Effects of bilateral sequential theta-burst stimulation on functional connectivity in treatment-resistant depression: first results

Abstract

Background: Previous studies suggest that transcranial magnetic stimulation exerts antidepressant effects by altering functional connectivity (FC). However, knowledge about this mechanism is still limited. Here, we aimed to investigate the effect of bilateral sequential theta-burst stimulation (TBS) on FC in treatment-resistant depression (TRD) in a sham-controlled longitudinal study. Methods: TRD patients (n = 20) underwent a three-week treatment of intermittent TBS of the left and continuous TBS of the right dorsolateral prefrontal cortex (DLPFC). Upon this trial's premature termination, 15 patients had received active TBS and five patients sham stimulation. Resting-state functional magnetic resonance imaging was performed at baseline and after treatment. FC (left and right DLPFC) was estimated for each participant, followed by group statistics (T-tests). Furthermore, depression scores were analyzed (linear mixed models analysis) and tested for correlation with FC. Results: Both groups exhibited reductions of depression scores, however, there was no significant main effect of group, or group and time. Anticorrelations between DLPFC and the subgenual cingulate cortex (sgACC) were observed for baseline FC, corresponding to changes in depression severity. Treatment did not significantly change DLPFC-sgACC connectivity, but significantly reduced FC between the left stimulation target and bilateral anterior insula. Conclusions: Our data is compatible with previous reports on the relevance of anticorrelation between DLPFC and sgACC for treatment success. Furthermore, FC changes between left DLPFC and bilateral anterior insula highlight the effect of TBS on the salience network. Limitations: Due to the limited sample size, results should be interpreted with caution and are of exploratory nature.

Accelerated theta-burst transcranial magnetic stimulation of the bilateral dorsolateral prefrontal cortex in a patient with post-traumatic stress disorder and major depressive disorder: Case report

“…A randomized sham-controlled study enrolling 60 treatment-refractory patients with recurrent major depressive disorder revealed that the mean antidepressant effect was highest in a combination of iTBS and cTBS (14). A threeweek treatment of iTBS over left DLPFC and cTBS of the right DLPFC (DLPFC) in patients with treatment-resistant depression (TRD) reported that significantly reduced functional connectivity between the left stimulation target and bilateral anterior insula (30). Third, our patient underwent accelerated iTBS over the left DLPFC with a 20 min interval, whereas the patients in the study by Philip et al received iTBS over the right DLPFC without interval.…”

Brain Perfusion Alterations Induced by Standalone and Combined Non-Invasive Brain Stimulation over the Dorsolateral Prefrontal Cortex

“…Recent studies suggest that the DLPFC and the right sgACC are functionally correlated during depressive episodes, and changes in their connectivity are associated with higher antidepressant efficacy for rTMS treatments [ 8 , 33 , 34 ]. Neither rTMS nor tDCS can reach the sgACC region directly, but a connectivity-based study by Fox and colleagues [ 8 ] showed that NIBS effects on the right sgACC depend on which specific location is targeted within the left DLPFC.…”

Normal component of TMS-induced electric field is correlated with depressive symptom relief in treatment-resistant depression

“…The analysis was based on a subsample of patients from a longitudinal, clinical trial published previously [6]. Data of twelve TRD patients were included.…”

“…Targets were based on a previous study that indicated largest antidepressant effects and strongest negative functional connectivity with the subgenual cingulate cortex compared with other DLPFC locations [7]. MRI scans and clinical assessments were performed at baseline and after the last TBS session (for details, see [6]). TBS induced EF were simulated in anatomically realistic, volume conductor head models by the finite element method (FEM) using SimNIBS v3.2 [8].…”