds in an overwhelming abundance in the cautious tone adopted by today’s studies. Many more scientists today, fewer job openings, one has a career to think about…

Digression aside, Hopkins went on later to prove that tryptophan is an essential amino acid by feeding mice a tryptophan-free diet (and the mice died). By 1929 he was knighted and he got the Nobel prize for his contributions in the vitamin field. Also, a little known fact for you, butter lovers, Hopkins proved that margarine is worse that butter because it lacks certain vitamins and you have him to thank for the vitamin-enriched margarine that you find today.

Reference: Hopkins FG & Cole SW (Dec 1901). A contribution to the chemistry of proteids: Part I. A preliminary study of a hitherto undescribed product of tryptic digestion. The Journal of Physiology, 27 (4-5): 418–28. doi:10.1113/jphysiol.1901.sp000880. PMC 1540554. PMID 16992614. Article | FREE FULLTEXT PDF

By Neuronicus, 27 November 2015

Lucy’s 9 vertebrae are actually 8

Lucy. Left: picture of the real skeleton. Middle and Right: reconstructions. Courtesy of Wikipedia

As Google reminded us, today is 41st anniversary of the finding of Lucy, the first discovered member of the species Australopithecus afarensis. Lucy lived in Ethiopia about 3.2 million years ago and the most extraordinary fact about her is that her fossil represents the first evidence of bipedalism in a hominin (we are also hominins).

Lucy is one “missing link” (not ‘missing’ anymore, obviously) between the common ancestor of humans and chimpanzees and humans because she has ape-like features (jaw, forehead, long arms, small cranium) and human-like features (knee, ankle, lumbar curve, pelvic bones) and walked upright.

Meyer et al. (2015) wanted to do a comprehensive reconstruction of Lucy for display at the American Museum of Natural History in New York. During this work they noticed that one vertebrae of the total of nine found is kindda small compared to the other ones. So they set to measure vertebrae form all sorts of other species, alive and extinct, and after some factor analysis they concluded that out of Lucy’s nine found vertebrae, the little one is not actually hers, but belongs to a different species from the genus Theropithecus (a baboon ancestor).

This finding is functionally uninformative and their “work does not refute previous work on Lucy or its importance for human evolution, but rather highlights the importance of studying original fossils, as well as the efficacy of the scientific method.” In other words, give the poor anthropologists not reconstructions but the original fossils to work with (most people worked with Lucy’s reconstructions which missed some details, thus allowing this pesky vertebra to remain miss-cataloged for 40 years).

The new alignment from doi: 10.1016/j.jhevol.2015.05.007

This is the first paper of pure anthropology that I have read in full and let me tell you that I found a lot of curious things, unrelated to Lucy. Like, for example, from an anthropologist’s point of view, an adult is someone with the third molar completely erupted. We should then look into the people’s mouths before giving them the keys to the wine cellar, because some 21-year olds are definitely not adults. Also, instead of a medical doctor, get an anthropologist to teach anatomy, because oh boy do these people know their skeletons! Here is an excerpt from the Methods section: “The overall size of the A.L. 288-1am partial vertebra was calculated as the geometric mean of six linear dimensions: lamina superoinferior height and dorsoventral thickness, pars interarticularis width, interarticular facet height, and superior and inferior articular interfacet maximum transverse widths. The pars interarticularis geometric mean includes three variables from the pars interarticularis: lamina superoinferior height and dorsoventral thickness, and pars interarticularis width” (p. 175).

All in all, nice!

Reference: Meyer MR, Williams SA, Smith MP, Sawyer GJ (August 2015, Epub 6 Jun 2015). Lucy’s back: Reassessment of fossils associated with the A.L. 288-1 vertebral column. Journal of Human Evolution, 85:174-80. doi: 10.1016/j.jhevol.2015.05.007. Article | FREE FULLTEXT PDF

By Neuronicus, 24 November 2015


Dead salmon engaged in human perspective-taking, uncorrected fMRI study reports


Subject. One mature Atlantic Salmon (Salmo salar) participated in the fMRI study. The salmon was approximately 18 inches long, weighed 3.8 lbs, and was not alive at the time of scanning.

Task. The task administered to the salmon involved completing an open-ended mentalizing task. The salmon was shown a series of photographs depicting human individuals in social situations with a specified emotional valence. The salmon was asked to determine what emotion the individual in the photo must have been experiencing.”

Before explaining why you read what you just read and if it’s true (it is!), let me tell you that for many people, me included, the imaging studies seem very straightforward compared to, say, immunohistochemistry protocols. I mean, what do you have to do? You stick a human in a big scanner (fMRI, PET, or what-have-you), you start the image acquisition software and then some magic happens and you get pretty pictures of the human brain on your computer associated with some arbitrary numbers. Then you tell the humans to do something and you acquire more images which come with a different set of numbers. Finally, you compare the two sets of numbers and voila!: the neural correlates of whatever. Easy-peasy.

Well, it turns out it’s not so easy-peasy. Those numbers correspond to voxels, something like a pixel only 3D; a voxel is a small cube of brain (with the side of, say, 2 or 3 mm) comprising of hundreds of thousands to millions of brain cells. After this division, depending on your voxel size, you end up with a whooping 40,000 to 130,000 voxels or thereabouts for one brain. So a lot of numbers to compare.

When you do so many comparisons, by chance alone, you will find some that are significant. This is nature’s perverse way to show relationships when there are none and to screw-up a PhD. Those relationships are called false positives and the more comparisons you do, the more likely it is to find something statistically significant. So, in the ’90s, when the problem became very pervasive with the staggering amount of data generated by an fMRI scan, researchers came up with mathematical ways to dodge the problem, called multiple comparisons corrections (like application of the Gaussian Random Field Theory). Unfortunately, even 20 years later one could still find imaging studies with uncorrected results.

To show how important it is to perform that statistical correction, Bennet et al. (2010) did an fMRI study on perspective taking on one subject: a salmon. The subject was dead at the time of scanning. Now you can re-read the above excerpt from the Methods section.

Scroll down a bit to the Results section: “Out of a search volume of 8064 voxels a total of 16 voxels were significant”, p(uncorrected) < 0.001, showing that the salmon was engaging in active perspective-taking.

After the multiple comparisons correction, no voxel lit up, meaning that the salmon was not really imagining what the humans are feeling. Bummer…

The study has been extensively covered by media and I jumped on that wagon too – even if a bit late – because I never tire of this study as it’s absolutely funny and timeless. The authors even received the 2012 IgNobel prize for Neuroscience, as justly deserved. I refrained from fish puns because there are aplenty in the links I provided for you after the Reference. Feel free to come up with your own. Enjoy!

Reference: Bennett, CM, Baird AA, Miller MB & Wolford GL (2010). Neural correlates of interspecies perspective taking in the post-mortem Atlantic Salmon: An argument for multiple comparisons correction. Journal of Serendipitous Unexpected Results, 1, 1–5, presented as poster at the 2009 Human Brain Mapping conference. PDF | Nature cover | Neuroskeptic cover | Scientific American full story

By Neuronicus, 23 November 2015

Pesticides reduce pollination

Close-up of a bee with pollen flying by a flower. Credit: Jon Sullivan. License: PD

Bees have difficult times these days, what with that mysterious colony collapse disorder on top of various viral, bacterial and parasitical diseases. Of course, the widespread use of pesticides did not help the thriving of the hive, as many pesticides have various deleterious effects on the bees, from poor foraging or less reproduction to even death.

The relatively new (’90s) class of insecticide – the neonicotinoids – has been met with great hope because has low toxic effects on birds and mammals, as opposed to the organophosphates, for example. Why that should be the case, is a mystery for me, because the neonicotinoids bind to the nicotinic receptors present in both peripheral and central nervous system in an irreversible manner, which does not put the neonicotinoids in a favorable light.

Now Stanley et al. (2015) have found that exposure to the neonicotinoid thiamethoxam reduces the pollination provided by the bumblebees to apples. They checked it using 24 bumblebee colonies and the exposure was at low levels over 13 days, trying to mimic realistic in-field exposure. The apples visited by the bumblebees exposed to insecticide had 36% reduction in apple seeds.

Almost 90% of the flowering plants need pollination to reproduce, so any threat to pollination can cause serious problems. Over the paste few years, virtually all USA corn had been treated with neonicotinoids; EU banned the thiamethoxam use in 2013. And, to make matters worse, neonicotinoids are but only one class of the many toxins affecting the bees.

Related post: Golf & Grapes OR Grandkids (but not both!)

Reference: Stanley DA, Garratt MP, Wickens JB, Wickens VJ, Potts SG, & Raine NE. (Epub 18 Nov 2015). Neonicotinoid pesticide exposure impairs crop pollination services provided by bumblebees. Nature, doi: 10.1038/nature16167. Article

By Neuronicus, 21 November 2015

Will you trust a pigeon pathologist? That’s right, he’s a bird. Stop being such an avesophobe!


From Levenson et al. (2015), doi: 10.1371/journal.pone.0141357. License: CC BY 4.0

Pigeons have amazing visual skills. They can remember facial expressions, recall almost 2000 images, recognizes all the letters of the alphabet (well, even I can do that), and even tell apart a Monet form a Picasso! (ok, birdie, you got me on that one).

Given their visual prowess, Levenson et al. (2015) figured that pigeons might be able to distinguish medically-relevant images (a bit of a big step in reasoning there, but let’s go with it). They got a few dozen pigeons, starved them a bit so the birds show motivation to work for food, and started training them on recognizing malignant versus non-malignant breast tumors histology pictures. These are the same exact pictures your radiologist looks at after a mammogram and your pathologist after a breast biopsy; they were not retouched in any way for the pigeon’s benefit (except to make it more difficult, see below). Every time the pigeon pecked on the correct image, it got a morsel of food (see picture). Training continued for a few weeks on over 100 images.

For biopsies, the birds had an overwhelming performance, reaching 99% accuracy, regardless of the magnification of the picture, and for mammograms, up to 80% accuracy, just like their human counterparts. Modifying the pictures’ attributes, like rotation, compression or color lowered somewhat their accuracy, but they were still able to score only marginally less than humans and considerably better than any computer software. More importantly, the pigeons were able to generalize, after training, to correctly classify previously unseen pictures.

Let’s be clear: I’m not talking about some fancy breed here, but your common beady-eyed, suspicious-sidling, feral-looking rock pigeon. Yes, the one and only pest that receives stones and bread in equal measures, the former usually accompanied by vicious swearings uttered by those that encountered their slushy “gifts” under the shoes, on the windshield or in the coffee and the latter offered by more kindly disposed and yet utterly naive individuals in the misguided hopes of befriending nature. Columba livia by its scientific name, at the same time an exasperating pest and an excellent pathologist! Who knew?!

The authors even suggest to use pigeons instead of training and paying clinicians. Hmmm… But who do I sue if my mother’s breast cancer gets missed by the bird, in one of those 1% chances? Because somehow making a pigeon face the guillotine does not seem like justice to me. Or is this yet another plot to get the clinicians off the hook for misdiagnoses? Leave the medical profession alone, birdies – is morally sensitive as it is -, and search employment in the police or Google; they always need better performance in the ever-challenging task of face-recognition in surveillance videos.

P.S. The reason why you didn’t recognized the word “avesophobe” in the title is because I just invented it, to distinguish the hate for birds from a more serious affliction, ornithophobia, the fear of birds.

Reference: Levenson RM, Krupinski EA, Navarro VM, & Wasserman EA (18 Nov 2015). Pigeons (Columba livia) as Trainable Observers of Pathology and Radiology Breast Cancer Images. PLoS One, 10(11):e0141357. doi: 10.1371/journal.pone.0141357.  Article | FREE FULLTEXT PDF

By Neuronicus, 19 November 2015

Prions in urine

toilet urine

This is one of the scariest papers I have read.

All prion diseases – like the mad cow disease, scrapie, Kuru or Creutzfeldt-Jacob (CJD) – are incurable and fatal. Up to recently, we thought the only way you can get it is by ingesting the meat of the affected animal. Or, as I reported a couple of months ago, by ingesting drugs derived from the pituitary glands of infected dead humans.

A paper published 4 years ago describes another unexpected way to contract this horrible deadly disease. Using electrophoresis, mass spectrometry and liquid chromatography selected reaction monitoring, Van Dorsselaer et al. (2011) found prion proteins in a class of infertility drugs, the injectable urine-derived gonadotropins. These drugs are given to hundreds of thousands of women in North America for infertility treatment. They are developed from the urine of donor women, who are screened for all sorts of diseases, but the CJD has a long incubation period (decades) and thus it may be un-detectable using non-invasive methods.

Now, this in itself is not so worrisome as additional screening of the final medicine can be done and eliminate the batches with prions. What scared the living you-know-what out of me is the thought that the infected humans pee in the toilet and then that goes to the water treatment plants and then comes to your faucet. My question is: can the purification done at the water treatment plant eliminate the prions? I really, really do not wish to be alarming and panicky, especially in a world where every other news you read/hear seems to be something scary, so I invite anybody with knowledge about water treatment to comment and let us all know that is impossible, or at least highly unlikely, to get prions from the drinkable water. I don’t know how, maybe some step in the water treatment kills proteins as a matter of course or something.

Reference:  Van Dorsselaer A, Carapito C, Delalande F, Schaeffer-Reiss C, Thierse D, Diemer H, McNair DS, Krewski D, & Cashman NR. (23 Mar 2011). Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach. PLoS One, 6(3):e17815. doi: 10.1371/journal.pone.0017815. Article | FREE FULLTEXT PDF

By Neuronicus, 18 November 2015


The werewolf and his low fibroblast growth factor 13 levels

Petrus Gonsalvus, by anonymous
Petrus Gonsalvus, anonymous painting of the first recorded case of hypertrichosis in 1642. License: PD

Although they are very rare, werewolves do exist. And now the qualifier: werewolves as in people with excessive hair growth all over the body and not the more familiar kind that changes into a wolf every time there is a new moon. The condition is called hypertrichosis and its various forms have been associated with distinct genetic abnormalities.

In a previous report, DeStefano et al. (2013) identified the genetic locus of the X-linked congenital generalized hypertrichosis (CGH), which is a 19-Mb region on Xq24-27 that spans about 82 genes, resulting mainly from insertions from chromosomes 4 and 5. Now, they wanted to see what is the responsible mechanism for the disease. First, they looked at the hair follicles of a man afflicted with CGH that has hair almost all over his body and noticed some structural abnormalities. Then, they analyzed the expression of several genes from the affected region of the chromosome in this man and others with CGH and they observed that only the levels of the Fibroblast Growth Factor 13 (FGF13), a protein found in hair follicles, are much lower in CGH. Then they did some more experiments to establish the crucial role of FGF13 in regulating the follicle growth.

An interesting find of the study is that, at least in the case of hypertrichosis, is not the content of the genomic sequences that were added to chromosome X that matter, but their presence, affecting a gene that is located 1.2 Mb away from the insertion.

Reference: DeStefano GM, Fantauzzo KA, Petukhova L, Kurban M, Tadin-Strapps M, Levy B, Warburton D, Cirulli ET, Han Y, Sun X, Shen Y, Shirazi M, Jobanputra V, Cepeda-Valdes R, Cesar Salas-Alanis J, & Christiano AM ( 7 May 2013, Epub 19 Apr 2013). Position effect on FGF13 associated with X-linked congenital generalized hypertrichosis. Proceedings of the National Academy of Sciences of the U.S.A., 110(19):7790-5. doi: 10.1073/pnas.1216412110. Article | FREE FULLTEXT PDF

By Neuronicus, 17 November 2015

Pic of the day: Evolution

06fossil - Copy.png

Dobzhansky was, in his words, an “evolutionist and creationist”, a geneticist with deep faith in God.

Reference: Dobzhansky, T. (Mar 1973). Nothing in Biology Makes Sense Except in the Light of Evolution,  American Biology Teacher, 35 (3): 125–129. DOI: 10.2307/4444260. Article | FULLTEXT PDF via Research Gate