Head Trauma Update: Halt the Headers?

Girl's header practice, on YouTube video.

What are we to do with children's header practices like the above? Ban them? But what about winning the game? Ban heading the ball? Maybe.



Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point) as well as indirect, goal-driven, or voluntary point responses (Anti-Point), thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction.

Citation: Zhang MR, Red SD, Lin AH, Patel SS, Sereno AB (2013) Evidence of Cognitive Dysfunction after Soccer Playing with Ball Heading Using a Novel Tablet-Based Approach. PLoS ONE 8(2): e57364. doi:10.1371/journal.pone.0057364

Editor: Corrado Sinigaglia, University of Milan, Italy

Received: August 21, 2012; Accepted: January 24, 2013; Published: February 27, 2013

The Rumor Flies: Parkin, K2, and Drosophila

I had someone tell me today that they had heard on talk radio over the weekend that there was a vitamin cure for Parkinson's and that the medical and drug establishment had been suppressing it.

So what was that all about?

First, we have a study in fruit flies which have a mutant parkin gene. Fruit flies, not humans. A mutant gene which most people with Parkinson disease do not have-- it causes the rare condition of autosomal recessive juvenile parkinsonism. In vertebrates, the protein is a component of a multiprotein E3 ubiquitin ligase complex which in turn is part of the ubiquitin-proteasome system that mediates the targeting of proteins for degradation. In addition, physiological studies of skin fibroblast cells from persons with autosomal recessive juvenile parkinsonism show significantly decreased mitochondrial complex I activity and ATP production in the cells (source: Leiden Open Variation Database, per The Parkinson's Institute). It is not certain which abnormality produces clinical human disease, though most pathological evidence, showing alpha-synuclein problems thought related to ubiquitin deficits, favors the deficit in ubiquitin.

Currently, there is no evidence, pro or con, that vitamin K2 affects hereditary forms or indeed any form of Parkinson's disease. Dietary plant vitamin K1 is converted to animal vitamin K2 and then stored for use in the K2 form by all mammals. In humans, vitamin K2 primarily acts as a cofactor in the production of blood clotting factors, with a secondary role in calcium and bone metabolism. Vitamin K2 deficiency causes clotting problems, but not parkinsonism.

The fruit fly insect has ubiquitin, but it does not have basal ganglia, and has no coagulation system for vitamin K2 to act upon. Instead, vitamin K2 acts to promote mitochondrial metabolism, a metabolism which is decreased in fruit flies with the aberrant parkin gene. Because mitochondria serve aerobic energy needs, the pathology in fruit flies affects the flies' aerobic exercise capacity: they have trouble with their muscles of flight. Vitamin K2 improves aerobic mitochondrial energy production in those fruit flies, helping them to fly.

Could the parkin mutation also be causing disease in humans via defective mitichondrial metabolism in the brain? Perhaps. However, we have no evidence, pro or con, that the ordinary, adult, sporadic form of Parkinson's is related to any use by brain mitochondria of the parkin protein. And we have no evidence, from what I can see, that the fruit fly illness is due to a fruit fly brain degeneration. So we have no evidence that vitamin K2 has anything to do with ordinary adult human Parkinson's disease. If there is such evidence in the future, well, bring it on -- we'll use it gladly :). The research does give a new potential direction for human studies.

Did the man I spoke to have any idea that the research promising him a vitamin cure on the radio was work done in fruit flies? No, none at all. That detail was left out of the radio show report's cure claim. As was the fact that the cured illness was not phenotypic Parkinson's disease.

So, the use of a vitamin in a tangentially related genetic anomaly in insects (homologous gene, questionable homology of use of that gene), via media distortion, becomes an expectation of a vitamin curing human disease today. Media hype leads to hyperinflated expectations of a cure, before any true human testing has been done. This then leads to disappointment, which causes a few to claim cures are being withheld via conspiracy, and thus props up the business models of alternative patent vitamin medicine hucksters.



Science. 2012 Jun 8;336(6086):1306-10. doi: 10.1126/science.1218632. Epub 2012 May 10.

Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency.

Vos M, Esposito G, Edirisinghe JN, Vilain S, Haddad DM, Slabbaert JR, Van Meensel S, Schaap O, De Strooper B, Meganathan R, Morais VA, Verstreken P.

VIB Center for the Biology of Disease, Leuven, Belgium.

Human UBIAD1 localizes to mitochondria and converts vitamin K(1) to vitamin K(2). Vitamin K(2) is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K(2) exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson's disease that affects mitochondrial function. We found that vitamin K(2) was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K(2), and, similar to ubiquinone, vitamin K(2) transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K(2) that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.


The Outliers

Why be careful about the tendency to generalize studies performed on American college students to humans as a whole? Here is another reason why: Americans are NOT necessarily typical of human beings. (Hat tip: Pacific Standard Magazine.)


The empirical foundation of the behavioral sciences comes principally from experiments with American undergraduates. The patterns we have identified in the available (albeit limited) data indicate that this sub‐subpopulation is highly unusual along many important psychological and behavioral dimensions. It is not merely that researchers frequently make generalizations from a narrow subpopulation. The concern is that this particular subpopulation is highly unrepresentative of the species. .

PDF Here:

( http://www2.psych.ubc.ca/~henrich/pdfs/Weird_People_BBS_final02.pdf ).

RIP Magic Slim.

Morris Holt (August 7, 1937 – February 21, 2013) better known in music as Magic Slim.

Blues legend. Rest in peace. Here's a sample.

The song Punahele, on slack key guitar, the Kī hōʻalu style (youtube.com)

With Ray Kane, here.

Punahele literally means favorite. Raymond Kaleoalohapoinaʻoleohelemanu Kāne's middle name means "the voice of love that comes and goes like a bird and will never be forgotten," which seems very appropriate for a musician and composer.

Leibniz' Mill Analogy Disproved?

Leibniz, in the Monadology, gives the famous analogy of the mill as a metaphor for the brain:

17. Moreover, it must be confessed that perception and that which depends upon it are inexplicable on mechanical grounds, that is to say, by means of figures and motions. And supposing there were a machine, so constructed as to think, feel, and have perception, it might be conceived as increased in size, while keeping the same proportions, so that one might go into it as into a mill. That being so, we should, on examining its interior, find only parts which work one upon another, and never anything by which to explain a perception [emphasis mine here--wh]. Thus it is in a simple substance, and not in a compound or in a machine, that perception must be sought for. Further, nothing but this (namely, perceptions and their changes) can be found in a simple substance. It is also in this alone that all the internal activities of simple substances can consist. (Theod. Pref. [E. 474; G. vi. 37].)

Now we have the metaphor of the mill done for real, in the virally expressed GCaMP3 mouse hippocampus of the brain.

See video link here, and abstract below:


Long-term dynamics of CA1 hippocampal place codes

Yaniv Ziv, Laurie D Burns, Eric D Cocker, Elizabeth O Hamel, Kunal K Ghosh, Lacey J Kitch, Abbas El Gamal, Mark J Schnitzer

Nature Neuroscience (2013) doi:10.1038/nn.3329 Received 29 October 2012 Accepted 09 January 2013 Published online 10 February 2013 Corrected online 11 February 2013

Using Ca2+ imaging in freely behaving mice that repeatedly explored a familiar environment, we tracked thousands of CA1 pyramidal cells' place fields over weeks. Place coding was dynamic, as each day the ensemble representation of this environment involved a unique subset of cells. However, cells in the ~15–25% overlap between any two of these subsets retained the same place fields, which sufficed to preserve an accurate spatial representation across weeks.


So, it seems that Leibniz was wrong, in part. He forgot that a skilled mill engineer could likely tell something about what the mill's activity was focused upon, to some degree, just by observing the activity of its components. Thus, mind reading might be possible, in the sense of knowing something of what the mouse is experiencing from observing the patterns of memory cells which are activated as the mouse visits the different sections of its enclosure.

What we still cannot tell is what it is like to be the mouse, even if we have an inkling of what topics are within the focus of its attentions. In that regard, at least, Leibniz is still right about perceptions.

So, will the likes of B&L or Allergan make infrared goggles for staff in the darkness of the Amblyopia Treament Unit some day?

Kitten research, not tested in human keiki yet.


Darkness Alters Maturation of Visual Cortex and Promotes Fast Recovery from Monocular Deprivation

Duffy, Kevin R.; Mitchell, Donald E.

Current biology : CB doi:10.1016/j.cub.2013.01.017

The existence of heightened brain plasticity during critical periods in early postnatal life is a central tenet of developmental sensory neuroscience and helps explain the enduring deficits induced by early abnormal sensory exposure [1, 2]. The human visual disorder amblyopia has been linked to unbalanced visual input to the two eyes in early postnatal visual cortical development and has been modeled in animals by depriving them of patterned visual input to one eye [3, 4], a procedure known as monocular deprivation (MD). We investigated the possibility that a period of darkness might reset the central visual pathways to a more plastic stage and hence increase the capacity for recovery from early MD. Here we show that a 10-day period of complete darkness reverses maturation of stable cytoskeleton components in kitten visual cortex and also results in rapid elimination of, or even immunity from, visual deficits linked to amblyogenic rearing by MD. The heightened instability of the cytoskeleton induced by darkness likely represents just one of many parallel molecular changes that promote visual recovery, possibly by release of the various brakes on cortical plasticity [2]. Neurofilament is reduced in kitten visual cortex after a short period of darkness. Darkness immediately after monocular deprivation prevents development of amblyopia. Darkness imposed after amblyopia develops results in its disappearance in 5 to 7 days. Short (10 day) periods of darkness may boost recovery from amblyopia in humans


Aloha Friday: Ku'u Kika Kahiko (Ozzie Kotani)

This shows all of the intricate note plucking of the classical hawaiian slack key guitar sound.


Twenty-First Century Phrenology: The Pop Quiz


The studies below, all published in the last three years, each called attention to anatomically or physiologically based differences in brain function between persons of varying political affiliations. Which of these studies either used a proper prospective design or were appropriately validated on a second population of subjects?

A. Screiber et al,in Plos One, February 2013, reported an fMRI difference between registered Republicans and registered Democrats regarding activated cortical areas during a gambling task involving decisions about risk. 1

B. Dhontet al, in Soc Cog Aff Neurosci, March 2012, reported an increase in late positive potentials on event-related EEG evoked potentials among anarchists versus moderates when presented with conficting (oddball) sets of attitudinally related stimuli.2

C. Veccatio et al, in Conf Proc IEEE Eng Med Biol Soc, 2010, found difference in EEG spectroscopy maps of subjects taken immediately after seeing a politician's face varied by whether the face was of a winner or a loser in a recent election, felt to reflect the level of trust in the face seen. 3

D. All of the above.

E. None of the above.


1 Schreiber D, Fonzo G, Simmons AN, Dawes CT, Flagan T, et al. (2013) Red Brain, Blue Brain: Evaluative Processes Differ in Democrats and Republicans. PLoS ONE 8(2): e52970. doi:10.1371/journal.pone.0052970

2Dhont K, Van Hiel A, Pattyn S, Onraet E, Severens E., A step into the anarchist's mind: examining political attitudes and ideology through event-related brain potentials. (2012) Soc Cogn Affect Neurosci. 2012 Mar;7(3):296-303. doi: 10.1093/scan/nsr009. Epub 2011 Mar 18.

3Vecchiato G, Toppi J, Cincotti F, Astolfi L, De Vico Fallani F, Aloise F, Mattia D, Bocale S, Vernucci F, Babiloni F., Neuropolitics: EEG spectral maps related to a political vote based on the first impression of the candidate's face. (2010) Conf Proc IEEE Eng Med Biol Soc. 2010;2010:2902-5. doi:10.1109/IEMBS.2010.5626324.

The correct answer is, of course, E. I am leaving out the links this time, for the sake of the value of the reader's time.

Here for a Valentine, though :)

MS Onset in Childhood, Obesity, and Menarche

First, the endocrinologists speak:

J Pediatr Endocrinol Metab. 2012;25(1-2):57-62. Association of early menarche age and overweight/obesity.

Bralić I, Tahirović H, Matanić D, Vrdoljak O, Stojanović-Spehar S, Kovacić V, Blazeković-Milaković S.


AIM: The aim of the study is to assess the association of overweight/obesity and early menarcheal age.

PATIENTS AND METHODS: The study comprised 2127 healthy girls aged 9 to 16 years. Menarcheal age was estimated by status quo method. The girls' body weight and height were measured and their body mass index (BMI) calculated. The diagnostic criteria of the WHO were used to define overweight and obesity. Girls with a BMI in the range of 1-2 for age and sex were considered overweight. Girls with a BMI >2 standard deviation (SD) for age and sex were considered obese. Girls with a BMI >1 SD for age and sex were considered overweight/obese. Social and economic status was analyzed according to years of education completed, parents' occupations, and the number of children in the family.

RESULTS: Median menarcheal age was 12.83 years; 25% girls had menarche before 11.98 years and 75% by 13.69 years. By 11.21 years, 10% of girls had had menarche, and 95% by 14.91 years. Girls who had menarche before 11.98 years had higher body weight values (48.5 vs. 40.2 kg) (p<0.001), height (159.3 vs. 149.2 cm) (p<0.001), and BMI (18.9 vs. 17.8 kg/m2) (p=0.003) than their peers without menarche. Girls with menarche before 11.98 years had significantly higher BMI values than girls with menarche after 13.69 years (18.94 vs. 17.84 kg/m2) (p=0.008). Girls with menarche before 11.98 years and those after 13.69 years differ significantly in distribution of thinness (3.4% vs. 2.54%), normal weight (85.3% vs. 91.8%), and overweight/obesity (11.2% vs. 5.7%) (p=0.002).

CONCLUSIONS: Girls who experienced early menarche are significantly more often overweight/obese. Overweight/obesity may be considered as one of the predictors for the early occurrence of menarche.

Now, the neurologists speak:

Neurology February 5, 2013 80:548-552; published ahead of print January 30, 2013,

Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome

Annette Langer-Gould, MD, PhD, Sonu M. Brara, MD, Brandon E. Beaber, MD and Corinna Koebnick, PhD


Objective: To determine whether childhood obesity is a risk factor for developing pediatric multiple sclerosis (MS) or clinically isolated syndrome (CIS).

Methods: Cases were identified through the Kaiser Permanente Southern California (KPSC) Pediatric Acquired Demyelinating Diseases Cohort between 2004 and 2010. For cases, body mass index (BMI) was obtained prior to symptom onset, for the underlying cohort BMI was obtained through the KPSC Children's health study (n = 913,097). Weight classes of normal weight, overweight, moderate obesity, and extreme obesity were assigned based on BMI specific for age and sex.

Results: We identified 75 newly diagnosed pediatric cases of MS or CIS, the majority of which were in girls (n = 41, 55%), age 11–18 (n = 54, 72%). Obesity was associated with a significantly increased risk of MS/CIS in girls (p = 0.005 for trend) but not in boys (p = 0.93). The adjusted odds ratio and 95% confidence intervals for CIS/MS among girls was 1.58 (0.71–3.50) for overweight compared to normal weight (reference category), 1.78 (0.70–4.49) for moderately obese, and 3.76 (1.54–9.16) for extremely obese. Moderately and extremely obese cases were more likely to present with transverse myelitis compared with normal/overweight children (p = 0.003).

Conclusion: Our findings suggest the childhood obesity epidemic is likely to lead to increased morbidity from MS/CIS, particularly in adolescent girls.


Hmm. An approximately twofold increase in early menarche, and an approximately twofold increase in risk of MS prior to adulthood. Roughly the same increases, seen with our spiking American childhood obesity. Shall we let the two specialties work this out together? I suppose so.

On AI and the brain

AGI [artificial general intelligence] must be possible. That is because of a deep property of the laws of physics, namely the universality of computation. It entails that everything that the laws of physics require physical objects to do can, in principle, be emulated in arbitrarily fine detail by some program on a general-purpose computer, provided it is given enough time and memory.
--David Deutch on his blog at the Guardian, 3 October 2012.

Why is this nonsense so loudly proclaimed by those who prefer to conceive of the brain, indeed life on Earth,  indeed the universe, as a mere computer?  Where is the fire in the equations? A computer simulation of a nuclear explosion, be it oh so accurate, is not a nuclear explosion! And those who claim that simulating intelligence via a computer would be intelligence unlike an explosion simulation being an explosion, since the output would be intelligent in content, are begging the question, since it would only be truly intelligent as a simulation if the simulation succeeded in being intelligent, which is the question at issue!

Let's quote Selim Akl about the fallacy of assuming that the finitely computable algorithms that are currently within reach of microprocessor technology will work for intelligence:

Non-universality in computation: Given n spatially and temporally connected physical variables, X1, X2, ..., Xn, where n is a positive integer, and a function F(X1, X2, ..., Xn) of these variables, no computer can evaluate F for any arbitrary n, unless it is capable of an infinite number of operations per time unit.
Note that F is readily computable by a machine M capable of exactly n operations per time unit. However, this machine cannot compute F when the number of variables is n+1. While a second machine M' capable of n+1 operations per time unit can now compute the function F of n+1 variables, M' is in turn defeated by a function of n+2 variables. This continues forever.
This point deserves emphasis. While the function F(X1, X2, ..., Xn+1) = F1(X1), F2(X2), ..., Fn+1(Xn+1) is easily computed by M', it cannot be computed by M. Even if given infinite amounts of time and space, machine M is incapable of simulating the actions of M'. Furthermore, machine M' is in turn thwarted by F(X1, X2, ..., Xn+2), a function computable by a third machine M''. This continues indefinitely. Therefore no computer is universal if it is capable of exactly T(i) operations during time unit i, where i is a positive integer, and T(i) is finite and fixed once and for all (for it will be faced with a computation requiring V(i) operations during time unit i, where V(i) > T(i) for all i).
Examples of such function F occur in:
1. Computations with time-varying variables: The variables, over which the function is to be computed, are themselves changing with time.
2. Computations with time-varying computational complexity: The computational complexity of the function to be computed is itself changing with time.
3. Computations with rank-varying computational complexity: Given several functions to be computed, and a schedule for computing them, the computational complexity of a function depends on its position in the schedule.
4. Computations with interacting variables: The variables of the function to be computed are parameters of a physical system that interact unpredictably when the system is disturbed.
5. Computations with global mathematical constraints: The function to be computed is over a system whose variables must collectively obey a mathematical condition at all times.
6. Computations with uncertain time constraints: There is uncertainty with regards to the input (when and for how long are the input data available), the calculation (what to do and when to do it), and the output (the deadlines are undefined at the outset); furthermore, the function that resolves each of these uncertainties itself has demanding time requirements.

--Akl, SG, in http://research.cs.queensu.ca/Parallel/projects.html;  see also Akl, S.G., The Myth of Universal Computation, in Parallel Numerics ’05,M. Vajterˇsic, R. Trobec, P. Zinterhof, A. Uhl (Eds.), chapter 7.

Especially, consider #4 above, since that is how the brain works. This is not to say that a breakthrough in intricacy of nanotechnology could not make AI a reality.  But Moore's Law alone acting on our current microprocessor based computer tech cannot achieve human-equivalent general purpose intelligence.

And right now, I'd be happy just with computer dictation of my notes that made less than 1 error per paragraph, Mr. Kurzweil. The computer-generated typos do creep in, and our current braindead (back to AI here) EMR is security-restricted to disallow corrections of finished notes.

Here's the Pew Health Trust on overuse of antibiotics in animals, which is probably a growing source of antibiotic-resistant bacteria in human infections.

On an Emergent Neutral Ontology: Part 4

Some will be tempted to say: if mathematical objects figure in the explanation of the motions of physical objects in the universe (e.g., the neurons in human brains), then it follows trivially that they are themselves physical, and not abstract. The move is common among naturalists. John Searle, for example, says that

For us [naturalists], if it should turn out that God exists, that would have to be a fact like any other. To the four basic forces of the universe—gravity, electromagnetism, weak and strong nuclear forces—we would add a fifth, the divine force . . . [I]t would still be all physics, albeit divine physics. If the supernatural existed, it too would have to be natural. [Searle, 1998, p. 35]

This sort of terminological appropriation, whether it is applied to God, numbers, or anything else, fails to address the underlying question. By decreeing that the word ‘natural’ (or ‘physical’) is to be applied to any phenomenon we discover, the naturalist robs naturalism of any content relevant to the substantive dispute between naturalists and those who disagree with them. I have claimed that efficient causal relations between non-spatial, necessary, eternal, unchanging objects and spatial, contingent, changing objects are strongly possible, and I have used the word ‘abstract’ to refer to the former sort of objects, and ‘physical’ or ‘material’ or ‘concrete’ for the latter sort. But the truth of my claim is not affected, or illuminated, if we decide to use these words in some other way instead.

-- Callard, Benjamin, The Conceivability of Platonism, Philosophia Mathematica (III) 15 (2007), pp. 347–356.

Neuro-doubt: fMRI, meta-analysis, and incorrect p value minimization

The current issue of Neuron includes an article by Mueller, Wang, Fox, Yeo, Sepulcre, Sabuncu, Shafee, Lu, and Liu which accomplishes the admirable task of assessing intersubject variability of fMRI activity in various brain regions. This kind of work is to be commended, since until we fully understand the range of normal brain activity in fMRI it will remain more a research tool and less one of clinical relevance.

The investigators looked at fMRI brain metabolic activity in 23 subjects and derived a per-corresponding-fMRI-cortical-vertex-point coefficient of variation between the subjects (each individual subject had 5 sequential scans).  The investigators noted that several cortical regions, such as the primary visual cortex, which are known to be highly conserved among primate species are also those which showed the least inter-subject variability among human subjects. Areas which are uniquely larger in humans compared to primates such as the macaque were those which showed more variability between human subjects.

The hypothesis that areas of brain similarity that are conserved across species are likely to be similarly conserved between individuals is a logical one, and their newly published meta-analysis supports this.  No problem, good study.

Except that the p value given for the metaanalysis seems quite high for 23 subjects: p < 0.0001, for a Pearson product-moment correlation coefficient r value of just 0.52!

Let us look at the scatter plot:

Figure 3. Functional Connectivity Variability and Evolutionary Cortical Expansion Are Highly Correlated(A) The regional evolutionary cortical expansion between an adult macaque and the average human adult PALS-B12 atlas. Data were provided by van Essen and colleagues (van Essen and Dierker, 2007). On a whole-surface level, evolutionary expansion and functional variability (B) were significantly associated (r = 0.52, p < 0.0001). The correlation was shown in the scatter plot (C) where each 100th vertex is represented by a small circle.


Now, what is the N for the study? 23 subjects? 115 fMRI scans? Thousands of verticies on the 115 scans? I fear that for the statistical package N was not the number of subjects. Let us look at the graph for N versus Pearson r (courtesy of Wikipedia) for significance (here, p< 0.05):

More specifically, if we consider the N to be the number of subjects, at an N of 23 we get a two-tailed Pearson probability of about 0.011. Significant, but over an order of magnitude less that the study reports.

Would an N of 115 (23 times 5, the number of scans) have been a valid N for degrees of freedom? No, because two measurements on the same subject lack true independence of the measure and so should drop the degrees of freedom.

The take home point here is that if even the people doing the basic normal variant work in the fMRI field may use statistical packages so as to overstate their statistical results, the clinical applications people are potentially hosed before they can start.

Here's the abstract:

Individual Variability in Functional Connectivity Architecture of the Human Brain

Mueller, Sophia; Wang, Danhong; Fox, Michael D.; Yeo, B.T. Thomas; Sepulcre, Jorge; Sabuncu, Mert R.; Shafee, Rebecca; Lu, Jie; Liu, Hesheng

Neuron doi:10.1016/j.neuron.2012.12.028 (volume 77 issue 3 pp.586 - 595)

The fact that people think or behave differently from one another is rooted in individual differences in brain anatomy and connectivity. Here, we used repeated-measurement resting-state functional MRI to explore intersubject variability in connectivity. Individual differences in functional connectivity were heterogeneous across the cortex, with significantly higher variability in heteromodal association cortex and lower variability in unimodal cortices. Intersubject variability in connectivity was significantly correlated with the degree of evolutionary cortical expansion, suggesting a potential evolutionary root of functional variability. The connectivity variability was also related to variability in sulcal depth but not cortical thickness, positively correlated with the degree of long-range connectivity but negatively correlated with local connectivity. A meta-analysis further revealed that regions predicting individual differences in cognitive domains are predominantly located in regions of high connectivity variability. Our findings have potential implications for understanding brain evolution and development, guiding intervention, and interpreting statistical maps in neuroimaging. Functional connectivity is most variable in association cortex Connectivity variability is rooted in evolutionary cortical expansion Variability is associated with cortical folding and long-range connection Brain regions of high connectivity variability predict behavioral differences Mueller et al. quantified interindividual variability in functional connectivity across the human brain and identified its relation to evolutionary cortical expansion and some anatomical characteristics.

Smoking Cannabis May Double the Risk of Stroke

It's not just tobacco smoke that harms the vascular system, it seems. From the International Stroke Conference in Honolulu. Here's the discussion in Medscape since the stroke conference website is down today.

Honolulu, Hawaii — More evidence that smoking cannabis is associated with an increased risk for stroke has come from a New Zealand study.

The first case-control study to investigate this association, presented at the American Stroke Association's International Stroke Conference (ISC) 2013, found that patients with ischemic stroke/transient ischemic attack (TIA) were twice as likely to have recently used cannabis as age-, sex-, and ethnicity-matched controls.

"Cannabis is generally perceived as having few serious adverse effects, but this study suggests that this may not be the case," lead author Alan Barber, PhD, MD, from University of Auckland, New Zealand, concluded.

For the study, Dr. Barber and colleagues tested urine for cannabis within 72 hours of hospital admission in 160 patients with ischemic stroke/TIA aged 18 to 55 years and 160 controls (patients admitted with nonstroke diagnoses, matched for age, sex, and ethnicity).

The cannabis screen was positive in 25 (16%) of the stroke/TIA group vs 13 of 160 (8%) control participants. Logistic regression analysis found an odds ratio of 2.30 (95% confidence interval, 1.07 - 4.95).

Dr. Barber said the 16% rate of cannabis use in the stroke patients "took us by surprise." Cannabis users were more likely to be male, tobacco smokers, and Maori. No other illicit drugs were detected.

The Star Trek emotion chip: carbon dioxide in bilateral amygdala damage

In the 1994 Star Trek film Star Trek Generations, the android Data, an intelligent ship's officer who had been deliberately constructed lacking common human emotions, is provided with an "emotion chip" to supplement his cognition with emotional reactions. To his dismay, the emotion chip causes him to feel so much fear during a firefight that his best friend Geordi is taken hostage as he cowers in a corner.

Can life have imitated art once again?

In this month's Nature Neuroscience, Feinstein et al studied three patients with the rare mixed skin and temporal lobe degeneration affliction referred to as Urbach-Wiethe disease. Persons with this condition lose the tissue in the paired brain structures of the amygdala, and as a result are incapable of feeling the ordinary fear persons have in potentially dangerous social circumstances. Surprisingly, the researches found that they were quite susceptible to extreme fear (to the point of panic attack) when exposed to higher than normal carbon dioxide concentrations, which normally induce only a slight feeling of suffocation. This suggests that the amygdala is important for avoiding environmental and social dangers, but that the amygdala is not needed to feel fear itself, since the patients certainly felt fear when confronted with one of the body's internal danger signals.

How is this like Commander Data's fictional predicament? Could it be that our tolerance of fear is improved by exposure to frequent low intensity stressors such as those associated with mild situational anxiety, and neither Data nor the patients were fear tolerant when they were confronted with fear as a novelty?

So, does tolerance eventually develop to CO2 inhalation in Urbach-Wiethe disease, one wonders?

Aloha Friday: Kuhio Bay

The humpback whales are back in Hilo Bay, including its south central shore, Kuhio Bay. You can see them breaching. By spring, with the example of their parents, the calves will become seasoned aquatic acrobats.

Why do the whales jump? For joy, perhaps. Perhaps to dislodge parasites. Who knows? But it's fun to watch.

Sometimes a diver in the bay can hear them, if you listen closely. The singing must carry a really long way underwater.

The song Kuhio Bay (youtube.com) Here.

No association worth making between EM fields and degenerative CNS disease

Journal of Occupational & Environmental Medicine: February 2013 - Volume 55 - Issue 2 - p 135–146 doi: 10.1097/JOM.0b013e31827f37f8

Occupational Exposure to Extremely Low-Frequency Magnetic Fields and Neurodegenerative Disease: A Meta-Analysis

Vergara, Ximena PhD; Kheifets, Leeka PhD; Greenland, Sander DrPH; Oksuzyan, Sona MD; Cho, Yong-Sung PhD; Mezei, Gabor MD, PhD


Objective: Previous studies reported associations of occupational electric and magnetic fields (MF) with neurodegenerative diseases (NDDs). Results differ between studies using proxy exposure based on occupational titles and estimated MF levels. We conducted a meta-analysis of occupational MF NDD, primarily Alzheimer disease (AD), and motor neuron diseases (MNDs) studies.

Methods: We identified 42 peer-reviewed publications and focused our analysis on study characteristics, exposure metrics, and publication bias.

Results: We found weak associations for occupational MF exposure proxies with AD and MND. Motor neuron disease risk was associated with occupational titles, whereas AD risk was associated with estimated MF levels. Results varied in study design, with dissimilar variation across diseases.

Conclusions: Our results do not support MF as the explanation for observed associations between occupational titles and MND. Disease misclassification, particularly for AD, and imprecise exposure assessment affected most studies.

Home EMG Kit

Electrodiagnosis for the masses? Surface EMG only, as far as I can see of it.


Native Hawaiians in Hawaii at Higher Risk for Cerebral Hemmorhage: News

News from the International Stroke Conference in Honolulu this week! Based on an extensive retrospective chart survey at the Queen's Hospital in Honululu.

Astract WP303: Disparities among Native Hawaiians and Pacific Islanders with Intracerebral Hemorrhage: Effect of Methamphetamine Abuse

Kazuma Nakagawa1; Megan A Vento; Matthew A Koenig; Susan M Asai; Cherylee W Chang; Todd B Seto

Background and Purpose: Native Hawaiians and other Pacific Islanders (NHPI) with intracerebral hemorrhage (ICH) are younger and have a higher burden of cardiovascular risk factors compared to other racial groups in Hawaii. Furthermore, NHPI in Hawaii have a higher prevalence of methamphetamine abuse compared to other major racial-ethnic groups. Therefore, it is unclear whether younger age of NHPI with ICH is due to methamphetamine abuse or untreated risk factors.

Methods: We conducted a retrospective study on consecutive patients hospitalized for acute ICH at a single tertiary center on Oahu between 2006 and 2010. To determine the factors associated with young ICH (age<45), we performed unadjusted and multivariable logistic regressions, adjusting for methamphetamine abuse, untreated hypertension and whether they were transferred from another hospital to account for a potential referral bias. Non-Hispanic whites were the reference group.

Results: A total of 384 consecutive ICH patients (NHPI 19%, Asians 65% and non-Hispanic whites 16%) were studied. Compared to non-Hispanic whites, NHPI were younger (mean ages, NHPI 54±16 vs. whites 68±16, p < 0.0001), and had higher prevalence of diabetes (NHPI 36% vs. whites 19%, p = 0.03) and untreated hypertension (NHPI 32% vs. whites 15%, p = 0.02). Young ICH (age<45) was more common among NHPI (26%) than Asians (9%) and non-Hispanic whites (6%) (p <0.05). Methamphetamine abuse was slightly more common among NHPIs than whites and Asians (10% vs. 3% vs. 6%, p = NS for all comparison). After controlling for potential confounders, young ICH (age<45) was independently associated with NHPI race (OR 5.07, 95% CI 1.55 to 16.62), methamphetamine abuse (OR 4.17, 95% CI 1.56 to 11.20) and being transferred from another hospital (OR 3.37, 95% CI 1.66 to 6.84).

Conclusions: Native Hawaiian and other Pacific Islander race and methamphetamine abuse are independently associated with young ICH in Hawaii. Further studies are needed to determine factors other than methamphetamine abuse that are contributing to the young age of ICH presentation in this unique racial group.

Thanks, Kazuma, Matthew, and Cherylee, neurologists at Queens, as well as all those who contributed! Now we just have to learn what more to do for prevention, other than treat hypertension better in the kanaka maoli, and maybe there won't have to be so many transfers someday :).

On an Emergent Neutral Ontology: Part 3

Continued from January 31, 2013, here.

Some difficulties with an emergent neutral monism: problems with a neutral emergence basis.

Neutral monism adds one extra level beneath the physical, since things that are physical objects would be from the base neutral stuff, configured so as to have physical properties. In other words, the physical is emergent from an underlying neutral stuff. Why not just start with a physical basis or a psychical basis, and add the other properties via emergence from one of those bases?

In reply, the type of neutral monism that I am suggesting for consideration also would allow objects with or without mental properties to either have or lack physical properties, unlike physicalist emergentism or panpsychism. Abstract objects such as those of mathematics thus may have a basis for existence without having to be some kind of dependent extension of the mental (Berkeley's problem, which he assigns to God to sustain). So I prefer a neutral basis as more versatile in its scope of explanation.

Note that I am not fully committed to some form of Platonism here. As are most of us who are trained in the neurosciences, I am suspicious of needless postulation of entities as existent without obvious pragmatic value. Verifying any given non-physical object actually existed would generally require empirical observation. Direct, objective observation may be lacking (consider the traditional skeptical problem of other minds). Empirical verification of objective evidence for non-physical things may be difficult because our observations of mental or abstract things, like our observations of physical properties, generally depend on the functioning of our physical bodies, making physical things implicitly more visible to us since they are automatically seen in a physical context. In that context, abstract things and mental properties other than our own may not be directly observable, even though the fact that we ourselves possess mental properties is subjectively obvious.

Scuba Diving and PFO Risks

Here is an excellent discussion (via the Divers Alert Network magazine) of patent foramen ovale and the risk of air embolism from diving, with or without other decompression sickness.

From the discussion:

It is important to keep in mind several issues. First, the relationship between PFO and DCS is an association. While there is a plausible explanation for the apparent connection (i.e., DCS triggered by arterial bubbles), this is not yet proven. Indeed, PFO has not been linked to the most common symptoms such as pain-only bends, numbness, tingling or fatigue. Second, PFO exists in 25 to 30 percent of people, and studies have shown that venous bubbles are extremely common after recreational dives. Therefore, many divers must be experiencing arterial bubbles, yet DCS is extremely rare (especially the more serious variety that is associated with PFO). Third, if the bubble explanation is correct, a PFO could precipitate DCS only after a dive of sufficient depth and duration to generate venous gas embolism. PFO is therefore unlikely to be a factor for mild DCS cases or ones that occur after short exposures or shallow depths (i.e., "undeserved"). Finally, most cases of DCS occur in divers without a PFO. It is difficult or impossible in an individual diver to ascribe a particular DCS occurrence to a PFO, as PFO will exist in nearly one-third of cases even if there is no causal relationship. Therefore, testing for a PFO is useful only in instances where there have been several DCS incidents of a type known to be PFO-associated, and the person cannot modify depth-time exposures or breathing gas.

Brain Science and Zombies

Here for video.

A slightly tongue-in-cheek discussion of what kind of brain pathology would simulate a horror movie zombie. No comments about any feared decline of TED as a serious forum, please :-).

Courtesy of Tim Verstynen, PhD, at who is now at Carnigie Mellon, I believe.

Richard III's Skull Shows Evidence of Head Injury In Ancient Warfare


International Stroke Conference, 2013

It's in Honolulu this year.

Plague in Paradise,1940's: the Weapon that Worked

Bubonic plague. In the 19th century it killed hundreds of people on Oahu. Only later did it spread to the Big Island of Hawai'i.

Throughout the early 20th century, from 1910 through 1950, the Hawaiian public health authorities waged war, with gases, bait poisons, and even with imported rat viruses, against the R. Hawaiiensis field rats around Hamakua, on the northeastern coast of the Big island.

 Yet they failed to make a significant dent in the rat population, and occasional transmissions of the plague bacteria Yesinia pestis via fleas to humans were generally fatal in those days, before antibiotics.

What finally seemed to eradicate the plague? Not removing the rats, but relieving them of their fleas, with DDT dust. How did they get the rats to dust themselves with flea powder, you ask? With the Rube Goldberg contraptions below:

Source: Bulletin of the World Health Org., 13(1):49-68, 1955.

Monday Blues Digression: Tedeschi Trucks

Bound for Glory. (live version): see also the Relevator album.

http://www.youtube.com/watch?v=hxaineCMv38 Here

Biweekly or Monthly Injections of Pegelated Beta Interferon Found Effective in Relapsing MS

Press release (warning: contains pharma corporatespeak) here.

Positive top-line results from Biogen Idec’s peginterferon beta-1a Phase 3 trial on RRMS

Published on January 28, 2013 at 2:56 AM ·

Peginterferon beta-1a reduced the risk of 12-week confirmed disability progression as measured by the Expanded Disability Status Scale (EDSS) by 38 percent in both dosing arms (p<0.04).

Peginterferon beta-1a reduced the proportion of patients who relapsed by 39 percent in the once every two-week dosing arm (p<0.001) and by 26 percent in the once every four-week dosing arm (p<0.03).

Peginterferon beta-1a reduced the number of new or newly enlarging T2-hyperintense lesions on brain MRI scans by 67 percent in the once every two-week dosing arm (p<0.001) and by 28 percent in the once every four-week dosing arm (p<0.001).

In ADVANCE, both dosing regimens showed favorable safety and tolerability profiles. The overall incidence of SAEs and AEs was similar among the peginterferon beta-1a and placebo groups. The most common SAE was infections, which was balanced across all treatment groups (≤1 percent per group).

Let's have some more of that Big Island grown roast....

To be presented at the 2013 AAN meeting:

Consumption of sweetened drinks, including artificially sweetened drinks, was associated with an increased risk of depression (about 20% increased risk). Coffee intake, on the other hand, was associated with a decreased risk of depression (about 10% decreased risk).




Abstract Title: Sweetened beverages, coffee and tea in relation to depression among older US adults

Press Release Title: Hold the Diet Soda? Sweetened Drinks Linked to Depression, Coffee May Lower Risk

Objective: To prospectively evaluate consumptions of sweetened beverages, coffee and tea in relation to depression among older US adults.

Author(s): Honglei Chen, MD, PhD, Xuguang Guo, Yikyung Park, Neal D. Freedman, Rashmi Shinha, Albert Hollenbeck and Aaron Blair

Background: Sweetened beverages, coffee and tea are commonly consumed worldwide and have important physical and mental health consequences.

Design/Methods: We prospectively evaluated consumptions of these beverages, in relation to depression among 263,925 older US adults. Beverage consumptions were assessed in 1995-1996, and 11,311 depression diagnoses since 2000 were self-reported in 2004-2006. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regressions.

Results: Drinking sweetened beverages was associated with higher depression risk, whereas coffee drinking was weakly related to lower risk. The OR and 95% CI comparing ≥4 cans/cups per day with none were 1.30 (1.17–1.44) for soft drinks, 1.38 (1.15-1.65) for fruit punches and 0.91 (0.84-0.98) for coffee (all P for trend < 0.0001). Further analysis seemed to suggest stronger associations with diet drinks than with regular. The ORs between extreme categories were 1.31 (1.16-1.47) for diet versus 1.22 (1.03-1.45) for regular soft drinks, 1.51 (1.18-1.92) for diet versus 1.08 (0.79-1.46) for regular fruit punches and 1.25 (1.10-1.41) for diet versus 0.94 (0.83-1.08) for regular iced tea. Consistently, constituent-based analyses showed higher depression risk with aspartame intake [ORs between extreme quintiles: 1.36 (1.29-1.44)], and lower risk with caffeine intake [corresponding OR 0.83 (0.78-0.89)].

Conclusions: This large prospective study suggests that frequent consumption of diet sweetened beverages may increase depression risk among older adults, whereas coffee consumption may lower the risk.

EEG-doubt, part 2: The Partially Vegetative State

This neurological controversy in The Lancet has also been discussed in Slashdot and by bloggers including Neuroskeptic. Here, via Medscape.

I personally think that the clinical boundaries between the vegetative state and partially conscious states are vague and variable enough so this controversy may well continue regardless of our statistical models.

Catnip: The Educational Video

Lolcat lolz! A new drug abuse parody from the Sundance Film Festival. Did curiosity kill the cat,or was it the drugs?

Valproate Anticonvulsant Treatment in Pregnancy Linked to Autism in Offspring

Now there may be yet another reason to avoid divalproex or valproate therapy during pregnancy. The other one, long known, is a risk of increased incidence of neural tube based birth defects. Taking recommended doses of folic acid and other vitamins daily during pregnancy might help, but it's better to avoid that risk altogether. Note that the other anticonvulsant drugs they studied seemed safe, as far as risk of autism was concerned.

Here's the abstract.

J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2012-304270

The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs

Rebecca Louise Bromley1, George E Mawer2, Maria Briggs2, Christopher Cheyne3, Jill Clayton-Smith2, Marta García-Fiñana3, Rachel Kneen4,5, Sam B Lucas2, Rebekah Shallcross6, Gus A Baker1, On Behalf of the Liverpool and Manchester Neurodevelopment Group


The aim of this study was to compare the prevalence of diagnosed neurodevelopmental disorders in children exposed, in utero, to different antiepileptic drug treatments. A prospective cohort of women with epilepsy and a control group of women without epilepsy were recruited from antenatal clinics. The children of this cohort were followed longitudinally until 6 years of age (n=415). Diagnosis of a neurodevelopmental disorder was made independently of the research team. Multiple logistic regression analysis revealed an increase in risk of neurodevelopmental disorders in children exposed to monotherapy sodium valproate (VPA) (6/50, 12.0%; aOR 6.05, 95%CI 1.65 to 24.53, p=0.007) and in those exposed to polytherapy with sodium VPA (3/20, 15.0%; aOR 9.97, 95% CI 1.82 to 49.40, p=0.005) compared with control children (4/214; 1.87%). Autistic spectrum disorder was the most frequent diagnosis. No significant increase was found among children exposed to carbamazepine (1/50) or lamotrigine (2/30). An accumulation of evidence demonstrates that the risks associated with prenatal sodium VPA exposure include an increased prevalence of neurodevelopmental disorders. Whether such disorders are discrete or represent the severe end of a continuum of altered neurodevelopmental functioning requires further investigation. Replication and extension of this research is required to investigate the mechanism(s) underpinning the relationship. Finally, the increased likelihood of neurodevelopmental disorders should be communicated to women for whom sodium VPA is a treatment option.

We have an old citrus tree in our front yard which bears pomelo most of the year:

The pomelo is an exotic large citrus fruit that is an ancient ancestor of the common grapefruit, which is actually a hybrid of the ancient pomelo and an orange. In fact, most types of today's oranges and grapefruits were produced by hybridization of products of crosses between the mandarin orange and the pomelo. The pomelo originated in southeast Asia, likely around Malaysia where it still grows wild. It was later introduced to Fiji and from there into Polynesia, and was grown in China by 200 B.C.

The pomelo is sweeter than the grapefruit, despite the grapefruit's being a cross with the still sweeter orange. It is the largest of the citrus fruits with a shape that can be fairly round or slightly pointed at one end (the fruit ranges from nearly round to oblate or pear-shaped). They range from cantaloupe-size to as large as a medium sized round watermelon and have very thick, soft rind. The skin is a pale green to yellow color,and the flesh color ranges from yellow-pink to red. The whitish membranes between the segments are tough and harsh and are usually peeled away from the segments before they are eaten.

In one cup (190 g) of pomelo, there are only 72 calories, but 116 mg (193% MDR) of vitamin C. Traces of minerals and other vitamins round out this wholesome food.

Old Fashion Kine: Aloha Friday

Hi'ilawe. http://www.youtube.com/watch?v=10Xir0eEDV4 .

Izy's version.   http://www.youtube.com/watch?v=tYCjWcIloBc


Hi`ilawe was probably written by Sam Li`a Kalainaina, Sr and Mrs. Kuakini
Translation - from Na Mele o Hawai`i Nei by Samuel H. Elbert and Noelani Mahoe

Kamaka ka ikena ia Hi`ilawe       All eyes are on Hi`ilawe
I ka papa lohi mai a`o Maukele    In the sparkling lowlands of Maukele

Pakele mai au i ka nui manu       I escape all the birds
Hauwala`au nei puni Waipi`o       Chattering everywhere in Waipi`o

A`ole no wau e loa`a mai          I am not caught
A he uhiwai au no ke kuahiwi      For I am the mist of the mountains

He hiwahiwa au no ka makua        I am the darling of the parents
A he lei `a`i na ke kupuna        And a lei for the necks of grandparents

Na Puna ke `ala i hali`ia mai     The fragrance is wafted from Puna
Noho i ka wailele a`o Hi`ilawe    And lives at Hi`ilawe

Ha`ina `ia mai ana ka puana       Tell the refrain
Kamaka ka `ikena ia Hi`ilawe      All eyes are on Hi`ilawe

Cartesian Theater, Meet the GMO Zebrafish.

Don't miss this: a video abstract of the brain of a baby zebrafish as the fish watches a paramecium swim by. Best with screen maximized.

Real live fish brain makes a cool video. Here's the abstract:

Akira Muto, Masamichi Ohkura, Gembu Abe, Junichi Nakai, Koichi Kawakami, Real-Time Visualization of Neuronal Activity during Perception, Current Biology, Available online 31 January 2013, ISSN 0960-9822, 10.1016/j.cub.2012.12.040. (http://www.sciencedirect.com/science/article/pii/S096098221300002X) Abstract: Summary To understand how the brain perceives the external world, it is desirable to observe neuronal activity in the brain in real time during perception. The zebrafish is a suitable model animal for fluorescence imaging studies to visualize neuronal activity because its body is transparent through the embryonic and larval stages. Imaging studies have been carried out to monitor neuronal activity in the larval spinal cord and brain using Ca2+ indicator dyes [1–3] and DNA-encoded Ca2+ indicators, such as Cameleon [4], GFP-aequorin [5], and GCaMPs [6–12]. However, temporal and spatial resolution and sensitivity of these tools are still limited, and imaging of brain activity during perception of a natural object has not yet been demonstrated. Here we demonstrate visualization of neuronal activity in the optic tectum of larval zebrafish by genetically expressing the new version of GCaMP. First, we demonstrate Ca2+ transients in the tectum evoked by a moving spot on a display and identify direction-selective neurons. Second, we show tectal activity during perception of a natural object, a swimming paramecium, revealing a functional visuotopic map. Finally, we image the tectal responses of a free-swimming larval fish to a paramecium and thereby correlate neuronal activity in the brain with prey capture behavior.

The best way to study cognition....

...is to study cognition, not the fMRI image which is variably correlated with metabolic activity, which is variably correlated with neural firing, which is variably correlated with cognition...

Cannabadiol For Epilepsy

Cannabadiol, an extract of marijuana different from the THC ingredient in which most forms of hemp used as a recreational drug are enriche...