Dopamine-Induced Dysconnectivity Between Salience Network and Auditory Cortex in Subjects With Psychotic-like Experiences: A Randomized Double-Blind Placebo-Controlled Study.
Level 2 - randomized trial
Individual randomized double-blind placebo-controlled trial
PubMed 31751466 · doi:10.1093/schbul/sbz110
What was done
Healthy, right-handed male volunteers were enrolled in a randomized, double-blind, placebo-controlled experiment. Baseline psychotic-like experiences were assessed with the revised Exceptional Experiences Questionnaire (PAGE-R). Participants received either oral placebo (n = 32) or 200 mg L-DOPA (n = 33) and underwent resting-state functional MRI. Functional connectivity changes with the right anterior insula (rAI), a core salience network hub, and their relationship with PAGE-R scores were evaluated using a seed-to-voxel approach.
What was found
L-DOPA reduced functional connectivity between the rAI and the left auditory cortex (planum polare). In the placebo group, rAI-to-planum polare connectivity correlated negatively with PAGE-R scores, whereas in the L-DOPA group, it correlated positively with PAGE-R scores. PAGE-R scores accounted for approximately 30% of the variance in rAI-to-planum polare connectivity across the two groups. Specific correlation coefficients, exact effect sizes, and p-values were not provided in the abstract.
Why it matters
These findings provide direct experimental evidence that dopamine modulates functional connections between sensory auditory areas and the salience network, offering a plausible mechanism for how altered dopamine signaling contributes to aberrant salience and psychotic-like experiences.
Limits
The abstract contains an internal sample size discrepancy, stating 54 subjects were enrolled while group totals sum to 65 (32 placebo, 33 L-DOPA). The cohort was restricted entirely to healthy, right-handed males, limiting generalizability to females and clinical populations with schizophrenia. The study used an acute single dose of L-DOPA, which may not reflect chronic dopaminergic pathophysiology, and exact numerical statistical values were omitted from the abstract.
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