Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) Induces Functional Connectivity Changes in Emotion Regulation Brain Areas for MDD Patients

BackgroundMajor depressive disorder (MDD) is prevalent and debilitating, and development of improved treatments is limited in part by insufficient understanding of the mechanism of disease remission. In turn, efforts to elucidate mechanisms have been challenging due to disease heterogeneity and limited effectiveness of treatments, which require weeks-to-months to induce remission. We recently developed a form of repetitive transcranial magnetic stimulation that induces remission in 90% of individuals with severe, treatment resistant MDD in 1-5 days (SAINT). This provides a new tool to begin exploring the network-level mechanisms of MDD remission. ObjectiveDetermine the functional connectivity (fc) changes that occur with SAINT in brain regions associated with emotion regulation. MethodsResting-state fMRI scans were performed just prior to (baseline), and following, open-label SAINT in 18 participants with severe, treatment-resistant MDD. Fc was determined between regions of interest (ROIs) defined a priori with well-described roles in emotion regulation. ResultsFollowing SAINT treatment fc was significantly decreased between the following ROI pairs: dorsolateral prefrontal cortex (DLPFC)-striatum, DLPFC-amygdala, default mode network (DMN)-subgenual cingulate cortex (sgACC), DMN-amygdala, DMN-striatum, amygdala-striatum, and between amygdala subregions. Greater clinical improvements were associated with larger decreases in fc between DLPFC-amygdala and DLPFC-insula. Greater clinical improvements were associated with smaller decreases in fc between sgACC-DMN. Significant increases and decreases in fc between insula-amygdala were observed depending on the subregions. Greater clinical improvements were associated with lower baseline fc between DMN-DLPFC, DMN-striatum, and DMN-ventrolateral prefrontal cortex. ConclusionSAINT-induced remission from depression is associated with fc changes that suggest improved regulation of emotion. Although preliminary, this leads us to hypothesize that interventions that augment top-down regulation of emotion may be effective depression treatments.