Category Archives: neuroscience

Seeing is believing : why delusions may arise from anomalous experiences

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I recently came across this article by Rosengren and Hickling about how children explain seemingly impossible or extraordinary transformations in terms of magic or trickery or natural/physical explanations based on their ages and developmental level.

To summarize the study , I’m presenting the abstract:

Children’s magical explanations and beliefs were investigated in 2 studies. In Study 1, we first asked 4- and 5-year-old children to judge the possibility of certain object transformations and to suggest mechanisms that might accomplish them. We then presented several commonplace transformations (e.g., cutting a string) and impossible events (magic tricks). Prior to viewing these transformations, children suggested predominantly physical mechanisms for the events and judged the magical ones to be impossible. After seeing the impossible events, many 4-year-olds explained them as “magic,” whereas 5- year-olds explained them as “tricks.” In Study 2, we replaced the magic tricks with “extraordinary” events brought about by physical or chemical reactions (e.g., heat causing paint on a toy car to change color). Prior to viewing the “extraordinary” transformations, children judged them to be impossible. After viewing these events, 4-yearolds gave more magical and fewer physical explanations than did 5-year-olds. Follow-up interviews revealed that most 4-year-olds viewed magic as possible under the control of an agent (magician) with special powers, whereas most 5-year-olds viewed magic as tricks that anyone can learn. In a third study, we surveyed parents to assess their perceptions and conceptions of children’s beliefs in magic and fantasy flgures. Parents perceived their children as believing in a number of magic and fantasy flgures and reported encouraging such beliefs to some degree. Taken together, these findings suggest that many 4-year-olds view magic as a plausible mechanism, yet reserve magical explanations for certain real world events which violate their causal
expectations.

In effect, the children were shown some impossible transformations like making color appear on the pages of a blank coloring book; at the same time they were also shown some commonplace transformations like a piece of Play-Doh changing shape. They were asked to provide causal reasons for these transformations both a priori and after the transformations were demonstrated. Important form my point of view was the finding that all children showed this effect that for impossible transformations though before the vent they provided physical/natural explanations, after seeing the event, they changed their stance and labeled them as ‘magic’ or ‘trick’ as per their development level. To quote:

Children of both ages gave more physical/natural explanations prior to seeing the transformations than after seeing the
events, F(l, 46) = 36, p < .001, but gave more trick and magic responses after seeing the transformations than before seeing them, Fs(l, 46) > 50, p < .001.
Very few magic explanations were provided for the commonplace events before or after the viewing of the events; however, both groups of children provided significantly more magic explanations following the magic events than prior to these events. There was no difference between the two age groups in the number of magic explanations given prior to seeing the magic events; however, after viewing the magic events the 4-ye£ir-oIds gave significantly more magic responses (M = 2.96) than the 5-year-oIds did (M = 1.09). Similar to the results for the magic explanations, few trick responses were provided for the commonplace events before or after the viewing of the commonplace events.

To me this is a significant result, that after seeing something impossible we classify it as either magic or trickery, but prior to that we believe we could have provided a natural and causal explanation. To take an example, we all know statistics and would agree that there is a statistical probability that we are thinking of someone and the person phones at the same time. However, when we do think of someone and he calls at the same time and this happens say once or twice in a row, we will not tend to resort to statistical reasoning; we’ll either think in magical terms (magical thinking– my intention to remember/talk to them caused them to phone me; or psychic ability– that there is a deep connection between us) or we will try to think this a as a trickery played on us (perhaps they or someone is secretly watching me and my intentions and as soon as I reach to make a phone call, they call me instead juts to make fun/play a silly trick). Both types of thinking are fertile ground for psychosis and delusions.

It is now known that many people prone to psychosis suffer from an unusual amounts of anomalous experiences and also have magical ideation. To those of us who do not have those unusual experiences, it is very easy to dismiss what the effects having such anomalous experiences would have on our causal thinking abilities. We in our blue-pill Matrix where things are ordered and in their place following known causal relations, believe everything is fine with the world. to someone who has taken the red pill and is having anomalous experiences, it is difficult to believe that there isn’t a world apart from the matrix where magical rules may apply! (OK, the matrix analogy is not good, but it does make a point that it is difficult to comprehend the reality that someone delusional may be living in).

To return to my example of thinking of calling someone and picking the phone and at the same time receibving a callfor that perosn, such coincidences may be marked as causal by psychosis prone minds beacue again they have been hypothesized to have high and sensitive coincidence detectors and a ‘jump to conclusions’ bias. Given these facts they may be more prone to attribute magical causality instead of normal causality and get freaked out. Magical thinking and delusions may follow naturally from these. Anomalous experience may not just be important to explain hallucinations, but may be important for explaining delusions too.

Rosengren, K., & Hickling, A. (1994). Seeing Is Believing: Children’s Explanations of Commonplace, Magical, and Extraordinary Transformations Child Development, 65 (6) DOI: 10.1111/j.1467-8624.1994.tb00838.x

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My 2 Brains: my new blog

I have just started a new blog called My 2 Brains and you can read more about that blog and what topics and themes it will cover over here.

One of the first posts is about the real-time stream and analyzes it from a psychological perspective focusing on the virtual self one can associate with one’s stream. I am planning to write the other posts too in a similar format, though the topics covered would range from sociology, culture and politics to current affairs.

Please do visit the My 2 Brains blog and give me some feedback as to how you like the concept and what topics/ themes you would like me to cover there.

The epigenetics of Autism: Oxytocin factor and implications for schizophrenia

*Description: Different types of :en:mutation ...
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Autism is a hard disorder to nail down genetically- single nucleotide polymorphisms (SNPs) or even multiple locus genetic effects are not able to account for the large genetic component to the disorder. In recent times, Copy number variations (CNVs) has come to the forefront of Autism research , suggesting that microdeletions, duplications etc may account for some cases. Another new , till now unsuspected mechanism that has recently been implicated in autism is epigenetic mechanism of increased methylation in promoter regions that has the effect of silencing/reducing the expression of genes involved to a certain extent. The recent study by Gregory et al, is just such a step in the right direction, which will hopefully bring us closer to the truth.

The study is available in full at BMC Medicine site and is accompanied by a must read commentary that explains a lot of things and puts the finding in context.

In a nutshell, the study authors used CNV determining methods to discover that a deletion of OXTR (oxytocin receptor) gene was presnet in an autistic subject and was not de novo , but the deletion was inherited from his mother. One of the affected siblings of the autistic subject, who too was autistic, on the other hand did not have a deletion, but had increased methylation of the OXTR. this led the study authors to revisit their genomics data and look at adta across all autistic subjects and controls and discover that indeed, in other autistics too the OXTR had increased methylation. Then they looked for expression of OXTR in peripheral blood cells and temporal cortex and found that indedd in autistics, as compared to controls, there was reduced expression of OXTR. This strongly suggest that the epigentic changes that lead to autism (the efffect of OXTR suppression) happen quite early in the devlopmenet and might happen in utero.

Before I elaborate on my take home from the study, there are some excerpts (as I know you didn’t read the originals)

Classic autism comprises a spectrum of behavioral and cognitive disturbances of childhood development. The core autism phenotype includes deficits in social interaction, language development and patterns of repetitive behaviors and/or restricted interests. The population prevalence of the spectrum of autism disorders is estimated to range between 1/300 [1] to 1/100 (http://www.nschdata.org/), with a male: female ratio of 4:1 [2,3]. The disorder has been shown to be highly heritable with the relative risk for siblings being approximately 2% to 8%, much higher than that of the general population [4]. To date, only a small percentage of autism cases (<10%) have been ascribed to single gene disorders such as fragile X syndrome, tuberous sclerosis [5] and Rett syndrome [6]. Numerous approaches including genetic linkage, genome-wide association, candidate gene association and gene expression analysis have been used to identify the additional genes
implicated in the development of autism [7,8]. However, the heterogeneous nature of autism and autism spectrum disorders has limited their success.

An additional approach to identify genes involved in autism is to characterize copy number variants (CNVs), that is, chromosomal deletions and duplications, that are known to be present within at least 5% of individuals with idiopathic autism [9]. Autism CNVs have been shown to involve almost all chromosomes [10,11], with the most frequently observed alteration localizing to chromosome 15q11-13 [12-23]. A number of different methods have been used to characterize autism related CNVs, including but not limited to, cytogenetic Gbanding [14,23,24], metaphase fluorescence in situ hybridization (FISH) [22], Southern blotting [18], loss of heterozygosity (LOH) analysis [15-17,19], quantitative polymerase chain reaction (PCR) [25] and, more recently, genotyping and representational oligonucleotide microarray analysis (ROMA) [26].
Here we describe the use of genome-wide tilepath microarrays and array comparative genomic hybridization (CGH) to identify CNVs in a dataset of 119 unrelated probands from multiplex autism families [27]. The genomic profiles of our autism dataset were compared to the array CGH profiles of 54 phenotypically normal individuals, to previously published CNVs present within the database of genomic variants [28] and to the Autism Chromosome Rearrangement Database (http://projects.tcag.ca/autism/). The most significant finding thus far from our analysis is a heterozygous deletion of the oxytocin receptor gene (OXTR) (MIM accession no.: 167055) in an individual with autism and his mother with putative obsessive-compulsive disorder (OCD). We further investigated the relationship between OXTR and autism by carrying out epigenetic analysis of the promoter region of OXTR. We show that the gene is hypermethylated in independent cohorts with autism as compared to controls, in both peripheral blood mononuclear cells (PBMCs) and the temporal cortex. Additionally, our analysis of expression levels of OXTR in the temporal cortex shows decreased levels of expression in individuals with autism as compared to controls matched for age and sex.

These data suggest that OXTR and the oxytocin signaling pathway play an important role in the etiology of autism and autism spectrum disorders and implicate epigenetic misregulation of OXTR in this complex disease.

Epigenetic control of autism susceptibility is a recent concept and most certainly a topic of great interest in the field. Over the past decade, researchers have uncovered suggestive links between epigenetics and autism, for example, autism is associated with duplications of 15q11-13 (especially maternally inherited), an imprinted region in the genome where DNA methylation status has been linked to Prader-Willi syndrome (PWS) and Angelman syndrome (AS) [66]; mutation within a gene that encodes a methyl-DNA-binding protein (MECP2, (MIM accession no.: 300005)) is the causative agent of Rett syndrome [67]; and mutation of this same gene has been associated with both autism and AS populations [55]. Nagarajan et al. have shown that 79% of autism cases have a decrease in MECP2 expression in the frontal cortex and that an increase in aberrant DNA methylation correlates with this decrease in MECP2 expression [68]. These data implicate epigenetic dysregulation as a mechanism for the development of autism and justify the examination of DNA methylation of autism candidate genes, such as OXTR identified in this study.

Now from the accompanying (more accessible) commentary:

The article by Gregory et al. published this month in BMC Medicine, reports on genomic and epigenetic alterations of OXTR, the gene encoding the receptor for oxytocin. The involvement of this gene was suggested by its deletion in an autistic patient. The subsequent analysis of a group of unrelated autistic subjects did not show an OXTR deletion, but rather hypermethylation of the gene promoter, with a reduced mRNA expression.

These findings address two major points of the current debate on the etiology and pathogenesis of autism: the role of oxytocin, known to be involved in modeling human behavior, and the possible involvement of epigenetic mechanisms. The nature of this epigenetic dysregulation is unknown but, if proved to be true, might explain the failure to identify sequence alterations in a host of candidate genes. Practical implications of these findings may be forthcoming, however not before extension and validation on a larger scale have confirmed their value.
..
The second issue raised by Gregory et al. deals with the epigenetic inhibition of OXTR expression in ASD. Such epigenetic modification, at least as reported so far, does not seem to be sequence based but rather of a different, as yet unknown nature. This might explain why researchers have been looking for decades for genetic mutations in ASD and yet have found almost none. An epigenetic mechanism would justify the ‘unusual’, non-Mendelian familial aggregations of ASD. In this respect, even the family with OXTR deficiency reported by Gregory et al. shows an unusual genotype-phenotype correlation, in that the same phenotype is caused by alterations of the same gene but due to different molecular defects (deletion versus hypermethylation).

Also, the possibility that in most ASD patients there might be an epigenomic instability is of interest in consideration of the fact that it has been shown that the epigenetic status in early fetal development can be reprogrammed by maternal behavior in a reversible way [34]. Therefore, other environmental factors, yet to be discovered, might also be able to reprogram the epigenotype of the embryo.

I hope the fact that epigenetic changes may happen during pregnancy line of reasoning does not lead to the harmful and without-any-basis vaccination is cause of autism arguments. On the other hand I had covered earlier how Autism is more likely if mother was exposed to valproate during pregnancy or the child soon after birth. What if valproate is instrumental in an epigenetic fashion in leading to more or less methylation and gene expression. It is well known that valproate and valporic acid is given as treatment for psychosis/bipolar. In a similar vein, I am inclined to stick my neck out and claim that in schizophrenics/psychotics , the OXTR should be more expressed : perhaps more methylation, duplications etc . However I am checked in my musings by these studies that claim that negative symptoms of schizophrneia may be associated with reduced oxytocin activity in the brain. Yet, all said and done I would like to see a study that analyzes for epigenetic mechanisms in schizophrneia especially at the OXTR locus. Although the negative symptoms like social withdrawal of schizophrenia may lead to the opposite hypothesis regarding schizophrenia and oxytocin correlation, I am inclined to believe that schizophrenics (at least those suffering from positive symptoms predominantly) are too much oxytocin guided , trusting and socially too much involved in others type of people.

Gregory, S., Connelly, J., Towers, A., Johnson, J., Biscocho, D., Markunas, C., Lintas, C., Abramson, R., Wright, H., Ellis, P., Langford, C., Worley, G., Delong, G., Murphy, S., Cuccaro, M., Persico, A., & Pericak-Vance, M. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism BMC Medicine, 7 (1) DOI: 10.1186/1741-7015-7-62
Gurrieri, F., & Neri, G. (2009). Defective oxytocin function: a clue to understanding the cause of autism? BMC Medicine, 7 (1) DOI: 10.1186/1741-7015-7-63
Hat tip to @Boraz for tweeting about this study.

This post was chosen as an Editor's Selection for ResearchBlogging.org

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Splitting the self : “me” and “I”:

The influential psychologist William James was...
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I came across this study article today by Farb et al, that talks about two distinct neural networks in the brain that are involved in self-reference. To be fair, the networks are somewhat blurred and overlap in naive people, while in people who practice mindfulness meditation, the networks are more distinct and non-overlapping. My interest was piqued as I am a keen follower of default-brain network , which has been implicated in self-referential thinking and this article seems to at one point argue that the narrative self viz ‘me’ is grounded in default brain network, while the experiencer ‘I” has some other nearby related areas as the neural substrates.

But first let us clarify what we mean by ‘me’ and ‘I’. For this I would like to quote form a Gallagher article:

Ever since William James (1890) provided a catalogue of different senses of the self, philosophers and psychologists have been hard at work refining and expanding the possible variations of this concept. Supplementing James’ inventory of physical self, mental self, spiritual self, and the ego, Neisser (1988), for example, suggested important distinctions between ecological, interpersonal, extended, private, and conceptual aspects of self. More recently, reviewing a contentious collection of essays from various disciplines, Strawson (1999) found an overabundance of delineations between cognitive, embodied, fictional, and narrative selves, among others. It would be impossible to review all of these diverse notions of self in this short paper, so I have focused on several recently developed approaches that promise the best exchange between philosophy of mind and the other cognitive sciences. Because these approaches move in divergent theoretical directions they should help to convey the breadth of philosophical analysis on this topic. They can be divided into two groups that are focused, respectively, on two important aspects of self.

A first approach involves various attempts to account for a ‘minimal’ sense of self. If we strip away all of the unessential features of self, the intuition is that there is a basic, immediate, or primitive something that we are still willing to call a self. This approach leaves aside questions about the degree to which the self is extended beyond the short-term or ‘specious’ present to include past thoughts and actions. Although identity over time is a major issue in the philosophical definition of personal identity, the concept of the minimal self is limited to that which is accessible to immediate and present self-consciousness. Non-philosophers have found that certain aspects of the minimal self are relevant to current research in robotics. Furthermore, aspects of the minimal self that involve senses of ownership and agency in the context of both motor action and cognition can be clarified by neurocognitive models (developed to explain pathologies such as schizophrenia) that suggest the involvement of specific brain systems (including prefrontal cortex, SMA, and cerebellum).

A second approach involves conceiving of the self in terms of narrative, a concept imported into the cognitive-science context by Dennett (1991) , but one which may have a more complex significance than indicated in Dennett’s account. The narrative self is extended in time to include memories of the past and intentions toward the future. It is what Neisser refers to as the extended self, and what Dennett calls a ‘nonminimal selfy’ self. Neuropsychological accounts of episodic memory or loss of memory can help to circumscribe the neurological underpinnings of the narrative self.

If you haven’t guessed by now, the minimal self is ‘I’: the doer , experiencer experiencing the immediate present; the narrative self is ‘me’ -an entity stretched in time and living as much in past and future as in the present. The study authors delineate the same as follows (note that they too start with William James reference):(* references removed)

Since William James’ early conceptualization, the ‘self ’ has been characterised as a source of permanence beneath the constantly shifting set of experiences that constitute conscious life. This permanence is often related to the construction of narratives that weave together the threads of temporally disparate experiences into a cohesive fabric. To account for this continuity, William James posited an explanatory ‘me’ to make sense of the ‘I’ acting in the present moment . Recently, progress has been made in characterizing the neural bases of the processes supporting William James’ ‘me’ in the form of ‘narrative’ self-reference , highlighting the role of the medial prefrontal cortices (mPFC) in supporting self awareness by linking subjective experiences across time . The mPFC has been shown to support an array of self-related capacities, including memory for self-traits , traits of similar others , reflected self-knowledge , and aspirations for the future . As such, cortical midline processes may be characterised as supporting narrative self-reference that maintains continuity of identity across time .

Narrative self-reference stands in stark contrast to the immediate, agentic ‘I’ supporting the notion of momentary experience as an expression of selfhood. Most examinations of self-reference ignore mechanisms of momentary consciousness, which may represent core aspects of self-experience achieved earlier in development and may have evolved in earlier animal species. Indeed, little is known about whether the neural substrates underlying momentary self-reference are one and the same, or distinct from, cortical midline structures supporting narrative experience. One hypothesis suggests that awareness of momentary self-reference is neurally distinct from narrative self-reference and is derived from neural markers of transient body states, in particular, right lateralised exteroceptive somatic and interoceptive insular cortices. In the present study, we examined this thesis.

In short using fMRI, they tried to find the different hypothesized neural networks underlying the two senses of self and did find evidence for clear segregation in those practicing mindfulness meditation. Their methodology however, is not fool proof and this they themselves note in their conclusions. Here are their findings:

Consistent with a theory of self-reference as mentalising, linguistically mediated and of higher order executive origin , participants engaged midline prefrontal cortices and a left lateralised linguistic-semantic network (inferior lateral PFC, middle temporal and angular gyri) during NF (narrative focus: ‘me’ condition). Demonstrating a default bias towards NF as previously revealed in ‘resting’ mind wandering states , relatively restricted reductions in the cortical midline network were found when attention was explicitly directed towards a moment-to-moment EF (experiential focus: ‘I’ condition) in novice participants with little training in this form of self-reflection. These individuals revealed increased left lateralised prefrontal-parietal activations during EF likely reflecting greater task-related linguistic processing that has been shown to be associated with decreased medial prefrontal recruitment .

nsm030f3

So what they found was that a part of default network was engaged in ‘me’ condition; while task-related areas were recruited in “I” condition and appropriate task-related suppression of some part of default network observed. This effect was with naive subjects, but with those trained in mindfulness meditation, they observed a sort of double dissociation:

Following an intensive 8 week course in mindfulness meditation, during which individuals learn to develop the capacity to monitor moment-to-moment experience, EF resulted in a pronounced shift away from midline cortices towards a right lateralised network comprised of the ventral and dorsolateral PFC, as well as right insula, SII and inferior parietal lobule. Consistent with a dual-mode hypothesis of self-awareness, these results suggest a fundamental neural dissociation in modes of self-representation that support distinct, but habitually integrated, aspects of self-reference: (i) higher order self-reference characterised by neural processes supporting awareness of a self that extends across time and (ii) more basic momentary self-reference characterised by neural changes supporting awareness of the psychological present. The latter, represented by evolutionary older neural regions, may represent a return to the neural origins of identity, in which self-awareness in each moment arises from the integration of basic interoceptive and exteroceptive bodily sensory processes. In contrast, the narrative mode of self-reference may represent an overlearned mode of information processing that has become automatic through practice, consistent with established findings on training-induced automaticity.

To me this sounds interesting: If I had to stretch my neck and relate this to autism and schizophrenia , I would say that based on earlier coverage on this blog: Schizophrenics have a higher default brain activity and perhaps try to spin too much of a narrative. Perhaps they are the ones that would best benefit with mindfulness meditation trainings to calm their default ‘me’ and activate the ‘I’ also at relevant times. On the opposite side, one is all too aware of the here-and-now feeling of self that many autistics have- a direct and immediate perceptual relation with world. Perhaps, they too can benefit from some for of mindfulness meditation by learning to use the default brain network too at times – letting teh mind wander and spinning a tale (however fictional) about themselves.

Farb, N., Segal, Z., Mayberg, H., Bean, J., McKeon, D., Fatima, Z., & Anderson, A. (2007). Attending to the present: mindfulness meditation reveals distinct neural modes of self-reference Social Cognitive and Affective Neuroscience, 2 (4), 313-322 DOI: 10.1093/scan/nsm030
Gallagher, S. (2000). Philosophical conceptions of the self: implications for cognitive science Trends in Cognitive Sciences, 4 (1), 14-21 DOI: 10.1016/S1364-6613(99)01417-5

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A brief history of Neuroscience

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The Society for Neuroscience(SfN) was formed 40 years ago and to commemorate the occasion, the journal of Neuroscience has made some review articles open-access. They are written by leading luminaries in their filed and are somewhat scholarly- though I found some of them pretty accessible too.

Two articles relate to reviewing memory research in the past 40 years and both are a pretty good read. The first is written by Larry Squire and gives you a broad overview of memory research. The second by Eric Kandel focuses more on the molecular aspects of memory formation- but is an excellent article and ends with 11 still unresolved questions for the next 40 years in the memory research.

There is another article by Marcus Raichle that I found pretty interesting, partly because of my continuing fascination with the default brain network and the intrinsic activity of the brain. this again is a very accessible article that brings one up to speed on the 40 yrs of imaging with special focus on the default brain network.

There are other retrospectives there including one on neurotransmitters so go to the source and enjoy the ride.

Hat Tip: Mind Hacks
Squire, L. (2009). Memory and Brain Systems: 1969-2009 Journal of Neuroscience, 29 (41), 12711-12716 DOI: 10.1523/JNEUROSCI.3575-09.2009
Kandel, E. (2009). The Biology of Memory: A Forty-Year Perspective Journal of Neuroscience, 29 (41), 12748-12756 DOI: 10.1523/JNEUROSCI.3958-09.2009
Raichle, M. (2009). A Paradigm Shift in Functional Brain Imaging Journal of Neuroscience, 29 (41), 12729-12734 DOI: 10.1523/JNEUROSCI.4366-09.2009

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Autism, Schizophrenia and CNV in 16p11.2

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There is a letter published in the advance online edition of Nature Genetics, that reports that microduplication of genes in the region 16p11.2 are associated with the risk of schizophrenia in a large cohort. It has been earlier shown that microdeletions in the same region confer the risk of Autism.Thus, it seems that the region codes for genes too much of which causes schizophrenia and too little autism.  Here is the abstract of the study:

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 times 10-5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 times 10-7), bipolar disorder (P = 0.017) and autism (P = 1.9 times 10-7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 times 10-13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).

Here is what medical news today (via which I found this article) has to say about the findings:

An international team of researchers led by geneticist Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL), has identified a mutation on human chromosome 16 that substantially increases risk for schizophrenia.

The mutation in question is what scientists call a copy number variant (CNV). CNVs are areas of the genome where the number of copies of genes differs between individuals. The CNV is located in a region referred to by scientists as 16p11.2. By studying the genomes of 4,551 patients and 6,391 healthy individuals, Sebat’s team has shown that having one extra copy of this region is associated with schizophrenia. The study appears online today ahead of print in the journal Nature Genetics.
Schizophrenia and autism: two sides of the same coin?

“This is not the first time that the 16p11.2 region has caught our eye,” says Sebat. It was previously spotted in a 2007 study with Professor Michael Wigler at CSHL — a deletion of the identical region was identified in a girl with autism. Studies by several other groups have shown that losing one copy of 16p11.2 confers high risk of autism and other developmental disorders in children.

Taken together these studies suggest that some genes are shared between schizophrenia and autism, according to Sebat and colleagues. “In some ways, we might consider the two disorders to be at opposite ends of the same neurobiological process” says Shane McCarthy, Ph.D., the lead author of the study, “and this process is influenced by the copy number of genes on chromosome 16.” One hypothesis is that the loss of 16p11.2 leads to the deprivation of key genes involved in brain development, while an extra copy of this region might have the opposite effect.

A correlation between 16p11.2 mutations and head size

It is not known what biological processes are affected by the copy number of 16p11.2, Sebat notes. He believes, however, that the team may have stumbled on to an important clue. By studying the clinical records of patients, they discovered that patients with deletions of the region differ significantly in head size from those with duplications of the same region. Sebat reports, “Head circumference of patients with the deletion were larger than average by more than one standard deviation. Head circumference was slightly below average in patients with the duplication.” These findings, he notes, are consistent with some previous studies that have observed a trend towards larger brain size in autism and an opposite trend toward smaller brain size in schizophrenia.

All this nicely fits in with what I have been proclaiming from the rooftops from the early days of this blog: that autism and Schizophrenia are opposites on the same continuum and the genes involved should also be the same. More copy numbers leading to propensity towards psychosis while lesser number or deletions associated with autistic traits. One more puzzle piece fits in and now we know why the brain size differences exist in autistic and schizophrenic persons and what the poetntial function (mentalizing) of region 16p11.2 may be.

McCarthy, S., Makarov, V., Kirov, G., Addington, A., McClellan, J., Yoon, S., Perkins, D., Dickel, D., Kusenda, M., Krastoshevsky, O., Krause, V., Kumar, R., Grozeva, D., Malhotra, D., Walsh, T., Zackai, E., Kaplan, P., Ganesh, J., Krantz, I., Spinner, N., Roccanova, P., Bhandari, A., Pavon, K., Lakshmi, B., Leotta, A., Kendall, J., Lee, Y., Vacic, V., Gary, S., Iakoucheva, L., Crow, T., Christian, S., Lieberman, J., Stroup, T., Lehtimäki, T., Puura, K., Haldeman-Englert, C., Pearl, J., Goodell, M., Willour, V., DeRosse, P., Steele, J., Kassem, L., Wolff, J., Chitkara, N., McMahon, F., Malhotra, A., Potash, J., Schulze, T., Nöthen, M., Cichon, S., Rietschel, M., Leibenluft, E., Kustanovich, V., Lajonchere, C., Sutcliffe, J., Skuse, D., Gill, M., Gallagher, L., Mendell, N., Craddock, N., Owen, M., O’Donovan, M., Shaikh, T., Susser, E., DeLisi, L., Sullivan, P., Deutsch, C., Rapoport, J., Levy, D., King, M., & Sebat, J. (2009). Microduplications of 16p11.2 are associated with schizophrenia Nature Genetics DOI: 10.1038/ng.474

UPDATE: I just revisited my 20th may 2008 post on the matter and realized how prophetic my musings were. Reproducing part of it below the fold for the benefit of newbies to this blog:

CNVs on the other hand present a different model of disease. One can have one or more types of CNVs (deletions, duplications, multiple duplications etc) associated with the same genetic code sequence and this in my view would lead to spectrum like diseases where one may find variations along a continuum on a particular trait- based on how many copies of the genetic sequence one has. One would remember that I adhere to a spectrum based view of schizophrenia/psychosis and also a spectrum based view of Autism. Moreover I believe that Schizophrenia and Autism are the opposite ends of the spectrum, whose middle is normalcy and that the appropriate traits may have to do with social brain, creativity etc.

now as it happen previous research has also found that CNVs are also found to a higher extent in autistics. Moreover, research has indicated that the same chromosomal regions have CNVs in both Autism and Schizophrenia. To me this is exciting news. Probably the chromosomal region (neurexin related is one such region) commonly involved in both schizophrenia and autism is related to cognitive style, creativity and social thinking. Qualitatively (deletions as opposed to duplications) and quantitatively (more duplications) different type of CNVs may lead to differential eruption of either Schizophrenia or Autism as the same underlying neural circuit gets affected due to CNVs, though in a different qualitative and quantitative way.

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Dopamine mediated ‘sign’ based learning

There is an interesting must watch Video of Paul Phillips discussing dopamine based learning and I have embedded the video below. Please do have a look. Original video with some other relevant information can be found here.

Paul discusses the dopamine surge at the Unconditioned Stimulus/reward (US) before the training being replaced by a dopamine surge at Conditioned stimulus(CS) after the learning and how this has led to the reward prediction theory (Schultz) of dopamine function. He also discusses the Cambridge(UK) or Ken Berridge group of objections to this and their discovery that different regions of the brain react differently (ventral and dorsal striatum have different dopamine surges associated with the same stimulus/reward pair in the same animal). He uses electrochemical methods (suing electrodes implanted in the rats brains) to measure tonic dopamine release and there are interesting and informative graphics as well as videso of rats indulging in approach behavior as soon as CS is presented (after conditioning).

He also discusses model-free and model-based reinforcement learning paradigms and discusses how dopamine is only necessary for model-free (simple value association) learning and is not necessarily involved in model-based learning. this he demonstrates beautifully with videos and graphs of selectively bred mice (bred for locomotion), in which high locomotors follow a different (sign-based or model-free) while the low locomotors display goal based or model-based learning. By dopamine manipulations (giving a dopamine antagonist) he is able to show that dopamine is not really necessary for model-based learning.

All in all a very engaging and informative video. A must, must watch that is very highly recommended for anybody who has given a minor thought also to dopamine and what it does in the brain.

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A brief history of autism

ResearchBlogging.org

{{en|Subject: Quinn, an ~18 month old boy with...
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A mouse trap reader, using skribit, asked me to write a blog post about the history of madness; that is a dauting task, as she herself mentioned that Foucault wrote an entire book on the subject; so though I promise to write that post, in the meantime here is a post about the history of Autism.  After this , the next in series  would be a brief history of Schizophrenia.

Two Furies, from an ancient vase.
Image via Wikipedia

References to schizophrenia can be found since time immemorial, though the actual term and diagnosis is recent. It is believed that the people haunted by Furies of ancient Greek were actually schizophrenics suffering from delusions and hallucinations. As I contrast Autism and Schizophrenia it is apt that I start here; for similar to the rich historic al tradition, Autism can be equated with the ,blessed Fools’ of old Russia, “who were revered for their unworldiness. The apparent insensitivity to pain, bizarre behaviour, innocence, and lack of social awareness that these “Blessed Fools” showed, suggest that they may have had autism. ” (Happe). Similarly in almost all cultures one can find anecdotes and folktales about foolish boys (note that it is a boy and not a girl as autism has always been more prevalent in boys) who take what their mother said too literally- word for word , rather than figuratively and metaphorically or idiomatically.

The modern diagnosis of autism starts with Leo Kanner. Kanner published his first paper about  autistic children in 1943, the full text of which can be found here.  Some excerpts from the paper, which has many case studies , should help:

Since 1938, there have come to our attention a number of children whose condition differs so markedly and uniquely from anything reported so far, that each case merits – and, I hope, will eventually receive – a detailed consideration of its fascinating peculiarities.

The outstanding, “pathognomonic,” fundamental disorder is the children’s inability to relate themselves in the ordinary way to people and situations from the begining of life. Their parents referred to them as having always been “self-sufficient”; “like in a shell”; “happiest when left alone”;“acting as if people weren’t there”; “perfectly oblivious to everything about him”; “giving the impression of silent wisdom”; “failing to develop the usual amount of social awareness”;“acting almost as hypnotized.”T his is not, as in schizophrenic children or adults, a departure from an initially present relationship; it is not a “withdrawal”from formerly existing participation. There is from the start an extreme autistic aloneness that, whenever possible, disregards, ignores, shuts out anything that comes to the child from the outside. Direct physical contact or such motion or noise as threatens to disrupt the aloneness is either treated “as if it weren’t there”or, if this is no longer sufficient, resented painfully as distressing interference.


Eight of the eleven children acquired the ability to speak either at the usual age or after some delay. Three (Richard, Herbert, Virginia) have so far remained “mute.”In none of the eight “speaking” children has language over a period of years served to convey meaning to others. They were, with the exception of John F., capable of clear articulation and phonation. Naming of objects presented no difficulty; even long and unusual words were learned and retained with remarkable facility. Almost all the parents reported, usually with much pride, that the children had learned at an early age to repeat an inordinate number of nursery rhymes, prayers, lists of animals, the roster of presidents, the alphabet forward and backward, even foreign-language (French) lullabies. Aside from the recital of sentences contained in the ready-made poems or other remembered pieces, it took a long time before they began to put words together. Other than that, “language”consisted mainly of “naming,”of nouns identifying objects, adjectives indicating colors, and numbers indicating nothing specific.
Their excellent rote memory, coupled with the inability to use language in any other way, often led the parents to stuff them more and more verses, zoologic and botanic names, titles and composers of Victrola record pieces, and the like. Thus, from the start, language-which the children did not use for the purpose of communication-was deflected in a considerable measure to a self-sufficient, semantically and conversationally valueless or grossly distorted memory exercise.

When sentences are finally formed, they are for a long time mostly parrot-like repetitions of heard word combinations. They are sometimes echoed immediately, but they are just as often “stored”by the child and uttered at a later date. One may, if one wishes, speak of delayed echolalia. Affirmation is indicated by literal repetition of a question. “Yes”is a concept that it takes the children many years to acquire. They are incapable of using it as a general symbol of assent. Donald learned to say “Yes”when his father told him that he would put him on his shoulders if he said “Yes.”This word then came to “mean”only the desire to be put on his father’s shoulders. It took many months before he could detach the word “Yes”from this specific situation, and it took much longer before he was able to use it as a general term of affirmation.

The same type of literalness exists also with regard to prepositions. Alfred, when asked, “What is this picture about?”replied:”People are moving about.”

John F. corrected his father’s statement about pictures on the wall; the pictures were “near the wall.” Donald T., requested to put something down, promptly put it on the floor. Apparently the meaning of a word becomes inflexible and cannot be used with any but the originally acquired connotation.

But the child’s noises and motions and all of his performances are as monotonously repetitious as are his verbal utterances. There is a marked limitation int he variety of his spontaneous activies. The child’s behavior is governed by an anxiously obsessive desire for the maintenance of sameness that nobody but the child himself may disrupt on rare occasions. Changes of routine, of furniture arrangement, of a pattern, of the [form] in which every-day acts are carried out, can drive him to despair. When John’s parents got ready to move to a new home, the child was frantic when he saw the moving men roll up the rug in his room. He was acutely upset until the moment when, in the new home, he saw his furniture arranged in the manner as before. He looked pleased, all anxiety was suddenly gone, and he went around affectionately patting each piece. Once blocks, beads, sticks have been put together in a certain way, they are always regrouped in exactly the same way, even though there was no definite design. The children’s memory ws phenomenal in this respect. after the lapse of several days, a multitude of blocks could be rearranged in precisely the same unoganized pattern, with the same color of each block turned up, with each picture or letter on the upper surface of each block facing in the same direction as before. The absence of a block or the presence of a supernumerary block was noticed immediately, and there was an imperative demand for the restoration of the missing piece. If someone removed a block, the child struggled to get it back, going into a panic tantrum until he regained it, and then promptly and with sudden calm after the storm returned to the design and replaced the block.

The children’s relation to people is altogether different. Every one of the children, upon entering the office, immediately went after blocks, toys, or other objects, without paying the least attention to the persons present. It would be wrong to say that they were not aware of the presence of persons. But the people, so long as they left the child alone, figured in about the same manner as did the desk, the bookshelf, or the filing cabinet. When the child was addressed, he was not bothered. He had the choice between not responding at all or, if a question was repeated too insistently, “getting it over with”and continuing with whatever he had been doing. Comings and goings, even of the mother, did not seem to register. Conversation going on in the room elicited no interest. If the adults did not try to enter the child’s domain, he would at times, while moving between them, gently touch a hand or a knee as on other occasions he patted the couch. But he never looked into anyone’s face. If an adult forcibly intruded himself by taking a block away or stepping on an object that child needed, the child struggled and became angry with the hand or the foot, and became angry with the hand or the foot, which was dealt with perse [?] and not as a part of a person. He never addressed a word or a look to the owner of the hand or foot. When the object was retrieved, the child’s mood changed abruptly to one of placitidy. When pricked, he showed fear of the pin but not of the person who pricked him.

Note already that all the currently accepted DSM-IV characteristics of Autism like communicative difficulties, social difficulties and stereotyped or repetitive behavior are already well delineated by Kanner. Here one has to pause and note that autism and autistics were used from the social aloofness first observed and documented in schizophrenics by Kreplin and we seem to have come a full circle now by positing that Autism and schizophrenia are opposites on a continuum. It is also heartening to note that Kanner was also way ahead of his times by focusing on the deficit in ‘mentalizing’ in autistic kids.

Just a year after, Hans Asperger , published his paper on ASD kids, and it is remarkable that despite not knowing about each others papers they came with similar terminology (autistic ) to describe the children and agreed on more points than they disagreed on.

Asperger published the first definition of Asperger Syndrome, in 1944. In four boys, he identified a pattern of behavior and abilities that he called “autistic psychopathy”, meaning autism (self) and psychopathy (personality disease). The pattern included “a lack of empathy, little ability to form friendships, one-sided conversation, intense absorption in a special interest, and clumsy movements.” Asperger called children with AS “little professors” because of their ability to talk about their favorite subject in great detail. It is commonly said that the paper was based on only four boys.

Asperger and Kanner agreed as well as disagreed on many things:

Hans Asperger deserves credit for some very striking insights into autism: some insights which Kanner (1943) lacked and which it has taken us many years of research to rediscover. Before considering these particular observations of Asperger’s, it is worth noting the many features on which the two physicians agreed.
Kanner’s and Asperger’s descriptions are surprisingly similar in many ways, especially when one remembers that each was unaware of the other’s ground-breaking paper. Their choice of the term “autistic” to label their patients is itself a striking coincidence. This choice reflects their common belief that the child’s social problems were the most important and characteristic feature of the disorder. The term “autistic” comes from Bleuler (1908), who used the word (from the Greek “autos” meaning “self”) to describe the social withdrawal seen in adults with schizophrenia. Both Kanner and Asperger believed the social handicap in autism to be innate (in Kanner’s words) or constitutional (as Asperger put it), and to persist through life into adulthood. In addition, Kanner and Asperger both noted the children’s poor eye contact, their stereotypies of word and movement, and their marked resistance to change. The two authors report the common finding of isolated special interests, often in bizarre and idiosyncratic objects or topics. Both seem to have been struck by the attractive appearance of the children they saw. Kanner and Asperger make a point of distinguishing the disorder they describe from schizophrenia, on the basis of three features: the improvement rather than deterioration in their patients, the absence of hallucinations, and the fact that these children appeared to be abnormal from their earliest years, rather than showing a decline in ability after initially good functioning. Lastly, both Kanner and Asperger believed that they had observed similar traits—of social withdrawal or incompetence, obsessive delight in routine, and the pursuit of special interests to the exclusion of all else—in the parents of many of their patients.
There are three main areas in which Asperger’s and Kanner’s reports disagree, if we believe that they were describing the same sort of child. The first and most striking of these is the child’s language abilities. Kanner reported that three of his 11 patients never spoke at all, and that the other children did not use what language they had to communicate: “As far as the communicative functions of speech are concerned, there is no fundamental difference between the eight speaking and the three mute children” (Kanner 1943). While phonology (as demonstrated in accurate echolalia) and vocabulary were often excellent, Kanner concluded that of his 11 cases “In none …has language…served to convey meaning”. The picture in all is of a child with profound communicative difficulties and delay; in seven of the 11 cases so profound that deafness was initially suspected (but ruled out). Asperger, by contrast, reported that each of his four case study patients (and, by implication, most of the unspecified number of such children he treated) spoke fluently. Although two of his patients showed some delay, this was followed in both cases by a rapid mastery of language, and it is difficult to imagine any of his cases having been mistaken for deaf. All four cases, by the age of examination (between 6 and 9 years old), spoke “like little adults”. Asperger notes their “freedom” and “originality” in language use, and reports that two of his four cases had a tendency to tell “fantastic stories”.
Asperger’s description also conflicts with Kanner’s on the subject of motor abilities and co-ordination. Kanner (1943) reported clumsiness in only one case, and remarks on the dexterity of four of his patients. He concluded that “several of the children were somewhat clumsy in gait and gross motor performance, but all were very skilful in terms of finer muscle coordination”—in line with their success on the Seguin form board (in which dexterity plays a part) and their ability to spin objects. Asperger, by contrast, described all four of his patients as clumsy, and recounted their problems not only with school sports (gross co-ordination), but also with fine motor skills such as writing. This feature is part of a larger contrast in Asperger’s and Kanner’s beliefs. Kanner believed the autistic child to have a specific impairment in social understanding, with better relations to objects than to people: while his children showed “excellent, purposeful and ‘intelligent’ relations to objects” their “relations to people [were] altogether different”. Asperger, on the other hand, believed that his patients showed disturbances in both areas: “the essential abnormality in autism is a disturbance of the lively relationship with the whole environment” (Asperger 1944, translated in Frith 1991b).
The last area of disagreement in the clinical pictures painted by Asperger and Kanner is that of the child’s learning abilities. Kanner believed that his patients were best at learning rote fashion, but Asperger felt that his patients performed “best when the child can produce spontaneously”, and suggests that they are “abstract thinkers”. (Happe)

We now know that many of the insights of Asperger were correct especially for those suffering from high-functioning autism or Asperger’s syndrome.

A dark period of autism research was the ‘refrigerator mother‘ hypothesis , which posited based on a psychogenic theory that autism was due to bad parenting. The seeds of this theory can be traced back to Kanner, but Bruno Bettelheim gave it a prominence. this theory as now been widely debunked and discredited and caused undue suffering and guilt to a generation of parents.

Leading researchers in the field after these have been Uta Frith, Leslie, Happe and Simon-Baron-Cohen with his ‘mind-blindness’ theory.

Before concluding please visit the DSM criteria and reassess them as now autism, at least by me and many leading researchers, is conceptualized more as a continuum disorder. Hope the DSM-V has a continuum framework for autism.

Kanner L (1968). Autistic disturbances of affective contact. Acta paedopsychiatrica, 35 (4), 100-36 PMID: 4880460

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The downside of cognitive enhancement

The Morris water maze task has been used to de...

Jonah Lehrer, has an article in this week’s Nature News, (find a PDF here) , regarding 30 or so cognitively enhanced mice strains that have been bred and genetically engineered.  As Lehrer  very elaborately documents, all these have enhanced LTP as an intervening mechanism that leads to improvements in learning and memory. Most of the genes involved affcet the LTP mechanism in one way or the other to breed super mnemonist mice. However, from the time of Luria, t has been well known that those who have enhanced memory also suffer from some of its disadvantages and that the ability to forget is also very important.

Little is known about the side effects and tradeoffs
of both the current usage or the drugs in
development, but initial clues offered by smart
mice raise concerns. The Hras strain developed
in Silva’s lab might be good at learning, but its
fear response for a relatively benign stimulus
would be counterproductive for a wild mouse.
Its enhanced memory is both a blessing and a
burden. Silva cites other strains of smart mice
that excel at solving complex exercises, such as
the Morris water maze, but that struggle with
simpler mazes. “It’s as if they remember too
much,” he says — possibly taking in irrelevant
information such as the position of windows
or lights but missing the big clues.
Farah sees a parallel between these mice
and one of the few case studies of an individual
with profoundly enhanced memory.
In the early 1920s, the Russian neurologist
Alexander Luria began studying the learning
skills of a newspaper reporter called Solomon
Shereshevsky, who had been referred to the
doctor by his editor. Shereshevsky had such
a perfect memory that he often struggled to
forget irrelevant details. After a single read of
Dante’s Divine Comedy, he was able to recite
the complete poem by heart. Although this

Little is known about the side effects and tradeoffs of both the current usage or the drugs in development, but initial clues offered by smart mice raise concerns. The Hras strain developed in Silva’s lab might be good at learning, but its fear response for a relatively benign stimulus would be counterproductive for a wild mouse. Its enhanced memory is both a blessing and a burden. Silva cites other strains of smart mice that excel at solving complex exercises, such as the Morris water maze, but that struggle with simpler mazes. “It’s as if they remember too much,” he says — possibly taking in irrelevant information such as the position of windows or lights but missing the big clues.

Farah sees a parallel between these mice and one of the few case studies of an individual with profoundly enhanced memory. In the early 1920s, the Russian neurologist Alexander Luria began studying the learning skills of a newspaper reporter called Solomon Shereshevsky, who had been referred to the doctor by his editor. Shereshevsky had such a perfect memory that he often struggled to forget irrelevant details. After a single read of Dante’s Divine Comedy, he was able to recite the complete poem by heart. Although this flawless memory occasionally helped Shereshevsky at work — he never needed to take notes — Luria also documented the profound disadvantages of such a capacious memory. Shereshevsky, for instance, was almost entirely unable to grasp metaphors, as his mind was so fixated on particulars. When he tried to read poetry, for example, “the obstacles to his understanding were overwhelming”, Luria wrote in his book The Mind of a Mnemonist. “Each expression gave rise to a remembered image; this, in turn, would conflict with another image that had been evoked.”

For Luria, Shereshevsky’s struggles were a powerful reminder that the ability to forget is as important as the ability to remember. Enhancing human memory in individuals without severe cognitive defects might prove counterproductive.

It is interesting to pause here and note that many savants who have excellent memory are also autistic and that schizophrenics on the opposite end of the spectrum are characterized by too much reliance of metaphors and too much generalizations and abstractions. Further Martha Farah notes the following:

Many scientists are concerned that the animal models of enhanced cognition might obscure subtle side effects, which can’t be studied in rodents or primates. Farah is currently looking at the trade-off between enhanced attention — she gives human subjects a mild amphetamine — and performance on creative tasks. Other researchers have used computer models to show that memory is actually optimized by slight imperfections, as they allow one to see connections between different but related events9. “The brain seems to have made a compromise in that having a more accurate memory interferes with the ability to generalize,” Farah says. “You need a little noise in order to be able to think abstractly, to get beyond the concrete and literal.”

Again, one can easily see the correlations with Autism and Schizophrenia- one end marked by too narrow a focus , while the other marked by too much noise and divergent creativity. I would have been happy to incorporate the more LTP as autistic and less LTP as schizophrenics, but it flies in face of my earlier findings regarding experience dependent plasticity in autism and schizophrenia where the conclusions were just the revers. Yet, it is clear that synaptic plasticity is a majo mechanism involved in the autism/psychosis differentiation. Do let me know if you can reconcile the new findings with the older ones to come up with the right LTP and psychosis/autism relationship.

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Living on the edge of chaos; implications for autism and psychosis

SMI32-stained pyramidal neurons in cerebral co...Image via Wikipedia

I serendipitously came cross this article today about how our brains are self-organized criticality or systems living on the edge of chaos. There are many interesting ideas and gold nuggets in that article, and I’ll briefly quote from it.

In reality, your brain operates on the edge of chaos. Though much of the time it runs in an orderly and stable way, every now and again it suddenly and unpredictably lurches into a blizzard of noise.

Neuroscientists have long suspected as much. Only recently, however, have they come up with proof that brains work this way. Now they are trying to work out why. Some believe that near-chaotic states may be crucial to memory, and could explain why some people are smarter than others.

In technical terms, systems on the edge of chaos are said to be in a state of “self-organised criticality”. These systems are right on the boundary between stable, orderly behaviour – such as a swinging pendulum – and the unpredictable world of chaos, as exemplified by turbulence.

The quintessential example of self-organised criticality is a growing sand pile. As grains build up, the pile grows in a predictable way until, suddenly and without warning, it hits a critical point and collapses. These “sand avalanches” occur spontaneously and are almost impossible to predict, so the system is said to be both critical and self-organising. Earthquakes, avalanches and wildfires are also thought to behave like this, with periods of stability followed by catastrophic periods of instability that rearrange the system into a new, temporarily stable state.

Self-organised criticality has another defining feature: even though individual sand avalanches are impossible to predict, their overall distribution is regular. The avalanches are “scale invariant”, which means that avalanches of all possible sizes occur. They also follow a “power law” distribution, which means bigger avalanches happen less often than smaller avalanches, according to a strict mathematical ratio. Earthquakes offer the best real-world example. Quakes of magnitude 5.0 on the Richter scale happen 10 times as often as quakes of magnitude 6.0, and 100 times as often as quakes of magnitude 7.0.

These are purely physical systems, but the brain has much in common with them. Networks of brain cells alternate between periods of calm and periods of instability – “avalanches” of electrical activity that cascade through the neurons. Like real avalanches, exactly how these cascades occur and the resulting state of the brain are unpredictable.

Two of the power laws that are found in human brains relate to the phase shift and phase lock periods of EEG/fMRI or human brain systems etc. As per this PLOS comp biology paper:

Self-organized criticality is an attractive model for human brain dynamics, but there has been little direct evidence for its existence in large-scale systems measured by neuroimaging. In general, critical systems are associated with fractal or power law scaling, long-range correlations in space and time, and rapid reconfiguration in response to external inputs. Here, we consider two measures of phase synchronization: the phase-lock interval, or duration of coupling between a pair of (neurophysiological) processes, and the lability of global synchronization of a (brain functional) network. Using computational simulations of two mechanistically distinct systems displaying complex dynamics, the Ising model and the Kuramoto model, we show that both synchronization metrics have power law probability distributions specifically when these systems are in a critical state. We then demonstrate power law scaling of both pairwise and global synchronization metrics in functional MRI and magnetoencephalographic data recorded from normal volunteers under resting conditions. These results strongly suggest that human brain functional systems exist in an endogenous state of dynamical criticality, characterized by a greater than random probability of both prolonged periods of phase-locking and occurrence of large rapid changes in the state of global synchronization, analogous to the neuronal “avalanches” previously described in cellular systems. Moreover, evidence for critical dynamics was identified consistently in neurophysiological systems operating at frequency intervals ranging from 0.05–0.11 to 62.5–125 Hz, confirming that criticality is a property of human brain functional network organization at all frequency intervals in the brain’s physiological bandwidth.

Further, as per research by Thatcher et al, the EEG phase shift is larger in people with high IQ, while phase lock is smaller in the people with high IQ.

Phase shift duration (40–90 ms) was positively related to intelligence (P < .00001) and the phase lock duration (100–800 ms) was negatively related to intelligence (P < .00001). Phase reset in short interelectrode distances (6 cm) was more highly correlated to I.Q. (P < .0001) than in long distances (> 12 cm).

Further, in this paper , thatcher eta look at autistics and conclude that the people with autism show some deficits in phase shift and phase lock.

Results: In both short (6 cm) and long (21 – 24 cm) inter-electrode distances phase shift duration in ASD subjects was significantly shorter in all frequency bands but especially in the alpha-1 frequency band (8 – 10 Hz) (P < .0001). Phase lock duration was significantly longer in the alpha-2 frequencyband (10 – 12 Hz) in ASD subjects (P < .0001). An anatomical gradient was present with the occipitalparietal regions the most significant.
Conclusions: The findings in this study support the hypothesis that neural resource recruitment occurs in the lower frequency bands and especially the alpha-1 frequency band while neural resource allocation occurs in the alpha-2 frequency band. The results are consistent with a general GABA inhibitory neurotransmitter deficiency resulting in reduced number and/or strength of thalamo-cortical connections in autistic subjects 

It is interesting that in the original new scientist article , thatcher speculates that the pattern in schizophrenia may be reverse of what is seen in autism (exactly my thoughts, though the confounding of low IQ with autism may explain his autism results to an extent):

He found that the length of time the children’s brains spent in both the stable phase-locked states and the unstable phase-shifting states correlated with their IQ scores. For example, phase shifts typically last 55 milliseconds, but an additional 1 millisecond seemed to add as many as 20 points to the child’s IQ. A shorter time in the stable phase-locked state also corresponded with greater intelligence – with a difference of 1 millisecond adding 4.6 IQ points to a child’s score (NeuroImage, vol 42, p 1639). Thatcher says this is because a longer phase shift allows the brain to recruit many more neurons for the problem at hand. “It’s like casting a net and capturing as many neurons as possible at any one time,” he says. The result is a greater overall processing power that contributes to higher intelligence. Hovering on the edge of chaos provides brains with their amazing capacity to process information and rapidly adapt to our ever-changing environment, but what happens if we stray either side of the boundary? The most obvious assumption would be that all of us are a short step away from mental illness. Meyer-Lindenberg suggests that schizophrenia may be caused by parts of the brain straying away from the critical point. However, for now that is purely speculative. Thatcher, meanwhile, has found that certain regions in the brains of people with autism spend less time than average in the unstable, phase-shifting states. These abnormalities reduce the capacity to process information and, suggestively, are found only in the regions associated with social behaviour. “These regions have shifted from chaos to more stable activity,” he says. The work might also help us understand epilepsy better: in an epileptic fit, the brain has a tendency to suddenly fire synchronously, and deviation from the critical point could explain this. “They say it’s a fine line between genius and madness,” says Liley. “Maybe we’re finally beginning to understand the wisdom of this statement.”

Thus, it seems Autism and Psychosis are just two ways in which self-organized criticality can cease to do what it was designed to do- live on the edge , without falling on either side of order or chaos.

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