Effect of Lithium Administration on Brain Activity Under an Emotion Regulation Paradigm in Healthy Participants: A Functional Magnetic Resonance Imaging Study

Abstract

Abstract Rationale: Emotion Regulation (ER) difficulties have been previously described in bipolar disorder (BD). Whilst lithium has been shown to be effective in the treatment of BD, the mechanisms underlying lithium’s effect on mood stabilisation remain unclear. Objectives Unravelling lithium’s effect on psychological processes impaired in BD, such as ER, could address this translational gap and inform the development of new treatments. Methods This study investigated the neural effects of lithium on ER in 36 healthy volunteers in a double-blind between-groups design, with randomised administration of lithium or placebo for 11 days. At treatment completion, participants underwent 3- Tesla functional magnetic resonance imaging while performing an ER task. Participants viewed negative images and were instructed to maintain or reappraise the elicited emotions and rate the negative affect experienced. Results During reappraisal (versus maintain), lithium increased activity in the right middle temporal gyrus (MTG, Z > 3.1, p < 0.05 corrected) and decreased activation in the left angular gyrus, the left anterior prefrontal cortex (or rostral PFC, BA10) and right superior frontal gyrus (Z > 2.3, p < 0.05 corrected). In addition, greater connectivity was found between the right MTG and left middle frontal gyrus for the lithium group compared to placebo, during reappraisal (versus maintain) (Z > 2.3, p < 0.05 corrected). Further effects of lithium were found in response to negative picture presentation, whereby decreased connectivity was found between the left amygdala and the frontal cortex, and greater connectivity between the right MTG and the bilateral medial prefrontal cortex extending into the paracingulate gyrus, compared to placebo (Z > 2.3, p < 0.05 corrected). Conclusions These results show a potential effect of lithium on ER through its effects on activity and connectivity, and further elaborate the neural underpinnings of cognitive reappraisal. Future work should investigate more extended effects of lithium on ER, ultimately benefitting the development of novel and more effective treatments for BD.