Explaining Delusions: Reducing Uncertainty Through Basic and Computational Neuroscience

Abstract

Delusions, the fixed false beliefs characteristic of psychotic illness, have long defied understanding despite their response to pharmacological treatments (e.g., D 2 receptor antagonists). However, it can be challenging to discern what makes beliefs delusional compared with other unusual or erroneous beliefs. We suggest mapping the putative biology to clinical phenomenology with a cognitive psychology of belief, culminating in a teleological approach to beliefs and brain function supported by animal and computational models. We argue that organisms strive to minimize uncertainty about their future states by forming and maintaining a set of beliefs (about the organism and the world) that are robust, but flexible. If uncertainty is generated endogenously, beliefs begin to depart from consensual reality and can manifest into delusions. Central to this scheme is the notion that formal associative learning theory can provide an explanation for the development and persistence of delusions. Beliefs, in animals and humans, may be associations between representations (e.g., of cause and effect) that are formed by minimizing uncertainty via new learning and attentional allocation. Animal research has equipped us with a deep mechanistic basis of these processes, which is now being applied to delusions. This work offers the exciting possibility of completing revolutions of translation, from the bedside to the bench and back again. The more we learn about animal beliefs, the more we may be able to apply to human beliefs and their aberrations, enabling a deeper mechanistic understanding.Key words: delusions/behavioral neuroscience/cognitive neuroscience/computational psychiatry/associative learning The End of the World and the Beginning of a TheoryIn December 1954, the Chicago Tribune reported that Dorothy Martin was relaying a prophecy from extra-terrestrials that the world was about to end. A number of followers flocked to her but her prophecy did not manifest. She ultimately settled in Sedona, Arizona where she lived until she was 92, continuing to proselytize about aliens but evading interaction with psychiatric services. Did Martin have delusions? What about her acolytes? Defining, explaining, and ultimately understanding delusions has proven challenging (see Freeman and Bebbington, this issue). In this article, we describe how neuroscientists have tried to meet that challenge. The approach demands some simplifying assumptions. Basic neuroscience in preclinical models will not recapitulate all of the features of delusions. However, simple models can be useful.

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