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
a scientific problem that came up during the challenger investigation was described repeatedly as ‘a pressure induced vorticity oscillatory wawa’. Feynman called it a whistle and then things became easier to understand 😉
That’s good! I am totally agreed with your article. 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. This article will be very helpful for people.
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