intelligence etiketine sahip kayıtlar gösteriliyor. Tüm kayıtları göster
intelligence etiketine sahip kayıtlar gösteriliyor. Tüm kayıtları göster

Running and neurogenesis; the plastic brain

A new paper online in the Journal of Physiology ("Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained," Nokia et al.), and described here by the NYT, reports that running is good for the brain.  At least the rat brain.

From the paper (emphasis mine):
Adult hippocampal neurogenesis (AHN) is a continuous process through which cells proliferate in the subgranular zone of the dentate gyrus, mature into granule cells, and ultimately become incorporated into hippocampal neuronal networks. In rodents, adult-born hippocampal neurons seem crucial for a variety of adaptive behaviors such as learning, pattern separation, and responses to stress. Aerobic exercise, e.g. running, increases AHN and improves cognitive performance in both male and female adult rodents. The increase in AHN in response to running is reported to be in part due to an increase in the number of surviving neuronal precursor cells (type 2) rather than to the shortening of the cell cycle. There are also studies indicating that running increases the survival and incorporation of newly divided hippocampal cells, born days before commencing training, to increase net neurogenesis. [See the paper for citations for reported findings, which I've removed here for length.]
It has already been well-established that aerobic exercise is associated with an increase in adult hipocampal neurogenesis, the number of neurons in the hippocampus, the region of the brain associated with producing long-term memory among other functions.  But, Nokia et al. wondered if it was only aerobic exercise, or whether other kinds of exercise have the same effect.

So they compared the number of neuronal cells of mice subjected to high-intensity interval training, resistance training and distance running.  They found no increase in the rats who did resistance training compared to sedentary rats, and a smaller than expected increase in rats that did the interval training.  It was only in the brains of the rats who did aerobic exercise that neurogenesis was significantly increased.  The authors hypothesize that this is because running stimulates the production of  brain-derived neurotrophic factor and insulin-like growth factor, which are associated with neurogenesis. The more aerobic exercise the animal does, the more of these the animal produces, and thus the more neurons.

Currently the best advice for preventing dementia in old age is to maintain a social life, quit smoking, and exercise.  And, if this rat study can be applied to humans, this should at least qualify that as aerobic exercise; running or biking, say.  As with all such lifestyle advice, this surely won't work for everyone, but the evidence is increasingly in its favor, at least on a population basis.

But there are deeper implications of this work, I think.  If exercise changes the architecture of the brain in ways that can affect learning, even in adults, and, as has been repeatedly demonstrated, stimulating children by reading to them, using lots of words, playing music to them, and so on, or the reverse, growing up in poverty,  or with disease, or amid famine all can affect brain architecture and thus cognitive ability for better or for worse, why do so many continue to privilege genes and genes alone -- or even more, a single gene -- for the creation of intelligence?



Source: "Effects on brain development leading to cognitive impairment:  A worldwide epidemic," Olness,
Journal of Developmental & Behavioral Pediatrics:
April 2003 - Volume 24 - Issue 2 - pp 120-130

It seems that the brain responds to experience at all ages, but it's possible that there's a 'sensitive period' for cognition.  As just one example, the cognitive abilities of children reared in institutions in Bucharest were compared to that of children never placed in an institution to those whose lives began there but who moved to foster care before age two.  Those who were reared entirely in institutions had much lower cognitive ability than the other two groups; the cognitive abilities of those who were moved to foster care before age two significantly improved.  The authors of this study suggest that there may be a sensitive period for developing cognitive ability, just as there is one for learning language, and many other aspects of brain function.

Of course, as with any trait, genes play a crucial role in the development of the brain.  But they don't do it alone.  E.g., a 2010 paper in Child Development describes the genetic underpinnings of the developing brain, but its plasticity as well.
The foundations of brain architecture are established early in life through a continuous series of dynamic interactions between genetic influences and environmental conditions and experiences (Friederici, 2006; Grossman, 2003; Hensch, 2005; Horn, 2004; Katz & Shatz, 1996; Majdan & Shatz, 2006; Singer, 1995). There is increasing evidence that environmental factors play a crucial role in coordinating the timing and pattern of gene expression, which in turn determines initial brain architecture. Because specific experiences potentiate or inhibit neural connectivity at key developmental stages, these time points are referred to as sensitive periods (Hess, 1973; Knudsen, 2004). Each one of our perceptual, cognitive, and emotional capabilities is built upon the scaffolding provided by early life experiences. Examples can be found in both the visual and auditory systems, where the foundation for later cognitive architecture is laid down during sensitive periods for basic neural circuitry.  
Genetic determinists might acknowledge the plasticity of the brain but then say that how the brain responds to experience is what's genetically determined, and thus that there are children who just aren't genetically equipped to be the next Einstein, or even to learn calculus.  We know this is true at least at one extreme of the distribution of intelligence, because there are many alleles known to be associated with low cognitive ability.  These usually cause syndromic conditions, however, so aren't related only to how quickly synapses are crossed, or memories made, or whatever it is that underlies -- or defines -- intelligence.  As with many other trait distributions, what happens at the extremes doesn't necessarily represent what's going on in the middle, so I think the jury is still out as to the overriding importance of single or even a small number of alleles in the development of normal or above normal intelligence (again, whatever that is -- for the moment, let's call it the ability to score well on IQ tests).  And indeed no genes with large effects on intelligence have yet been identified, despite decades of looking.  That has so far included comparison of the tails of the distribution among individuals without a clear-cut pathology.

So, of course there are genes involved in how quickly people think, or make connections between ideas, or memorize, or invent things, or remember -- how people learn.  But it's not either mainly genes or environment.  It's both, interacting, and molding the reactive brain.  There is enough evidence now to show that the brain is a hungry organ, soaking up and responding to experience at all times, throughout life.  Whether or not we believe that society should be investing in optimizing the environment of every child to maximize their potential is a social and political decision, not a scientific one.

Let's be intelligent about intelligence

A lot of confusion reins over assertions about whether a physical or even behavioral trait is  'genetic'. There are several reasons for this.  One is the difference between mechanism and variation. Every human trait is genetic in the first sense: an organism develops from a fertilized egg because it has genes, and without its genes it could do or even be nothing.  So every trait is 'genetic' in the mechanism sense. But the other meaning of 'genetic' has to do with variation, and that is where the difficulty and often the contention lies.  The assertion that a trait is 'genetic' in this sense means that some people with a trait, or a particular trait measure, have it because of some particular genotype. That is, we all differ in the trait because of causal genetic differences.  Identifying genetic mechanisms or demonstrating that genetic variation is responsible for variation in a trait are genuine challenges.

Searching for genetic mechanisms responsible for, say, heart disease is one of those challenges.  It's difficult scientifically, but unlike with some other traits, the scientific question isn't politically loaded. Many people fervently want to stress the genetic role in intelligence, for example, and it's often for thinly disguised racist or elitist reasons.  A common response to almost any suggestion that an individual's intelligence might not be inborn, due to variants in his/her inherited genotype (meaning built-into the person's DNA sequence), is an accusation that the person is in denial of reality (but see our Dec 14 post about genetics and dialectics).  But who is really denying reality in such cases?  In our view, it is those who misperceive or misuse measures like heritability and have deep, emotional commitment to inborn destiny.

And, again, it's pretty clear that just slightly beneath the surface is often a racist or other discriminatory agenda: "let's identify 'them' and do something about it, to 'improve' them or prevent them from harming everybody else" (Trump's throw the Muslims out campaign, or the reluctance to invest 'our' resources in groups with inferior IQ, or in the worst case, eliminate them). If it's important to understand why people behave as they do (intelligence being just one aspect of behavior; there are of course many others), the argument goes, then one needs to know if it's genetic, that is, built into the genome at conception!  Again, then depending on who such knowledge is important to, individuals in the population can (should, must) be tested.

Of course, it's worth asking carefully whether what's really being looked for are individual differences, or group differences.  Why 'we' (those in power) 'need' (that is, want) to know which of 'their' behaviors are built-in, is unclear, but seems frequently to justify acting in discriminatory ways, favoring some and neglecting others.  In other words, of course intelligence is the result of gene action, but the argument is really about variation rather than mechanism.

But before we address these issues, it is worth providing a quick description of the core of the 'scientific' basis of the argument, which typically rests on a measure called 'heritability' (denoted here by H but typically written h-squared).

Heritability: simple-sounding word, but a slippery measure
When the genetics of intelligence, or most other behavioral traits for that matter, is considered, the proof that they are genetic is usually that their heritability is high.  Heritability has been known for decades to be a rough indirect indicator of genetic mechanistic cause, but it's a very elusive measure. The usual measure of H is basically the ratio of the amount of variation in genes (G) divided by the amount of variation in genes + variation in environment, G/(G+E), all within a particular sample at a particular time.  This is estimated typically by comparing the trait measure in relatives, since close relatives share specifiable fractions of their respective genetic variants.

This figure schematically shows the scatter of genetic similarities, each dot being values of the measure in an offspring compared to the average of its mother and father.  The figure shows the difference in such correlations if environmental effects are great and genetic variation accounts for only 10% of the similarity (left panel), or small where the environments contribute only 10% (right).

From Wikimedia images, taken from Nature


H in itself measures no specific genes or gene-variants, nor any specific environmental variants.  To avoid some confounding or confusing contributors to the trait, various additional types of sample are often studied or comparisons made, such as between adoptees vs biological children, or dizygous vs monozygous twins. Heritability studies also often try to remove correlations among relatives that are due to shared family environments that could, in the computation, falsely appear as genetic.  While these strategies are not useless, they are well-known to be imperfect.

Since the measure H is a ratio that depends on the particular conditions in your particular sample, if one of the terms (G or E) were to change, even within that same sample, the H value would also change. In other words, let the same population (the exact same set of genotypes) experience changed environments, and H will change. In that sense H is not an absolute measure of how genetic a trait is, but of how relatively important it is.  Let us repeat that--heritability is not a definitive measure of the genetic contribution to a trait.  It is about its context in a particular sample.

Every study of traits like IQ test scores, used as hopeful stand-ins for 'intelligence', shows that there is substantial heritability, though usually far below 1.0.  That means that environmental effects are important, usually predominant, even if genetic variation is contributing as well.  That's about all that H measures show.  'Environment' in this sense tells us nothing in itself about what the specific individual contributing factors might be, because they don't behave the way genetic factors do, thanks to the rules of genetic transmission from parent to offspring; environmental factors don't have theoretically specifiable patterns of clustering among people or even among relatives. The apparent environmental component estimated in H studies can also include things like chance, testing inadequacy, measurement error and so on.

The undeniable bottom line is that variation in traits like intelligence test performance is certainly affected by genetic variation because the trait itself is mechanistically affected by genes. But that is a crude and almost useless fact because the genetic component is generally polygenic, meaning that it is affected by large numbers of varying genomic elements, each making very small individual contributions. Here, we conveniently ignore whether current fad factors such as microbiomic or epigenetic effects are relevant, because each of them is variable, in each population or sample, and over time--even in each individual over time--and could in principle be inherited and hence appear in families as being 'genetic'.

What this means is that even each individual's inborn genetic component will be very different, that is, each of us will have different combinations of variants at tens or hundreds (or more) of contributing gene regions.  The predictability of achieved results from genomes, much less individual variants, will be correspondingly small, practically useless, as we've clearly seen for so many other complex traits (GWAS results, for example, even of IQ test scores). If we could measure environments the way we can measure genomic variation, they would be similarly complex with many individual factors involved, most with individually weak effects.  As with genotypes, the complexity of these environmental factors would mean each person is unique and predictions are weak, and that changing circumstances and imprecision in the risk estimates would have a large potential effect on each person's achieved results.  We've discussed these limitations (and the overselling) of genetic association studies many times here.

But, if one is determined to pry into everyone's inherent worth, here's how to do it properly:
Here's an idea: Let society decide that we want to know the real genetic truth about behaviors, not just the mechanisms but the effect of variation among individuals.  To do that, we must pass legislation to ensure that all environmental factors that contribute to behavior--all of them!--are exactly the same for everyone, from conception onward.  Once that is done, variation in test performance will be entirely due to genes, since the environmental variance, E, would be zero, so that H would be 1.0.  Now we can see how strongly genes in general, or individual genetic variants, determined results.  However, we assert with confidence that the result of individual genetic prediction would still be hopelessly complex in most cases (excepting, for example, clearly pathogenic genetic variants, which we know to be rare, and even they are usually not simple).

But this is of course a fantasy: making environmental effects uniform for everyone is obviously impossible, for at least two reasons.  First, we can't make the climate in Maine like that in Florida or California.  We can't have identical schools everywhere, or the same number of books in every home, or the same number of words spoken to each infant at each developmental stage.  And so on.  So maybe a more realistic idea would be to make the environmental variation the same everywhere, so that in a sense it was a kind of uniformly distributed 'error' term in measuring genetic effects.  Of course that can't be done either, for the same sorts of reason.

Secondly, genes don't work on their own, but interact with 'environments' in almost every imaginable way, and certainly in the development of the brain.  That means that separating G and E (as in G+E) is clearly an oversimplification of something very poorly understood.  Even fixing the same environment everywhere would not have the same effect on every genotype.

The bottom line, in reality, is that arguments, usually by those in privilege, that behaviors (and hence their societal value) are inherent, are almost inevitably working some other form of self-advantaging agenda.  Racism is right beneath the surface in much of this, but so are xenophobia and class differences.  So are hopes of producing babies with some desired property.  That's clear from the history of the subject.

Since it's impossible to think that society could make environments uniform for everyone so all that's left is genetic variation, the next most salubrious thing a society could do would be to provide the best environmental conditions for all of its members to thrive in, not expecting everyone to achieve the same but at least to have safe, satisfactory lives.  More socioeconomic equity by the elimination of poverty and privilege would be a solution if such equity were the real objective. Of course since the beginning of history this has been the stated goal of those who bemoan the unfairness of society (though less so of others who say we're inherently unequal and we ought to reward the privileged).  We gain little by peering into individual genomic 'souls' and condemning those found genetically wanting to fates that we, in the elite, decide is best for them (inevitably making sure we stay at the top).

This doesn't seem too cynical a view of the subject: If what those who assert the deep importance of genetics of behavior really want is for society to be fair, the first thing is to understand the environmental effects that obviously are the predominant causes of behavioral variation, and rectify the inequities.  Let society ensure that everyone has the same conditions: no upper class advantages in schools, ballet lessons, Kaplan prep courses for SATs to get them into Princeton, no jobs to get through family or parents' contacts, same number of books in every house, no corner drug dealers nor rats in the hallways in poor neighborhoods......  Or, how about broader 'intelligence' testing ideas, to include smarts like the ability to read defenses in basketball while flying through the air, or work a fork-lift efficiently, or fix one of today's complicated cars....

is a complex factor that is misused as much as it is used, because there are too many reasons to interpret its computational subtleties in ways that conveniently favor one's own social agenda. Not everyone interprets these issues in this way, but behaviors like intelligence are too juicy for those with such intentions to resist.  But, yes, let's be scientific, and commit to a concerted effort to make H approach 1.0, so that we can really understand the genetic contributions--that is, to make test-score differences really 'genetic'!  Then we could make sense of 'genetic' causes.  But, would any serious thinker believe it would be very useful?

Rare Disease Day and the promises of personalized medicine

O ur daughter Ellen wrote the post that I republish below 3 years ago, and we've reposted it in commemoration of Rare Disease Day, Febru...