An online personality guessing experiment

I came to know of You Just Get Me experiment today, courtsey PsychCentrals post on the top 10 online psychology experiments .

In a nutshell, the site lets you guess the personality of a person based on clues he provides. In my case the public clues I have provided are my photograph and my facebook profile. Now, as a fun experiment, I'll request all my readers to go to that site and try to guess my personality from these , as well as additional clues you might have got following my blogging practices and habits. Its bound to be fun and I believe the questionnaire has correctly guessed my personality (OCEAN based) and I have a separate application on facebook that profiles my personality (please do not take a sneak peak at it to guess my personality) and I found that the two personality characterizations do corroborate each other.

So, please go ahead and guess me; and of course if yopu like put some data on the site for your personality analysis too. Go to this link to guess my personality.

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Encephalon #64 up at the Neurocritic

The 64th edition of Encephalon is up at the Neurocritic and has been exceptionally well presented. Neurocritic embeds all the articles in context, sometimes linking to other external sources, and also providing a seamless flow between the varied topics that are covered. The articles themselves are very good, and include submissions from some new blogs other than the usual suspects.A couple of my favorites include a construal level-procrastination linkage study and a DAT-KO mice couldn't get high on cocaine study. There is more at the source, so head over to there.

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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.

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

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On Reading Darwin

12 th of February was Darwin day, and I decided to study an original text of Darwin to honor the occasion. I chose the 'Expression of emotions in Man and animals' as my first text as I am familiar with the work of Paul Ekman and have had a deep fascination with the subject and wanted to find out how much Darwin had anticipated and got right in his times.I have only read the introduction and the first chapter till now, but am surprised at the level of modernity visible in Darwin's analysis.

Of course Darwin takes an evolutionary view on the subject and is also cognizant of the subtleness of the entire field.

He who admits on general grounds that the structure and habits of all animals have been gradually evolved, will look at the whole subject of Expression in a new and interesting light.

The study of Expression is difficult, owing to the movements being often extremely slight, and of a fleeting nature. A difference may be clearly perceived, and yet it may be impossible, at least I have found it so, to state in what the difference consists. When we witness any deep emotion, our sympathy is so strongly excited, that close observation is forgotten or rendered almost impossible; of which fact I have had many curious proofs. Our imagination is another and still more serious source of error; for if from the nature of the circumstances we expect to see any expression, we readily imagine its presence. Notwithstanding Dr. Duchenne's great experience, he for a long time fancied, as he states, that several muscles contracted under certain emotions, whereas he ultimately convinced himself that the movement was confined to a single muscle.

He then lists the various ways he plans to get to universal features of emotional expressions. These involve using questionnaires given to various anthropologists to discover if the emotions are expressed in a similar fashion all over the world ;and the study of infants and insane as they may have unadulterated / extreme emotional expressions respectively. He also briefly touches upon the usefulness of studying emotional expressions as depicted by Masters in painting in sculpture but finds the method wanting. Lats , but not the least, he studied emotional expression in other animals and treated emotional expression as a continuum.

Sixthly, and lastly, I have attended. as closely as I could, to the expression of the several passions in some of the commoner animals; and this I believe to be of paramount importance, not of course for deciding how far in man certain expressions are characteristic of certain states of mind, but as affording the safest basis for generalisation on the causes, or origin, of the various movements of Expression. In observing animals, we are not so likely to be biassed by our imagination; and we may feel safe that their expressions are not conventional.

He then lists the three basic principles of emotional expressions. I list them verbatim.

I. _The principle of serviceable associated Habits_.--Certain complex actions are of direct or indirect service under certain states of the mind, in order to relieve or gratify certain sensations, desires, &c.; and whenever the same state of mind is induced, however feebly, there is a tendency through the force of habit and association for the same movements to be performed, though they may not then be of the least use. Some actions ordinarily associated through habit with certain states of the mind may be partially repressed through the will, and in such cases the muscles which are least under the separate control of the will are the most liable still to act, causing movements which we recognize as expressive. In certain other cases the checking of one habitual movement requires other slight movements; and these are likewise expressive.

II. _The principle of Antithesis_.--Certain states of the mind lead to certain habitual actions, which are of service, as under our first principle. Now when a directly opposite state of mind is induced, there is a strong and involuntary tendency to the performance of movements of a directly opposite nature, though these are of no use; and such movements are in some cases highly expressive.

III. _The principle of actions due to the constitution of the Nervous System, independently from the first of the Will, and independently to a certain extent of Habit_.--- When the sensorium is strongly excited, nerve-force is generated in excess, and is transmitted in certain definite directions, depending on the connection of the nerve-cells, and partly on habit: or the supply of nerve-force may, as it appears, be interrupted. Effects are thus produced which we recognize as expressive. This third principle may, for the sake of brevity, be called that of the direct action of the nervous system

.

The first principal is easy to understand. It basically states that facial expression etc are associated with mental emotional states and do so by way of habit formation or association. Now, this should not exclude instinctual emotional expressions like smiling as they become fixed by the action of evolution.

The second principle has had only some relatively moderate success. I remember a recent study claiming that Fear and Disgust had opposite effects on facial muscle movements such that Fear led to movements (like broadening of eyes/ dilation of pupils)that allowed more information/material to be ingested; while disgust led to constriction of nose, eye, mouth etc. although Fear and disgust are not antithetical, one may discern similar patterns in other movements.

The third again, I believe has mixed success. It can be ralete to Jams-lange theory of emtoions, where nervous arousal happens first, and emotional feeling or expressions accompanying them follow next.


I am only thus far in my reading of Darwin, but surely will keep doing follow up posts.

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Psychosis and Salience dysregulation

Regular readers of this blog will know that I subscribe to the incentive salience theory of doapmaine propounded by Berridge et al. As per this theory dopamine mediates the salience of an internal/ external stimulus and endows and activates the motivational salience related to that stimulus. In simple words the mesolimbic dopamine systems serves to identify the importance of a stimulus to us- be it aversive or pleasurable. This conceptualization is different from the hedonic pleasure theory of dopamine and distinguishes between 'wanting/ dreading' and 'liking/ disliking'. Thus, the amount of doapminergic activity will affect the degree of dread or want associated with a stimulus, but not the actual liking/ disliking of the reward/punishment administered following the stimulus. Till now we have been talking mostly in terms of classical Pavlovian conditioning, but the same incentive salience can be extended to operant conditioning paradigm, with the external stimulus being replaced by an internal intention and the mesolimbic dopamine system activity determining whether, and to what degree,  one is motivated to perform the intended action. Again the motivational component should be separated from our actual liking/disliking of the expected outcomes of the behavioral measures.  Thus, we may actually like the reward at the end of operant behavior less , but still be highly motivated to perform the action depending on high dopaminergic activity that confers a very positive incentive salience to that operant behavior. Consider the gambler for whom winning the jackpot is motivationally very salient , but the actual pleasure he may derive or hedonistic value he may get from spending the lottery amount may not be that much. Or consider the carving of a drug addict for the dope- the drug administered may not feel that pleasurable ,  but the wanting is strong.

We also know about the reward error-prediction theory of dopamine, and that in my opinion is not incompatible with the incentive salience theory. The error coding signal of dopamine surge or ebb signals that the stimulus has become meaningful and salient and needs to be (re)coded. Thus, in most basic terms dopamine will signal whether the stimulus is meaningful for the organism and as it could be meaningful in both positive and negative sense , the dopamine activity will lead to subjective feelings of either alarm or significance associated with that stimulus. In either case, the stimulus would 'grab our attention' and become salient (this may happen unconsciously) and perhaps if the activity is sustained also become consciously significant and enter consciousness.

Now, consider a dysregulated mesolimbic dopamine system that is hyperactive and is characterized by excessive dopamine synthesis, release and synaptic presence. Here , for a given stimulus, that usually, and in normal individuals,  grabs the unconscious attention and is unconsciously and automatically evaluated , the dopamenirgic activity may be sustained and lead to conscious perception of/ attention to the stimulus and a conscious evaluation or appraisal of the stimulus. The individual with such a hyperactive dopaminergic system would start paying conscious attention to many stimulus that were earlier processed subliminally and start noticing a much deeper sensory (external) and cognitive( internal) world. But the effect would not just be a richness of sensation and distractibility, the dopamine surge will also label the stimulus to which the attention has thus been directed salient and the individual will try to reason why that stimulus is significant.So first sensory (vividness)  and cognitive (racing thoughts) richness arrives, along with an overwhelming subjective feeling that they are important and later with a need to create a story as to why the stimulus (internal/ external)  is important comes rationalizing and delusions that serve to jutify the significance of things that were earlier not consciously significant/threatening. Thus, the delusions of grandeur and persecution.  Also, sometimes the dopamine surges may happen without any associated external and internal stimulus. We know that when one is not task-oriented (either task involving external stimulus or internal goal-directed activity), then the default network that is usually associated with self-system and imagination takes over. In such conditions when the default network is active and one is just focused on self and internal imaginary world, a dopamine surge may signal that the self and imagination is very salient or important. The self thus becoming salient may get associated with other arbitrary external stimulus happening at that time and one may get delusions of reference whereby seemingly innocuous and impersonal external communications/ references are deemed to refer to the self.  thus, delusions may be partly explained by stimuli becoming consciously significant and also stimuli/ self becoming salient out of context.  Hallucinations might also be explained partly by the imaginative activity of the default newtrok becoming salient , meaningful, conscious and life-like and thus sort of 'real'. Thus, while many have outgrown the unconscious-becoming-conscious theories of psychosis, I see some scope for more work here and a possible mechanism too.

Of course the above incentive salience hyper activation can work in conjunction with other deficits/abnormalities like self-monitoring deficit, theory-of-mined hyperactivity, intentional attribution hyperactivity, need for more control in lieu of facing an unpredictable environment, jumping-to-conclusion bias etc to foster full fledged symptoms of psychosis in some individuals.

I am grateful to Mind Hacks for discovering the Shitij Kapur paper on the incentive dysregulation theory of psychosis and I now quote extensively form the paper.

First the paper establishes the dopamine theory of psychosis by looking at anti-psychotic drug action and also the effect of dopamine administration.

The dopamine hypothesis of schizophrenia has comprised two distinct ideas: a dopamine hypothesis of antipsychotic action and a dopamine hypothesis of psychosis. The two are related but different. The dopamine hypothesis of antipsychotic medications can be traced to the early observation that antipsychotics increase the turnover of monoamines , more specifically, dopamine , and this observation anticipated the discovery of the "neuroleptic receptor" , now called the dopamine D2 receptor, providing a mechanistic basis for the dopamine hypothesis of antipsychotic action. A central role for D2 receptor occupancy in antipsychotic action is now well established, buttressed by neuroimaging studies using positron emission tomography and single photon emission computed tomography. However, the importance of dopamine receptors in the treatment of psychosis does not by itself constitute proof of the involvement of dopamine in psychosis .

Early evidence for a role of dopamine in psychosis was the observation that psychostimulant agents that trigger release of dopamine are associated with de novo psychosis and cause the worsening of psychotic symptoms in patients with partial remissions. Further evidence came from postmortem studies that showed abnormalities in dopaminergic indexes in schizophrenia, although the interpretation of these data was always confounded by drug effects . The most compelling evidence in favor of the dopamine hypothesis emerges from neuroimaging studies . Several studies have shown that patients with schizophrenia, when psychotic, show a heightened synthesis of dopamine , a heightened dopamine release in response to an impulse , and a heightened level of synaptic dopamine . While there are some indications of a change in the number of receptors , the claim remains controversial . Thus, on balance there is reasonable evidence of heightened dopaminergic transmission, more likely a presynaptic dysregulation than a change in receptor number, in patients with schizophrenia. This role of dopamine in psychosis and schizophrenia needs to be put in perspective. First, it is quite likely that the dopaminergic abnormality in schizophrenia is not exclusive (as other systems are involved), and it may not even be primary . Second, the dopaminergic disturbance is likely a "state" abnormality associated with the dimension of psychosis-in-schizophrenia, as opposed to being the fundamental abnormality in schizophrenia . As suggested by Laruelle and Abi-Dargham , "Dopamine [is] the wind of the psychotic fire." If so, how does dopamine, a neurochemical, stoke the experience of psychosis?

After this he looks at the incentive salience theory of dopamine.

Another account of the roles of dopamine is the incentive/motivational salience hypothesis of Berridge and Robinson and similar proposals by others . This latter conceptualization provides the most plausible framework for the current discussion and will be detailed further in this article.

The motivational salience hypothesis in its current form builds on the previous ideas of Bindra and Toates , who have written about incentive motivation, and of neurobiologists such as Fibiger and Phillips , Robbins and Everitt , Di Chiara , Panksepp , and others who have speculated on the role of dopamine in these motivated behaviors. According to this hypothesis, dopamine mediates the conversion of the neural representation of an external stimulus from a neutral and cold bit of information into an attractive or aversive entity . In particular, the mesolimbic dopamine system is seen as a critical component in the "attribution of salience," a process whereby events and thoughts come to grab attention, drive action, and influence goal-directed behavior because of their association with reward or punishment . This role of dopamine in the attribution of motivational salience does not exclude the roles suggested by previous theorists; instead it provides an interface whereby the hedonic subjective pleasure, the ability to predict reward, and the learning mechanisms allow the organism to focus its efforts on what it deems valuable and allows for the seamless conversion of motivation into action . When used in this sense, the concept of motivational salience brings us a step closer to concepts such as "decision utility" that are used to explain and understand the evaluations and choices that humans make . Conceived in this way, the role of dopamine as a mediator of motivational salience provides a valuable heuristic bridge to address the brain-mind question of psychosis-in-schizophrenia.

Then he goes to his main thesis that psychosis can be considered as a disorder of salience. Note the similarities as well as differences from my conceptualization as above.

It is postulated that before experiencing psychosis, patients develop an exaggerated release of dopamine, independent of and out of synchrony with the context. This leads to the assignment of inappropriate salience and motivational significance to external and internal stimuli. At its earliest stage this induces a somewhat novel and perplexing state marked by exaggerated importance of certain percepts and ideas. Given that most patients come to the attention of clinicians after the onset of psychosis, phenomenological accounts of the onset of psychosis are largely anecdotal or post hoc. However, patients report experiences such as, "‘I developed a greater awareness of.... My senses were sharpened. I became fascinated by the little insignificant things around me’" ; "Sights and sounds possessed a keenness that he had never experienced before" ; "‘It was as if parts of my brain awoke, which had been dormant’" ; or "‘My senses seemed alive.... Things seemed clearcut, I noticed things I had never noticed before’" . Most patients report that something in the world around them is changing, leaving them somewhat confused and looking for an explanation. This stage of perplexity and anxiety has been recognized by several authors and is best captured in the accounts of patients: "‘I felt that there was some overwhelming significance in this’" ; "‘I felt like I was putting a piece of the puzzle together’" .

If this were an isolated incident, perhaps it would be no different from the everyday life experience of having one’s attention drawn to or distracted by something that is momentarily salient and then passes. What is unique about the aberrant saliences that lead to psychosis is their persistence in the absence of sustaining stimuli. This experience of aberrant salience is well captured by this patient’s account: "‘My capacities for aesthetic appreciation and heightened sensory receptiveness...were very keen at this time. I had had the same intensity of experience at other times when I was normal, but such periods were not sustained for long and had also been integrated with other feelings’" . From days to years (the prodrome) , patients continue in this state of subtly altered experience of the world, accumulating experiences of aberrant salience without a clear reason or explanation for the patient.

Delusions in this framework are a "top-down" cognitive explanation that the individual imposes on these experiences of aberrant salience in an effort to make sense of them. Since delusions are constructed by the individual, they are imbued with the psychodynamic themes relevant to the individual and are embedded in the cultural context of the individual. This explains how the same neurochemical dysregulation leads to variable phenomenological expression: a patient in Africa struggling to make sense of aberrant saliences is much more likely to accord them to the evil ministrations of a shaman, while the one living in Toronto is more likely to see them as the machinations of the Royal Canadian Mounted Police. Once the patient arrives at such an explanation, it provides an "insight relief" or a "psychotic insight" and serves as a guiding cognitive scheme for further thoughts and actions. It drives the patients to find further confirmatory evidence—in the glances of strangers, in the headlines of newspapers, and in the lapel pins of newscasters.

Hallucinations in this framework arise from a conceptually similar and more direct process: the abnormal salience of the internal representations of percepts and memories. This could account for the gradation in the severity of hallucinations, whereby to some people they seem like their own "internal thoughts," to others their own "voice," to others the voice of a third party, and to some others the voice of an alien coming from without . So long as these events (delusions and hallucinations) remain private affairs, they are not an illness by society’s standards . It is only when the patient chooses to share these mental experiences with others, or when these thoughts and percepts become so salient that they start affecting the behavior of the individual, that they cross over into the domain of clinical psychosis.

In the remaining part of the paper the author proposes how anti-psychotics work by dampening the salience of things and how they should be adjuncted with psychotherapy as the salience of delusional ideas/ hallucinations may be dampened immediately, but it takes traditional psychological work on the part of the patients to attenuate/overcome the already established beliefs/ perceptions that are no longer salient. I recommended reading the article in full as it has immense treatment implications.

Another implication of the paper is questioning the categorical diagnostic criteria of schizophrenia/ psychosis and making it more dimensional in nature by positing that the dysregulations of incentive salience happens in a continuum. this theme is more boldly covered in a recent BJP paper that argues that we rename schizophrenia to incentive dysregulation syndrome.

Analogous to the metabolic syndrome, although in need of improving on the weaknesses that since its introduction have become apparent, many people with positive psychotic experiences, that have been shown to constitute a fundamental alteration in salience attribution, also display evidence of alterations in other dimensions of psychopathology such as mania,disorganisation and developmental cognitive deficit. This may be referred to as the salience dysregulation syndrome. If the values of the dimensional components in this syndrome rise above a certain threshold, need for care (formal or informal) may arise. Depending on which combinations of dimensional psychopathology are most prominent in this salience dysregulation syndrome and taking into account which elements have been shown to possess the best diagnostic specificity, as discussed above, the categorical representation of this dimensional psychopathology may be expressed using three sub-categories: with affective expression (high in mania/depression dimension); with developmental expression (high in developmental cognitive deficit/negative symptoms); and not otherwise specified. The first two sub-categories are based on evidence of specificity and the more agnostic category of ‘not otherwise specified’ reflects the continuing gap in knowledge.

This I believe is welcome change and I have been arguing endlessly for psychosis to be seen as more of a dimensional syndrome (with autism at the other end) and in continuum with normality.

Shitij Kapur (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. (160), 13-23
J. van Os (2009). A salience dysregulation syndrome The British Journal of Psychiatry, 194 (2), 101-103 DOI: 10.1192/bjp.bp.108.054254

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Why Science Matters: a Year of the Science 2009 question

COPUS has been celebrating the Year Of Science 2009 and on the their main page their is a link to Why Science Matters that links to Alom Shaha's site Why is Science Important.

Now we all know that EDGE asks an annual question to leading figures in academia/ intelligentsia and compiles their answers together and publishes as a book. That to me has always provided a rich perspective on contemporary matters. Alom and COPUS, in a similar vein, have asked a very topical question for the Year of Science 2009, which is as to Why Science Matters. This question they have put to prominent people in science education, research, writing, teaching and journalism (bloggers included). People who have answered include scientists  like Dr Susan Blackmore, and there are a variety of perspectives from scientists steeped in diverse fields ranging theoretical physics to molecular biology.

I have been honored to participate in the same and you can read my full response here. Below, I am just providing a small teaser so that you indeed go to the main site to read my and others opinions as to why science matters.

Consider the problem posed by some people whose behavior is crazy or erratic as compared to the rest of the ‘normal’ and ‘sane’ individuals. These might have been labeled heretics or witches in the dark ages and deemed to be possessed by demons / spirits. Lacking a scientific insight into what really haunts and ails this ‘mad’ condition, the cure advised for the treatment / containment of the problem (insanity) would also be similarly non-scientific and irrational. Thus the burning at stakes in the middle ages of those who were perhaps suffering from some form of a mental illness, but were nevertheless characterized as being possessed by ‘spirits’ and thus in need of exorcism. If insanity is seen form this dualistic lens of an alien spirit having possessed the body, then one can easily see how witch-burning might have been a legitimate solution to the problem of insanity.

.......

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Perosnality and Neurotransmitters

Although all introductory Psychology textbooks warn against any simplistic correlations between neurotransmitters and complex behavioral and cognitive measures like Personality traits, I am going to do exactly that in this post. In an earlier post , I had related personality traits to neurotransmitter systems and operant learning paradigm and here I present some corroborating evidence for the personality- neurotransmitter system linkage.

First to recap:

1. Nueroticism/ Harm Avoidance: Serotonin system
2. Conscentiousness/ novelty seeking: Dopamine system
3. Extarversion/ Reward Dependence:  Norepinephrine system 
4. Agreeableness/ Persistance: Epinepherine system
5. Openesses/ Rebeliious-conformity/self-directedness: Histamine system

 First off to bat consider the following- Neuroticism is manifested as anxiety and if serotonin system is implicated , then genes affecting the serotonin system should affect the neuroticism levels of individuals . This is exactly what was found by Lesh et al.

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.

Next comes a recent study finding that a gene variant related to NO (a neurotrasmitter) is related to Impulsiveness. Now One of the defining traits of NS/ C is Impulsiveness. This has been found related to NOS1 gene. Here is the original study.

Context Human personality is characterized by substantial heritability but few functional gene variants have been identified. Although rodent data suggest that the neuronal isoform of nitric oxide synthase (NOS-I) modifies diverse behaviors including aggression, this has not been translated to human studies.

Objectives To investigate the functionality of an NOS1 promoter repeat length variation (NOS1 Ex1f variable number tandem repeat [VNTR]) and to test whether it is associated with phenotypes relevant to impulsivity.

Design Molecular biological studies assessed the cellular consequences of NOS1 Ex1f VNTR; association studies were conducted to investigate the impact of this genetic variant on impulsivity; imaging genetics was applied to determine whether the polymorphism is functional on a neurobiological level.

Setting Three psychiatric university clinics in Germany.

Participants More than 3200 subjects were included in the association study: 1954 controls, 403 patients with personality disorder, 383 patients with adult attention-deficit/hyperactivity disorder (ADHD), 151 with familial ADHD, 189 suicide attempters, and 182 criminal offenders.

Main Outcome Measures For the association studies, the major outcome criteria were phenotypes relevant to impulsivity, namely, the dimensional phenotype conscientiousness and the categorical phenotypes adult ADHD, aggression, and cluster B personality disorder.

Results A novel functional promoter polymorphism in NOS1 was associated with traits related to impulsivity, including hyperactive and aggressive behaviors. Specifically, the short repeat variant was more frequent in adult ADHD, cluster B personality disorder, and autoaggressive and heteroaggressive behavior. This short variant came along with decreased transcriptional activity of the NOS1 exon 1f promoter and alterations in the neuronal transcriptome including RGS4 and GRIN1. On a systems level, it was associated with hypoactivation of the anterior cingulate cortex, which is involved in the processing of emotion and reward in behavioral control.

Conclusion These findings implicate deficits in neuronal signaling via nitric oxide in moderation of prefrontal circuits underlying impulsivity-related behavior in humans.

Now there does exist a relationship between NO and dopamine (but then which two neurotransmitter systems are not related) and that way I can still save my face by claiming that it is the dopamine that is finally mediating the impulsivity and not NO.

There is evidence suggesting that nitric oxide (NO) may play an important role in dopamine (DA) cell death. NO may act as a neuroprotector or neurotoxic agent in dopamine neurons, depending on cell redox status. Glutathione (GSH) depletion is the earliest biochemical alteration shown to date in brains of Parkinson's disease (PD) patients. However, data from animal models show that GSH depletion by itself is not sufficient to induce nigral degeneration. Low NO concentrations have neurotrophic effects on DA cells via a cGMP-independent mechanism that may implicate up-regulation of GSH. On the other hand, higher levels of NO induce cell death in both DA neurons and mature oligodendrocytes that is totally reverted by soluble factors released from glia. Alterations in GSH levels change the neurotrophic effects of NO in dopamine function into neurotoxic, under these conditions, NO triggers a programmed cell death with markers of both apoptosis and necrosis characterised by an early production of free radicals followed by late activation of the sGC/cGMP/PKG pathway. Arachidonic acid metabolism through the 12-lipoxygenase (12-LOX) pathway is also central for this GSH-NO interaction. Neurotrophism of NO switches into neurotoxicity after GSH depletion, due to persistent activation of the ERK-1/2 signaling pathway in glial cells. The implication of these cell death signaling pathways in pathological conditions like Parkinson's disease, where GSH depletion, glial dysfunction and NO overproduction have been documented, are discussed.

Next we move to the sociability factor underlying Extraversion/ Reward dependence. Here studies show that Noardrenaline is related to sociability/ dependence etc. Here is a study showing effects of NA on sociability.

Rationale: Treatment with antidepressants has been shown to affect social functioning, but drugs with actions on different neurotransmitters may have a different profile of effects. Objective: To study the effects of acute manipulation of two neurotransmitters, serotonin and noradrenaline, on social behaviour in healthy volunteers. Methods: Sixty volunteers were randomly assigned to a single dose of a selective noradrenaline reuptake inhibitor, reboxetine (4 mg), a selective serotonin reuptake inhibitor, citalopram (10 mg), or placebo. They socially interacted with a confederate behaving in a non-sociable manner in a stranger-dyadic social interaction paradigm 1.5 h postdrug. Social behaviour during the interaction was video recorded by a hidden camera and subsequently analysed. After the interaction, volunteers played the mixed-motive game with the confederate. This game has been shown to measure cooperative behaviour and communication. Volunteers read a short story and rated their mood predrug and before and after the interaction. Results: Subjects on reboxetine showed reduced hand fiddling during the interaction and gave significantly more cooperative communications during the mixed-motive game. More volunteers on reboxetine were classified as cooperative players. On the reading task, the speech of subjects on citalopram showed less reduction of energy variation after the social interaction. Conclusion: Reboxetine had clear effects on social behaviour. Noradrenaline was related to increased social engagement and cooperation and a reduction in self-focus. Citalopram had less effect on cooperative behaviour but serotonin may be associated with protection of the self from the negative consequences of social interaction.

Also, Zuckerman has clearly related NA to sociability and dependence.As per him:

Ellison studies the effects of chemical lesions of either dopamine or noradrenaline system in rats. ...Norepeinepherine-lesioned rats spent more time in their burrows and less time in a behavioral arena in which spontaneous social interactions could occur....

That takes us to the fourth trait of agreeableness and the related Empathy system . Here the famous Scacter- singer experiment of administering Adrenaline and then finding that the mood became congruent with that of other people has to be reinterpreted in terms of empathy at work rather than james-lange two-step appraisal of emotion. Do read the expermine in more detail at the above link.

The Experiment in a nut shell.
Independent Variables

1. Injected Adrenaline or Saline solution
2. The subjects were given a description of side-effects, misinformed about the side-effects, or told nothing.
3. The subjects were placed in a 'Euphoric' (Happy) or 'Angry' situation.

Dependent Variables

1. Observed signs of happiness
2. Observed signs of anger
3. Self-report of happiness or anger

Results:
Euphoria: As expected, the adrenaline misinformed group, and the adrenaline ignorant group, reported being happiest
Anger:  This didn't work. Most subjects were positive about their feelings. Schachter and Singer attribute this to the fact that they were students eager to please their tutors

It is important that those people who were placed with confederates exhibiting happy states felt happy and the same was felt by those who received adrenaline; a more valid interpretation is that adrenaline increased the empathetic feelings and lead to transmission or contagion of mood. the situational variable where one tried to induce anger by being irritable did not lead to to anger; perhaps if the confederate was irritated, they might have become irritated too due to empathy; but no anger is expected as per my interpretation that it is empathy that is primary and not the cognitive appraisal of emotional physiological state.

Finally I agree that I have not been able to find much about histamine system and how it may be affect the openness/ rebellious/conformity trait. As an exercise to reader here are some low histamine condition links.

That is it for now. would love if somebody points to some other studies that corroborate the case.

K.-P. Lesch, D. Bengel, A. Heils, S. Z. Sabol, B. D. Greenberg, S. Petri, J. Benjamin, C. R. Muller, D. H. Hamer, D. L. Murphy (1996). Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region Science, 274 (5292), 1527-1531 DOI: 10.1126/science.274.5292.1527
Wai Tse, Alyson Bond (2002). Difference in serotonergic and noradrenergic regulation of human social behaviours Psychopharmacology, 159 (2), 216-221 DOI: 10.1007/s00213-001-0926-9

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The Default Brain Network: implications for Autism and Schizophrenia

This blog post has been triggered by a recent news article that found that the default network in schizophrenics was both hyperactive and hyperconnected during rest, and it remained so as they performed demanding cognitive tasks. To quote:

The researchers were especially interested in the default system, a network of brain regions whose activity is suppressed when people perform demanding mental tasks. This network includes the medial prefrontal cortex and the posterior cingulate cortex, regions that are associated with self-reflection and autobiographical memories and which become connected into a synchronously active network when the mind is allowed to wander.

Whitfield-Gabrieli found that in the schizophrenia patients, the default system was both hyperactive and hyperconnected during rest, and it remained so as they performed the memory tasks. In other words, the patients were less able than healthy control subjects to suppress the activity of this network during the task. Interestingly, the less the suppression and the greater the connectivity, the worse they performed on the hard memory task, and the more severe their clinical symptoms.

“We think this may reflect an inability of people with schizophrenia to direct mental resources away from internal thoughts and feelings and toward the external world in order to perform difficult tasks,” Whitfield-Gabrieli explained.

The hyperactive default system could also help to explain hallucinations and paranoia by making neutral external stimuli seem inappropriately self-relevant. For instance, if brain regions whose activity normally signifies self-focus are active while listening to a voice on television, the person may perceive that the voice is speaking directly to them.

The default system is also overactive, though to a lesser extent, in first-degree relatives of schizophrenia patients who did not themselves have the disease. This suggests that overactivation of the default system may be linked to the genetic cause of the disease rather than its consequences.

The study on which this report is based , is supposedly published in advanced online PNAS edition of 19 jan, but I am unable to locate it. However, my readers know my obsession with Autism and Schizophrenia as diametrically opposed disorders theory and so I was seen reading all the other relevant studies related to default Network and especially how it may be differentially and oppositely activated in Autism and Schizophrenia.

First I would like to refer you to an extremely good overview of Default Network by Buckner, Schacter et al which is freely available. I'll now present some quotes from the paper that are relevant to my thesis. I start with the abstract:

Thirty years of brain imaging research has converged to define the brain's default network—a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.

Some snippets from the introduction:

A common observation in brain imaging research is that a specific set of brain regions—referred to as the default network—is engaged when individuals are left to think to themselves undisturbed . Probing this phenomenon further reveals that other kinds of situations, beyond freethinking, engage the default network. For example, remembering the past, envisioning future events, and considering the thoughts and perspectives of other people all activate multiple regions within the default network . These observations prompt one to ask such questions as: What do these tasks and spontaneous cognition share in common? and what is the significance of this network to adaptive function? The default network is also disrupted in autism, schizophrenia, and Alzheimer's disease, further encouraging one to consider how the functions of the default network might be important to understanding diseases of the mind. (emphasis mine)

Then they review some history including how default brain activity was recognized when it was found that metabolic demands and blood glucose consumption of brain as a whole remained the same even when the brain was at 'rest' viv-a-vis involved in an active task. They also review how when baseline PET/fMRI rest activity was compared to many disparate tasks related fMRI/ PET activity , then while some task-relevant areas showed activations related to baseline, many correlated areas of brain, the default network, showed deactivation in the task-related conditions as compared to baseline. The modern interpretation is that the default network is active at rest and places metabolic demands on the brain. They then reference the seminal work of Rachile et al and how that made the default network as a study area in itself.

They further elaborate on how the default network may be identified as an interconnected and functional brain system and list various approaches like spontaneous correlations at rest, seeding from a RoI and determining the areas correlated to activity in seed region etc, to determine the components of the default network. While dMPFC and PCC are implicated in all analysis, the case for vMPFC, IPL, HF+ and LTC is also strong.

I'll skip most of this stuff , including comparative analysis. Suffice it to note here that the default brain regions are up to 30% more metabolically demanding then the rest of the brain and are recently evolved/ selected for. this becomes significant in view of recent studies showing that schizophrenia may be a result of selection for metabolism related genes.

The interesting part begins when trying to determine the behavioral/cognitive correlates of this default brain activity. The consensus seems to be that it is used for daydreaming, reconstructing the past, simulating the future, taking other peoples perspective, self-referential processes and in general stimulus independent thought.

A shared human experience is our active internal mental life. Left without an immediate task that demands full attention, our minds wander jumping from one passing thought to next—what William James (1890) called the "stream of consciousness." We muse about past happenings, envision possible future events, and lapse into ideations about worlds that are far from our immediate surroundings. In lay terms, these are the mental processes that make up fantasy, imagination, daydreams, and thought. A central issue for our present purposes is to understand to what degree, if any, the default network mediates these forms of spontaneous cognition. The observation that the default network is most active during passive cognitive states, when thought is directed toward internal channels, encourages serious consideration of the possibility that the default network is the core brain system associated with spontaneous cognition, and further that people have a strong tendency to engage the default network during moments when they are not otherwise occupied by external tasks.

Support for the same is then provided. The next task the authors undertake is that of determining the function, usefulness and evolutionary rationale for this default brain activity. Two ,in my opinion not mutually exclusive, theories are offered. One is simulation of something that is not tied to current reality (whether it be past memories, future expectations and scenarios or other peoples intentions, beliefs, perspectives). The other theory is that the default mode is a diffused attentional/ exploration state and is suppressed by foveal attention/task focus. The over activity of default network in Schizophrenia can be related to both theories equally well.

In this section, we explore two possible functions of the network, while recognizing that it is too soon to rule out various alternatives. One possibility is that the default network directly supports internal mentation that is largely detached from the external world. Within this possibility, the default network plays a role in constructing dynamic mental simulations based on personal past experiences such as used during remembering, thinking about the future, and generally when imagining alternative perspectives and scenarios to the present. This possibility is consistent with a growing number of studies that activate components of the default network during diverse forms of self-relevant mentalizing as well as with the anatomic observation that the default network is coupled to memory systems and not sensory systems. Another possibility is that the default network functions to support exploratory monitoring of the external environment when focused attention is relaxed. This alternative possibility is consistent with more traditional ideas of posterior parietal function but does not explain other aspects of the data such as the default network's association with memory structures. It is important to recognize that the correlational nature of available data makes it difficult to differentiate between possibilities, especially because focus on internal channels of thought is almost always correlated with a change in external attention . We also explore in this section an intriguing functional property of the default network: the default network operates in opposition to other brain systems that are used for focused external attention and sensory processing. When the default network is most active, the external attention system is attenuated and vice versa.

To me both the Sentinel and the Internal Mentation hypothesis appear to be somewhat valid and relevant to Schizophrenia. One can attribute Psychosis to both increased 'watchfulness' and and increased internal mentation or mentalizing and I have written about the second hypothesis in detail previously.

The most relevant part of the paper is their discussion of Autism, Schizophrenia and Alzheimer's. I reproduce the entire autism and Schizophrenia section , highlighting a few points:

Autism Spectrum Disorders

The autism spectrum disorders (ASD) are developmental disorders characterized by impaired social interactions and communication. Symptoms emerge by early childhood and include stereotyped (repetitive) behaviors. Baron-Cohen and colleagues (1985) proposed that a core deficit in many children with ASD is the failure to represent the mental states of others, as needed to solve theory-of-mind tasks. Based on an extensive review of the functional anatomy that supports theory-of-mind and social interaction skills, Mundy (2003) proposed that the MPFC may be central for understanding the disturbances in ASD. Given the convergent evidence presented here that suggests the default network contributes to such functions, it is natural to explore whether the default network is disrupted in ASD.

Developmental disruption of the default network, in particular disruption linked to the MPFC, might result in a mind that is environmentally focused and absent a conception of other people's thoughts. The inability to interact with others in social contexts would be an expected behavioral consequence. It is important to also note that such disruptions, if identified, may not be linked to the originating developmental events that cause ASD but rather reflect a developmental endpoint. That is, dysfunction of the default network and associated symptoms may emerge as an indirect consequence of early developmental events that begin outside the network.

Many studies have explored whether ASD is associated with morphological differences in brain structure. The general conclusion from this literature is that the brain changes are complex, reflecting differences in growth rates and attenuation of growth (see Brambilla et al. 2003 for review). At certain developmental stages these differences are manifest as overgrowth and at later stages as undergrowth. Early observations have implicated the cerebellum. A further consistent observation has been that the amygdala is increased in volume in children with ASD (e.g., Abell et al. 1999, Schumann et al. 2004), perhaps as a reflection of abnormal regulation of brain growth (Courchesne et al. 2001). While not discussed earlier because of our focus on cortical regions, the amygdala is known to contribute to social cognition (Brothers 1990, Adolphs 2001, Phelps 2006) and interacts with regions within the default network. The amygdala has extensive projections to orbital frontal cortex (OFC) and vMPFC (Carmichael & Price 1995).

Of perhaps more direct relevance to the default network, dMPFC has shown volume reduction in several studies of ASD that used survey methods to explore regional differences in brain volume (Abell et al. 1999, McAlonan et al. 2005). The effects are subtle and will require further exploration, but it is noteworthy that, of those studies that have looked, several have noted dMPFC volume reductions in ASD. Of interest, a study using voxel-based morphometry to investigate grey matter differences in male adolescents with ASD noted that several regions within the default network exhibited a relative increase in grey matter volume compared to the control population (Waiter et al. 2004). Because this observation has generally not been replicated in adult ASD groups, future studies should investigate whether complex patterns of overgrowth and undergrowth of the regions within the default network exist in ASD and, if so, whether they track behavioral improvement on tests of social function (see also Carper & Courchesne 2005).

Kennedy and colleagues (2006) recently used fMRI to directly explore the functional integrity of the default network in ASD. In their study, young adults with ASD and age-matched individuals without ASD were imaged during passive tasks and demanding active tasks that elicit strong activity differences in the default network. While the control participants showed the typical pattern of activity in the default network during the passive tasks, such activity was absent in the individuals with ASD. Direct comparison between the groups revealed differences in vMPFC and PCC. Moreover, in an exploratory analysis of individual differences within the ASD group, those individuals with the greatest social impairment (measured using a standardized diagnostic inventory) were those with the most atypical vMPFC activity levels (Fig. 16). An intriguing possibility suggested by the authors of the study and extended by Iacoboni (2006) is that the failure to modulate the default network in ASD is driven by differential cognitive mentation during rest, specifically a lack of self-referential processing.

Another recent study using analysis of intrinsic functional correlations showed that the default network correlations were weaker in ASD (Cherkassky et al. 2006).Of note, the individuals with ASD showed differences in a fronto-parietal network that has been recently hypothesized to control interactions between the default network and brain systems linked to external attention (Vincent et al. 2007b). These data in ASD suggest an interesting possibility: the default network may be largely intact in ASD but under utilized perhaps because of a dysfunction in control systems that regulate its use.

Schizophrenia

Schizophrenia is a mental illness characterized by altered perceptions of reality. Auditory hallucinations, paranoid and bizarre delusions, and disorganized speech are common positive clinical symptoms (Liddle 1987). Cognitive tests also reveal negative symptoms, including impaired memory and attention (Kuperberg & Heckers 2000). These symptoms lead to questions about their relationship to the default network for a few reasons. The first reason surrounds the association of the default network with internal mentation. Many symptoms of schizophrenia stem from misattributions of thought and therefore raise the question of an association with the default network because of its functional connection with mental simulation. A second related reason has to do with the broader context of control of the default network. While still poorly understood, there appears to be dynamic competition between the default network and brain systems supporting focused external attention (Fransson 2005, Fox et al. 2005, Golland et al. 2007, Tian et al. 2007, see also Williamson 2007). Frontal-parietal systems are candidates for controlling these interactions (Vincent et al. 2007b). The complex symptoms of schizophrenia could arise from a disruption in this control system resulting in an overactive (or inappropriately active) default network. The normally strongly defined boundary between perceptions arising from imagined scenarios and those from the external world might become blurry, including the boundary between self and other (similar to that proposed by Frith 1996).

Three studies have provided preliminary data supporting the possibility that the default network is functionally overactive. Garrity and colleagues (2007) recently reported an analysis of correlations among default network regions in patients with schizophrenia. Studying a sizable data sample (21 patients and 22 controls), they explored task-associated activity modulations within the default network and identified largely similar correlations among default network regions in patients and controls. Differences were noted in specific subregions, as were differences in the dynamics of activity as measured from the timecourses of the fMRI signal. Of particular interest, they noted that within the patient group, the positive symptoms of the disease (e.g., hallucinations, delusions, and thought confusions) were correlated with increased default network activity during the passive epochs, including MPFC and PCC/Rsp. In a related analysis, Harrison et al. (2007) noted accentuated default network activity during passive task epochs in patients with schizophrenia as contrasted to controls, again suggesting an overactive default network. Moreover, within the patient group, poor performance was again correlated with MPFC activation during the passive as compared to the active tasks. Finally, Zhou and colleagues (2007) found that regions constituting the default network were functionally correlated with each other to a significantly higher degree in patients than in control participants. Thus, while the data are limited, these studies converge to suggest that patients with schizophrenia have an overactive default network, as would be expected if the boundary between imagination and reality were disrupted. Overactivity within the network correlates with task performance (Harrison et al. 2007) and clinical symptoms (Garrity et al. 2007).

I now link to two abstracts form Autism and default network research by Kennedy et al:

Several regions of the brain (including medial prefrontal cortex, rostral anterior cingulate, posterior cingulate, and precuneus) are known to have high metabolic activity during rest, which is suppressed during cognitively demanding tasks. With functional magnetic resonance imaging (fMRI), this suppression of activity is observed as “deactivations,” which are thought to be indicative of an interruption of the mental activity that persists during rest. Thus, measuring deactivation provides a means by which rest-associated functional activity can be quantitatively examined. Applying this approach to autism, we found that the autism group failed to demonstrate this deactivation effect. Furthermore, there was a strong correlation between a clinical measure of social impairment and functional activity within the ventral medial prefrontal cortex. We speculate that the lack of deactivation in the autism group is indicative of abnormal internally directed processes at rest, which may be an important contribution to the social and emotional deficits of autism.

In their discussion they make explicit the fact that in Autism, the default Netwrok may be under active.

There are two possible reasons why the ASD group failed to show the typical deactivation effect. One possibility is that midline resting network activity during both rest and task performance is high, and, thus, a subtraction between these conditions would reveal no difference in activity levels. We believe, however, that it is unlikely that high midline network activity was maintained during the cognitively demanding number task in autism for several reasons. First, as mentioned previously, behavioral performance was similar between control and ASD groups. This result, however, would be unexpected if the ASD group were carrying out additional mental processing that control subjects inhibit during cognitively demanding conditions. Second, positron-emission tomography studies of autism, which provide an absolute measure of brain metabolism, have found reduced, as opposed to increased, glucose metabolism in rACC and PCC (36) during task performance, as compared with controls. Furthermore, one positron-emission tomography study found that lower blood flow in MPFC and rACC at rest was correlated with more severe social and communicative impairments in subjects with autism (37), a finding similar to our correlational results. Third, reduced anatomical volumes and neurochemical deficiencies have consistently been observed in MPFC∕rACC in adults with autism (reviewed in ref. 26), likely indicative of a reduced functioning of these regions. Therefore, an alternative explanation, the one to which we attribute the lack of deactivation, is that midline activity is low during rest. We suggest, then, that the absence of deactivation in this network indicates that the mental processes that normally occur at rest are absent or abnormal in autism.

What are these mental processes that dominate during rest? Evidence in the literature to date seems to suggest that tasks that induce certain types of internal processing activate this resting network. Examples of such tasks are self- and other-person judgments (4, 6, 7, 19–22, 38–45), person familiarity judgments (24, 25), emotion processing (15–17, 46), perspective-taking (22, 47), passive observation of social interactions vs. nonsocial interactions (18), relaxation based on interoceptive biofeedback (48, 49), conceptual judgments (based on internal knowledge stores) vs. perceptual judgments (50), and episodic memory tasks (51), among others [moral decision making (52), joint attention experience (23), and pleasantness judgments (53)]. Therefore, the activity in these regions at rest might simply reflect the extent to which these types of internally directed thoughts are engaged at rest. In fact, a particularly intriguing behavioral study found that individuals with ASD report very different internal thoughts than control subjects (54, 55), lending support to our interpretation that an absence of this resting activity in autism may be directly related to abnormal internal thought. Admittedly, this is a speculative hypothesis but one that can be explicitly tested.

Another of their recent papers comes to the same conclusion.

Recent studies of autism have identified functional abnormalities of the default network during a passive resting state. Since the default network is also typically engaged during social, emotional and introspective processing, dysfunction of this network may underlie some of the difficulties individuals with autism exhibit in these broad domains. In the present experiment, we attempted to further delineate the nature of default network abnormality in autism using experimentally constrained social and introspective tasks. Thirteen autism and 12 control participants were scanned while making true/false judgments for various statements about themselves (SELF condition) or a close other person (OTHER), and pertaining to either psychological personality traits (INTERNAL) or observable characteristics and behaviors (EXTERNAL). In the ventral medial prefrontal cortex/ventral anterior cingulate cortex, activity was reduced in the autism group across all judgment conditions and also during a resting condition, suggestive of task-independent dysfunction of this region. In other default network regions, overall levels of activity were not different between groups. Furthermore, in several of these regions, we found group by condition interactions only for INTERNAL/EXTERNAL judgments, and not SELF/OTHER judgments, suggestive of task-specific dysfunction. Overall, these results provide a more detailed view of default network functionality and abnormality in autism.

If you want to read more about Schizophrenia - default network linkage , read here. If you want to read about Default Network in general , read here ( a very good blog I have recently discovered).

I think the case is settled that at least in the case of Default Network activations, Schizophrenia and Autism are on opposite poles. One has too much default brain activity, the other too little. Also, the function of default network suggests that it is primarily the focus on self and the ability to imagine that is disrupted in autism and heightend to dramatic effects in Schizophrenics.


R. L. BUCKNER, J. R. ANDREWS-HANNA, D. L. SCHACTER (2008). The Brain's Default Network: Anatomy, Function, and Relevance to Disease Annals of the New York Academy of Sciences, 1124 (1), 1-38 DOI: 10.1196/annals.1440.011
D. P. Kennedy, E. Courchesne (2008). Functional abnormalities of the default network during self- and other-reflection in autism Social Cognitive and Affective Neuroscience, 3 (2), 177-190 DOI: 10.1093/scan/nsn011
D. P. Kennedy (2006). Failing to deactivate: Resting functional abnormalities in autism Proceedings of the National Academy of Sciences, 103 (21), 8275-8280 DOI: 10.1073/pnas.0600674103

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