cortex maturation: lag, span and thickness: ADHD, Schizophrenia, autism , IQ

There is an article making waves regarding the delayed maturation of the cortex of children with ADHD and so I thought I will throw in my two cents and try to simplify things.

First what is cortex maturation- the cortex of normal children first increases in size (as presumably new connections are made) , reaches a peak around 8 years of age and then the cortex thins (as spurious connections are pruned). We normally think of more connections being more beneficial, so it stands to reason why pruning should happen- but more connections do not translate into better connections- we only need to retain the right connections - the spurious connections need to be mercilessly pruned, if we are to function correctly. A theory based on this logic also asserts that we are born synaesthetes, but the spurious connections get pruned under normal development.


Now there are several things that can go wrong with this wiring and pruning process. Too much wiring can leave you with a thicker than normal cortex , too much pruning can leave you with lesser connections than required for normal functioning. Also the achievement of normal thickness, and subsequent thinnness can be developmentally shifted or lag from the normal developmental plan. Finally the thickening and thinnening may be squeezed in time and may happen at a faster rate for some individuals. Conversely, this may be spread over a broader time period and o9ccur at a relatively slower rate for other individuals. Considering the three factors of Size ( peak thichkness/ thinnness achieved), Lag (start and end of thickening and thinning process) and Rate (faster development over small time frame or longer span with slow rate of pruning/ initial connection formation) one gets 6 combinations (if we treat them as independent of each other) . Also considering that Thickening (initial connection formation) and Thinning (subsequent pruning) may also be independent one gets 12 combinations. these are sufficiently complex for me to abstain from making any sweeping generalizations. So I'll go to data:
1. In ADHD, new research (as also highlighted above) reveals, that the development (thickening and thinning ) of cortex is similar to normal individuals- only it is slightly shifted and starts later. this explains why ADHD disappears after teenage and is a problem only in childhood.

2. Children with higher IQ have faster rate of thickening and thinning of cortex as seen from graphic below.

3. Research from Paul Thomsaon's lab at UCLA has shown that in schizophrenia the normal pruning process does not stop in teenage as in normal adults, but continues beyond the early teenage resulting in more pruning than is normal.
4. I've read claims that in Autism the cortex is thicker and that it matures early. I'm tempted to posit Autism as a reverse trend of schizophrenic maturation, but need more accurate refernces and would be highly obliged if someone points me to appropriate resources.


All this seems very promising and I would be watching ne23s related to these developments more closely in future , considering that some of these are comorbid - like autism and IQ in high functioning ASDers and Creativity and Schizophrenia.

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Schizophrenia: sensory gating and extracting meaning from noise

I have blogged extensively in the past regarding schizophrenia and how people that are on that end of the cognitive thinking style are marked by a propensity to abstract meaning from apparent noise and meaningless or coincidental events. This, I have contrasted with Autistic thinking style which does not endow meaning even where it is legitimate.

It is also well known that Schizophrenics have a deficit with sensory gating and thus have loose attention/ loose associations etc. and are generally marked by less focal attention. This may lead to lowered filtering of irrelevant stimuli, which may lead to unusual experiences.

It is my contention that these two aspects may be independent of each other and when they come together may lead to psychosis. The deficits in sensory gating give rise to unusual experiences, while the normal confabulating left-brain mechanisms would try to explain the unusual experiences or noise in terms of a coherent narrative. If the first propensity to endow more meaning to even meaningless stimuli gets conjuncted with sensory gating, one may strew together a narrative that is not in touch with reality and thus lead to full blown psychosis, including delusions and hallucinations.

A recent study has just demonstrated that Schizophrenics have a propensity to derive meaning out of what is auditory noise for other normal people. I think there are two issues involved here- first more words were extracted from the auditory noise signal by the schizophrenics, and second they gave meaning to those words by strewing them together as 'phrases'. The length of the phrases heard for prodormant schizophrenics, indicated whether they were likely to suffer from schizophrenia in the future, if not on medication. thus both sensory gating deficits and meaning-endowing deficits seem to be at work.

A tendency to extract messages from meaningless noise could be an early sign of schizophrenia, according to a study by Yale School of Medicine researchers.

The study this month in the British Journal of Psychiatry reported on 43 participants diagnosed with "prodromal symptoms"- meaning they exhibited early warning signs of psychosis such as social withdrawal, mild perceptual alterations, or misinterpretation of social cues.

Participants in the study were randomly assigned to take the anti-psychotic medication olanzapine or a placebo, and then symptoms and neuropsychological function were assessed for up to two years.

During the "babble task," participants listened with headphones to overlapping recordings of six speakers reading neutral texts, which made the words virtually incomprehensible. The participants were asked to repeat any words or phrases that they heard. Only four words-"increase," "children," "A-OK," and "Republican"-were consistently reproduced.

Eighty percent of the participants who "heard" phrases of four or more words in length went on to develop a schizophrenia-related illness during times that they were not taking olanzapine, said the lead author, Ralph Hoffman, M.D., associate professor of psychiatry. In contrast, only six percent of those in the study converted to schizophrenia-related illness if the phrases "heard" were less than three words in length.

"A tendency to extract message-like meaning from meaningless sensory information can, over time, produce a 'matrix of unreality' that triggers the initial psychotic phase of schizophrenia-spectrum disorders," Hoffman said.

To me, this is further support for my hypothesis that Schizophrenic thinking style is marked by extracting too much meaning and it also supports the popular attention-arousal model of schizophrenia that considers the sensory gating deficits leading to hyperarousal and that in turn leading to loose and defocussed attention and this feeding on itself in a downward spiral. you can learn more about the theory by watching this excellent video.

Note related, though relevant to schizophrenia, is a new study that finds that Schizophrenics are more 'theoretically ' rational as compared to normal people.

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Nature via Nurture: IQ via breastfeeding

The Nature vs Nurture debate is now old-fashioned and instead enlightened people like Malcom Gladwell have been reformulating it as Nature via Nurture where, for genes to make their impact, appropriate environmental agents have to be present. Ed Yong of the excellent Not Exactly rocket Science blog, blogs about a recent study that shows that IQ differences (of up to 7 points) in people with two different variants of a gene, FADS2, can be accomplished under the environmental conditions of breastfeeding. Thus, the gene, which is instrumental in metabolism of some fatty acids, leads to increase in IQ points, but only if the babies are breast-fed. The link seems that this gene is necessary to metabolize some of the the fatty acids present in mother's milk.

I especially like the implications for genetics, that Yong derives from this study.

The study also has big implications for gene-hunters. The usual tactic for finding genes linked to physical traits or behaviours is to scan the entire genome for genes that have direct and prominent effects.

But if the team had used this tactic, they would never have billed FADS2 as an IQ-related gene (I’m avoiding using the phrase “a gene for IQ” because it’s trite and misleading). That’s because there are no significant differences between the IQ scores of people with the two FADS2 variants if you take breastfeeding out of the equation. The upshot is that geneticists can look to the environment for important clues when looking for genes that affect human behaviour and health.

For the foreseeable future, it looks like the dichotomy of nature and nurture is dying. It’s proving to be far more interesting to look at how the two interact, and good examples are springing up fast.

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Terror Management, Death and Psychological Immune response

There is a new article in Time that reports on a new study that found that when people are confronted with existential anxiety provoked by thoughts of their imminent death, then instead of becoming sad, they paradoxically become happier, although the effect is subconscious.

Here's one for the annals of counterintuitive findings: When asked to contemplate the occasion of their own demise, people become happier than usual, instead of sadder, according to a new study in the November issue of Psychological Science. Researchers say it's a kind of psychological immune response — faced with thoughts of our own death, our brains automatically cope with the conscious feelings of distress by non consciously seeking out and triggering happy feelings, a mechanism that scientists theorize helps protect us from permanent depression or paralyzing despair.

It might explain the shift toward more positive emotions and thought processes as people age and approach death, and the preternaturally positive outlook that some terminally ill patients seem to muster.

There is a plenty of literature on Terror Management Theory that posits that when confronted with thoughts of our death (and the corresponding terror) we manage that terror by reaffirming our cultural identities and sense of self-esteem. The culture, and self esteem, presumably provides a meaning to our lives and as such are helpful in alleviating the terror of self death. The researcher, DeWall, was experimenting on TMT, when he came across this phenomenon, which has been dubbed as a psychological immune response. In the test, the affect , after mortality salience, was measured by having the students fill words that could either be filled as positive words or as neutral/ negative words. this is a good test of unconscious affect and they found that those exposed to mortality salience condition had unconscious positive affect.

About half of the students were asked to contemplate dying and being dead, and to write short essays describing what they imagined happening to them as they physically died. The other half of the group was asked to think and write about dental pain — decidedly unpleasant, but not quite as threatening. The researchers then set about evaluating the volunteers' emotions: First, the students were given standard psychological questionnaires designed to measure explicit affect and mood. Then they were given assessments of nonconscious mood: in word tests, volunteers were asked to complete fragments such as jo_ or ang_ _ with letters of their choice. Some word stems were intended to prompt either neutral or emotionally positive responses, such as jog or joy; others could be filled in neutrally or negatively — angle versus angry. In a separate word test, students paired a target word such as mouth with its best match: cheek, which is similar in meaning, or smile, which is similar in positive emotional content.

Another important finding the team found was that in depression, the psychological immune system is dysfunctional. thus, depressive people may go in a downward spiral as they contemplate their inevitable death or other social/ personal threats to their self-esteem etc.

In his current research, DeWall is finding that other threats, such as that of social rejection, elicit a similar psychological immune response — except, intriguingly, in depressed people — and he thinks that it's a mechanism that healthy people are probably employing constantly, as a way of fending off a lifetime of serious misfortunes: not just the looming specter of death, but also the fact that you're not going to get that promotion, or that your spouse is cheating on you, or that your kid is on drugs. "It's very difficult to keep people in bad moods, and I think this is one of the reasons why," says DeWall. "Let's say we didn't have this. I think we would have a lot more difficulty coping with failure and threats and our own mortality. It would be difficult for us to find solutions. We would be thinking about how bad we were feeling all the time."

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Consciousness continued: what vegetative patients can tell us about it.

A recent New Yorker article discusses patients in a vegetative or minimally conscious state and what the recent research about their consciousness status can inform us about consciousness in general. The article starts with the much publicized research of Owen's group that found that a woman, in a vegetative state, responded to verbal instructions and could imagine playing tennis. It also discusses what blindsight and neglect can tell us about (un)consciousness.

In the nineteen-eighties, researchers determined that patients who had the syndrome—now called “neglect”—could process some objects in the left field of vision. In one experiment, a patient was shown two pictures of a house. The images were identical except that, in one, flames were emerging from a window on the left side of the façade. The patient said that she couldn’t see any difference between the images, but, when she was asked which house she would want to occupy, she almost always chose the one that was not on fire. “This is more complex than blindsight, because it means that the patient was unconsciously able to interpret and understand the symbolic meaning of the pictures,” Naccache said. “It is a powerful experiment to demonstrate that unconscious perception and unconscious cognition can reach upper levels of the brain.”

The article then goes on to discuss Naccache's theories and here I can see parallels to both Greenfield's (sustained representation) and Koch's views (focus on content, an 'ignition' and networks).

“When we are conscious, the key property is our ability to report to ourselves or to others the content of the representation—as when I say, for example, ‘I am perceiving a flower,’ or the fact that I am conscious of speaking with you now on the telephone,” Naccache told me. “You have patients who are conscious, or who are able to make reports, but you can prove that some stimuli escaped their conscious reports, as in the case of blindsight or neglect. You can study the neural fate of these representations by showing that, even if the stimuli were not reported by the subject, they were still processed in the brain.”

Naccache believes that consciousness also requires an ability to sustain a representation over time, which Owen’s patient clearly was able to do. “In assessing apparently vegetative patients who are unable to speak, and thus report, the direction of research should be to look for sustained representation,” he said. “If we can prove by neuroimaging techniques that this person is able to actively maintain a given representation during tens of seconds, it provides strong evidence of conscious processing.”

Naccache has recently incorporated a third neurological feature into his definition of consciousness: broadcasting. In a person who is conscious, he explained, information entering the brain is processed in a few areas and then distributed—or broadcast—to many others. “It’s as though there is a kind of ignition in the brain, and then information is made available to a very rich number of regions,” Naccache told me. “And that makes sense, that the information is initially represented locally and then made available to a vast network, because the person has this ability to maintain the representation within the network for a long time.

The article also covers Giacino's work that supports more of Greenfields views with consciousness dependent on levels of arousal (which may map to the quantity of neuronal assemblies of Susan).

The woman had what Giacino calls a “drive disorder,” in which a patient is unable to speak, move, or, possibly, think unless physically stimulated—by touch. Doctors believe that such disorders are caused by damage to the limbic lobes or to other parts of the brain that trigger and sustain behavioral responses. Some patients with drive disorders respond to drugs that increase brain levels of dopamine, a neurotransmitter that is associated with arousal. “Imagine if the woman were in a nursing home,” Giacino said. “Somebody would stop by for three minutes, check her bedpan, and present simple commands like ‘Squeeze my hand,’ ‘Close your eyes,’ and ‘Open your mouth.’ She is not going to do any of those things, but she clearly had a significant amount of preserved function. It had to be harnessed externally.” At J.F.K. Johnson, patients with drive disorders receive behavioral and drug therapy. (Some patients improve, but prospects for recovery are largely determined by the extent and nature of the damage to the drive system.)

Giacino applied Deep brain stimulation to one such patient and got spectacular results.

The researchers speculated that, because of damage to the man’s frontal lobe, thalamus, and brain stem—areas involved in regulating arousal—the nerve signals in his brain were muted. As Nicholas Schiff, a neurologist at Weill Cornell Medical College who led the study of the man’s brain, put it, “It’s as if a radio were turned to such a low volume that you couldn’t hear the music distinctly.” He added, “The scans confirmed our expectation that this patient had a greater capacity for language than he demonstrated.”

The researchers described implanting electrodes in the man’s thalamus, which, by stimulating the brain tissue, had enabled him to regain considerable physical and mental function. “Deep brain stimulation can promote significant late functional recovery from severe traumatic brain injury,” they wrote. When the electrodes were turned on in the man’s thalamus, his speech improved, his movements became more fluid, and he was able to chew and swallow. When the researchers turned off the electrical stimulation, the man soon relapsed.

This is close to associating arousal with a minimum quantity to synchronous firing of neuronal assemblies; but what I most like is the ignition analogy of Naccache.

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The great consciousness debate

Over at the Mind blog, Deric has just posted a very fascinating exchange of opinions amongst Christof Koch and Susan Greenfield regarding the neural correlates of consciousness. the exchange seems to be from Scientific American, and in it both Christof and Susan put forward their views on the NCC and then have minor quibbles over particular conscious experiences / phenomenon. While Koch believes that consciousness of a percept arises from activation of a unique set of neurons, that form assemblies and networks and the neurons themselves differ from normal neurons (he implicates a strong role for layer 5 pyramidal neurons in Frontal cortex, having synapses with occipital visual areas, as being crucial for a conscious percept) , Susan insists that consciousness arises because of synchronous firing of neuronal assemblies - and the degree of consciousness depends on the number of neurons involved in that synchronous assembly (that lats up to millisecond intervals) . Thus while Koch focuses more on content of consciousness (and despite Susan's criticism that is an important area of investigation) and how it arises from a qualitative phenomenon (different types of neurons - pyramidal- involved), Susan focuses more on degrees of consciousness and takes consciousness to be a qualitative phenomenon. I, like Deric , find merit in both arguments.

Some excerpts:

Koch's view:

Physiologically, the likely substrate for NCC is a coalition of pyramidal neurons--a type of neuron that communicates over long ranges--within the cerebral cortex. Perhaps only a million such neurons--out of the 50 billion to 100 billion in our heads--are needed to form one of these coalitions. When, say, Susan enters a crowded room and I see her face, a coalition of neurons suddenly chatters in concert for a fraction of a second or longer. The coalition reaches from the back of the cortex, where representations of visual stimuli are first processed, into the front of the cortex, which carries out executive functions such as providing perspective and enabling planning. Such a coalition would be reinforced if I paid attention to the stimulus of her image on my retina, which would strengthen the amplitude or the synchrony of the activity among the select neurons. The coalition sustains itself and suppresses competing coalitions by feeding excitatory signals back and forth among the neurons in the back and front of the cortex. If, suddenly, someone calls my name, a different coalition of neurons in the auditory cortex arises. This coalition establishes two-way communication with the front of the brain and focuses my consciousness on the voice, suppressing the earlier coalition representing Susan's face, which fades from my awareness.

This notion about networks of neurons has received a boost from recent results by researchers at the Mount Sinai School of Medicine, Columbia University and the New York State Psychiatric Institute, working under Stuart C. Sealfon of Mount Sinai and Jay A. Gingrich of Columbia. Sealfon's and Gingrich's teams have demonstrated in genetically modified mice that hallucinogens--such as LSD, psilocybin (an ingredient of mushrooms) and mescaline--act on a type of molecule, called a serotonin receptor, found on the pyramidal cells that cluster in layer 5. The hypothesis that the mind-bending effects of hallucinogenic compounds come from activation of one receptor type on a specific set of neurons--rather than from "messing up" the brain's circuits in some holistic manner--can be further tested with molecular tools that can toggle layer 5 pyramidal cells on and off until the exact set of neurons being affected is identified.

Susan's views:

My own starting assumption is that there is no intrinsic, magical quality in any particular brain region or set of neurons that accounts for consciousness. We need to identify a special process within the brain. And to be a truly robust correlate of consciousness, this neuronal process must account for a variety of everyday phenomena, including the efficacy of an alarm clock, the action of anesthetics, the distinction of dreams from wakefulness, the existence of self-consciousness, the possible difference between human and animal consciousness, and the possible existence of fetal consciousness. A more plausible view of consciousness is that it is not generated by a qualitatively distinct property of the brain but by a quantitative increase in the holistic functioning of the brain. Consciousness grows as brains grow.

The central problem is that models developed by Llinas and others conceive of consciousness as an all-or-nothing condition. They fail to describe how the physical brain can accommodate the ebb and flow of a continuously variable conscious state. I favor an alternative. For more than a decade, scientists have known that the activity of tens of millions of neurons can synchronize for a few hundred milliseconds, then disband in less than a second. These "assemblies" of coordinating cells can vary continuously in just the right space and timescales for the here-and-now experience of consciousness. Wide-ranging networks of neurons assemble, disassemble and reassemble in coalitions that are unique to each moment. My model is that consciousness varies in degree from one moment to the next and that the number of neurons active within an assembly correlates with the degree of consciousness present at any given time.

This neuronal correlate of consciousness--the transient assembly--satisfies all the items on the shopping list of phenomena above. The efficacy of an alarm clock is explained as a very vigorous sensory input that triggers a large, synchronous assembly. Dreams and wakefulness differ because dreams result from a small assembly driven by weak internal stimuli, whereas wakefulness results from a larger assembly driven by stronger external stimuli. Anesthetics restrict the size of assemblies, thus inducing unconsciousness. Self-consciousness can arise only in a brain large and interconnected enough to devise extensive neuronal networks. The degree of consciousness in an animal or a human fetus depends on the sizes of their assemblies, too.

Take a look at the original debate as there is an even more more stimulating point-counterpoint section too.

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'Right brain thinking' and 'diffuse thinking' linked as the 'creative thinking' style

In a recent article, Kounios, J., et al., The origins of insight in resting-state brain activity, Neuropsychologia (2007), it has been shown that creative thinking style , associated with an 'AHA' moment of problem-solving using insight, deploys more Right brain areas and also is characterized by a more diffused visual attention; as compared to an analytic style , which used search as a strategy and was characterized by more focussed visual attention.

As I had been linking to some articles on brain asymmetry , I found this article worth linking to. The paper basically uses self-report measures to ascertain whether an anagram ( scrambled words like XPELAME for EXAMPLE) was solved by creative insight or by analytic search. It then divided the subjects into two groups- those utilizing insight as a strategy most of the time and those utilizing search as a strategy most of the time. then they looked at the EEG activations, both prior to the assignment (when the subjects were not even aware of the purpose of the study) and while the people solved the anagrams. The first EEG measure that refers to the resting style of a person, showed clear differences between the two groups. It was found that the creatives or insight people had more diffused visual attention, while the analytic searchers had more center-increase/surround-decrease type of cortical activity whihc would be correlated with more focused attention, in both visual areas as well as semantical areas. The creatives on the other hand, had resting EEG that implicated more loose semantic associations at the periphery.

The second interesting result was regarding the overall activation of right hemisphere versus left hemispheres in the creative vs analytic groups. Here again, High Insight group showed more right Hemisphere activations across many regions of interest and on many bands (alpha, gamma etc) of EEG frequencies.

I had approached the paper with a critical bent of mind as soon as I read that they had used self-reports, but it seems that they could find some indirect evidence as to whether the self-report measure styles did correspond to the actual styles employed. They reason, and show, that if a problem is being solved by insight, then the solution would be available in a a one-or-nothing sort of consciousness of the solution; hence the creatives would do more errors of omission, where they would timeout when given a deadline to solve the problem; on the other hand the analytics would be solving the problem in a piece-meal fashion, with the solution being formed bit-by0-bit in their consciousness and are thus more likely to do acts of commissions, where when confronted with a deadline, they give a wrong response. this is exactly what they found, moreover there was no differences in response times, error rate or any other measures that could have explained things otherwise, and I find their argument convincing.

The present study demonstrates that goal-oriented, event related,cognitive processing is not completely determined by goals or task demands. Individual differences in resting state brain activity also influence such neural computations. Specifically, subjects’ preferred strategy for solving a series of anagrams (insight versus search), was influenced by characteristics of their prior resting state. This phenomenon is fundamentally different from the previous demonstration of a relationship between problem-solving strategy and transient preparatory activity immediately preceding the presentation of an anticipated problem .

The results were organized around two hypotheses. The first was based on previous research demonstrating that highly creative individuals exhibit diffuse attention allowing input of a greater range of environmental stimuli, in contrast to less creative individuals who tend to focus their attention more narrowly, thereby sampling a smaller range of environmental stimuli . It was therefore predicted that HI subjects would have less resting-state occipital alpha-band activity, reflecting less inhibition of the visual system, and that LI subjects have more occipital beta activity, consistent with heightened focused attention. These predictions were supported by the results.

The second hypothesis was that HI and LI subjects would exhibit different patterns of resting-state hemispheric asymmetry at electrodes over lateral association cortex. This hypothesis was based on prior findings that creative cognition recruits RH association areas involved in semantic information processing relatively more than does noncreative cognition . The results provided broad support for the hypothesis that during a resting state HI subjects would show generally greater RH activity and less LH activity relative to LI subjects, with the most prominent effects being greater activity for HI subjects at right dorsal–frontal (lowalpha band), right inferior–frontal (beta and gamma bands) and right parietal (gamma band) electrodes, and greater activity at left inferior–frontal and left anterior–temporal electrodes for LI subjects in the low-alpha band.

Importantly, the behavioral results demonstrated that the HI and LI groups used different cognitive strategies to solve the anagrams. Consistent with the notion that insight processing yields information about the correct response in a discrete, all-or-none, fashion, while noninsight processing yields partial response information before the processing of a problem has been completed , the present results showed that subjects who tended to solve problems with self-reported insight tended to make errors of omission, while subjects who tended to solve the problems with self-reported noninsight processing tended to make errors of commission.

As such, I am excited by this research which adds not only to our understanding of the 'insight' problem solving, but also adds to the knowledge base on brain asymmetry.

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The right brain/ left brain asymmetry debate

Over at the Health Information blog, they have just posted 5 articles (mostly form other sources on the net) regarding the left brain/ right brain asymmetry debate.

I, in particular, liked the article by Gazzaniga, in which he discusses amongst other things the confabulaory nature of left hemisphere 'interpreter' or 'narrator'. Another article I liked was by John McCrone and focussed more on the global versus Local style of processing style differences amongst the two hemispheres. Head over and have a read. I myself have strong opinions about the asymmetry and specialization and would like to see gender differences too taken in account, as I believe Men and Women do use different processing styles and this may have to do with using the hemispheres differently.

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