Dopamine-Induced Dysconnectivity Between Salience Network and Auditory Cortex in Subjects With Psychotic-like Experiences: A Randomized Double-Blind Placebo-Controlled Study
Julian Rössler, Wulf Rössler, Erich Seifritz, Lui Unterrassner, Thomas Wyss, Hélène Haker, Diana Wotruba
Schizophrenia Bulletin October 8, 2019 Peer reviewed DOI: 10.1093/schbul/sbz110 via OpenAlex
Summary
Dopamine reduces functional connectivity between the right anterior insula, a hub of the salience network, and the left auditory cortex planum polare. In healthy men given a placebo, higher scores on psychotic-like experiences correlated with weaker connectivity between these regions; in those given L-DOPA, higher scores correlated with stronger connectivity. The score explained about 30% of the variation in connectivity. This suggests psychotic-like experiences involve dopamine-induced disruption of auditory input to the salience network, possibly leading to aberrant salience attribution.
Study at a glance
| Design | randomized, double-blind, cross-sectional placebo-controlled experiment |
|---|---|
| Sample size | 54 |
| Population | healthy, right-handed male subjects |
| Key finding | L-DOPA reduced functional connectivity between the right anterior insula and left auditory cortex planum polare, and the direction of correlation between psychotic-like experiences and this connectivity differed between placebo and L-DOPA groups. |
Abstract
Dopamine is involved in the pathophysiology of schizophrenia. Disrupted salience processing by the salience network (SN) may be a central link between dysregulated dopamine function and psychotic symptoms. However, dopaminergic influence on the SN and its presumed influence on psychotic and subpsychotic symptoms or psychotic-like experiences in healthy individuals remain unclear. Therefore, we investigated dopamine-induced changes in functional connectivity of the right anterior insula (rAI), a central SN hub, and their association with psychotic-like experiences. We enrolled 54 healthy, right-handed male subjects in a randomized, double-blind, cross-sectional placebo-controlled experiment. Psychotic-like experiences were assessed using the revised Exceptional Experiences Questionnaire (PAGE-R). They then received either placebo (n = 32) or 200 mg L-DOPA (n = 33), a dopamine precursor, orally and underwent resting-state functional magnetic resonance imaging. In a seed-to-voxel approach, we analyzed dopamine-induced changes in functional connectivity of the rAI and assessed the relationship between functional connectivity changes and PAGE-R score. L-DOPA reduced functional connectivity between the rAI and the left auditory cortex planum polare. In the placebo group, we found a strong negative correlation between PAGE-R score and rAI to planum polare functional connectivity; in the L-DOPA group, there was a strong positive correlation between PAGE-R score and functional connectivity between rAI and planum polare. The PAGE-R score explained about 30% of the functional connectivity variation between rAI and planum polare in the two groups. Our findings suggest that psychotic-like experiences are associated with dopamine-induced disruption of auditory input to the SN, which may lead to aberrant attribution of salience.