Category Archives: psychosis

Autism and Schizophrenia: proof from comparative genomics

ResearchBlogging.org

An overview of the structure of DNA.
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I have blogged extensively about the Autism and Schizophrenia as opposites on a continuum theory. I remember first putting this theory in words in an article 3 yrs back on the mouse trap titled Autism and Schizophrenia: the two cultures. That 2006 article, in turn, was inspired by Daniel Nettle’s 2005 article in Journal of Research in Personality where Nettle had also proposed the dichotomy and that paper helped crystallize my thoughts on the subject, a theory which I had been building on my own and now supported by someone like Nettle who I respect a lot. Important to note that at that time I was blissfully unaware of Badcock or Crespi and their work. It is to the credit of Badcock that he had published in 2006 his own theory of Autism and Schizophrenia as opposites on a continuum based on parental imprinting of genes and proposed a mechanism. Crespi I guess got involved in Badcocks’s efforts later on and gave it more experimental and theoretic grounding. I firts became aware of Badcock and Crespi’s work in early 2008.

The wider world became aware of the Autism/Schizophrenia dichotomy sometime in late 2008 (November 2008) . at that time too, I was a little disappointed because most of the coverage did not mention Daniel Nettle, who I think should be credited for this work and line of reasoning too. As a consolation, some reports did mention Chris Frith who has also been partly supporting the thesis.

I wanted to give a historical perspective, because I am sure the recent Crespi article would be grabbed on by mainstream media and the pioneers Chris Frith/Nettle perhaps overlooked- but to me they too are heroes for having come up with such profound early insights. this is not to discredit teh work of Badcock and Crespi- they are doing a thorough job of convincing the skeptics and delineating the exact mechanism and genetics involved.

While we are on the topic of historical perspective , let me also pat myself on the back. In May 2008, a study came out that de novo Copy Number Variations’s (CNVs) were quite high in schizophrenics and they are in the same region as that for autistics who also have high CNVs in the same region. While some took that result to imply that Schizophrenia and Autism are same and are not different, I persisted and proposed a mechanism, whereby they could still be opposites : To quote:

Now as it happens 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.

Now one and half year later Crespi et al report the results of their study which has found exactly the same- that is, if deletions in some locus lead to autism, duplications lead to schizophrenia and vice versa. That to me is clinching evidence of my thesis. Who says Science does not happen on blogs- I proposed something to flow as a consequence of theory and exactly the same thing is found as per the hypothesis. I feel vindicated and emotional to some extent. Loves labor has not been lost to deaf ears.

Let us then return to the new and latest study that has sort of proven that Autism and Schizophrenia are opposites, genetically. Crespi et al, report in the latest PNAS edition that comparative genomics leads to that conclusion. What Crespi et al did was look at theCNV s and the locus whee CNV in both Autism and Schizophrenia are involved and sure enough they found the pattern I had proposed. I’ll now quote from the abstract and the article extensively:

We used data from studies of copy-number variants (CNVs), singlegene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (i) autism subsumed in schizophrenia, (ii) independence, (iii) diametric, and (iv) partialoverlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance. However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia. Evidence from the effects of risk variants on growth-signaling pathways shows that autism-spectrum conditions tend to be associated with upregulation of pathways due to loss of function mutations in negative regulators, whereas schizophrenia is associated with reduced pathway activation. Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth.These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain.

Copy Number Data. Rare copy-number variants (CNVs) at seven loci, 1q21.1, 15q13.3, 16p11.2, 16p13.1, 17p12, 22q11.21, and 22q13.3 (Tables S1 and S2), have been independently ascertained and associated with autism and schizophrenia in a sufficient number of microarray-based comparative genomic hybridization (aCGH) and SNP-based studies to allow statistical analysis of the frequencies of deletions versus duplications in these two conditions (Table 1, Tables S3–S9). For five of the loci (1q21.1, 16p11.2, 16p13.1, 22q11.21, and 22q13.3), specific risk variants have been statistically supported for both autism and schizophrenia using case-control comparisons, which allows direct evaluation of the alternative hypotheses in Fig. 1. One locus (16p13.1) supports a model of overlap, and four loci support the reciprocal model, such that deletions are associated with increased risk of autism and duplications with increased risk of schizophrenia (16p11.2, 22q13.3), or deletions are associated with increased risk of schizophrenia and duplications with increased risk of autism (1q21.1, 22q11.21). For 1q21.1 and 22q11.21, contingency table analyses also indicate highly significant differences in the frequencies of deletions compared with duplications for the two disorders, such that schizophrenia is differentially associated with deletions and autism with duplications. By contrast, for 16p11.2 and 22q13.3 such analyses show that autism is differentially associated with deletions and schizophrenia with duplications.

Model_1

I cannot cut n paste the table, but a look at the table clears all doubts. They also look at gene association data and come to a similar conclusion ruling out model A (autism, subsumed in schizophrenia) or model B (autism and schizophrenia are independent of each other).

Models 1C (diametric) and 1D (overlapping) both predict broad overlap in risk genes between autism and schizophrenia, and do not necessarily predict an absence or paucity of genes affecting one condition but not the other. In theory, these models can be differentiated by using data on specific risk alleles for specific loci (such as single-nucleotide polymorphisms, haplotypes, or genotypes), which should be partially shared under the overlapping model but different under the diametric model. For the genes DAO, DISC1, GRIK2, GSTM1, and MTHFR, the same allele, genotype, or haplotype was associated with both autism and schizophrenia, and for the genes AHI1, APOE, DRD1, FOXP2, HLA-DRB1, and SHANK3, alternative alleles, genotypes, or haplotypes at the same loci appear to mediate risk of these two conditions (SI Text). For the other genes that have been associated with both conditions, heterogeneity in the genetic markers used, heterogeneity among results from multiple studies of the same genes, and the general lack of functional information preclude interpretation in terms of shared or alternative risk factors.

Models of autism as a subset of schizophrenia (Fig. 1A), and autism and schizophrenia as independent or separate (model 1B), can be rejected with some degree of confidence, but models involving diametric etiology (model 1C) or partial overlap (model 1D) cannot be clearly rejected. Taken together, most of the data and analyses described here appear to support the hypothesis of autism and schizophrenia as diametric conditions, based primarily on the findings that reciprocal variants at 1q21.1, 16p11.2, 22q11.21, and 22q13.3 represent statistically-supported, highly-penetrant risk factors for the two conditions (Table 1), and that for a number of genes, alternative alleles or haplotypes appear to mediate risk of autism versus schizophrenia.
Additional lines of evidence supporting the diametric hypothesis, from previous studies of autism and schizophrenia, include:

  • 1. Data showing notable rarity of familial coaggregation of autism with schizophrenia (38), in contrast, for example, to strong patterns of co-occurance within pedigrees of schizophrenia, schizoaffective disorder, and bipolar disorder (39).
  • 2. Psychiatric contrasts of Smith-Magenis syndrome with Potocki-Lupski syndrome (due to the reciprocal duplication at the Smith-Magenis locus), Williams syndrome with cases of Williams-syndrome region duplication, and Klinefelter syndrome with Turner syndrome, each of which tends to involve psychotic-affective spectrum phenotypes in the former syndrome, and autistic spectrum conditions in the latter (5, 40).
  • 3. Effects of autism and schizophrenia risk alleles on common growth-signaling pathways, such that autism has been associated with loss of function in genes, such as FMR1, NF1, PTEN, TSC1, and TSC2 that act as negative regulators of the PI3K, Akt, mTOR, or other growth-signaling pathways (41–45), whereas schizophrenia tends to be associated with reduced function or activity of genes that up-regulate the PI3K, Akt, and other growth-related pathways (46–49).
  • 4. Increased average head size, childhood brain volume, or cortical thickness in individuals with: (i) idiopathic autism (50–53), (ii) the autism-associated duplications at 1q21.1 (17) and 16p13.1 (32) and the autism-associated deletions at 6p11.2 (31), and (iii) autism due to loss of function (or haploinsufficiency) of FMR1 (54), NF1 (55), PTEN (56) and RNF135 (57). By contrast, reduced average values for brain size and cortical thickness, due to some combination of reduced growth and accelerated gray matter loss, have been demonstrated with notable consistency across studies of schizophrenia (58–62), and such reduced head or brain size has also been associated with the schizophrenia-linked CNVs at 1q21.1 and 22q11.21 (17, 63, 64), and with deletions of 16p13.1 (65).

I am more than pleased with these results. Badcock too is. You can read his comments here. What about you? What would it take to convince you? 🙂

Crespi, B., Stead, P., & Elliot, M. (2009). Evolution in Health and Medicine Sackler Colloquium: Comparative genomics of autism and schizophrenia Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0906080106

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Seeing is believing : why delusions may arise from anomalous experiences

ResearchBlogging.org

An amateur magician performing.
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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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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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The Sculptor and the Sandman: A novel as much about psychosis as about the human condition

Last night I somehow got inspired, brushed my manuscript that was written about 6 yrs earlier, and in a span of just 4-5 hrs was able to create a sell able paperback book out of it, all thanks to new publishing tools like the lulu.com. Of course, the manuscript, had been read/ re-read, revised and edited by me, all these years, so I’m sure the quality of the product would be great.

Some of you may be aware that I write prose and poetry and have a poetry focussed blog called The Fools Quest. Perhaps, the right place to promote my novel, The Sculptor and the Sandman, would be that blog, instead of the mouse trap; but then again, that novel is as much a piece of fiction, as it is a psychological treatise- my view of what psychosis is, how it manifests and what some of the triggers may be. The tale is grounded in my undersantding of the psychotic condition and I am sure that my readers with exclusive interest in the psychologcial aspects would still find reading that novel worthwhile. Of course, I know that many of your are multi-dimensional, and value arts, as much as science, and reading the novel would be an artistic pleasure in itself- even when not being bogged down by the psychological aspects and the truth or falsity of my depiction of the psychotic condition – the novel can be enjoyed in its own right . Reading it may also help you connect with me on a different level- exposing aspects of myself that were never apparent while reading the mouse trap.

As always I would love feedback, reviews etc and would sincerely request that you give the novel a try. The paperback edition is priced at $10.80 and a downloadable version is priced at $2.50; I am sure it would prove value for money and you will end up buying further copies for your friends and recommending it to others. It is at present just available at lulu.com , but soon will be available at all other major stores like amazon.com.

You can read an excerpt from the novel at the lulu.com site and here is the blurb from the back cover:

The sculptor and the sandman is a fable set in the India of the twenty first century. A tale of passion, obsession, madness and rebellion, the story revolves around how the protagonists move in and out of madness, competing as well as caring for each other, and how their life becomes inextricably twined with that of the narrator, a coconut water vendor.

A tale in which episodes of frank psychosis seem more understandable and reasonable than the unbearable normality of everyday life, the tale is a grim reminder of how misunderstandings and malice work together to weave the different strands of our life together and how silver linings are present in the darkest of clouds hovering over the horizon.

Seen from another perspective, the tale documents different approaches to find meaning and value in this modern world, a world devoid of absolutes. One approach may seem more absurd and futile than the other, but perhaps it is not so much about the ‘right’ value system or frame of meaning, as it is about the need for ‘a’ value system or a frame of meaning- to each his own cross.

Please, Please, Please do read the novel (for that you’l need to buy it!), share it with others( if you indeed like it) , recommend/review it on your blogs and do send me comments, either using this page, the lulu reviews page etc or by directly sending your comments to me at sandygautam@yahoo.com, even if the comments are not positive or encouraging. Any feedback is much better than no feedback. Depending on the feedback, I have the sequel to the sculptor and sandman already in draft stage but I need some reassurance as to whether the efforts are worthwhile and whether  there is a need and appreciation for this type of writing.

What it is like to be a zombie?

I am sure many of you are already familiar with Nagel’s perennial question ‘what it is like to be a bat?  (see this one with some added commentary too). Today I propose to ask a slightly different question ‘what it is like to be a zombie‘? That may seem absurd at the outset, as in many people’s mind Zombies are synonymous with no consciousness. I beg to differ. As I have already indicated in my last post on major conscious and unconscious processes in the brain, there is an easy problem of A-consciousness and there is a hard problem of P-consciousness. I have already tried to breakup A-consciousness in its parts and  I similarly think that P-consciousness is much more that qualia (qualia I envisage as more grounded in sensory or perceptive systems). So given the fact that most zombies are behaviorurally indistinguishable from normal humans, and given the fact that most people who argue for zombie models of humans (that ‘there is no one home to watch/direct the picture’) do still endow the zombie and themselves with the A-consciousness aspects – they do not deny that a representation is made and is consciously available for processing (the theater of consciousness) , it is reasonable to speculate that although lacking full P-consciousness, it would still be something like to feel like a zombie. Let me draw an analogy, in some dissociative disorders, one starts seeing the world as unreal (derealization)  and the self as unreal (depersonalization) ; yet even though one believes oneself to be unreal there is still something it is like to exist in that ‘unreal’ state.

Similarly, though one may model oneself and others as zombies, still it would be something like it is to be in a state that thinks and believes that one is a zombie and also acts accordingly. I am making a leap here. I am assuming that awareness or modeling of ones A-conscious experiences leads to or affects one’s phenomenal consciousness. Thus, in my view , someone who models oneself and others as a zombie, would have a different sort of P-consciousness or what it feels-to-be-like, than a person who models oneself and others as sentient agents  and his P-cosnsciousness would be of a different nature.

Now consider the problem we face when confronted with a world which is deterministic and chaotic at the same time, and which is inhabited by agents which seem to be unpredicatable and constrained at the same time. I have already indicated elsewhere, that people may form tow types of model- one is a statistical/ deterministic model that they may apply to the world; another is a probabilisitic/agentic model that they may apply to the self (as well as other sentient beings).  If one keeps these domains of folk-physics and folk-psychology separate, all is hunky dory; all hell breaks lose (pun intended; zombies are correlated with dead apocalypse scenarios in popular culture) when one applies a deterministic  model (that fits the world) to the self/others. Similarly all hell breaks loose, when one applies an agentic/indetrminsitc model (that fits the sefl/others) to the world.

For today, we will focus on the problem of modeling self, and leave the problem of modeling world for a later day. A self may act differently in many similar/same situations. If it acts the same on each occasion, given the same situation; we can easily say that the situation causes the action. This poses no problem for the zombie (I will refer to a zombie as a person whose self/other conceptualization is as that of oneself/others as machines), as one has a deterministic rule that defines the self- (given situation A-> action B), and thus one can keep one’s model of self as-a-deterministic-being consistent. On the other hand, if the situation A sometimes leads to action B, but at other times to action C, then one has to explain the variance in the behavioral output. Consider first the problem of explaining the variance between-subjects. Given the same situation A, subject Z acts in way B while the subject Y acts in way C.   There is considerable variance. If one assumes all selves as created equal, then all should have behaved similarly. Either one has to grant an extraordinariness and uniqueness to all selves, or if one has a statistical  and ordinary nature of human beings, one has to grant that the subject given the same situation, should have behaved identically. But we all see that there is considerable variance.  This variance is individualistc and one may try to explain this between-subjects variance using subject’s personal history (prior conditioning: a behavioristic model; or repressed emotional experiences/memories: psychoanalytical theory), one may also look at subject’s common ancestral history and use that to explain behavior (genetic differences: evolutionary biology; cultural differences : anthropology ) or one may even look at his holistic experiences and use that individualistic experiential history as a basis for explaining behavior ( consider two identical twins that because of their different sampling of environment may end up as differently conditioned etc). Phew that covers all the major psychological theories that I could remember.

Now lets focus on the problem of explaining within-subjects variance ; given the fact that the Situation is the same (situation A)  and the subject is the same (subject Z), why does the same subject react differently to the same situation (acts in ways B and C). This is a relatively hard problem. One could deny the problem itself and claim that no situation is identical, but hey we are doing armchair philosophy right now, and we have already agreed to the premise of existence of a same situation A when we discussed between-subjects variance above, so it doesn’t hurt to concede that the situation A can be same for subject Z, but he may still react differently in ways B and C. None of the above psychological approaches, if applied in a strict, causal deterministic sense can explain the same subject Z reacting differently to situation A , as the subject Z’s personal history (conditioning, repressed memories) or ancestral history (genes, cultural influences) or even previous experiences and choices remain the same and thus should ideally have led to the same behavior. I am making an assumption here that situation A is repeated twice or more in succession (closely in time) so that one cannot counter and say that conditioning (to take an example) has changed in meanwhile due to situation A itself and thus, as the subject Z (at time t=1) has changed to an extent (by delta effect of situation A on the ‘earlier’ subject Z at time t=0) , so he may react differently at tome t=1 from how he reacted at time t=0.   What we are really doing is doing away with a term of the equation; we are saying subject Z is not constant (it  keep changing- self as constantly changing- a Buddhist philosophical premise and also favored by many in psychology) , but in the spirit of Camus’s Absurdity argument in Myth of Sisyphus, I am not satisfied with doing away one of the variables of the equation itself, so let us see, where this model of self-as-a-deterministic-being leads us to. Now that subject Z remains the same for two iterations of situation A, how can one explain the variance that results in action B at one time and action C at the other. One can again try to dissolve the equation by claiming that there is no unified self in space (earlier argument was that there is no unified self in time- it is a constantly changing in time self) – that is we are not a single self , but made up of many different selves- some conscious, some unconscious etc. Different selves may compete with each other and whoever wins at the moment, directs the show. Again assuming different selves cohabiting the same person doesn’t really feel what-it-is like to-be-oneself , and apart from some multiple-personality disorder (DID) this has not been frequently reported; but more importantly . Granting multiple selves to subject Z  again vanishes one of the terms of the equation, and I am not interested, I want to stay and see where my inquiry takes me to.

If the situation is same, the subject is same and a single one, than what explains the within-subject variance? One has to grant unpredictability to a self that was assumed to be deterministic to begin with. One can now take two routes, either resort to the magical mumbo-jumbo of quantum world and indeterminacy and uncertainty; or  stay in the deterministic world but look at complex systems/ chaos theory etc to explain the apparent indeterminacy.  I believe a zombie will prefer the second route and model the self as a complex-system/chaotic self. One could say that the self/ others are still completely determined, but due to an initial ‘butterfly flapping wings effect‘ the self seems or appears to be unpredictable and will continue to remain unpredicatble because of that ‘original sin’. The original sin may be how the infant took the first breath, whether he cried or laughed when born; what the time of conception was etc etc. Whatever may be the initial condition that escaped measuring, it leads to an unperdicatble self, a chaotic self that one cannot measure in the present and thus cannot predict in the long term- a self that is as fickle and as perdicatble as the waether.

There are important implications to seeing / modeling the self as a chaotic system. That leads to a diminished sense of agency / responsibility as perhaps there is not much one can do to correct the original sin and thus modify/ change ones long term behavior. This diminished p-consciousness of agency and the consequent differential experiences of sensations/ perceptions should also lead to diminished qualia or what-it-feels-to be-like feeling.  Maybe the zombies do feel really like zombies- mechanical and chaotic- going along the life stream in a mechanical , predetermined manner- seeing all and understanding all, even acting and reacting, but feeling impotent and lifeless, perhaps just fulfilling a role which has been scripted by someone else (the initial butterfly flapping its wings or the original sin).

This is a good point to stop, but I would like to thank Melbren, a reader of this blog, who commented on my last post and asked me if I would re-define , give a new name to Autism spectrum disorders. Thta made me think and somehow led to this post. But first his comment:

Very cool post. And I love your blog. I am trying to think about this particular post in terms of your psychotic spectrum–most specifically as it relates to autism. But I am impeded by an overwhelming feeling that if we have a new spectrum–we’ll need new terms. The term “autism” has outgrown its usefulness, don’t you think?

For one thing–if we are to use the framework of a psychosis spectrum–I think there will be a lot of people currently diagnosed with autism who are, in fact, organically more biased toward the opposite end of the spectrum. However, such individuals may still have “stereotypies” that we have come to associate with the term “autism.”

That being said–if you were appointed “word czar of the day,” and, as such, had the authority to scrap all of our conventional terminology and come up with “new and improved” terms that are more in alignment with a psychosis spectrum–what new terms would you choose?

I conceptualize autism as defect whereby people falsely apply a deterministic model (relevant for the world/ non-living things) to the self/others (living things) ; I consider of psychosis as the reverse, whereby one applies an agentic model to the world, thus exhibiting magical thinking etc. Because psychotic spectrum is consptualised in terms of a disability (loss of contact with reality), I would rechristen autism spectrum as the zombie spectrum (loss of contact with agency); of course, If I indeed am the ‘word czar of the day’ I’ll probably rename both as consciousness-orientation (psychotic spectrum)  and reality-orientation (autistic spectrum) and highlight the good aspects of both- shaministic Altered states of consciousness and creativity of schizotypals and the scientific and savantic abilities of the Aspergers. Of course, in a lighter vein, perhaps the autistic spectrum people are ‘muggles’  (believers in ordinariness ) who still have to come to terms with the ‘magic’ (believers in extraordinariness)  of consciousness.

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synaptic plasticity: angelman’s/autism and psychosis

There is a recent article in Nature Neuroscience by Philpot et al regarding how experience-dependent synaptic plasticity is downregulated in Angelmans’ syndrome and perhaps in Autism too, as the Ube3a gene involved is implicated in both disorders.

First a little history about Angelman– it is a disorder caused by deletion/lack of a maternally imprinted UBE3a gene in chromosomal region 15q11-q13 . It is typically contrasted with Prader-Willi syndrome which is caused by a paternally imprinted gene malfunction in the same chromosomal region. Christopher Badcock has used this to contrast Autism (related to Angelman) and Psychosis (more common in PWS) to argue that Autism and Psychosis are due to a genomic imprinting tug of war between fathers and mothers genes.

I have written about Badcock’s and Crespi’s thesis before and how it fits in with my views on Autism and Psychosis; suffice it to say that I am seeing the new study primarily from this prism of Autism and Psychosis dichotomy.

First , let us see what the study tells us:

It uses mouse model that contains silenced maternal Ube3a genes (Ube3a m-p+ mouse), thus trying to make a mouse model of Angelman.

What it found was:

1)    Ube3a expression was markedly reduced in Ube3am-/p+ mice compared with wild-type mice in all three brain regions (visual neocortex, hippocampus,cerebellam). Consistent with previous observations, this attenuation was brain specific, as Ube3a was highly expressed in the liver of both Ube3am+/p- and Ube3am-/p+ mice.

2) To determine the physiological consequences of Ube3a loss on neocortical development, we examined the developmental acquisition of spontaneous excitatory synaptic transmission by recording miniature excitatory postsynaptic currents (mEPSCs) in layer 2/3 pyramidal neurons of visual cortex (see Supplementary Table 1 online for intrinsic membrane properties of recorded neurons). Consistent with previous findings24, 25, mEPSC amplitudes decreased and frequency increased during development in wild-type mice . Just before eye opening (postnatal day 10, P10), mEPSC frequency and amplitude were indistinguishable between wild-type and Ube3am-/p+ mice . Thereafter, mEPSC frequency failed to develop normally in Ube3am-/p+ mice

3)Although dark rearing had no measurable effect on mEPSC amplitude in wild-type mice at P25 , sensory deprivation strongly attenuated the normal developmental increase in mEPSC frequency in wild-type mice . In contrast, dark rearing did not affect mEPSC amplitude or frequency in Ube3am-/p+ mice. Consequently, mEPSC frequency in normally reared Ube3am-/p+ mice was not significantly different from that of dark-reared wild-type mice . These findings demonstrate that, although Ube3a is not necessary for the initial sensory-independent establishment of synaptic connectivity, it is selectively required for experience-dependent maturation of excitatory circuits.

4)We therefore compared the properties of neocortical long-term depression (LTD) and LTP at layer 2/3 synapses in visual cortex of wild-type and Ube3am-/p+ mice at both young (P25) and adult (P100) ages. Because layer 2/3 pyramidal neurons receive major inputs from layer 4 pyramidal neurons, layer 2/3 field potentials were evoked by layer 4 stimulation . We began by measuring LTD in young mice using a standard stimulation protocol (1 Hz for 15 min). Although LTD was reliably induced in young wild-type mice, it was absent in young Ube3am-/p+ mice . We also observed deficits in LTP induction. A relatively weak induction protocol (three 1-s trains of 40-Hz stimulation) elicited LTP in young wild-type mice, but failed to reliably induce LTP in young Ube3am-/p+ mice . To test whether the neocortex of Ube3am-/p+ mice was capable of expressing LTP, we also applied a strong LTP stimulation protocol (two 1-s trains of 100-Hz stimulation). This protocol consistently induced LTP in both Ube3am-/p+ and wild-type mice. Thus, as with LTP deficits in hippocampus8, 9, the LTP induction machinery is impaired in the visual cortex of Ube3am-/p+ mice and this deficit in LTP can be overcome with strong stimulation.

5)To determine whether the plasticity deficits in Angelman syndrome mice persisted into adulthood, we tested LTD and LTP in adults (P100). In adult wild-type mice, LTD induced by 1-Hz stimulation was absent, as expected27, whereas LTP could be induced with strong stimulation. In adult Ube3am-/p+ mice, however, neither of these protocols were effective at modifying synaptic strength. These results indicate that wild-type mice show attenuated neocortical plasticity as they mature and that this attenuation of plasticity is more severe in the absence of Ube3a . Furthermore, these data indicate that plasticity defects in Angelman syndrome mice persist into adulthood.

..and so on (go read the full paper)

In a nutshell, what they found was that in presence of visual stimuli, the plasticity (measured by LTP/LTD ) of visual cortex was adversely affected. As sensory stimulus would normally be available while developing, this would adversely affect the plasticity in adolescence/ critical periods and also continue into adulthood.

Thus, Autism/ Angelman are charechterised by less synaptic plasticity in adulthood and during critical development periods. Paradoxically, this loss of synaptic plasticity is concomitant on their it being experience-dependent or having sensory stimuli. If the organism is sensory deprived, it may still retain the normal synaptic plasticity exhibited by similar sensory deprived normal people.

How does this relate to Psychosis? If my thesis is correct that autism and Psychosis are opposites, then I would predict that in either prader-willi or in Psychosis (scheziphrenia etc) there should be excessive experience-dependent plasticity. I was glad to learn that I am not the first one to make that proposition, but someone back in 1995 has argued for Hippocampal synaptic plasticity as an endophenotyoe for Episodic Psychosis. I now quote heavily form that article.

Here is the abstract:

Structural change in the hippocampal formation has become popular as a proposed neurobiological substrate for schizophrenic disorders. It is postulated that behavioral plasticity in the form of long-term potentiation of hippocampal synaptic transmission is an attractive putative mechanism for the mediation of transient psychosis. Moreover, the disturbed hippocampal neuroarchitecture found in schizophrenic brain may be susceptible to potentiation and dysfunctional to the degree that delusions and hallucinations develop. Partial and selective blockade of the receptors mediating potentiation may prove to be an efficient means of preventing psychotic episodes and avoiding further damage to the involved network. Basic research, utilizing experimental models such as intraventricular kainic acid injection, may help to clarify the anatomical and physiological substrate of psychosis.

The Main thesis of the paper is:

1. Anatomical, physiological, pharmacological, and behavioral findings are most consistent with the view that neuropathological changes within the limbic system, specifically within the hippocampal formation, may represent a biological substrate of schizophrenia.

2. The biological mechanism underlying transient psychosis may be long-term potentiation (LTP) of synaptic transmission within the hippocampal formation.

3. The effects of dopamine manipulation on these behaviors may be mediated by direct actions on the compromised limbic system of the psychotic patient.

Further:

Associative plasticity within hippocampus occurs in the form of long-term potentiation (LTP), an experience-dependent increase in synaptic efficacy. Experimentally, LTP is produced by tetanic stimulation of afferent systems (Bliss and Lomo 1973) and has been shown to facilitate simple associative learning (Berger 1984) but disrupt more complex forms of associative plasticity (Robinson et al 1989). Hippocampal LTP has been observed to occur as a consequence of stimulus pairings in classical conditioning (Weisz et al 1984) and appears to be mediated by N-methyl-Daspartate (NMDA) receptors (Harris et al 1984). Pharmacological blockade of NMDA receptors has been shown to disrupt learning and memory in a variety of forms, including simple associations (Stillwell and Robinson 1990), spatial learning (Morris et al 1986; Heale and Harley 1990; Shapiro and Caramanos 1990), conditioned fear (Miserendino et al 1990; Kim et al 1991), olfactory memory (Staubli et al 1989) and gustatory memory (Welzl et al 1990). Some evidence, however, suggests that deficits involve motor impairment as well as disrupted learning (Keith and Rudy 1990)

Hippocampal function is particularly sensitive to neurochemical modulation, and the expression of monoamine receptors in the temporal lobe is altered in schizophrenics (Joyce 1993). Antipsychotics that reduce endogenous dopamine levels (Losonczy et al 1987) exert significant effects on the hippocampus and LTP. Trifluoperazine inhibits induction of LTP in hippocampus (Finn et al 1980), whereas the dopamine antagonist domperidone has been shown to prevent the maintenance of LTP (Frey et al 1990). Long-term effects of antipsychotic drugs include functional supersensitivity of hippocampal pyramidal neurons (Bijak and Smialowski 1989). Thus, individuals with deranged hippocampal neuroarchitecture would be prone to cognitive dysfunction (including, perhaps, perceptual distortion and other schizophrenic symptoms), differentially susceptible to stress, and responsive to amelioration of symptoms via dopamine antagonism. It may be more than coincidence that the time lag between administration of antipsychotic medication (which results in near immediate decrement in dopamine levels) and the attenuation of psychotic symptoms weeks later (Kane 1987) is remarkably consistent with the time parameters of LTP decay (Douglas and Goddard 1975). Also, the selective disruption of “weak” associative responses by antipsychotic drugs (van der Heyden and Bradford 1988) is consistent with interactions between NMDA-receptor blockade and stimulation intensity on induction of LTP (Reed and Robinson 1991).

From the above, at least to me, it is clear that anti-psychotics may work by decreasing LTP/LTD that is enhanced in episodic psychosis. A propensity towards increased experience-dependent enhancement of synaptic palsticty may be at work here and paradoxically the same approach of sensory deprivation, as in Angelman/ Autism may work here too.

Here is the summary:

In summary, potentiation of hippocampal synaptic transmission may be the neurophysiological basis of episodic psychosis. (Post [1993] has proposed a similar process in the amygdala as a useful model in understanding the progression of recurrent affective disorders.) More selective blockade of the NMDA receptor, which mediates LTP, may prove an effective means of attenuating positive symptoms and preventing further accrual of cellular damage in hippocampus.

In my own summation, I am convinced that we would find more synaptic plasticity in Psychotic people and that hyper-plasticity to hypo-plasticity is another dimension on which the autistics and psychotics differ and this again is a result of the genomic imprinting mediated tug-pf-war between the maternal and paternal genomes.

ResearchBlogging.org
PORT, R., & SEYBOLD, K. (1995). Hippocampal synaptic plasticity as a biological substrate underlying episodic psychosis Biological Psychiatry, 37 (5), 318-324 DOI: 10.1016/0006-3223(94)00128-P
Koji Yashiro, Thorfinn T Riday, Kathryn H Condon, Adam C Roberts, Danilo R Bernardo, Rohit Prakash, Richard J Weinberg, Michael D Ehlers & Benjamin D Philpot (2009). Ube3a is required for experience-dependent maturation of the neocortex Nature Neuroscience

Low Latent Inhibition, high faith in intuition and psychosis/creativity

Well, the cluster goes together. Previous research has found that Low LI and psychosis (schizophrenia) and creativity are related; previous research has also found that psychotic /some types of creative people have more faith in intuition; and this research ties things by showing that Low LI and high faith in intuition are correlated.

The research under question is by Kaufman and in it he explores the dual-process theories of cognition- the popular slow high road of deliberate conscious reasoning and the fast low road of unconscious processing. I would rather have the high road consist of both cognitive and affective factors and similarly the unconscious low road consist of both cognitive and affective factors. Kaufman focuses on the unconscious low road and his factor analysis reveal three factors: Faith in intuition: a meta cognition about ones tendency to use intuition; Holistic intuition: the cognitive factor; and affective intuition: the affective factor. with this in mind let us see what Kaufman’s thesis is:

He first introduces the low road and the high road:

In recent years, dual-process theories of cognition have become increasingly popular in explaining cognitive, personality, and social processes (Evans & Frankish, 2009). Although individual differences in the controlled, deliberate, reflective processes that underlay System 2 are strongly related to psychometric intelligence (Spearman, 1904) and working memory (Conway, Jarrold, Kane, Miyake, & Towse, 2007), few research studies have investigated individual differences in the automatic, associative, nonconscious processes that underlay System 1. Creativity and intelligence researchers might benefit from taking into account dual-process theories of cognition in their models and research, especially when exploring individual differences in nonconscious cognitive processes.

Then he explain LI:

Here I present new data, using a measure of implicit processing called latent inhibition (LI; Lubow, Ingberg-Sachs, Zalstein-Orda, & Gewirtz, 1992). LI reflects the brain’s capacity to screen from current attentional focus stimuli previously tagged as irrelevant (Lubow, 1989). LI is often characterized as a preconscious gating mechanism that automatically inhibits stimuli that have been previously experienced as irrelevant from entering awareness, and those with increased LI show higher levels of this form of inhibition (Peterson, Smith, & Carson, 2002). Variation in LI has been documented across a variety of mammalian species and, at least in other animals, has a known biological basis (Lubow & Gerwirtz, 1995). LI is surely important in people’s everyday lives—if people had to consciously decide at all times what stimuli to ignore, they would quickly become overstimulated.
Indeed, prior research has documented an association between decreased LI and acute-phase schizophrenia (Baruch, Hemsley, & Gray, 1988a, 1988b; Lubow et al., 1992). It is known, however, that schizophrenia is also associated with low executive functioning (Barch, 2005). Recent research has suggested that in highfunctioning individuals (in this case, Harvard students) with high IQs, decreased LI is associated with increased creative achievement (Carson et al., 2003). Therefore, decreased LI may make an individual more likely to perceive and make connections that others do not see and, in combination with high executive functioning, may lead to the highest levels of creative achievement. Indeed, the link between low LI and creativity is part of Eysenck’s (1995) model of creative potential, and Martindale (1999) has argued that a major contributor to creative thought is cognitive disinhibition.

He then relates this to intuition and presents his thesis:

A concept related to LI is intuition. Jung’s (1923/1971, p. 538) original conception of intuition is “perception via the unconscious.” Two of the most widely used measures of individual differences in the tendency to rely on an intuitive information-processing style are Epstein’s Rational- Experiential Inventory (REI; Pacini & Epstein, 1999) and the Myers-Briggs Type Indicator (MBTI) Intuition/Sensation subscale (Myers, McCaulley, Quenk, & Hammer, 1998). Both of these measures have demonstrated correlations with openness to experience (Keller, Bohner, & Erb, 2000; McCrae, 1994; Pacini & Epstein, 1999), a construct that has in turn shown associations with a reduced LI (Peterson & Carson, 2000; Peterson et al., 2002), as well as with divergent thinking (McCrae, 1987) and creative achievement.

The main hypothesis was that intuitive cognitive style is associated with decreased latent inhibition.

He found support for the hypothesis from his data. It seemed people with low LI were high in faith in intuition factor. Here is what he discusses:

The results of the current study suggest that faith in intuition, as assessed by the REI and the MBTI Thinking/Feeling subscale, is associated with decreased LI. Furthermore, a factor consisting of abstract, conceptual, holistic thought is not related to LI. Consistent with Pretz and Totz (2007), exploratory factor analysis revealed a distinction between a factor consisting of REI Experiential and MBTI Thinking/Feeling and a factor consisting of MBTI Intuition/Sensation and REI Rational Favorability. This further supports Epstein’s (1994) theory that the experiential system is directly tied to affect. The finding that MBTI Intuition/Sensation and REI Rational Favorability loaded on the same factor supports the idea that the type of intuition that is being measured by these tasks is affect neutral and more related to abstract, conceptual, holistic thought than to the gut feelings that are part of the Faith in Intuition factor.

Here are the broader implications:

The current study adds to a growing literature on the potential benefits of a decreased LI for creative cognition. Hopefully, with further research on the biological basis of LI, as well as its associated behaviors, including interactions with IQ and working memory, we can develop a more nuanced understanding of creative cognition. There is already promising theoretical progress in this direction.

Peterson et al. (2002) and Peterson and Carson (2000) found a significant relationship between low LI and three personality measures relating to an approach-oriented response and sensation-seeking behavior: openness to experience, psychoticism, and extraversion. Peterson et al. found that a combined measure of openness and extraversion (which was referred to as plasticity) provided a more differentiated prediction of decreased LI.

Peterson et al. (2002) argued that individual differences in a tendency toward exploratory behavior and cognition may be related to the activity of the mesolimbic dopamine system and predispose an individual to perceive even preexposed stimuli as interesting and novel, resulting in low LI. Moreover, under stressful or novel conditions, the dopamine system in these individuals will become more activated and the individual will instigate exploratory behavior. Under such conditions, decreased LI could help the individual by allowing him or her more options for reconsideration and thereby more ways to resolve the incongruity. It could also be disadvantageous in that the stressed individual risks becoming overwhelmed with possibilities. Research has shown that the combination of high IQ and reduced LI predicts creative achievement (Carson et al., 2003). Therefore, the individual predisposed to schizophrenia may suffer from an influx of experiential sensations and possess insufficient executive functioning to cope with the influx, whereas the healthy individual low in LI and open to experience (particularly an openness and faith in his or her gut feelings) may be better able to use the information effectively while not becoming overwhelmed or stressed out by the incongruity of the situation. Clearly, further research will need to investigate these ideas, but an understanding of the biological basis of individual differences in different forms of implicit processing and their relationship to openness to experience and intuition will surely increase our understanding of how certain individuals attain the highest levels of creative accomplishment.

To me this is exciting, the triad of creative/psychotic cognitive style, intuition and Latent Inhibition seem to gel together. the only grip eI have is that the author could also have measured intuition directly by using some insight problems requiring ‘aha’ solutions; maybe that is a project for future!
ResearchBlogging.org
Kaufman, S. (2009). Faith in intuition is associated with decreased latent inhibition in a sample of high-achieving adolescents. Psychology of Aesthetics, Creativity, and the Arts, 3 (1), 28-34 DOI: 10.1037/a0014822

The bipolar phenotype: Excessive self-regulatory focus?

In my last post I had hinted that bipolar mania and depression may both be characterized by an excessive and overactive self-regulatory focus: with promotion focus being related to Mania and prevention focus being related to depression. It is important to pause and note that the bipolar propensity is towards more self-referential goal-directed activity resulting in excessive use of self-regulatory focus. To clarify, I am sticking my neck out and claiming that depression is marked by an excessive obsession with self-oriented goal directed activities- but with a preventive focus thus focusing more on self’s responsibilities and duties , obligations etc with respect to other near and dear ones. Mania on the other hand, also has excessive self-oriented goal-directed focus, but the focus is promotional with obsession with hopes, aspirations etc, which are relatively more inward-focused and not too much dependent on significant others.

Thus, my characterization of depression as a state where regulatory reference is negative (one is focused on avoiding landing up in a negative end-state like being a burden on others), the regulatory anticipation is negative ( one anticipates pain as a result of almost any act one may perform and thus dreads day-to-day- activity) and the regulatory focus is negative (preventive focus whereby one is more concerned with duties and obligations to perform and security is a paramount need). The entire depressive syndrome can be summed up as an over activity of avoidance based mechanisms. However, please note that still there is an excess of self-referential/self-focused thinking and one is greatly motivated (although might be lacking energy) to bridge the differences between the real self and the ‘ought’ self. One can say that one’s whole life revolves around trying to become the ‘ought’ self, or rather one conceptualizes oneself in terms of the ‘ought’ self.

Contrast this with Mania, where the regulatory reference is positive (one is focused on achieving something grandiose ) , regulatory anticipation is positive (one feels in control and believes that only good things can happen to the self) and regulatory focus is positive (promotional focus whereby one is more concerned with hopes, aspirations etc and growth / actualization needs). Still, juts like in depression there is an excess of focus on self and one is greatly motivated (and also has the energy) to bridge the difference between the real and the ‘ideal’ self. One can say that one’s whole life revolves around trying to become the ‘ideal’ self , or rather one conceptualizes oneslef in terms of an ‘ideal’ self.

What can we predict from above: we know that brain’s default network is involved in self-focused thoughts and ruminations. We can predict, and know for a fact, that the default network is overactive in schizophrenics (and thus by extension in bipolars who I believe have the same underlying pathology, at least as far as psychotic spectrum is concerned)and thus we can say with confidence that indeed the regulatory focus should be high for bipolars and this should be correlated with default network activity. We can also predict that during the Manic phase, the promotion focus related neural network should be more active and in depressive phase the prevention-related areas of the brain should be more active. this last hypothesis still needs experimentation, but lets backtrack a bit and first look at the neural correlates of the promotion and preventive regulatory self-focus.

For this, I refer the readers to an , in my view, important study that tried to dissociate the medial PFC and PCC activity (both of which belong to the default network) while people engaged in self-reflection. Here is the abstract of the study:

Motivationally significant agendas guide perception, thought and behaviour, helping one to define a ‘self’ and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus.

The authors then touch upon something similar to what I have said above, that one can be too much planful or goal-directed (bipolar propensity) , but it would still make sense to find whether the focus is promotional or preventive. To quote:

The idea of variation in individuals’ regulatory focus highlights the difference between agendas and traits; two people could both be described by the trait ‘planful’, but planful about what? A person with a predominantly promotion focus would be more likely to be planful about attaining positive rewards or outcomes, while a person with a predominantly prevention focus would be more likely to be planful about avoiding negative events or outcomes. Although a promotion or prevention focus may dominate, the aspects of the self that are active change dynamically across situations (e.g. Markus and Wurf, 1987), thus most individuals have both promotion and prevention agendas. For example, the same person can hold both the hope of becoming rich (a promotion agenda) and the duty to support an aging parent (a prevention agenda), or the aspiration to be a good citizen and the obligation to be a well-informed voter. As individuals, hopes and aspirations and duties and obligations make up a large part of our mental life and constitute the motivational scaffolding for much of our behaviour.

Now comes the study design:

The present studies investigated neural activity when participants were asked to think about self-relevant agendas related to either a promotion (think about your hopes and aspirations) or prevention (think about your duties and obligations) focus. We compared neural activity associated with thinking about these two different types of self-relevant agendas and with thinking about non-self-relevant topics (distraction). We expected greater activity in anterior and/or posterior medial regions associated with these two self-reflection conditions compared with the distraction control condition because thinking about one’s agendas, like thinking about one’s traits, is self-referential. Such a finding would also be consistent, for example, with Luu and Tucker’s (2004) proposal that both anterior cingulate and posterior cingulate cortex contribute to action regulation by representing goals and expectancies.

And this is what they found:

A double dissociation was found when participants were cued to think about promotion and prevention agendas on different trials for the first time during scanning (Experiment 2) and when they spent several minutes thinking about either promotion or prevention agendas before scanning (Experiment 1), indicating that it results from what participants are thinking about during the scan and not from some general effect (e.g. mood) carried over from the pre-scan period of self-reflection,

Here is what they discuss:

In short, the double dissociation between medial PFC and anterior/inferior medial posterior areas and our two self-reflection conditions indicates that these brain areas serve somewhat different functions during self-focus. There are a number of interesting possibilities that remain to be sorted out. Differential activity in these anterior medial and posterior medial regions as a function of the types of agendas participants were asked to think about could reflect: (i) differences in the representational content in the specific features of agendas, schemas, possible selves and so forth that constitute hopes and aspirations on the one hand and duties and obligations on the other (cf. Luu and Tucker, 2004); (ii) differences in the type(s) of component processes these agendas are likely to engage and/or the representational content they are likely to activate, for example, discovering new possibilities (hopes) vs retrieving episodic memories (e.g. Maddock et al., 2001) of past commitments (duties); (iii) differences in affective significance of hopes and aspirations (attaining the positive) and duties and obligations (avoiding the negative, Higgins, 1997; 1998); (iv) different aspects of the subjective experience of self, such as the subjective experience of control (an instrumental self) vs the subjective experience of awareness (an experiential self; Johnson, 1991; Johnson and Reeder, 1997; compare, e.g. Searle, 1992 and Weiskrantz, 1997, vs Shallice, 1978 and Umilta, 1988); (v) differences in the social significance of hopes and aspirations (more individual) and duties and obligations (involving others). This last possibility is suggested by findings linking the posterior cingulate with taking the perspective of another (Jackson et al., 2006). It may be that thinking about duties and obligations (a more outward focus) tends to involve more perspective-taking than does thinking about hopes and aspirations (a more inward focus). The greater number of mental/emotional references from the promotion group on the pre-scan essay and the tendency for a greater number of references to others from the prevention group are consistent with the hypothesis that medial PFC activity is associated with a more inward focus whereas posterior cingulate/precuneus activity is associated with a more outward, social focus. Clarifying the basis of the similarities and differences between neural activation associated with thinking about hopes and aspirations vs duties and obligations would begin to help differentiate the relative roles of brain regions in different types of self-reflective processing.

They do discuss clinical significance of their studies , but not in terms I would have loved to. I would like to see, whether there is state/trait hyperactivity and dissociation between the mPFC and PCC activation when the variable of depressive episode or manic episode subject is introduced. I’ll place my bets that there would be an interaction between the type of episode and the over activity in the corresponding default-brain regions; but would like to see that data collected.

So my thesis is that the self-reflective and focused default network is overactive in biploar/psychotic spectrum people, but a bias or tilt towards promotion or preventive focus leads to their recurring and periodic episdoes of mania and depression.

Lastly let me touch upon affect in these state and what Higgins had to say about this in his paper covered yesterday. Higgins proposed that bipolar is due to a promotional focus, with mania induced when there is not much mismatch (or awareness of mismatch) between the ideal and real self; while depression or sadness and melancholia induced when one becomes aware of the discrepancy between the ideal and the real self. He proposes that ‘ought’ and real self discrepancy leads to anxiety and nervousness/ agitation; while a preventive focus and congruency between ‘ought’ and real leads to calmness/quiescence.

I disagree with his formulations, in as much as I differentiate between a regulatory focus and the corresponding awareness of discrepancies in that direction. To Higgins they are the same; if someone has a promotional focus , he would also be more aware of the discrepancies between his ideal and real self and thus be saddened. I disagree. I believe that if one has a promotional focus one is driven by goals to make the resl self as close to the ideal self as possible and if one is not able to do so, one would use defense mechanisms to delude oneself , but will not admit to its reality, as the reality of incongruence along the focused dimension is too painful. However, because on is consciously focused on promotions, one would be aware of trade-offs and will acknowledge to himself that his ‘ought’ self, which anyway is not too important for his self-concept, is not congruent to the real self. Thus, one wit a predominant promotion focus may be painfully aware of the discrepancy between his ‘ought’ and real self and thus might be nervous, agitated/ irritable- all symptoms of Mania.

A depressive person on the other hand has a predominant preventive focus and all actions/ ruminations are driven by responsibilities and obligations. Here acknowledging to oneself that one has failed in meeting obligations may be catastrophic so one will try to delude oneself that one is closer to the ‘ought’ self than is the case. However, one may not require any defense mechanisms when judging the discrepancy between the ‘ideal’ and real self as that ‘ideal’ self is no longer a matter of life and death! One would be aware that one is not focusing too much on hopes and aspirations and thus feel despondent/ sad/ melancholic – again classical symptoms of depression. Yet, despite the affect of sadness, all rumination would be focused on ‘ought’ self and thus the content be of guilt, duties, burden, responsibilities, etc.

I’m sure there is some grain of truth in my formulation, but wont be able to state emphatically unless the above proposed dissociation study involving default region and bipolar people is done. If one of you decide to do that, do let me know the results, even if they contradict the thesis.

ResearchBlogging.org
Johnson, M. (2006). Dissociating medial frontal and posterior cingulate activity during self-reflection Social Cognitive and Affective Neuroscience, 1 (1), 56-64 DOI: 10.1093/scan/nsl004
Higgins, E. T. (1997). Beyond pleasure and pain American Psychologist (52), 1280-1300

Self relevance and the reality-fictional blur

There is a new study in PLOS One that argues that we make reality-fictional distinction on the basis of how personally relevant the event in question is. To be fair, the study focuses on fictional, famous or familiar (friends and family) entities like Cinderella, Obama or our mother and based on the fact that these are arranged in increasing order of personal relevance, as well as represent fictional and real characters, tries to show that one of the means by which we try to distinguish fictional from real characters is by the degree of personal relevance these characters are able to invoke in us.

The authors build upon their previous work that showed that amPFC(anterior medial prefrontal cortex) and PCC (Posterior Cingulate cortex), which are part of the default brain network, are differentially recruited when people are exposed to contexts involving real as opposed to fictional entities. From this neural correlate of the regions involved in distinguishing fiction from reality, and from the known functions of these brain regions in self-referential thinking and autobiographical memory retrieval, the authors hypothesized that the reality-fictional distinction may be mediated by the relevance to self and this difference in self-relevance leads to differential engagement of these brain areas. I quote form the paper:

In the first attempt to tackle this issue using functional magnetic resonance imaging (fMRI), we aimed to uncover which brain regions were preferentially engaged when processing either real or fictional scenarios . The findings demonstrated that processing contexts containing real people (e.g., George Bush) compared to contexts containing fictional characters (e.g., Cinderella) led to activations in the anterior medial prefrontal cortex (amPFC) and the posterior cingulate cortex (PCC).

These findings were intriguing for two reasons. First, the identified brain areas have been previously implicated in self-referential thinking and autobiographical memory retrieval. This suggested that information about real people, in contrast to fictional characters, may be coded in a manner that leads to the triggering of automatic self-referential and autobiographical processing. This led to the hypothesis that information about real people may be coded in more personally relevant terms than that of fictional characters. We do, after all, occupy a common social world and have a wider range of associations in relation to famous people. These may be spontaneously triggered and processed further when reading about them. A logical extension of this premise would be that explicitly self-relevant information should therefore elicit such processing to an even greater extent.

To study the above hypothesis they used an experimental study that used behavioral measures like reaction time, correctness and perceived difficulty of judging propositions involving fictional, famous and close entities. Meanwhile they also measured , using fMRI, the differential recruitment of brain areas as the subjects performed under the different entity conditions. The experimental design is best summarized by having a look at the below figure.

What they found was that for the control condition and the fictional condition the reaction time , correctness and perceived difficulty associated with the proposition was signifciantkly different (lower RT, lower correctness and more perceived difficulty) than for the famous and friend entities condition. Thus, from the behavioral data is was apparent that real characters were judged faster , accurately and more easily than fictional characters. The FMRI data showed that , as hypothesiszed, amPFC and PCC were recruited significantly more in personal relevance contexts and showed a gradient in the expected direction. The below figure should summariz the findings:

In particular, in line with our predictions, regions in and near the amPFC (including the ventral mPFC) and PCC (including the retrosplenial cortex) were modulated by the degree of personal relevance associated with the presented entities. These regions were most strongly engaged when processing high personal relevance contexts (friend-real), secondarily for medium relevance contexts (famous-real) and least of all in the low personal relevance contexts (fiction) (high relevance>medium relevance>low relevance).

The amPFC and PCC regions are known to be commonly engaged during autobiographical and episodic memory retrieval as well as during self-referential processing. Regarding their specific roles, there is evidence indicating that amPFC is comparatively more selective for self-referential processing whereas the PCC/RSC is more selective for episodic memory retrieval . The results of the present study contribute to the understanding of processes implemented in these regions by showing that the demands on autobiographical retrieval processes and self-referential mentation are affected by the degree of personal relevance associated with a processed scenario. It should additionally be noted that the extension of the activations in anterior and ventral PFC regions into subgenual cingulate areas indicates that the degree of personal relevance also modulated responsiveness in affective or emotional regions of the brain .

Here is what the authors have to say about the wider ramifications:

That core regions of the brain’s default network are spontaneously modulated by the degree of stimulus-associated personal relevance is a consequential finding for two reasons. Firstly, the findings suggest that one of the factors that guide our implicit knowledge of what is real and unreal is the degree of coded personal relevance associated with a particular entity/character representation.

….

What this might translate to at a phenomenological level is that a real person feels more “real” to us than a fictional character because we automatically have access to far more comprehensive and multi-flavored conceptual knowledge in relation to the real people than fictional characters. This would also explain why a real person we know personally (a friend) feels more real to us than a real person who we do not know personally (George Bush).

I would say that there are other broader implications. First it is important to note that phenomenologically, Schizophrenia/psychosis is charachterized by an inability to distinguish reality from fiction. What is fictious also starts seeming real. A putative mechanism of why even fictional things start assuming ‘real’ dimensions may be the attribution of personal relevance or significance to those fictional entities. If something, even though fictional in nature, become highly personally relevant, then it would be easier to treat it as real. What ties things together is the fact that the default brain network is indeed overactive in the schizophrenics. If the PCC and amPFC are hyperactive, no wonder even fictional entities would be attributed personal relevance and incorporated into reality. I had earlier too discussed the delusions of reference with respect to default network hyperactivity in shizophrenics and this can be easily extended to now account for the loss of contact with reality , with the relevance and reality linkage in place. when everything is self relevant everything is real.

As always I am excited and would like some experiments done with schizophrnics/scizotypals using the same experimental paradigm and finding whether there is significant differences in the behavioral measures between controls and subjects and whether that is mediated by differential engagement of the default brain network. In autistics of course I hypothesize the opposite effects.

Needless to say I am grateful to Neuronarrative for reporting on this and helping me make one more puzzle piece fit in place.

ResearchBlogging.org

Abraham, A., & von Cramon, D. (2009). Reality?=?Relevance? Insights from Spontaneous Modulations of the Brain’s Default Network when Telling Apart Reality from Fiction PLoS ONE, 4 (3) DOI: 10.1371/journal.pone.0004741

Support for the Aberrant Salience hypothesis of Psychosis

Last week I wrote about the aberrant salience theory of psychosis, and luckily, this week itself a new study has surfaced that corroborates that theory with some preliminary evidence.

Thanks to BPS research digest, I have come across this open source research article in Psychological Medicine, that has found evidence for the aberrant salience hypothesis.

What Rosier et al did was to administer a Salience Attribution Test to both patients with Schizophrenia and normal controls, and to look for differences in the adaptive and aberrant salience. It is important to realize that most of the patients were medicated on anti-psychotics, and as per the theory advocated by Shitij Kapur, the anti-psychotics would dampen the normal adaptive salience too as psychosis is due to hyper reactivity of dopamine system and anti-psychotics are supposed to work by attenuating that behavior. More specifically, the predictions were:

It has been hypothesized that dopamine antagonists reduce both adaptive and aberrant salience, and that in the absence of effective treatment patients with schizophrenia exhibit aberrant salience (Kapur, 2003). Therefore, our first prediction was that that medicated patients with schizophrenia would exhibit reduced adaptive salience relative to controls, representing an undesirable side-effect of anti-psychotic medication. Our second prediction was that medicated patients with schizophrenia would exhibit equivalent aberrant salience to controls, representing the beneficial effect of anti-psychotic medication, which is hypothesized to normalize aberrant salience from a previously elevated level (Kapur, 2003). Our third prediction was that those patients with persistent positive symptoms, in whom medication is not entirely effective, would exhibit greater aberrant salience than patients without positive symptoms. Our fourth prediction was that in the controls, individual differences in aberrant salience would be related to the personality trait of schizotypy, considered to be an index of psychosis proneness (Chapman et al. 1994; Claridge, 1994; Stefanis et al. 2004).

All of their predictions were supported by the test results. The SAT paradigm is really simple and depends on reaction time measures following CS+ and CS-; with CS+ reaction times quantifying adaptive salience and CS- reaction times quantifying aberrant salience attribution. Read the methods section for more on the SAT.

Interestingly in patients, those with persisting delusions as well as those high on Negative symptoms exhibited higher aberrant salience as compared to patients/ controls without any delusional symptoms.Also, in controls the introverted anhedonia subscale of schizotypy correlated signficantly with the aberrant salience, thus indicating a role for negative symptom formation/ explanation too as apart of the aberrant salience. This is how the authors interpret their findings:

Aberrant salience and positive symptoms of schizophrenia

One explanation of increased aberrant salience in patients with positive symptoms concerns aberrant dopamine signalling. Contemporary accounts of reward learning suggest that phasic dopamine firing codes reward prediction errors (Schultz et al. 1997), for example, those arising from temporal difference models of reinforcement learning (Dayan & Balleine, 2002). Such models elegantly account for changes in both the firing patterns of ventral tegmental area dopamine neurons in monkeys (Schultz, 1997), and ventral striatal responses in humans (Pessiglione et al. 2006; Seymour et al. 2007), as reward-learning progresses. If phasic dopamine release signals reinforcement prediction errors, any large stochastic fluctuation in dopamine release may disrupt learning about stimulus–reinforcement associations, generating a state in which motivational salience could be misattributed to neutral stimuli, or what might be termed a ‘false-positive’ phasic dopamine signal; such events have been proposed to result in positive symptoms (Kapur, 2003).
In the present study, patients for whom medication had effectively eliminated positive symptoms actually exhibited significantly less aberrant salience than controls, supporting the hypothesis that the beneficial effects of antipsychotic medications on positive symptoms are related to their ability to dampen-down aberrant salience (Kapur, 2003). However, independent of symptoms at the time of testing, the patients with schizophrenia exhibited significantly less adaptive salience than controls. Antipsychotic medication has long been considered to exacerbate negative symptoms in schizophrenia, which may be related to reduced adaptive salience [see discussion below and Schooler (1994) ]. Our findings support the suggestion of Kapur (2003) that this may be a necessary corollary to the beneficial effect of antipsychotic medication on positive symptoms.

Previous studies suggest that antipsychotic medication does not necessarily normalize abnormal dopamine signalling in psychotic patients. For example, functional neuroimaging studies have shown dopamine dysregulation in both medicated and unmedicated patients (Hietala et al. 1995; Abi-Dargham, 2004; McGowan et al. 2004). Therefore persistent symptoms in medicated patients might still be related to aberrant salience. Furthermore, the only other study investigating stimulus–reinforcement learning for appetitive outcomes in psychosis found that both medicated and unmedicated patients responded more quickly to a CS? than controls, a finding interpreted as aberrant salience (Murray et al. 2008). This study also reported that patients exhibited reduced haemodynamic correlates of reward prediction errors in the ventral striatum relative to controls, consistent with other findings in medicated patients (Juckel et al. 2006; Jensen et al. 2008). Nevertheless it will be important to confirm our findings in unmedicated patients.

Aberrant salience and negative symptoms of schizophrenia

Although positive symptoms were associated with increased aberrant salience, our data also suggest a link between aberrant salience and negative symptoms. Aberrant salience correlated not only with negative symptoms in the patients, but also with O-LIFE introvertive anhedonia, which relates to reduced interest and social withdrawal, in the controls. If dopamine transmission is dysregulated in psychosis (Abi-Dargham, 2004), it is possible that ‘false negatives’ in the phasic dopamine signal might occur, i.e. a reinforcement-related stimulus fails to elicit a sufficiently large phasic dopamine response. False negatives would decrease the value of motivationally salient stimuli, possibly leading to symptoms such as avolition, apathy and social withdrawal. Consistent with this explanation, other studies that investigated responses to emotionally salient images in medicated patients with schizophrenia reported decreased responding for (Heerey & Gold, 2007) and ventral striatal responses to (Taylor et al. 2005) positive emotional stimuli relative to controls.

This explanation is also consistent with data from a functional magnetic resonance imaging study investigating the effects of d-amphetamine on reward processing in healthy volunteers. Knutson et al. (2004) found that amphetamine administration paradoxically decreased the magnitude of phasic ventral striatal haemodynamic responses in response to a CS+ that signalled reward (i.e. increasing the potential for a false negative). In the same study, amphetamine administration caused significant phasic haemodynamic responses in the ventral striatum following CS+ that signalled potential monetary loss, an effect that was absent under placebo, possibly reflecting a loss of specificity of dopamine signalling (i.e. increasing the potential for a false positive). The aberrant salience model might therefore explain both positive and negative symptoms by appealing to a common neurobiological mechanism, namely a loss of signal:noise ratio in the mesolimbic dopamine system, possibly as a result of increased tonic dopamine activity (Grace, 1991; Winterer & Weinberger, 2004).

I believe they are on to something, but the explanation for negative symptoms is still not fully fleshed out or convincing. and of course one has to remember that these results are juts with 20 patients so need to be replicated before being put to use/ accepted as orthodoxy.
ResearchBlogging.org
J. P. Roiser, K. E. Stephan, H. E. M. den Ouden, T. R. E. Barnes, K. J. Friston, E. M. Joyce (2008). Do patients with schizophrenia exhibit aberrant salience? Psychological Medicine, 39 (02) DOI: 10.1017/S0033291708003863