Toward a neurobiology of delusions

Abstract

Delusions are the false and often incorrigible beliefs that can cause severe suffering in mental illness. We cannot yet explain them in terms of underlying neurobiological abnormalities. However, by drawing on recent advances in the biological, computational and psychological processes of reinforcement learning, memory, and perception it may be feasible to account for delusions in terms of cognition and brain function. The account focuses on a particular parameter, prediction error--the mismatch between expectation and experience--that provides a computational mechanism common to cortical hierarchies, fronto-striatal circuits and the amygdala as well as parietal cortices. We suggest that delusions result from aberrations in how brain circuits specify hierarchical predictions, and how they compute and respond to prediction errors. Defects in these fundamental brain mechanisms can vitiate perception, memory, bodily agency and social learning such that individuals with delusions experience an internal and external world that healthy individuals would find difficult to comprehend. The present model attempts to provide a framework through which we can build a mechanistic and translational understanding of these puzzling symptoms.

Figure 1. Neural Instantiation of predictive learning and belief

Theoretical model: Schematic of reward prediction error signals before learning, following learning and during extinction Health: Right DLPFC prediction error response during casual learning in healthy subjects (Corlett et al, 2004) – V: Violation of expectancy, C: Confirmation of expectancy Disease: Aberrant right frontal prediction error response in patients with first episode psychosis. The more profound the disruption, the more severe the delusions (Corlett et al, 2007b) - C: Controls, P: Patients with Psychosis

Figure 2. Learning Memory and Belief Alter Perception

Theoretical model: Feedforward and feedback thalamocortical projections (adapted from http://wiki.tkk.fi/display/SYNB/Neocortex). Health: The rotating hollow mask is continuously perceived as convex due to our consistent experience of faces as convex. Disease: Individuals prone to or experiencing psychosis report the hollow mask as a hollow percept (Emrich et al, 1988).

Figure 3. Neural Circuitry of Goal Directedness (knowledge) and habit (belief)

With repetition, rumination and reconsolidation, the control of behavior shifts from flexible goal-directed ventral cortcostriatal control toward control by the inflexible dorsal striatum and motor cortex.

Figure 4. Putative Delusion Circuits

Salience/Reference: A circuit incorporating the midbrain dopaminergic nuclei, the associative striatum and frontal cortex. Aberrant prediction errors in midbrain update expectancies in the frontal cortex leading to aberrantly salient percepts. Agency/others: The midbrain, PFC, Parietal cortex and cerebellum as well as the bimodal cells of the putamen. This circuit describes forward model predictions used to discern whether sensory stimulation was internally of externally generated. A breakdown in this predictive mechanism would manifest as hallucinatory tactile percepts and inferences of external control of intentional action. Fear/Paranoia: A circuit incorporating the midbrain, amygdala, frontal and parietal cortices. Here, neutral or irelevent stimuli, thoughts and percepts come to engender fear and anxiety. A dysfunction in frontoparietal circuitry engenders inappropriate social predictions and maladaptive inferences about the intentions of others. Interaction between circuits: These circuits interact and likely mutually reinforce one another.