Archive for August, 2006

Recently Thomas wrote about a paper by Yulia Kovas and Robert Plomin in the May issue of TICS discussing the implications of the fact that a great number of genes – dubbed “generalist” genes – affect not one, but most cognitive abilities. One obvious implication is that, if most genes being expressed in the brain affect several areas of the brain, the massive modularity hypothesis (MMH) might not hold true. As Kovas and Plomin wrote in the conclusion to their paper:

Our opinion outlined in this article is that the generalist genes hypothesis is correct and that genetic input into brain structure and function is general (distributed) not specific (modular). The key genetic concepts of pleiotropy and polygenicity increase the plausibility of this opinion. Generalist genes have far-reaching implications for cognitive neuroscience because their pleiotropic and polygenic effects perfuse the transcriptome, the proteome and the brain. This is more than a ‘life-is-complicated’ message. DNA and RNA microarrays provide powerful tools that will ultimately make it possible for cognitive neuroscience to incorporate the trait-specific genome and transcriptome even if hundreds of genes affect individual differences in a particular brain or cognitive trait. The more immediate impact of generalist genes will be to change the way in which we think about the relationship among the genome, the transcriptome and the ‘phenome’ of the brain and cognition.

As Thomas was quick to remark, this idea is of course sure to infuriate proponents of the MMH. Therefore, it comes as no surprise that Gary Marcus and Hugh Rabagliati has a letter in next month’s TICS criticizing Kovas and Plomin’s article. Here is their argument for upholding the MMH:

Genes are in essence instructions for fabricating biological structure. In the construction of a house, one finds both some repeated motifs and some specializations for particular rooms. Every room has doors, electrical wiring, insulation and walls built upon a frame of wooden studs. However, the washroom and kitchen vary in the particulars of how they use plumbing array fixtures, and only a garage is likely to be equipped with electric doors (using a novel combination of electrical wiring and ‘doorness’). Constructing a home requires both domain-general and domain-specific techniques. The specialization of a given room principally derives from the ways in which high-level directives guide the precise implementation of low-level domain-general techniques. When it comes to neural function, the real question is how ‘generalist genes’ fit into the larger picture. Continuing the analogy, one might ask whether different ‘rooms’ of the brain are all built according to exactly the same plan, or whether they differ in important ways, while depending on common infrastructure. Kovas and Plomin presume that the sheer preponderance of domain-general genes implies a single common blueprint for the mind, but it is possible that the generalist genes are responsible only for infrastructure (e.g. the construction of receptors, neurotransmitters, dendritic spines, synaptic vesicles and axonal filaments), with a smaller number of specialist genes supervising in a way that still yields a substantial amount of modular structure.

The interesting thing about this discussion between Plomin and Marcus is the fact that the question that they raise can be investigated empirically, as Kovas and Plomin note in a reply to Marcus and Rabagliati:

Finding high genetic correlations means that genes must be generalists at the psychometric level at which
these traits have been assessed. Therefore, a genetic polymorphism that is associated with individual differences in a particular cognitive ability will also be associated with other abilities. The question is how these generalist genes work in the brain. Does a genetic polymorphism affect just one brain structure or function, which then affects many cognitive processes, as suggested by a modular view of brain structure and function (mechanism 1 in [Kovas and Plomin’s original article])? This model assumes that brain structures and functions are not genetically correlated – genetic correlations arise only at the level of cognition. Another possibility, which we think is more probable, is that the origin of the general effect of a genetic polymorphism is in the brain because the polymorphism affects many brain structures and functions (mechanisms 2 and 3 in [Kovas and Plomin’s original article]). Of course, some polymorphisms might have general effects via mechanism 1 and other polymorphisms might have general effects via mechanisms 2 and 3, as Marcus and Rabagliati suggest. Fortunately, this is an empirical issue about DNA polymorphisms that does not require resorting to metaphors such as house-building. We did not say that the case for mechanism 3 was proven, which is what Marcus and Rabagliati imply with their partial quote. The full quote from our article is: ‘In our opinion, these two key genetic concepts of pleiotropy and polygenicity suggest that the genetic input into brain structure and function is general not modular’. Pleiotropy (in which a gene affects many traits) is a general rule of genetics. Polygenicity (in which many genes affect a trait) is becoming another rule of genetics for complex traits and common disorders. As we point out, polygenicity greatly multiplies and magnifies the pleiotropic effects of generalist genes. A more empirical reason for suggesting that the origin of generalist genes is in the brain is that gene-expression maps of the brain generally indicate widespread expression of cognition related genes throughout the brain.

I second that sentiment. It would be a big step forward if the massively modularity discussion would move beyond mere speculation and become grounded in empirical data.


Kovas, Y. & Plomin, R. (2006): Generalist genes: implications for the cognitive sciences. Trends in Cognitive Science 10: 198-203.

Marcus, G. & Rabagliata, H (2006): Genes and domain specificity. Trends in Cognitive Science, in press.

Kovas, Y. & Plomin, R. (2006): Response to Marcus and Rabagliata. Trends in Cognitive Science, in press.



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huxley.jpgI just saw the TV documentary “The root of all evil?” hosted by Richard Dawkins, who is one of today’s most ardent defenders of evolutionary theory, and of science in general. Over two episodes Dawkins argues that the world would be better off without religion, since it distorts our view of ourselves as human beings and our place in the universe, of society and of morals and law.Dawkins seeks out confrontation with religious leaders such as Pastor Ted Haggard in The New Life Church in Colorado Springs, and Joseph Cohen, now Yousef al-Khattab in Jerusalem, an American-born Jew who came to Israel as a settler before converting to Islam. On both occasions, Dawkins attempts to discuss the difference in their respective understandings of humanity, the world, morals and so on. The problem is that neither Haggard or al-Khattab agree that scientific evidence must be regarded as true. Basically, they think that science is “just another religion”, and that you have to believe it, just as you do in God or Allah.

So what does Dawkins do, this ardent proponent of evolution? He goes numb! No doubt he is utterly suprised of the backwards logic that the religious representatives display. But why doesn’t he do as he says in the beginning of his documentary:

The time has come for people of reason to say: enough is enough. Religious faith discourages independent thought, it’s divisive, and it’s dangerous.

No, Dawkins goes numb and has little else to say, it seems. Although Wikipedia gives you the details of this documentary, it does not convey fully how Dawkins fails to apply his otherwise crisp and clear logic, as you can read in any of his books.

I think what we need is a new Darwin’s bulldog, or maybe a Dawkin’s bulldog? Or even better, evolution needs a butcher. We need someone who can piece out every single misinformation, failed logic and stupidity that can be found in religion. We need it to happen on-line, in front of our eyes, on the tele, on the radio. We need someone to ridicule religious belief, to show how it relies on nothing but anecdotes presented as axioms. That they are cultural memes, potential lethal mental viruses. Someone who asks “why should I believe in your religion rather than this over here?”, “why cannot my self-made, armchair philosophy religion be just as good as yours?”. Someone who get rabbis, muftis and bishops together to tell us what’s really right, why we should listen to only some of the Bible, or Koran, and decline other parts as culturally twisted tales.

Science has played the nice guy all along, because science is not a movement. It’s a method. It’s a way of asking “is this true, and can you prove it or reject it?”. How you choose to study a phenomenon is your own choice, but you open up to test whether theory A, B, and C are correct, whether only one is correct or whether all are false.

So we need a butcher, probably a whole association of evolutionary butchers. Let’s call them Dawkins’ Butchers. Who wants to join?


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beer.jpgAs noted in my previous post, the impact of alcohol on brain maturation in adolescence is still considered an open question, although studies indicate that early exposure to alcohol is even more damaging in adolescence than in adulthood. It’s not surprising at all. Alcohol crosses the blood-brain barrier to influence the function of neurons. Actually, influence is not the right term: intoxicates or poisons the brain is more correct. After all, the effect of alcohol on your state of mind is due to a state of intoxication.Alcohol is of course only one of many substances that have an impact on brain function, and that are used for recreational purposes. Other psychoactive substances include nicotine/tobacco, cannabis, cocaine and LSD. In a population of adolescents the young vary in their use of such drugs, both the debut, the regularity of use, and the combined – or polydrug – use. The question is, then, what causes this variation?

In a special issue of Behavioral Genetics the genetic and environmental causes of substance use are explored and reviewed. For example, Jason Pagan and colleagues study the causes of alcohol use in adolescence, and conclude that

(…) there was no significant evidence of shared environmental influences on alcohol problems in early adulthood. Problems were largely influenced by genetic factors that overlapped with genetic influences on frequency of use. Unique environmental factors were largely specific to each stage, with some overlap between alcohol problems and frequency of use at age 25.
Danielle Dick and her colleagues, on the other hand, find that a specific gene, GABRA2, shows two specific patterns in relation to adolescent and adult alcohol abuse. First they found that aconsistent elevation in risk for alcohol dependence associated with GABRA2 is not evident until the mid-20s and then remains throughout adulthood. On the other hand, GABRA2 was also associated with other drug dependence in their sample, both in adolescence and adulthood. So this gene can indeed be a causative factor in the forming of drug use in general, which some findings seem to indicate. GABRA2 has been shown several times to be coupled to alcoholism. For example, Danielle Dick herself has published data showing a complex relationship between martial status, alcohol dependence and GABRA2, concluding in another publication this year:

These analyses provide evidence of both gene-environment correlation and gene-environment interaction associated with GABRA2, marital status, and alcohol dependence. They illustrate the complex pathways by which genotype and environmental risk factors act and interact to influence alcohol dependence and challenge traditional conceptualizations of “environmental” risk factors.
Anyway, the special issue in Behavior Genetics has several good articles on the gene-environment interaction effects on the development of substance use disorders. It’s a must-read to anyone interested in genes, brain and behaviour.


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alcohol.gifAdolescence is a period of dramatic transformation in the healthy human brain, leading to both regional and general brain volume changes. Recent high-resolution Magnetic Resonance Imaging (MRI) studies emphasize the effects of ongoing myelination, indicating a substantial maturation process (see Figure 1). The period of adolescence is often defined as spanning the second decade of life, although some researchers expand their definition of adolescence to include the early 20s as well. Research into brain maturation in adolescence is particularly important, given that it is normally considered the peak period of neural reorganization that contributes to normal variation in cognitive skills and personality Additionally, it is seen as the period of major mental illness onset, such as schizophrenia. Despite growing evidence for pronounced changes in both the structure and function of the brain during adolescence and early adulthood, few studies have explored this relationship directly using in vivo imaging methods. Thus, little is still known about the relationship between adolescent behaviour and outcomes, and maturational effects on morphological and functional aspects of the brain.


Figure 1Brain development during adolescence

The psychological and social changes of that occur during adolescence include a higher level or orientation towards and identification with peers, group socialism and personality consolidation. A main social behavioural change is the tendency to use alcohol and other stimulants. In European countries and especially Denmark, 60% of all adolescents report having had their first alcoholic whole drink before age 15, the majority reporting a debut at around age 12 (see Figure 2). Today, alcohol is considered a normal part of adolescent culture.



Figure 2Age of alcohol use debut, as measured by the first consumption of a full alcoholic unit. Note that the majority of debuts are around 12 years. Furthermore, note the relatively high number (8%) reporting a <9 year old debut. (x-axis numbers indicate age of reported first full drink of alcoholic beverage; “yngre end 9” = “younger than 9”; “jeg har ikke drukket” = “I have not yet tried alcohol”)

The effects of prolonged regular alcohol consumption in adults are today considered well documented. Studies of extreme cases such as Wernicke’s encephalopathy and foetal alcohol syndrome have shown that alcohol at critical periods or over time can have severe effects on significant modification and damage of brain structure, physiology and function. In adults, heavy alcohol consumption results in atrophy of grey and white matter, particularly in the frontal lobes, cerebellum, and limbic structures. Heavy drinking also raises the risk of ischemic and hemorrhagic stroke.

Adolescents tend to drink larger quantities on each drinking occasion that adults, possibly a combination of lower sensitivity to some of the unpleasant effects of intoxication and altered patterns of social interaction, including a willingness to indulge in more risky activities. However, it has been suggested that adolescents may be more sensitive to some of alcohol’s harmful effects on brain function. Research now suggests that, even over the shorter time frame of adolescence, drinking alcohol can harm the liver, bones, endocrine system, and brain, and interfere with normal growth. Studies in humans have found that alcohol can lower the levels of growth- and sex hormones in both adolescent genders.

Recent studies using animal models have demonstrated that the adolescent brain is even more sensitive to alcohol consumption. Alcohol inhibits normal neurogenesis, the process in which neurons are created. The magnitude of this effect has been related to the level of consumption; higher levels of consumption (e.g. binge consumption) had the most severe effects on the brain. Furthermore, alcohol impairs spatial memory function in adolescent animals more than adults, a result that is thought to be mediated by a larger inhibitory effect of alcohol on neural transmission in adolescence.

The long-term effects of alcohol consumption on brain maturation are yet poorly understood in human adolescence. Studies report that a history of high alcohol consumption in adolescence has been associated with reduced hippocampal volumes (see Figure 3), and with subtle white-matter microstructure abnormalities in the corpus callosum. In order to understand the effects of alcohol on the brain these findings must be compared to several factors pertaining to alcohol consumption in young adults, including 1) onset of alcohol use; 2) amount of alcohol consumed regularly; 3) type of alcohol consumption (regular use or binge drinking). In addition, a number of confounding factors need to be addressed and controlled between different study groups, including 1) general cognitive function; 2) the effects of gender and pubic stage; 3) gender-related preferences for alcoholic beverages; and 4) the effects of gene-related differences in neurotransmitter function.


Figure 3Hippocampus volume differences in adolescents with alcohol use disorder (AAU, right) compared to healthy adolescents (left). Volume estimation is corrected for general brain size.

So who says alcohol is not damaging? We know it is in adults. We know it is in prenatal development. Why not during adolescence? Even more so; during this period of brain development so much is happening; the continuation of brain development; pruning and consolidation of brain, cognition and personality; all combined with the coctail of changes resulting from hormonal changes. Add alcohol, and in heavy doses in binge drinking, and you’ve got a recipe for brain dysfunction and detrimental brain development.

In most cultures, alcohol is seen as acceptable, even for adolescents. Alcohol is possibly even more problematic in countries such as Denmark, since it is not illegal for children and adolescents to drink alcoholic beverages (although it is strangely enough illegal for them to buy it; i.e. they have to get it from their parents or another >15 year old). Statistically, Denmark ranges among the countries that has the earliest alcohol debut and the highest mean weekly/monthly alcohol consumption in adolescence. In general, alcohol is more socially and culturally accepted in the Western world (or all cultures?). But given that alcohol has such damaging effects should we allow it if it turns out to have detrimental effects on brain development and cognitive functions?

You can put it another way: given that you know this, would you allow your teenage son or daughter to drink alcohol? If you knew that her or his brain would respond negatively (both long and short term) to the alcohol, would you let it happen? Thick twice


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carmelite-nuns.jpgResearch using fMRI to investigate complex cognitive behaviour, or controversial political issues, is often criticized – sometimes unfairly, but also often for good reasons. (A colleague of mine is prone to quip: “You shouldn’t conduct fMRI experiments that involve regions anterior to the central sulcus!”) In general, many of the problems with such fMRI studies stem from a more fundamental problem: on the one hand we want to know more about the most complex behaviour and cognitive mechanisms exhibited by the human brain (how are political beliefs formed?, what is romantic love?, etc.); on the other hand, due to this complexity, it is seldom possible to design experiments that lend themselves to a straightforward, and clear cut, interpretation.

A new study, in press at Neuroscience Letters, illustrates this conundrum. Mario Beauregard and Vincent Paquette scanned 15 Carmelite nuns as they experienced what the abstract refer to as a “a state of union with God”. In other words, Beauregard and Paquette have tried to design an imaging study that can tell us something about what goes on in the brain of people having a mystical experience. There are several reasons why this is interesting. One, mystical experiences are clearly, by themselves, a fascinating type of phenomenal experience. Scondly, since mystical experiences are very rare, it is naturally of interest to know more about why people sometimes leave their normal state of mind and engage in such “spiritual” experiences. And thirdly, understanding the neurobiological underpinnings of mystical experiences can help us understand the more basic question why religions are such an attraction to humans.

The problem with Beauregard and Paquette’s study lies in the unprecise nature of the experimental design. Beauregard and Paquette acquired MR images of the nuns’ BOLD signal vis-a-vis three different conditions: (1) a mystical condition, (2) a control condition, and (3) a baseline condition. Here’s how these three conditions are described in the paper:

In the Mystical condition, subjects were asked to remember and relive (eyes closed) the most intense
mystical experience ever felt in their lives as a member of the Carmelite Order. This strategy was adopted given that the nuns told us before the onset of the study that “God can’t be summoned at will.” In the Control condition, subjects were instructed to remember and relive (eyes closed) the most intense state of union with another human ever felt in their lives while being affiliated with the Carmelite Order. The week preceding the experiment, subjects were requested to practice these two tasks. The Baseline condition was a normal restful state (eyes closed).

In other words, what was actually investigated was the memory of previous mystical experiences, more so than the actual “union with God” proclaimed in the abstract. Beauregard and Paquette’s idea i now to compare the mystical condition with the control and the baseline condition. It is however somewhat unclear how the memory of a mystical experience match the memory of an “intense state of union with another human” (who?), and thus how the two conditions can be compared.

Another concern is the very long duration of the individual blocks. Each block lasted 5 minutes, which makes perfect sense from the point of view of the task (after all, the subject needs time to bring about the two principal conditions), but makes it enormously difficult to know what is being modelled by the analysis. To my knowledge no theory exists detailing how the time-course of calling up a memory of a mystical experience unfolds; hence, exactly what cognitive processes are reflected by the BOLD signal remain uncertain. Moreover, it is hard to make sure that people concentrate on just one cognitive task for such a long time, so the results may be contamined by unrelated mental activity.

Still, with these serious caveats in mind, it is interesting to see that the contrast between remembering the experience of a union with God and remembering the experience of a union with another human produce significant acitivity in a number of brain areas (medial OFC, medial PFC, dorsal ACC, middle temporal cortex, and the inferior and superior parietal lobule), albeit at p<0.001, uncorrected for multiple comparisons. This result indicate that (the memory of) mystical experiences do have some particular neural correlate, although the design of the experiment makes it impossible to say what the function of the brain regions mentioned above amount to.

Now, it is obviously highly unclear what this experiment shows, but this doesn’t make it a failed study in my view. Whenever we deal with complex cognitive processes, we have to start somewhere. If other researchers use others conditions we may slowly be able to piece together the puzzle of what these activations mean.


Beauregard, M. & Paquette, V. (2006): Neural correlates of a mystical experience in Carmelite nuns. Neuroscience Letters, in press.


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brainy.jpgToday, a post is up at Meme Therapy on the ethical aspects of techological and scientific advances. It is an interview with a lot of different people with diverse backgrounds. Jose Garcia asks:

We seem to be awash in technological/scientific issues that raise serious ethical questions nowadays. Of these which concern/interest you the most?

You can find my answer down the line, probably the most lengthy of the replies (duh?). Basically, I’m pointing to two major points: 1) the technical advancements that have already occur and will continue to happen, will challenge our current views of humanism, law and morale, volition and other aspects of human affairs. However, 2) how this knowledge is communicated, understood and misunderstood due to everything from bad explanation to religious beliefs, is just as important an issue.

I’d say that today we have a vast majority of academics that accept the Modern Synthesis of the theory of evolution, while a large part of the population as such a) do not believe in evolution; b) think evolution may be correct, but that humans are still “spiritual beings”; c) think that all is right and do not acknowledge that there are any inconsistencies between religion and science; d) think science is “bad” and that it should be discarded altogether.

So where does that put us today? Indeed, if I claimed that I really believed that Santa Claus existed, I’d be able to make use of all the same arguments that those proposing an intelligent design theory rathern than evolutionary theory  of human (and anima) evolution. Yes, I believe that Santa exists, living at the North Pole (or was it Greenland, Norway or Finland, or what?). Just because we can’t see him, doesn’t mean he doesn’t exist, does it? He’s giving you the presents at X-mas, not your parents (just a cover-up). You want me to prove it? No, I don’t believe in science, you can’t measure everything, right? There is more between heaven and earth than that!


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