The FIRSTS: The Name of Myelin (1854)

One reason why I don’t post more often is that I have such a hard time deciding what to cover (Hint: send me stuff YOU find awesome). Most of the cool and new stuff is already covered by big platforms with full-time employees and I try to stay away of the media-grabbers. Mostly. Some papers I find so cool that it doesn’t matter that professional science journalists have already covered them and I too jump on the wagon with my meager contribution. Anyway, here is a glimpse on how my train of thought goes on inspiration-less days.

Inner monologue: Check the usual journals’ current issues. Nothing catches my eye. Maybe I’ll feature a historical. Open Wikipedia front page and see what happened today throughout history. Aha, apparently Babinski died in 1932. He’s the one who described the Babinski’s sign. Normally, when the sole of the foot is stroked, the big toe flexes inwards, towards the sole. If it extends upwards, then that’s a sure sign of neurological damage, the Babinski’s sign. But healthy infants can have that sign too not because they have neurological damage, but because their corticospinal neurons are not fully myelinated. Myelin, who discovered that? Probably Schwann. Quick search on PubMed. Too many. Restrict to ‘history”. I hate the search function on PubMed, it brings either to many or no hits, no matter the parameters. Ah, look, Virchow. Interesting. Aha. Find the original reference. Aha. Springer charges 40 bucks for a paper published in 1854?! The hell with that! I’m not even going to check if I have institutional access. Get the pdf from other sources. It’s in German. Bummer. Go to Highwire. Find recent history of myelin. Mielinization? Myelination? Myelinification? All have hits… Get “Fundamental Neuroscience” off of the shelf and check… aha, myelination. Ok. Look at the pretty diagram with the saltatory conduction! Enough! Go back to Virchow. Does it have pictures, maybe I can navigate the legend? Nope. Check if any German speaking friends are online. Nope, they’re probably asleep, which is what I should be doing. Drat. Refine Highwire search. Evrika! “Hystory of Myelin” by Boullerne, 2016. Got the author manuscript. Hurray. Read. Write.

Myelinated fibers, a.k.a. white matter has been observed and described by various anatomists, as early as the 16th century, Boullerne (2016) informs us. But the name of myelin was given only in 1854 by Rudolph Virchow, a physician with a rich academic and public life. Although Virchow introduced the term to distinguish between bone marrow and the medullary substance, paradoxically, he managed to muddy waters even more because he did not restrict the usage of the term mylein to … well, myelin. He used it also to refer to substances in blood cells and egg’s yolk and spleen and, frankly, from the quotes provided in the paper, I cannot make heads or tails of what Virchow thought myelin was. The word myelin comes form the Greek myelos or muelos, which means marrow.

Boullerne (2016) obviously did a lot of research, as the 53-page account is full of quotes from original references. Being such a scholar on the history of myelin I have no choice but to believe her when she says: “In 1868, the neurologist Jean-Martin Charcot (1825-1893) used myelin (myéline) in what can be considered its first correct attribution.”

So even if Virchow coined the term, he was using it incorrectly! Nevertheless, in 1858 he correctly identified the main role of myelin: electrical insulation of the axon. Genial insight for the time.

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I love historical reviews of sciency stuff. This one is a ‘must-have’ for any biologist or neuroscientist. Chemists and physicists, too, don’t shy away; the paper has something for you too, like myelin’s biochemistry or its birefringence properties.

Reference: Boullerne, AI (Sep 2016, Epub 8 Jun 2016). The history of myelin. Experimental Neurology, 283(Pt B): 431-45. doi: 10.1016/j.expneurol.2016.06.005. ARTICLE

Original Reference: Virchow R. (Dec 1854). Ueber das ausgebreitete Vorkommen einer dem Nervenmark analogen Substanz in den thierischen Geweben. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin, 6(4): 562–572. doi:10.1007/BF02116709. ARTICLE

P.S. I don’t think is right that Springer can retain the copyright for the Virchow paper and charge $39.95 for it. I don’t think they have the copyright for it anyway, despite their claims, because the paper is 162 years old. I am aware of no German or American copyright law that extends for so long. So, if you need it for academic purposes, write to me and thou shall have it.

By Neuronicus, 29 October 2016

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Video games and depression

There’s a lot of talk these days about the harm or benefit of playing video games, a lot of time ignoring the issue of what kind of video games we’re talking about.

Merry et al. (2012) designed a game for helping adolescents with depression. The game is called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts) and is based on the cognitive behavioral therapy (CBT) principles.

CBT has been proven to be more efficacious that other forms of therapy, like psychoanalysis, psychodynamic, transpersonal and so on in treating (or at least alleviating) a variety of mental disorders, from depression to anxiety, form substance abuse to eating disorders. Its aim is to identify maladaptive thoughts (the ‘cognitive’ bit) and behaviors (the ‘behavior’ bit), change those thoughts and behaviors in order to feel better. It is more active and more focused than other therapies, in the sense that during the course of a CBT session, the patient and therapist discuss one problem and tackle it.

SPARX is a simple interactive fantasy game with 7 levels (Cave, Ice, Volcano, Mountain, Swamp, Bridgeland, Canyon) and the purpose is to fight the GNATs (Gloomy Negative Automatic Thoughts) by mastering several techniques, like breathing and progressive relaxation and acquiring skills, like scheduling and problem solving. You can customize your avatar and you get a guide throughout the game that also assess your progress and gives you real-life quests, a. k. a. therapeutic homework. If the player does not show the expected improvements after each level, s/he is directed to seek help from a real-life therapist. Luckily, the researchers also employed the help of true game designers, so the game looks at least half-decent and engaging, not a lame-worst-graphic-ever-bleah sort of thing I was kind of expecting.

To see if their game helps with depression, Merry et al. (2012) enrolled in an intervention program 187 adolescents (aged between 12-19 years) that sought help for depression; half of the subjects played the game for about 4 – 7 weeks, and the other half did traditional CBT with a qualified therapist for the same amount of time.  The patients have been assessed for depression at regular intervals before, during and after the therapy, up to 3 months post therapy. The conclusion?

SPARX “was at least as good as treatment as usual in primary healthcare sites in New Zealand” (p. 8)

Not bad for an RPG! The remission rates were higher for the SPARX group that in treatment as usual group. Also, the majority of participants liked the game and would recommend it. Additionally, SPARX was more effective than CBT for people who were less depressed than the ones who scored higher on the depression scales.

And now, coming back to my intro point, the fact that this game seems to be beneficial does not mean all of them are. There are studies that show that some games have deleterious effects on the developing brain. In the same vein, the fact that some shoddy company sells games that are supposed to boost your brain function (I always wandered which function…) that doesn’t mean they are actually good for you. Without the research to back up the claims, anybody can say anything and it becomes a “Buyer Beware!” game. They may call it cognitive enhancement, memory boosters or some other brainy catch phrase, but without the research to back up the claims, it’s nothing but placebo in the best case scenario. So it gives me hope – and great pleasure – that some real psychologists at a real university are developing a video game and then do the necessary research to validate it as a helping tool before marketing it.

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Oh, an afterthought: this paper is 4 years old so I wondered what happened in the meantime, is it on the market or what? On the research databases I couldn’t find much, except that it was tested this year on Dutch population with pretty much similar results. But Wikipedia tells us that is was released in 2013 and is free online for New Zealanders! The game’s website says it may become available to other countries as well.

Reference: Merry SN, Stasiak K, Shepherd M, Frampton C, Fleming T, & Lucassen MF. (18 Apr 2012). The effectiveness of SPARX, a computerised self help intervention for adolescents seeking help for depression: randomised controlled non-inferiority trial. The British Medical Journal, 344:e2598. doi: 10.1136/bmj.e2598. PMID: 22517917, PMCID: PMC3330131. ARTICLE | FREE FULLTEXT PDF  | Wikipedia page | Watch the authors talk about the game

By Neuronicus, 15 October 2016

Drink before sleep

Among the many humorous sayings, puns, and jokes that one inevitably encounters on any social medium account, one that was popular this year was about the similarity between putting a 2 year old to bed and putting your drunk friend to bed, which went like this: they both sing to themselves, request water, mumble and blabber incoherently, do some weird yoga posses, cry, hiccup, and then they pass out. The joke manages to steal a smile only if someone has been through both situations, otherwise it looses its appeal.

Being exposed to both situations, I thought that while the water request from the drunk friend is a response to the dehydrating effects of alcohol, the water request from the toddler is probably nothing more than a delaying tactic to postpone bedtime. Whether there may or may not be some truth to my assumption in the case of the toddler, here is a paper to show that there is definitely more to the water request than meets the eye.

Generally, thirst is generated by the hypothalamus when its neurons and neurons from organum vasculosum lamina terminalis (OVLT) in the brainstem sense that the blood is either too viscous (hypovolaemia) or too salty (hyperosmolality), both phenomena indicating a need for water. Ingesting water would bring these indices to homeostatic values.

More than a decade ago, researchers observed that rodents get a good gulp of water just before going to sleep. This surge was not motivated by thirst because the mice were not feverish, were not hungry and they did not have a too viscous or a too salty blood. So why do it then? If the rodents are restricted from drinking the water they get dehydrated, so obviously the behavior has function. But is not motivated by thirst, at least not the way we know it. Huh… The authors call this “anticipatory thirst”, because it keeps the animal from becoming dehydrated later on.

Since the behavior occurs with regularity, maybe the neurons that control circadian rhythms have something to do with it. So Gizowski et al. (2016) took a closer look at  the activity of clock neurons from the suprachiasmatic nucleus (SCN), a well known hypothalamic nucleus heavily involved in circadian rhythms. The authors did a lot of work on SCN and OVLT neurons: fluorescent labeling, c-fos expression, anatomical tracing, optogenetics, genetic knockouts, pharmacological manipulations, electrophysiological  recordings, and behavioral experiments. All these to come to this conclusion:

SCN neurons release vasopressin and that excites the OVLT neurons via V1a receptors. This is necessary and sufficient to make the animal drink the water, even if it’s not thirsty.

That’s a lot of techniques used in a lot of experiments for only three authors. Ten years ago, you needed only one, maybe two techniques to prove the same point. Either there have been a lot of students and technicians who did not get credit (there isn’t even an Acknowledgements section. EDIT: yes, there is, see the comments below or, if they’re missing, the P.S.) or these three authors are experts in all these techniques. In this day and age, I wouldn’t be surprised by either option. No wonder small universities have difficulty publishing in Big Name journals; they don’t have the resources to compete. And without publishing, no tenure… And without tenure, less research… And thus shall the gap widen.

Musings about workload aside, this is a great paper, shedding light on yet another mysterious behavior and elucidating the mechanism behind it. There’s still work to be done though, like answering how accurate is the SCN in predicting bedtime to activate the drinking behavior. Does it take its cues from light only? Does ambient temperature play a role and so on. This line of work can help people that work in shifts to prevent certain health problems. Their SCN is out of rhythm and that can influence deleteriously the activity of a whole slew of organs.

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Summary of the doi: 10.1038/nature19756 findings. 1) The light is a cue for suprachiasmatic nulceus (SCN) that bedtime is near. 2) The SCN vasopressin neurons that project to organum vasculosum lamina terminalis (OVLT) are activated. 3) The OVLT generates the anticipatory thirst. 4) The animal drinks fluids.

Reference: Gizowski C, Zaelzer C, Bourque CW. (28 Sep 2016). Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep. Nature, 537(7622): 685-688. PMID: 27680940. DOI: 10.1038/nature19756. ARTICLE

By Neuronicus, 5 October 2016

EDIT (12 Oct 2016): P.S. The blog comments are automatically deleted after a period of time. In case of this post that would be a pity because I have been fortunate to receive comments from at least one of the authors of the paper, the PI, Dr. Charles Bourque and, presumably under pseudonym, but I don’t know that for sure, also the first author, Claire Gizowski. So I will include here, in a post scriptum, the main idea of their comments. Here is an excerpt from Dr. Bourque’s comment:

“Let me state for the record that Claire accomplished pretty much ALL of the work in this paper (there is a description of who did what at the end of the paper). More importantly, there were no “unthanked” undergraduates, volunteers or other parties that contributed to this work.”

My hat, Ms. Gizowski. It is tipped. To you. Congratulations! With such an impressive work I am sure I will hear about you again and that pretty soon I will blog about Dr. Gizowski.