Dopamine-Induced Dysconnectivity Between Salience Network and Auditory Cortex in Subjects With Psychotic-like Experiences: A Randomized Double-Blind Placebo-Controlled Study

• Published in: Schizophrenia bulletin Vol. 46; no. 3; pp. 732 - 740
• Main Authors: Rössler, Julian, Rössler, Wulf, Seifritz, Erich, Unterrassner, Lui, Wyss, Thomas, Haker, Helene, Wotruba, Diana
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 10.04.2020
• Subjects: Adult; Auditory Cortex - diagnostic imaging; Auditory Cortex - drug effects; Auditory Cortex - metabolism; Auditory Cortex - physiopathology; Auditory Perception - physiology; Connectome; Cross-Sectional Studies; Dopamine; Dopamine - metabolism; Dopamine Agents - administration & dosage; Dopamine Agents - pharmacology; Double-Blind Method; Humans; Levodopa - administration & dosage; Levodopa - pharmacology; Magnetic Resonance Imaging; Male; Nerve Net - diagnostic imaging; Nerve Net - drug effects; Nerve Net - metabolism; Nerve Net - physiopathology; Psychosis; Psychotic Disorders - diagnostic imaging; Psychotic Disorders - metabolism; Psychotic Disorders - physiopathology; Regular; Young Adult; resting-state functional magnetic resonance imaging; exceptional experiences; salience; planum polare; functional connectivity; L-DOPA
• ISSN: 0586-7614; 1745-1701; 1745-1701
• DOI: 10.1093/schbul/sbz110

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.