Category Archives: psychosis

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.
ResearchBlogging.org
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

Badcock on Edge: the imprinted gene theory of ASD/ PSD

This edition of Edge features an article by Christopher Badcock, about the imprinted gene theory of Autism Spectrum disorders and the psychotic spectrum disorders that he has been developing with Crespi.  It is a must read and has been very nicely done.

He goes on to list the differences between autism and psychosis in a tabular form and then extends this to list the differences between mentalistic and mechansitic cognitions.




Autism/Asperger’s syndrome Psychosis/Paranoid schizophrenia
gaze-monitoring deficits delusions of being watched/spied on
apparent deafness/insensitivity to voices hallucination of and hyper-sensitivity to voices
deficits in interpreting others’ intentions erotomania/delusions of persecution
deficits in appreciating shared-attention/groups delusions of conspiracy
theory of mind deficits magical ideation/delusions of reference
deficit in sense of personal agency/episodic memory megalomania/delusions of grandeur
literalness/inability to deceive delusional self-deception
pathological single-mindedness pathological ambivalence
early onset late onset



Mentalistic Cognition Mechanistic Cognition
psychological interaction with self and others physical interaction with nature and objects
uses social, psychological, and political skills uses mechanical, spatial, and engineering skills
deficits in autism, augmented in women accentuated in autism, augmented in men
voluntaristic, subjective, particularistic deterministic, objective, universal
abstract, general, ambivalent concrete, specific, single-minded
verbal, metaphoric, conformist visual, literal, eccentric
top-down, holistic, centrally-coherent bottom-up, reductionistic, field-independent
epitomized in literature, politics, and religion epitomized in science, engineering, and technology
‘pseudo-science’: astrology, alchemy, creationism ‘hard science’: astronomy, chemistry, Darwinism
nurtured: culturally- and personally-determined natural: factually- and genetically-determined
belief-based therapies: placebos, faith-healing, psychotherapy etc. physical effect-based therapies: drugs, surgery, physiotherapy, etc.

He lists down some of the other arguments that I have made viz the fact that Valproic acid exposure in childhood/ pregnancy causes Autism, while valproic acid is used for treating psychosis. Overall it is a very interesting read and a must read.

He also tries to address the mCDD (or simultaneous occurence of Autism and Schizophrenia) in his article, though I find that part the least convincing. Here is what he has to say:

The model appears to rule out anyone suffering from an ASD and a PSD simultaneously, and such co-morbidity does appear to be rare—but is not unknown. However, I know of cases of individuals diagnosed with bipolar disorder who also show unmistakable signs of ASD during their non-manic phases. Indeed, I have research on one individual who suffers from severe gaze-aversion, autistic deficits in a sense of self and social anxiety most of the time, but who becomes comfortable with other people during manic episodes when his sense of self hypertrophies into megalomania with the feeling that he is the returned Jesus Christ! Furthermore, there is evidence of both ASD and PSD in Newton and Beethoven, and incontrovertibly so in the Nobel-prize winning mathematician John Nash. Here the theory predicts that the ASD must come first (typically in childhood) and leave a permanent savant-like basis later built on by hyper-mentalistic tendencies to produce an unusually broadened and dynamically-balanced cognitive configuration: that of true genius.

I find this fascinating and agree with Badcock that the theory leads to many predictions and all these are testable; so we are witnessing a new paradigmatic shift in our understanding of these neurodevelopmental disorders and further experiments would definitely lend more credence to this theory in my view.

Decision-making research in autism and schizophrenia: Implications for each other

Today I would like to review two recent articles on decision-making: one concerned with autism or ASD and the other with Schizophrenia individuals. I would like to demonstrate how some of the findings fit in, in the larger context of Autism and Schizophrenia as diametrical poles on a continuum.

The first article is by Martino et al, and discusses a finding that those with ASD display more consistent and logical decision-making that is immune to framing effects.  Here is the abstract of the study:

The emotional responses elicited by the way options are framed often results in lack of logical consistency in human decision making. In this study, we investigated subjects with autism spectrum disorder (ASD) using a financial task in which the monetary prospects were presented as either loss or gain. We report both behavioral evidence that ASD subjects show a reduced susceptibility to the framing effect and psycho-physiological evidence that they fail to incorporate emotional context into the decision-making process. On this basis, we suggest that this insensitivity to contextual frame, although enhancing choice consistency in ASD, may also underpin core deficits in this disorder. These data highlight both benefits and costs arising from multiple decision processes in human cognition.

Here is the introduction:

Logical consistency across decisions, regardless of how choices are presented, is a central tenet of rational choice theory and the cornerstone of modern economic and political science. Empirical data challenge this perspective by showing that humans are highly susceptible to the manner or context in which options are cast, resulting in a decision bias termed the “framing effect”. We have previously shown that the amygdala mediates this framing bias, a finding that highlights the importance of incorporating emotional processes within models of human decision making. An ability to integrate emotional contextual information into the decision process provides a useful heuristic in decision making under uncertainty. This is a factor that is likely to assume considerable importance during social interactions in which information about others is often incomplete, ambiguous, and not easily amenable to standard inferential reasoning processes.

In this study, we investigated the effect of contextual frame on choice behavior of individuals with autistic spectrum disorder (ASD). Autism is a neurodevelopmental disorder characterized by deficits in social interaction, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior, interests, and activities. From Kanner’s earliest description, it has been recognized that individuals with ASD have a strong tendency to focus on parts rather than global aspects of objects of interest and are unable to integrate disparate information into a meaningful whole (weak central coherence theory).

We previously proposed that susceptibility to a framing bias reflects the operation of an affect heuristic. Here, we show that individuals with ASD, a condition characterized by marked behavioral inflexibility, demonstrate a decreased susceptibility to framing resulting in an unusual enhancement in logical consistency that is paradoxically more in line with the normative prescriptions of rationality at the core of the current economics theory. Furthermore, insensitivity in these subjects to a contextual framing bias was associated with a failure to express a differential autonomic response to contextual cues as indexed in skin conductance responses (SCRs), a standard measure of emotional processing. Our findings suggest that a more consistent pattern of choice in the ASD group reflects a failure to incorporate emotional cues into the decision process, an enhanced economic “rationality” that may come at a cost of reduced behavioral flexibility.

The experimental procedure used framing of gambles in terms of loss and gain and it is a well established paradigm that shows that normal people are risk-averse when the same gamble is framed in gain terms and risk-prone when the same gamble is framed in loss terms. Autistcis were not only more risk-averse in general , but their responses did not differ in relation to whether the frame was of loss or of gain. Thus, they were consistent in both the framing conditions. also , a measure fo their skin conductance did not show differential activation in the two frames of loss and gain; while the SCR of controls differed significantly. thus, teh authors conclude that it is the inability to take into account emotional information, that results in the consistent response of the autistics.Here is the discussion:

These findings suggest the ASD group fail to integrate emotional contextual cues into the decision-making process. This is evident both in a reduced behavioral susceptibility of a framing effect and an absence of a differential SCR response to our contextual manipulation. The concept that ASD individuals fail to integrate information across cognitive domains also informs the suggestion that an uneven profile of abilities and deficiencies in autistic individuals may reveal an imbalance in empathizing and systemizing behaviors (Baron-Cohen and Belmonte, 2005)

They discuss these findings in terms of the two-system theory of decision-making and here is what they have to say:

Recent theoretical accounts of decision making have put forward a “two-systems” model of human judgment (Evans, 2003). This view proposes that human decision making arises through a combination of intuitive and analytic processes. This model proposes that intuitive reasoning is rapid and capable of processing large amounts of information in parallel; however, it is prone to mistakes and strongly influenced by contextual emotional information (Kahneman, 2003). In contrast, analytical reasoning is more accurate but slow and computationally demanding. According to this view, the framing bias reflects an affect heuristic by which normal individuals incorporate a potentially broad range of additional emotional information into the decision process. In evolutionary terms, this mechanism may confer a strong advantage because such contextual cues may carry useful, even critical, information that dictates a rapid response. We propose that this ability is particularly crucial in a social context in that subtle contextual cues communicate knowledge elements (possibly unconscious) that allow optimal decisions to be made in uncertain environments (Stanovich and West, 2002).

In the context of the “two-systems” model of decision making described above, these results suggest that ASD individuals have an increased tendency toward the analytic type of decision making, attributable to impairment within their intuitive reasoning mechanisms. This interpretation would also support the empathizing-systemizing (E-S) theory of autism (Baron-Cohen and Belmonte, 2005). The E-S theory proposes that the imbalance between analytic and empathic behavior underlies both the impairment in social skills in ASD and their enhanced analytical skills. During the framing task, ASD subjects were better able to ignore biasing contextual information and isolate the critical information about the numerical value of the sure and risky options. This result is consistent with other experimental findings showing that ASD have enhanced attention for the task’s details but reduced capacity to deal with the global aspect of the task as predicted by weak coherence theory (Frith and Happé, 1994).

Now, I am just overjoyed reading the above. It has always been my contention that Autistics use a more deliberate, rational approach to decisions while schizophrenics are at the opposite end relying on the intuitive part. I elaborated it in the form of Maximisers and Satisficers distinction that Barry Scwatrz has proposed and extended it to include exploration and exploitation in general. In short my thesis was, and remains, that autistics are more analytical while decision-making and schizophrenics more intuitive . the former does not take the context or frames into account while making decisions while the other takes into account too much context and is susceptible to too much framing effects.

If the above thesis is correct it leads to many testable predictions:

  • 1) Schizophnrenics/ Schizotypal individuals should be more susceptible to framing effects and should show greater inconsistencies in decision-making under uncertainity as compared to controls.
  • 2) They may also show more SCR variability when different frames of loss and gain are presented to them as compared to controls.
  • 3) They may have higher baseline risk-prone behavior than controls in all conditions.
  • 4) They may have higher activation in amygdala than controls as they use affect heuristic quite frequently while making decisions.

Part of this prediction may be satisfied by this decision-making and schizophrenia study by Ludwig et al  that found decision-making dysregulation in first episode Schizophrneia patients. Here is the abstract of the study:

Studies with chronic schizophrenia patients have demonstrated that patients fluctuate between rigid and unpredictable responses in decision-making situations, a phenomenon which has been called dysregulation. The aim of this study was to investigate whether schizophrenia patients already display dysregulated behavior at the beginning of their illness. Thirty-two first-episode schizophrenia or schizophreniform patients and 30 healthy controls performed the two-choice prediction task. The decision-making behavior of first-episode patients was shown to be characterized by a high degree of dysregulation accompanied by low metric entropy and a tendency towards increased mutual information. These results indicate that behavioral abnormalities during the two-choice prediction task are already present during the early stages of the illness.

The authors used the CT paradigm and it is important to explain that a bit here:

The purpose of the CT is to quantify decision-making characteristics based on the individuals’ sequential response patterns, which result from repeated selections of different alternatives associated with an uncertain outcome. Each subject received computerized instructions. The subject’s task is to predict on which side a stimulus (a car on the screen) will appear and select a response (to match up one of 2 figures shown on the screen) accordingly. The outcome is shown for 250 milliseconds after the subject has selected as response. A new trial begins immediately after the car has been displayed. The subject is not given any information about the sequence of the stimulus presentations, i.e., whether the stimulus is presented randomly or in any kind of order. Unbeknownst to the subjects, the location of the car shown is based on the subject’s response, i.e., the subject “correctly” predicts the location of the car in 64 trials. The basic measurements consist of the subject’s response, the presentation of the car and the latency of the response selection process, i.e., the time from the beginning of the trial to the pressing of the button. For the behavioral analysis, we used nonlinear methods— described elsewhere in detail (Paulus et al., 2001)—to obtain the following key measures:

Dysregulation: Dysregulation quantifies the range of response sequence entropies during the course of an experiment.A high dysregulation value indicates that the response sequences occurring during the experiment are characterized by botho¨perseverative tendencies“ and highly unpredictable or dynamically ”chaotic” strategies.

Metric entropy: Entropy measures the “sequential order” within sequences of responses. Whereas low entropy indicates that the response sequences are highly predictable, high entropy implies highly unpredictable response sequences. Thus, predictability is a collateral measure for the degree to which sequences of responses are based on a consistent internal strategy. However,this measure does not take into account the dependence of the response sequence on external stimuli, which is measured by the cross-mutual information (see below).

Mutual information: Mutual information quantifies the degree to which the previous response predicted the current response and provides a measure of the immediate influence of the past response on the decision in the current trial.

Cross-mutual information: Cross-mutual information quantifies the degree to which the previous location of the stimulus (presentation of the car on the LEFT or RIGHT hand side) is able to predict the current response. As opposed to entropy and mutual information, this measure quantifies the influence of external stimuli on the response sequences.

Switching probability: the probability of using the simple strategy RIGHT – LEFT.

Reaction time: the time between stimulus and response.

What they observed is summarized below:

As shown above in the results section, first-episode patients performing this decision-making test, irrespective of whether they were unmedicated or recently medicated, can be observed to have (a) more dysregulated behavior, (b) a reduced metric entropy, and (c) a tendency towards increased mutual information. As a specific response behavior (d), the patients used the switching strategy more intensely (switching between pushing the right and the left button). This study has supported our main hypothesis that decision-making dysfunctions are already present in first-episode schizophrenia (or SZ) patients.

I believe the results need some explanation, and I will stick my neck out here. More dysregulated behavior in my view, is due to the schizophrenic either trying too hard to remain consistent (when in self-aware frame of mind) or trying to be unpredictable (when in other-aware and being-watched frame of mind). The reduced metric entropy can be explained similarly . Tendency towards increased mutual information is quite informative in my view. It seems that the schizophenreic is working on the basis of an internal model and is ignoring external feedback: thus his reliance on previous response.I propose that an opposite pattern would be observed in Autistics with Autistics showing no or less mutual information, as they have poor self-models; but greater cross-mutual information , as they would base their decisions more on external stimuli or feedback.

Some other predictions, keeping in mind the autism is opposite of Schizophrenia theory are:

  • 1) Autistcis should show lesser dysregulation and more rational behavior than even controls.
  • 2) autistcis should show greater cross-mutual information than controls.
  • 3) Autistcis may or may not show lesser mutual information.
  • 4) Autistcis should use less switching strategy than controls.

All these are testable predictions and I hope someone out there tests these and lets me know!
ResearchBlogging.org
B. De Martino, N. A. Harrison, S. Knafo, G. Bird, R. J. Dolan (2008). Explaining Enhanced Logical Consistency during Decision Making in Autism Journal of Neuroscience, 28 (42), 10746-10750 DOI: 10.1523/JNEUROSCI.2895-08.2008
Cattapan-Ludewig Katja; Ludewig Stephan; Messerli Nadine; Vollenweider Franz X; Seitz Antonia; Feldon Joram; Paulus Martin P (2008). Decision-Making Dysregulation in First-Episode
Schizophrenia The Journal of nervous and mental disease, 196 (2), 157-160

Better late than never: Mainstream media rises to Autism and Schizophrenia polarity

Readers of this blog will be familiar with two of my passionate theory building exercises- the first concerned with the eight stage developmental/ evolutionary stage theories and the second being the Autism and Schizophrenia /Psychosis as opposite poles on a continuum theory. While the first premise of stage theories was recently attached by Micaheal Shermer in Mainstream media of Scientific American; the other theory seems to have caught the fancy of Mainstream Media. Two days ago there were two articles by people I admire a lot, in magazines I admire a lot, that elucidated the Autism and Schizophrenia as opposite poles theory. The first was an article by Benedict Carrey in NYT and the second was an article by Carl Zimmer in Discover magazine. The two synchronous reporting are a result of a Baddock and Crespi article in Nature , this august. But the mainstream media, as always, is late to the party when compared with the blogosphere. 

I have been proposing and promoting the Autism and Schizophrenia as opposite poles argument since the inception of this blog, but the ideas crystallized about two year back based on work of Nettle. Since then I have found evidence from different quarters including Chris Frith and Baddock and Crespi. I covered the Baddock and Crespi original article (not the Nature opinion piece) about a year back, though it didn’t find many takers at that time. I am glad that the same is finding acceptance now and is going mainstream. The Discover magazine article is really good and gives you some analysis of how gene imprinting works and how that may be instrumental in differential outcomes in the two cases of Autism and Schizophrenia and I recommend reading it as well as the NYT arcticle. If you want to read more about this theory, of course the first recommendation from me would be to read all the Mouse Trap articles labeled Autism or Schizophrenia or Psychosis. If you are more scientifically inclined, go read the original Baddock and Crespi paper amongst others. If you would just like to see the buzz in blogosphere and for some more context see the Mind Hacks article (that correctly mentions Chris Frith as a pioneer, but sadly does not mention efforts of Nettle in the same Autism-Schizophrenia model development) or see the Peter Cramer blog at In Practice from which I originally came to know of this mainstream media acceptance.

I hope that one day the eight stage model will also find the same sort of media acceptance and will lead to more stimulating work.

Magical thinking and feelings of control

A recent article in Science Magazine relates Magical thinking to feelings of control. It is an interesting paper and here is the abstract:

We present six experiments that tested whether lacking control increases illusory pattern perception,which we define as the identification of a coherent and meaningful interrelationship among a set of random or unrelated stimuli. Participants who lacked control were more likely to perceive a variety of illusory patterns, including seeing images in noise, forming illusory correlations in stock market information, perceiving conspiracies, and developing superstitions. Additionally, we demonstrated that increased pattern perception has a motivational basis by measuring the need for structure directly and showing that the causal link between lack of control and illusory pattern perception is reduced by affirming the self. Although these many disparate forms of pattern perception are typically discussed as separate phenomena, the current results suggest that there is a common motive underlying them.

More discussion of the studies can be found at Mind Hacks and Psychology Today Blog Brainstorm
To me, it is exciting that Magical thinking  and feelings of control are linked together. It is my thesis that Manic episodes and frank psychosis are marked by presence of Magical Thinking to a large and  non-adaptive degree.  Sometimes severe depression too causes Psychosis and I presume that Magical thinking in that case too may be increased. If so, one of the frameworks for understanding depression is that of learned helplessness paradigm , whereby mice are exposed to uncontrollable shocks and then do not even try to avoid the shocks , even after the external environment has changed and they could now possibly avoid them by correct behaviour. One explanation for psychosis in severe depression may be that feelings of lack of control rise to such a level that one starts indulging in Magical thinking and starts creating and seeing patterns that are not there and thus loosing touch with Reality. 
This raises another question of whether Manic psychosis may itself be due to the same stress and feelings of non-control, but this time not leading to Depression but Mania. We all know that bipolarity is a stress-diatheisis model and maybe whenever stress causes feelings of lack of control the bipolar people have a tendency to exaggerated magical thinking: When mood is good this may lead to Manic psychosis; while when mood is low the same magical thinking may lead to depressive psychosis. Does anyone know any literature on bipolar people being more magical thinkers? does the same reason also work well for them and endow them with creativity? Another related question would be whether bipolar people have more feelings of being out of control? And what about self-esteem, do those in Mania , who get psychosis, also suffer from lack of self-esteem and this is mediated by the role of self-esteem in protecting against magical thinking? 
    

Exploration/ Exploitation == Maximisers/ Satisficers?

There is an interesting research coverage at We are Only Human blog regarding whether people may have two different cognitive styles- one based on exploration of novel ideas and the other based on exploitation or focus on a particular familiar idea. The study employs evolutionary concepts and theorizes that these different cognitive styles may be a reflection of the different foraging styles that might have been selected for and relevant in EEA.

Specifically, while foraging for food in a habitat where the food supply and resources are unpredictable , one is faced with a choice when one has discovered a food source: whether to exploit this food source (a jungle area having sparse edible leaves) or to move ahead in search of a potentially better food source (a jungle area having abundant edible and nutritious fruits) . Both strategies , that of exploring or exploiting can be advantageous and may have been selected for. It is also possible that humans can use either of the strategies based on the environment- (food source distribution) , but may be inclined towards one strategy or the other. The authors of the study surmised that both the strategies have been selected for and we have the potential to use either of the strategy. Moreover, the same foraging strategy we use or are primed of, would also be visible in the cognitive strategy we use.

They used an ingenious technique to prime the subjects with either of the foraging strategies (go read the excellent We are only human blog post) and found that humans were flexible in the use of the appropriate strategy, given the appropriate context, and that the foraging strategy primed the corresponding cognitive strategy. To boot, those primed with an exploratory foraging strategy would be more prone to using exploratory cognitive strategies when confronted with a cognitive task and vice versa. They also found systematic differences between individuals cognitive and foraging styles- some were more exploratory than the others.

This reminds me of the Maximizers/ Satisficers distinction in decision-making style that Barry Scwatrz has introduced and brought to public attention. Basically a Maximizer , when faced with a decision and choice, would go on computing the utility of different choices and try to choose the option that maximizes his utility and is the ‘best’. A Satisficer, on the other hand would also explore options, but stop his exploration, when he finds an option that is ‘good enough’. I wonder, if just like the exploratory/ Exploitative cognitive and foraging styles, this is just another dimension of the same underlying phenomenon- whether to explore more – or to exploit what is available. To take an example, for marriage, a satisficing strategy may work best – as told in “The Little Prince” one should stop searching for more flowers if one has already had the fortune of possessing a flower.

“People where you live,” the little prince said, “grow five thousand roses in one garden… yet they don’t find what they’re looking for…”

“They don’t find it,” I answered.

“And yet what they’re looking for could be found in a single rose, or a little water…”

An interesting experiment would be to see, if the foraging style, the cognitive style, and the decisions style are all correlated within individuals and if priming one can influence the outcome of the other style.

If so, could there be an underlying neural phenomenon , common to all?

Wray, the author of We are only human blog makes a bold conjecture and relates this to the finding that dopamine levels.

Exploratory and inattentive foraging—actual or abstract—appears linked to decreases in the brain chemical dopamine.

He even relates this to cognitive disorders like Autism and ADHD.

By analogy, in conditions where baseline dopamine is more, like in bipolar and psychosis, one may be more inclined to a more staisficing/ ‘I’m feeling Lucky’ strategy in which the very first option is acceptable. This may explain the ‘jumping-to-conclusions’ bias in schizophrenia/ psychosis.

To make things more explicit, though the leading dopamine theory in vogue now is of ‘error-prediction’ , a competing, and to me more reasonable, view of dopamine function is incentive salience i.e. what ‘value’/ importance does the stimuli have for the person in question. The importance can be both positive and negative and thus we have found that dopamine is involved in both dread and desire. The dominant reward prediction theory faces many challenges, the least of which is response of dopamine neurons to novel events. A dopamine burst is also associated with ‘novel’ events and thus dopamine is somehow involved in/ triggered by Novelty. Baseline dopamine may constrain the dopamine surge felt on a novel event. Thus, in schizophrenia/ psychosis , with baseline dopamine high, a dopamine burst on novelty detection may be high enough so that it is meaningful and may not lead to more exploratory behavior. While in the disorders where baseline dopamine is low, one may require a more profound dopamine burst before the stimuli becoming meaningful and thus may go on seeking novel stimulus till one finds one ‘big enough to trigger salience’.

We may extend the salience argument to other domains than incentive. If the chief function of dopamine is to mark salience, then it may also be instrumental in memory and attention. Only what is Salient gets attention, and only what is salient gets into Working Memory. Thus,a high dopamine level may predispose to treating almost everything as salient, leading to delusions of reference (everything is meaningfully related to self etc) etc. Working Memory may be taxed due to everything trying to get in- and thus poor WM in people with schizophrenia. Also, every trivial thing may grab attention- leading to poor sensory gating and conditions like lack of pre-pulse inhibition. On the flip side, while making sense of ones experience, one may accept the first possible explanation and do not search further – thus leading to persistence of delusions.

An opposite scenario would be when one keeps exploring the environment and nothing seems novel due to low dopamine levels. This would be the classical Autistic repetitive and stereotype behaviors. There would be sensory over stimulation, as nothing is salient and one needs to explore more and more. On the other hand, WM capabilities may be good/ savant like, as not every piece of information grabs attention. Everything should seem insignificant and the only way to arrive at decision / choose action would be via exhaustive enumeration and logical evaluations of all options. even after obvious explanations for phenomenon, one may keep looking for a better explanation. No wonder , as per my theory, more scientists would be autistic.

Perhaps, I am stretching things too far, but to me the dopamine connection to Salience/ Meaning/ Importance is sort of worth exploring and I will write more about that in future. For now, let us be willing to associate Salience not just with stimuli related to motivation, but also with stimuli relevant in sensation, perception,learning and memory. If so the common underlying mechanism responsible for differentiating us as a exploratory and expolitatory forager (food) may also be related to our different cognitive styles, our different decision-making styles and our different baseline dopamine levels.

Dopamine though is most strongly related to food and sex. I could even stretch this argument and say this may be related to r and K reproductive styles (note these styles are species specific, but I believe individuals in a specie may also vary on the reproductive strategy along this dimension). Thus, while explorers may have r type of reproductive style, the exploiters may have a K reproductive style.

At one extreme are r-strategies, emphasizing gamete production, mating behavior, and high reproductive rates, and at the other extreme are K-strategies, emphasizing high levels of parental care, resource acquisition, kin provisioning, and social complexity.

If K-strategy is what humans have chosen, maybe exploitation in all areas (cognitive, decision-making, foraging) is more relevant and in tune with our nature. Maybe that’s why I’ll always be on the side of Psychosis than Autism!! Though, to put things in perspective, maybe humans have evolved to use both strategies as the situations demands , and the best thing would be to use the strategy situation-specific and not lean towards either extremes.

A new Paranoia quiz

As regular readers of this blog would have noted, I had promised to use the left hand menu quite frequently and post some quiz questions there. for quite some time, the left hand menu contained a Schizophrenia quiz. I have replaced it with a paranoia quiz. In case you are reading from a feed reader , do go to The Mouse Trap blog and take the quiz.

Supporting material can be obtained from this Freeman and Garety article on how to use CBT in paranoia.

God is just a type I error!

Yes, believe me God is an error and that too a type I error. But before we appreciate the subtleties of that argument, we have to first learn a bit about error management theory ( not to be confused with the TMT or terror management theory about which too I have blogged previously). EMT in simple terms is an evolutionary theory that posits that we do not minimize the number of errors that are possible when we are faced with ambiguous situations and corresponding ambiguous decisions to make; but that we minimize the total costs associated with making the errors. To simplify, whenever we make a decision about reality that is based on our inferences then we can make two types of errors : in type I errors we assume/ infer something to be real, while the phenomenon is itself unreal (this is a false positive);l while in type II errors we assume/infer something to be unreal while the phenomenon is real.

To take by the way of an example , if we are in a jungle and hear a sound in a bush ; then if the sound was from a lion and we inferred that it was not from a lion we make a type II error; if the sound was not from a lion, but we infer that it was from a lion we make a type I error. Obviously in this case it is best to make a type I error as a type II error can mean death. Evolution would thus select for a behavior that is biased towards the flase positive inferences in this case.

I’ll now let Haselton define the theory and give examples:

Error management theory proposes that the direction of a bias in social judgment is tied to how costly different kinds of errors are. For example, consider how smoke alarms are designed. Failures to detect fires (false negative errors) are extremely costly, whereas false alarms (false positives) are usually just inconvenient. So, when engineers make smoke alarms, they tend design them to be biased away from the more costly false negative error by setting a low threshold for fire detection. As a consequence, smoke alarms will tend to be systematically biased toward false positive errors (false alarms). A low threshold for fire detection will cause smoke alarms to make more errors overall, but it will minimize the cost of errors when they inevitably occur (i.e., the errors will tend to be false alarms rather than missed fires).

Error management theory proposes that the same principle of design applies to the evolution of judgment mechanisms in the human mind. Ancestrally, in many areas of social judgment, the costs of false positive and false negative errors differed. When the costs of false negatives are greater, error management theory predicts a bias toward false positives (as in the smoke alarm example); when the costs of false positives are greater, error management theory predicts a bias toward false negatives.

One example of a false-positive bias is in men’s estimations of women’s sexual interest. For an ancestral man, failing to detect sexual interest in a woman resulted in a missed reproductive opportunity, which was highly costly to his reproductive success. The opposite error (believing that a woman was interested when she was not) was perhaps a bit embarrassing, but probably was less costly overall. Thus, error management theory predicts that natural selection designed a bias in men toward slightly overestimating a woman’s sexual interest in order to reduce the likelihood of a missed sexual opportunity; this leads modern men to “overpercieve” women’s sexual interest.

Satoshi Kanazawa, who has applied the error management theory to the above men-think-women-are-attracted-to-them behavior has a two part post over at his psychology today blog that is worth reading in entirety. There he argues that we believe in god, because of an inbuilt bias to detect agency. He says that detecting agency when none is there can only lead to paranoia in the worst case, while not detecting agency when there was one could lead to death. He has a beautiful figure illustrating the same and I post it here.

Different theorists call this innate human tendency to commit false-positive errors rather than false-negative errors (and as a consequence be a bit paranoid) “animistic bias” or “the agency-detector mechanism.” These theorists argue that the evolutionary origins of religious beliefs in supernatural forces may have come from such an innate cognitive bias to commit false-positive errors rather than false-negative errors, and thus overinfer personal, intentional, and animate forces behind otherwise perfectly natural phenomena.

You see a bush on fire. It could have been caused by an impersonal, inanimate, and unintentional force (lightning striking the bush and setting it on fire), or it could have been caused by a personal, animate, and intentional force (God trying to communicate with you). The “animistic bias” or “agency-detector mechanism” predisposes you to opt for the latter explanation rather than the former. It predisposes you to see the hands of God at work behind natural, physical phenomena whose exact causes are unknown.

In this view, religiosity (the human capacity for belief in supernatural beings) is not an evolved tendency per se; after all, religion in itself is not adaptive. It is instead a byproduct of animistic bias or the agency-detector mechanism, the tendency to be paranoid, which is adaptive because it can save your life. Humans did not evolve to be religious; they evolved to be paranoid. And humans are religious because they are paranoid

It is interesting to note that Kanazawa mentions the research of Nettle as I am myself a big fan of his work, but never knew that he had contributed to the EMT too. I myself have speculated on the close association of religiosity with psychosis and the Kanzawa post just bolsters the arguments there.

To sum up, it is perhaps better to be paranoid and suffer from the God delusion! You would at least survive to pass your genes along!!

Art and Insanity: is there risk involved in artistic creation?

William Schultz has just posted a blog entry regarding how artistic creation may have an associated risk of suicide/ depression/ psychosis and how exploring the depths of one’s psyche may lead one to the downward spiral that ends with taking one;s own life. He gives Sylvia Plath and Diane Arbus as examples and I agree with his basic premise that writers/ artists are especially vulnerable to extreme mental states as they try to explore the depths of human experience by imagining the extremes that are possible.

I ,myself, consider myself to have moderately good writing talent, and have found that when I write literature , be it poems or short stroies or novellas, the theme of the creation starts taking its hold. this is most apparent when for example I recently added a few sonnets to my epic-in-making The Fools Quest. The initial sonnets depict a person who is on a brink of new journey, somewhat facing an existential angst and in general questioning both his past and his future. now, though, I myself am very well adjusted and happy with my life as it is going, just creating in myself the protagonists mindset led to a state where I myself started feeling restless, unsatisfied and in general more eager for change and willing to rock the boat. This may seem anecdotal evidence, but there is good statistics showing prevalence of mental health disorders in artists in general and writers in particular.

I would now quote a bit from Schultz’ post (italics mine):

What’s going on here? It’s more than a little uncanny. As Wendell Berry once said: “To go in the dark with a light is to know the light. To know the dark, go dark.” Both Plath and Arbus knew the dark, but this knowing came at a massive price. The dark stayed dark. Forever. Some artists–not all–do not survive the hero’s quest. Maybe, when the moment comes, they lack the requisite “ego strength” to re-compose after the decompensation that a certain category of art requires. Or else: once they achieve genius, the question becomes: Where do I go from here? Having reached the top of the mountain, there is nothing left but the descent, and the idea of descending is simply intolerable, ultimately depressing.

I don’t know, whether my quest is a hero’s quest or a fool’s quest , but I definitely know that I have slowed down as I saw that the quest was affecting my mood. Hopefully, as the quest moves to more adventurous phases and away from the initial dilemmas , it would have more uplifting effects. Hopefully, I wont fall from the cliff like my Fool is planning to!

Autism, the middle cingulate and reputation management

There was an article on which I had wanted to comment earlier. the study by Chiu et al shows that in autistic individuals the middle cingulate cortex is hypofunctional during the self phase of the iterated Trust game, wherein one has to infer the mind of another, decide whether to trust him or her and accordingly decide what money to give to the trustee and what to keep for oneself.

Recent work using the multiround trust game has identified activations along human
cingulate cortex consistent with agent-specific response patterns generated during interpersonal exchange with another human. These patterns differentiate outcomes following revelation of the partner’s decision (‘‘not self’’ or ‘‘other’’ response) from those following submission of one’s own decision (‘‘self’’ response). Remarkably, the patterns are spatially complementary , and almost no manipulation perturbs them except one: the removal of the interactive partner . Removal of the social partner causes the cingulate response patterns to disappear even though the sensory, motor, and reward elements of the task remain intact. These results from the trust game are consistent with agent specific cingulate responses observed in a range of other experiments. Anterior and posterior cingulate activation occurs in response to the revelation of decisions of others in two-person games like the Ultimatum and Prisoner’s Dilemma games. Furthermore, increased middle cingulate activation is commonly observed in response to one’s own social decisions or emotions.

Chris and Uta Frith do an excellent job of putting these findings in perspective and argue that the autistic is less concerned with reputation management (as it has inability to infer others mind states it does not care hat they think) and suggest a simple experiment that could elucidate the point.

Our speculation is that this process of reputation management is impaired in autistic individuals, because it depends on the ability to read the minds of others. This hypothesis can be tested experimentally. If we are concerned with our reputation then our behavior will be strongly affected by whether or not an audience is present to observe our actions. Consider, for instance, another sharing game known as the dictator game. One player is given $100 and is allowed to share any amount he or she chooses with the other player. In this situation, the rational thing to do would be to give the other player no money at all, because the second player is powerless to respond. Even “dictators” will typically dole out a small proportion of the money, however. When there is an audience for the transaction, dictators give away even more money. Presumably, they do not want to have a reputation for meanness or for acting unfairly. If autistic people are not concerned with their own reputation, then their behaviour should not be affected by the presence of an audience.

I would like to extend their experiment and suggest one for those susceptible to psychosis. I have argued that Autism and Schizophrenia/ psychosis are extreme ends of a continuum and would thus conclude that in the iterated trust game, psychotics/ those susceptible to psychosis would show hyperfunctioning of middle cingulate cortex. I have elsewhere already argued that Psychotics have an enhanced ToM or mind reading ability. I would also hypothesize that psychotics would also show enhanced reputation management and an enhanced donation of money in the trust game when an audience is present as compared to controls or the autistics.

While an experiment is the best to settle such conjectures, it is tempting to see how this adds up and can explain certain symptoms of psychosis/ mania. If one is overly concerned with reputation management one can end up being a spendthrift / show irresponsible financial behavior as one tries to build a hypothetical reputation in the minds of the audience. Taken with the fact that psychosis comes clubbed with a belief in supernatural agents, magical thinking and super agency detection etc, one may not even need an actual audience – a make-believe audience may suffice to make one get overly concerned with reputation management and thus trusting too much the others -even with their money. when reality proves otherwise and people prove to be not worthy of the trust, one may dissociate with reality altogether and become paranoid on the other extreme. We know that the ACC is dysfunctional in schizophrenics, what about the middle cingulate? is it hypoactive during trust games in the self condition? Only a hypothesis, but worth investigating!