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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Get High on Encephalon #62

Welcome to the 62nd brain-dope edition of the brain carnival Encephalon.

Sci@Neurotopia, sets the stage by asking the question whether Prozac and other anti-depressants can be called addictive. While we all know that drugs like cocaine and heroin can be addictive, yet can other benign drugs that we take to relive symptoms that are problematic in the first place, can also be classified as being addictive based on the fact that these drugs show at least two of the DSM criteria for addiction- tolerance and withdrawal? What about their non-high nature or non-craving properties? An interesting discussion ensues, but Sci also seemingly puts her-foot-in-her-mouth by trying to argue that there are two types of addictions- physical and psychological! She makes amend for the same by writing a subsequent post that clarifies that she is not a Dualist who believes that psychological symptoms of addiction like craving are not a result of brain chemistry but indeed does believe that they are as physical in origins as the 'physical' withdrawal symptoms such as constipation. An undertone of the post and comments was that perhaps we need different categories for addiction - one based solely on substance abuse and other more general addiction based on craving and other psychological components included too. DrugMonkey however, seemed to think that this opens a Pandora box for other spurious addictions like net or video-games addiction.

Daniel@Neuroanthropology however is not afraid of rocking the boat, and clearly and persuasively argues for recogintion of psychological as well as physical aspects of addiction. He argues that the fact that we use two systems of inferring causality- the intention based model applied to human interactions and the billiard-ball model of physical causality applied to non-animate interactions; is relevant to addiction and how that is viewed in terms of a disease model or a morality model.Based on his interaction with his class students, he is inclined to believe that we apply intentional model and subjectivity when referring to our own obsessions and to substance dependence, but a disease model when applied to substance abuse. Dependence, involving psychological components , he believes to be more critical.

Although Daniel mentions facebook and related obsession and dependence and not in terms of addiction per se, we all know too well Vaughan's view on the matters of internet and related addictions. This time however, Vaughan@MindHacks is in not a critical mood, but laughing all the way  with the recent discovery that laughing gas (N2O), not to be confused with the brain neuro transmitter nitric oxide, has some hitherto unknown effects on those inhaling it. Laughing gas is a popular anesthetic and it has been found that it increases imagination and suggestibility.It can be safely concluded that suggesting that the surgery will not cause pain, would just enhance the anesthetic effects of N2O by using its suggestibility effects too to the fullest. All that remains to be seen is is N2O addictive and if so would people line up for repetitive surgeries or dental procedures given the ability-to-make-one laugh (and thus imaginably get oneself 'high':-)  effects of the gas!

While inhaling the N20 may not really present an addictive conundrum, what about Deep Brain Stimulation for Pleasure? Sajid@BrainBlogger reports that some studies at Oxford are being carried to ascertain the DBS effects in orbital PFC and how that may affect reward/ pleasure/ Libido. The benefits are to be found in female sexual dysfunction, but bypassing the normal brain circuitry and directly stimulating the brain for pleasure may be more akin to the way the addictive drugs act. what about tolerance and increasing DBS to get the same quantity of reward? What if someone removes the implant , would there be withdrawal effects?

A different type of conundrum is posed by Maria@BrianBlogger as she reports on the face transplant follow-up studies that found that the woman who received face transplant was pleased with the effects though she ostensibly sees a different face in the mirror daily.   She concludes that one should not just screen for organ compatibility, but also psychological coping mechanisms in the case of face transplant as psychological issues are involved here.

When one talks of Psychological coping, who else needs more support than the one being stalked? In the national stalking awareness month swivelchair@NeurologicalCorrelates focuses on stalking and highlights research that found that stalking involved many components of OCD like cognitive inflexibility (being obsessed and feeling compelled) and source-monitoring issues with memory (inability to recall the source of memory) apart from other deficits like lacking an ability to take others' perspective. while we treat stalking as related to OCD, should we also extend and relate it to addiction in general? Is craving for a non-responding beloved the same as craving for a substance as the beloved has been 'objectified' and is worth only as a an object and not as a person? should the same environmental sensitivity and cue based approaches to addiction recovery be applied to stalkers too? Does it make sense to restrict the stalkers from any access to the 'drug' or any environment that reminds them of the 'drug'?

Swivelchair@NeurologicalCorrelates also sends in a post regarding  a hypothesis that aggression may be a result of excessive pruning of white matter tracts. He arrives at this by putting the fact that an ErbB4 gene variant leads  to demyelenation/ less connectivity of left frontotemporal brain region. This region, is also implicated in aggression/hostility and thus his deduction. I have doubts as he mentions the same gene and brain region also implicated in schizophrenia/Psychosis and I disagree that psychotics are in general more aggressive than the normal human population. (although, to be fair, this is not explicitly claimed by Swivelchair anywhere).

Talking of Schizophrrenia, how did such a disease evolve and get fixed in the human population at such a high level of incidence? Walter@HighlightHealth writes about a study that found that genes in the human lineage that were under recent selection pressure and diverged from the chimpanzees , were also related to energy metabolism in the brain and on the same locus are present some of the schizophrenia genes. Thus, he concludes that Schizophrenia is a direct costly byproduct  to the cognitive demands placed during human evolution especially the demands of brain metabolism and maintaining a big brain for greater cognitive work and thus the need to increase efficiency of metabolisms etc. Thus, the assertion that Schizophrenia is a direct result of  changes in metabolism during human brain evolution.

Talking about evolution and comparative methods, did you know how manual dexterity evolved in humans? Mo@Neurophilosophy illustrates how manual dexterity evolved in humans giving us the ability of fine motor control. He notes that we have a direct (synapsing directly on motor neurons)  as well as indirect (involving inter neurons) path from the primary motor coretx to the motor neurons. Also, their appear to be two distinct sub regions of M1- one involving neurons synapsing directly onto the motor neurons and the other synpasing via inter neurons in the spinal chord. Also doing a comparative analysis on Capuchin (who have a prominenet direct as well as indirect pathway like humans)  and Squirrel monkey (who only have the weak direct path) reveals that Capuchins are manually dexterous while Squirrels are not, thus confirming that it is the direct pathway which is anatomically recent and used in fine motor control. Now this is called cutting edge science reporting.   

DoctorSpurt@EffortlessIncitement reports on a study that found correlation between physicological traits like EMG and skin conductance and political attitudes like high support for preserving the social structure form internal/ external threats. In brief, and in a crude reading it found that 'conservatives are cowards'. Put other way, using a variety of measure sit was found that threatening stimuli caused more physiological reaction in those who were of a conservative bent of mind. Now that is some correlation between political attitudes, personality and fearfulness.  

We have talked about aggression and fearfulness and we have talked about evolution. And we know that people differ from each other in their baseline aggressive and fearfulness rates. How does this difference come about. I@TheMouseTrap present evolutionary perspectives on personality traits and I owe a post that would  link the evolution of personality traits to evolution of co-operation/ altruism.

Now, if you have read the Mouse Trap posts, you may wonder if some of the correlations I see between different personality traits and evolutionary adaptive tasks are not spurious and voodoo like? A different kind of voodoo correlation is examined by Neurocrtic , this time referring to the exaggerated and spurious correlation found between fMRI brain regions identified in social cognitive neuroscience and behavioral and personality measures. I haven't read the Vul et al paper, but Neurocritc presents a good summary and details the points-counterpoints that are raised. One thing that caught my attention, off-the-bat,  was the confusion of state personality variables with trait variables (anxiety or empathy can be measured as both trait and state variables). While the trait variable correlations in personality psychology may be low (~ 0.7); I'm not sure the measures that measure state variables (like anxiety at the present moment ) suffer from same level of reliability concerns (but how can we test-retest a state...isn't the state bound to change with each experiment). Anyway the discussion is very enlightening and Neurocritic rejoices in seeing the others slither in pain as their studies are put to question . Oh Schadenfreude.!   

One thing however that Neurocritic does put into question is the allure of fMRI brain scans and how having a brain scan in a study can lead to credibility.Dr Deb at her blog links to a provocative study that found that more brain areas lit up when net surfing than when reading. So do we conclude that net surfing, is good for your health? If so, as its effects are largely beneficial, can we still consider it as an addiction? We seem to have come a full circle.

Before I conclude, just a brief note to let all of you know that you can now subscribe to the encephalon feed here and to many other health and medicine related carnivals here.

That is all for this edition. hope you got your kicks and are dependent on the fortnightly dose of enecpehalon to maintain your sanity. BTW, did anyone miss the 5 Jan edition of encepahlon....did someone suffer from withdrawal symptoms? do let us know via comments!

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The Varieties of Altruistic Experiences

Altruism is a very heavily loaded word  in evolutionary psychology/ biology and I would not add to the confusion by defining the term myself. Suffice it to say , that I will use it in all of its various intuitive and theoretical usages.

The evolution of biological Altruism is generally considered as a challenge to Darwinian evolution and there are thought to be two main theories of how Altruism is possible or has evolved. These are Hamilton's Kin-selection and inclusive fitness theory and Trivers' Reciprocal Altruism theory, though some prominent people disagree that there are indeed two separate phenomenon at work and try to argue that they are one and the same phenomenon. 

I would argue instead that there are more varieties of Altruism than the above two- and that it may also be beneficial to decompose the phenomenon of kin selection and reciprocal altruism into their sub components and to to derive/ elucidate the proximate mechanisms that are involved in these phenomenon as opposed to a single-minded focus on the ultimate explanations of why and how such models can give rise to altruism.

To that effect I would like to separate the parental-investment and parent-child 'kid-selection' effects from other genetic relatives or 'kin-selection' effects. The reason I believe they are separate is because having a child or Kid involves bringing in a new relative with 0.5 relatedness in this world , so the cost to bring in to the parent can be very high as post facto (childbirth) the inclusive fitness becomes 1.5 +0.5b-c (cost) while earlier it was only 1.  Thus, the act can be undertaken if 0.5 +0.5b>c.  In the kin selection case however the inclusive fitness is 1-c +0.5+ 0.5*b after the altruistic act vis-a-vis 1.5 before the act ; so  the act can only be undertaken if 0.5b>c . the addition of a constant 0.5 to the first equation changes the dynamics to a large extent and thus my idea to keep the two phenomenon separate.

Also, reciprocal altruism can itself be broken into some differing phenomenons. The first phenomenon is generalized reciprocity (which is even found in rats , see also this) and others are direct, indirect and strong reciprocity. To summarize form an earlier post:

As per what is know about the evolution of Altruism, it is surmised that co-operation in groups emerges based on four types of reciprocity- direct, indirect, strong and generalized.

In direct reciprocity, one helps another person/animal because the other animal has helped oneself in the past. This requires cognitive capacities to recognize different individuals and require social memory as to which member of the group had helped and which had defected or free loafed. While some animals like the Elephant have good social memories and the ability to remember and recognize different individuals, most animals fall short on these traits.

In indirect reciprocity, one helps another because one has observed the other guy to have helped someone else. This again requires cognitive capacities to recognize and also to remember This is more so based on a reputation system, wherein you start trusting someone more if you observe him doing good deeds. In return you are likely to help the do-gooder , when he is in time of need.

In strong reciprocity, people punish the defectors or free-loafers or non-cooperators. This requires sophisticated cognitive abilities to recognize the defectors and a willingness to undergo cost to oneself while punishing the defector. This too, along with the above two, has rarely been observed in animals apart from humans.

Finally, generalized reciprocity happens when one indulges in good deeds towards a stranger just based on the fact that one has in the near future received such help from other strangers/ con specifics. There are variations on this theme, whereby if people have been put in a good mood (which is a substitute for having received a good deed) they are more likely to indulge in altruistic acts like picking up books dropped by a confederate. This type of reciprocity does not make very strong cognitive demands as one just has to remember the summary of whether the environment is cooperative or not, to produce the right kind of behavior.

So based on above I would like to differentiate between two clusters of reciprocity: Generalized reciprocity not requiring sophisticated cognitive mechanisms, but requiring global assumptions about the social environment; and strong, direct and indirect reciprocity - all involving sophisticated cognitive mechanisms but not dependent on assumptions about the global social environment.

With this I would now like to move to my main thesis. I argue that altruism is a social and group phenomenon and to understand all the proximal mechanisms that are involved in altruistic acts we have to appreciate the mechanisms and drives that lead to group formation, group cohesion and expansion and finally group thriving or differential success from other similar groups based on selection of members belonging to the group such that their is non-zero sum benefits of being in the group.

I would argue that all of the above can be understood in the eight stage framework, with the first three stages related to group formation; the next two related to investment in group (expanding or making it cohesive) and the last three related to populating the group with better individuals/ creating a suitable group that has maximum payoffs for all.

To start with , let us revisit the eight basic adaptive problems as elaborated here and here.

1. The first problem to be solved 'foe' is also the first primary driver for the evolution of groups. Groups or herd evolve per se, because a solitary creature is more vulnerable to predation than as part of a group. This is how herding evolved. The proximate mechanism working at this level is that of merging with a group. 
2. The second problem to be solved 'food' is the secondary driver for evolution of groups. It is envisaged that hunting/ gathering as part of a group leads to better  and bigger catches than are individually possible. this provides the incentive to work with other group members to hunt/ forage. This introduces the problem of who would eat the catch when one of them kills, but others are part of the raid party. The solution to the above problem is achieved using the mechanisms of sharing of the spoils. Thus, the proximate mechanism working at this level is a tendency to share the food / resources when begged for by those who are of the same band/ herd/ raiding party.  
3. The third problem to be solved is 'friends' or con-specifics themselves. As all the group members  are competitors in the same niche, they have to learn to form alliances and co-operate in non-zero sum games with other partners when such co-operation does not entail a price and leads to mutual benefit.the example here would be that of grooming. A bird cannot remove lice from the top of its own head , but can do so easily if another friend removes the lice for her. This is a nonzero sum game. by co-operating both gain and nobody loses. The grooming can happen simultaneously so there is no reciprocity or memory involved. The proximate mechanism here is that of grooming or befriending (spending time with other just to make the alliance better).
4. The fourth problem to be solved is that of 'kids' and how to help those vulnerable, but related individuals. The kid-selection and parental investment concerns dominate here and lead to emergence of altruism directed towards ones offspring. Now the proximate mechanism devised to help in kid selection is that of care or empathy and this extends to all those who are sick,  vulnerable, infirm or unable to fend for themselves. The care ethic is born and is most visible in contexts where the mother-child or provider-infirm relationship can be activated. Help in rearing infants by related aunts etc is an example of this mechanisms.
   
5. The fifth problem to be solved is that of 'kin' or all the other related individuals in the group. Kin selection comes into picture, but for it to work one has to properly identify 'like' people, who are likely to share genes. It is presumed that selection favored those who can judge likeness of phenotype from likeness of genotype and a a simplistic scenario could be that all the group members are considered as like and one tries to identify with them. This is as opposed to trying to differentiate from them and treating them as not-like. Thus, the proximate mechanism involved could be that of loyalty to the group and identification with the group as opposed to rebelliousness/ unconventionality/ differentiation from the group. The drive to find 'like' and 'related' individuals could easily lead to the ethic of community/ loyalty towards the self identified group. Also, forgiveness instinct towards those considered part of group and hence pertaining to valuable relationships that should be maintained despite small annoyances.
   
6. The sixth problem to be solved is that of 'selecting' a partner/ partners with which one could indulge in altruistic games. Here the payoff to another would be at a cost to oneself and hence it is not a simple case of co-operation or mutualism in which both parties would benefit. Ideally, when partners have not been determined a priori and one has to discover the characteristics of the majority of the partners (or the population)  and at the same time not harm oneself by unconditional altruistic costs, the viable strategy would be to play with many diverse individuals and play using a generalized reciprocity scheme. At the end of many iterations, one can look at ones strategy and depending on how much altruistic or selfish it is, determine the characteristics of the population. This requires minimal cognitive demands as in not requiring the ability to remember individual interactions. In simple words this can be dubbed as Trust. You trust other people as you do not really know them, except in so far as they are part of the group and hence likely to have a majority group characteristic.  thus, a typical example would be ultimatum game. though the person with which you may playing may be stranger, you know a few things from your generalized reciprocity interactions with other individuals to know that majority of them are fair (make offers at 50 %) and also punish small splits. Thus, based on how you yourself have been given endowments in the past (and how others have rejected endowments given by you) you can reasonably play an ultimatum game with a stranger with same population wide results. Thus, the proximate mechanism here is that of Trusting others to be like the general population stereotype. thus, in humans, most of us are 'altruistic'/ 'good' and hence we trust well rather than be suspicious.             
7. The seventh task is that of seducing or attracting the right kind of partners so that the payoff the group, and hence yours, increases. Three separate mechanisms are at work here. Direct reciprocity harnesses our ability to remember individuals to pay them back in the future. Gratitude is the proximal mechanism that ensures that we do indeed pay back when time comes. Strong reciprocity ensures that we pay back, in another sense of the term, to the free-riders / defectors. By having punishment in the system one can ensure that the group is not overtaken by free-riders and defectors. The proximal mechanism active here is that of vengeance and not letting the culprits go off scot free. Indirect reciprocity on the other hand works on third party interactions and is based on respect , that is a generalized reputation of an agent to be 'good'/'bad' and acting towards them based on their reputations rather than their immediate behaviors. The proximate mechanism active here is respect/ authority. 
8. The eighth task is to secure the group or keep the group well-knit and isolate form other 'corrosive' groups. One problem that poses a hurdle to group securing is unexpected payoffs (like war loot) and how they are handled by the group. They may be distributed to everyone equally, distributed as per a hierarchy or consumed by a few dominant individuals.Here the ethics of fairness and equality is the proximate mechanism that is used to settle matters. Another important factor here is not to let other group members infiltrate the successful group and subvert it from within. This gives rise to the ethic of purity and sanctity : the group is considered pure and sanctimonious and only other pure individual are allowed to join the group. The perverts within the group may be destroyed/ redeemed/ salvaged.                     

Thus, in my view, altruism involves all these proximal mechanisms: merging, sharing, grooming and befriending, caring, loyalty (identifying and forgiving), trusting; justice as in gratitude (positive justice),vengeance (negative justice) and respect (generalized justice); and finally the ethics of fairness/equality and purity /sanctity. Some of these can be easily mapped to Haidt's five basic moral foundations.

In a follow-up post I will try to show how these eight altruistic proximate mechanism are reflected in personality traits especially with reference to HEXACO personality model to which one of my readers pointed me to.

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