Effects of combined theta burst stimulation and transcranial direct current stimulation of the dorsolateral prefrontal cortex on stress

Clin Neurophysiol. 2021 May;132(5):1116-1125. doi: 10.1016/j.clinph.2021.01.025. Epub 2021 Mar 10.


Objective: Research suggests that the combination of different non-invasive brain stimulation techniques, such as intermittent theta-burst stimulation (iTBS) and transcranial direct current stimulation (tDCS), could enhance the effects of stimulation. Studies investigating the combination of tDCS and iTBS over the dorsolateral prefrontal cortex (DLPFC) are lacking. In this within-subjects study, we evaluated the additive effects of iTBS with tDCS on psychophysiological measures of stress.

Method: Sixty-eight healthy individuals were submitted to a bifrontaltDCS + iTBS and shamtDCS + iTBS protocol targeting the DLPFC with a one-week interval. The Maastricht Acute Stress Test was used to activate the stress system after stimulation. Stress reactivity and recovery were assessed using physiological and self-report measures.

Results: The stressor evoked significant psychophysiological changes in both stimulation conditions. However, no evidence was found for differences between them in stress reactivity and recovery. Participants reported more pain and feelings of discomfort to the bifrontaltDCS + iTBS protocol.

Conclusion: In this study set-up, iTBS plus tDCS was not superior to iTBS in downregulating stress in healthy subjects.

Significance: There is no evidence for an effect of combined tDCS-iTBS of the DLPFC on stress according to the parameters employed in our study. Future studies should explore other stimulation parameters, additive approaches and/or neurobiological markers.

Keywords: Dorsolateral Prefrontal Cortex (DLPFC); Intermittent Theta Burst Stimulation (iTBS); Non-invasive Brain Stimulation; Psychophysiology; Stress; Transcranial Direct Current Stimulation (tDCS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prefrontal Cortex / physiology
  • Prefrontal Cortex / physiopathology
  • Stress, Psychological / physiopathology*
  • Theta Rhythm*
  • Transcranial Direct Current Stimulation*