Single-dose serotonergic stimulation shows widespread effects on functional brain connectivity

Area of Science:

• Neuroscience
• Pharmacology
• Neuroimaging

Background:

• The serotonergic system is crucial for mood regulation and other brain functions.
• Resting-state functional magnetic resonance imaging (RS-fMRI) allows investigation of whole-brain functional connectivity.
• Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat mood disorders.

Purpose of the Study:

• To investigate the acute pharmacological effects of sertraline on brain functional connectivity using RS-fMRI.
• To examine how sertraline influences interactions within and between multiple functional brain networks.
• To assess the sensitivity of RS-fMRI in detecting drug-induced changes in brain function.

Main Methods:

• A randomized, double-blind, placebo-controlled, crossover study involving 12 healthy volunteers.
• RS-fMRI scans were acquired at baseline and at multiple time points after administering sertraline (75 mg) or placebo.
• Voxelwise functional connectivity analyses were performed across ten functional networks, controlling for physiological and motion covariates.

Main Results:

• Sertraline significantly altered functional connectivity in widespread brain networks, including the default mode, executive control, visual, sensorimotor, and auditory networks.
• The precuneus and posterior cingulate cortex showed consistent involvement across affected networks.
• Cognitive and subjective measures did not reveal significant treatment effects, highlighting RS-fMRI's sensitivity.

Conclusions:

• Acute administration of sertraline induces broad changes in brain functional connectivity.
• The findings support an extensive role for the serotonergic system in modulating diverse brain functions.
• The precuneus and cingulate cortex may play a key role in mediating the effects of serotonin on brain networks.