Abstract

Intermittent theta burst stimulation (iTBS) delivered to the dorsolateral prefrontal cortex (DLPFC) has been investigated as a promising treatment for stress and stress‐related mental disorders such as major depression, yet large individual differences in responsiveness demand further exploration and optimization of its effectiveness. Clinical research suggests that resting‐state functional connectivity (rsFC) between the DLPFC and the anterior cingulate cortex (ACC) can predict iTBS treatment response in depression. The present study aimed to investigate whether rsFC between the left DLPFC and ACC subregions could predict the degree to which the stress system is affected by iTBS. After assessment of baseline resting‐state fMRI data, 34 healthy female participants performed the Trier Social Stress Test on two separate days, each followed by active or sham iTBS over the left DLPFC. To evaluate iTBS effects on the stress‐system, salivary cortisol was measured throughout the procedure. Our results showed that a stronger negative correlation between the left DLPFC and the caudal ACC was linked to a larger attenuation of stress‐system sensitivity during active, but not during sham iTBS. In conclusion, based on individual rsFC between left DLPFC and caudal ACC, iTBS could be optimized to more effectively attenuate deregulation of the stress system.

Highlights

  • Modern life stress is taking its toll on mental health worldwide (Hidaka, 2012)

  • When considering individual differences in resting-state functional connectivity (rsFC) strengths, and with active Intermittent theta burst stimulation (iTBS) only, we found that stronger baseline rsFC anticorrelations between the individual stimulation site and the left Caudal ACC (cACC) showed predictive value for lower cortisol levels (AUCi) after stress

  • Our results imply that a stronger anticorrelated rsFC between the left dorsolateral prefrontal cortex (DLPFC) and left cACC in healthy individuals can be predictive for more effectiveness of iTBS in the regulation of hypothalamic–pituitary axis (HPA)-axis activity

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Summary

Introduction

The burden of mood and stress-related disorders on both individuals and society has been assuming alarming proportions for decades, yet relatively little progress is being made regarding treatment efficacy. Noninvasive brain stimulation techniques such as (repetitive) transcranial magnetic stimulation (rTMS) have been showing promising effects on stress regulation and mood improvement in both neuroscientific as well as clinical contexts (Baeken et al, 2019; Blumberger et al, 2018b; Chen, Chang, Chen, & Lin, 2013; Lefaucheur et al, 2020), a growing number of studies report substantial interindividual variability in responsiveness toward TMS, as its working mechanisms are not yet fully understood Taking individual differences into consideration is essential for expanding our insight in the working mechanisms of rTMS and possibly the further optimization of its therapeutic efficacy

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