20 Years of Aberrant Salience in Psychosis: What Have We Learned?

Abstract

"Psychosis as a state of aberrant salience" was published 20 years ago in the American Journal of Psychiatry (1). In the intervening years it has been cited more than 3000 times. It is a work of brilliance-elegantly weaving connections between clinical phenomenology, psychopharmacology, and behavioral neuroscience, via a concept from addiction-incentive salience (2). It aims to answer the question, oft posed by patients: "Why, when I take antipsychotic drugs, do my delusions and hallucinations go away?" The piece provides a perspicuous answer: Psychosis (hallucinations and delusions) is caused by excessive dopamine levels, which cause events (internal and external) that are merely coincident with a dopamine peak to be imbued with aberrant incentive salience-such that they command attention and drive goal-directed behavior and manifest ultimately as psychotic symptoms; attempts to explain away the aberrant salience (1). When treated with drugs which block dopamine receptors, the aberrant salience abates, and symptoms resolve (1). Here we review the work that has gone on considering the theory, how it has been received, and what our field continues to get wrong about aberrant salience, in light of our evolving understanding of dopamine function, incentive salience attribution, and clinical computational neuroscience. What predictions does the theory offer, and how have they fared under empirical scrutiny? We think there are 2 critical predictions made by the theory: 1. Positive symptoms (largely delusions) should relate to the neurobehavioral ascription of incentive salience 2. The dopamine abnormality in psychosis should be in the ventral striatum What have we learned in the intervening years? 1. Delusions should relate to the neurobehavioral ascription of incentive salience Throughout this piece we will mostly focus on incentive salience attribution and delusions. Kapur offered a briefer explanation of hallucinations as the attribution of incentive salience to one's own inner speech, such that it becomes so salient it must have emanated from another agent (1). We shall return to hallucinations later in our piece.Kapur's ideas about delusions and incentive salience attribution have received more empirical attention. Consider the Salience Attribution Task, a probabilistic reward-learning task featuring compound cue stimuli that vary along two dimensions, one task-relevant and one task-irrelevant. Performance in this task can be 1 Twenty years ago Shitij Kapur's "Psychosis as a state of aberrant salience" captured the attention of clinicians, cognitive, and behavioral neuroscientists. It has become the de facto way of talking about delusion formation in labs and clinics. Here, we critically evaluate the original theory considering evolving data since its publication. We examine its specific predictions, regarding the neural and behavioral loci of dopamine dysfunction in psychosis and find them lacking. Furthermore, we explore our ever-expanding knowledge of the dopamine system and its impacts on behavior following the explosion of new tools and probes for precise measurement and manipulation of dopaminergic circuits. We pay particular attention to theories that have developed since Kapur, which suggest a role for dopamine in belief formation, belief updating under uncertainty, and abductive inference to the best explanation for some set of circumstances-all of which we believe fit better with the work in patients with delusions and hallucinations, how they behave and what we know about their dopamine function. We admire the scope and vision of the original work, and we continue to follow its example by trying to unite neurochemical dysfunction to clinical phenomenology through computational cognitive neuroscience. PREPRINT