Effects of L-Dopa and Oxazepam on Resting-State Functional Magnetic Resonance Imaging Connectivity: A Randomized, Cross-Sectional Placebo Study

Pharmacological functional brain imaging has traditionally focused on neuropharmacological modulations of event-related responses. The current study is a randomized, cross-sectional resting-state functional magnetic resonance imaging study where a single dose of commonly prescribed amounts of either benzodiazepine (oxazepam), L-dopa, or placebo was given to 81 healthy subjects. It was hypothesized that the connectivity in resting-state networks would be altered, and that the strength of connectivity in areas rich in target receptors would be particularly affected. Additionally, based on known anxiolytic mechanisms of benzodiazepines, modulated amygdala (Am) connectivity was predicted. To test this, seed region-based correlational analysis was performed using seven seeds placed in well-characterized resting-state networks, in regions with above-average densities of GABA-A or dopamine receptors and in Am. To alleviate the anatomical bias introduced by the a priori selected seed regions, whole-brain exploratory analysis of regional homogeneity and fractional amplitude of low-frequency fluctuations (fALFF) was also carried out. Oxazepam increased functional connectivity between midline regions of the default-mode network (DMN) and the prefrontal, parietal, and cerebellar areas, but decreased connectivity between, for example, the Am and temporal cortex. L-dopa mainly decreased connectivity between the Am and bilateral inferior frontal gyri and between midline regions of the DMN. The fALFF analysis revealed that L-dopa decreased low-frequency fluctuations in the cerebellum. It was concluded that the overall effects of single administrations of oxazepam and L-dopa on resting-state connectivity were small both in strength and in spatial extent, and were on par with placebo effects as revealed by comparing the two placebo groups.