Disruption of dopamine D2/D3 system function impairs the human ability to understand the mental states of other people

Abstract

Difficulties in reasoning about others' mental states (i.e., mentalising/Theory of Mind) are highly prevalent among disorders featuring dopamine dysfunctions (e.g., Parkinson's disease) and significantly affect individuals' quality of life. However, due to multiple confounding factors inherent to existing patient studies, currently little is known about whether these sociocognitive symptoms originate from aberrant dopamine signalling or from psychosocial changes unrelated to dopamine. The present study, therefore, investigated the role of dopamine in modulating mentalising in a sample of healthy volunteers. We used a double-blind, placebo-controlled procedure to test the effect of the D2/D3 antagonist haloperidol on mental state attribution, using an adaptation of the Heider and Simmel (1944) animations task. On 2 separate days, once after receiving 2.5 mg haloperidol and once after receiving placebo, 33 healthy adult participants viewed and labelled short videos of 2 triangles depicting mental state (involving mentalistic interaction wherein 1 triangle intends to cause or act upon a particular mental state in the other, e.g., surprising) and non-mental state (involving reciprocal interaction without the intention to cause/act upon the other triangle's mental state, e.g., following) interactions. Using Bayesian mixed effects models, we observed that haloperidol decreased accuracy in labelling both mental and non-mental state animations. Our secondary analyses suggest that dopamine modulates inference from mental and non-mental state animations via independent mechanisms, pointing towards 2 putative pathways underlying the dopaminergic modulation of mental state attribution: action representation and a shared mechanism supporting mentalising and emotion recognition. We conclude that dopaminergic pathways impact Theory of Mind, at least indirectly. Our results have implications for the neurochemical basis of sociocognitive difficulties in patients with dopamine dysfunctions and generate new hypotheses about the specific dopamine-mediated mechanisms underlying social cognition.

Fig 1. Drug effects on accuracy by mental state condition.

HAL, haloperidol; PLA, placebo. Central marks of box plots correspond to the median; outer hinges correspond to the first and third quartiles (25th and 75th percentiles). Upper and lower whiskers extend to largest and lowest values at most 1.5 * IQR of the hinge. Data and code required to reproduce this figure available at https://osf.io/xm7ty/.

Fig 2. Relationship between jerk difference and accuracy depends on how jerk difference was calculated.

(A) Placebo condition. (B) Haloperidol condition, jerk difference based on movement in haloperidol condition. (C) Haloperidol condition, jerk difference based on movement in placebo condition. Data and code required to reproduce this figure available at https://osf.io/xm7ty/.

Fig 3. Relationship between drug effects on animations task performance and emotion recognition performance.

Vertical jitter was added to the raw data points for display purposes. Data and code required to reproduce this figure available at https://osf.io/xm7ty/.