Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 23.
doi: 10.3758/s13415-025-01305-0. Online ahead of print.

Investigating the neural and behavioral correlates of the stress-rumination link in healthy humans by modulating the left Dorsolateral Prefrontal Cortex using Theta Burst Stimulation

Isabell Int-Veen  1 , Ute Eßer  2   3 , Sandra Ladegast  2   3 , Leonhard Liermann  2 , Ramona Täglich  2 , Betti Schopp  2 , Hans-Christoph Nuerk  3   4 , Christian Plewnia  2   4 , Agnes Kroczek  2 , Stefanie De Smet  5   6   7 , Marie-Anne Vanderhasselt  5   6 , Andreas J Fallgatter  2   4   8 , Ann-Christine Ehlis  2   4   8 , Beatrix Barth  2   4   8 , David Rosenbaum  2
Affiliations

Investigating the neural and behavioral correlates of the stress-rumination link in healthy humans by modulating the left Dorsolateral Prefrontal Cortex using Theta Burst Stimulation

Isabell Int-Veen et al. Cogn Affect Behav Neurosci. .

Abstract

Theta Burst Stimulation (TBS) offers a noninvasive way to modulate neural activation patterns, helping to explore the causal role of brain regions in psychiatric symptoms. Prefrontal hypoactivation is commonly observed in high ruminators and patients with depression during stress. However, the impact of modulating Dorsolateral Prefrontal Cortex (DLPFC) activity via excitatory and inhibitory TBS during stress remains unexplored. We studied 88 healthy participants (44 low, 44 high ruminators), each attending two appointments that included stress induction using the Trier Social Stress Test (TSST) and cortical oxygenation assessment with functional Near-Infrared Spectroscopy (fNIRS). Participants received either intermittent TBS (iTBS) or continuous TBS (cTBS) applied to the left DLPFC, with sessions randomized between active and sham stimulation. While TBS had no impact on positive affect, TSST performance, or heart rate, we observed effects on stress, state rumination, negative affect, and cortical oxygenation. We observed higher stress and higher negative affect during and after the TSST in high ruminators receiving iTBS compared with sham TBS (sTBS). Low ruminators showed reduced state rumination increases after iTBS compared with sTBS at their second appointment. fNIRS data revealed cortical oxygenation differences during the TSST, although only without multiple comparison corrections. Descriptively, we observed higher activation in the left Ventrolateral Prefrontal Cortex (VLPFC) following cTBS compared with sTBS in high ruminators but lower cortical oxygenation following cTBS compared with sTBS in low ruminators but only when participants received active stimulation first. This suggests stimulation sequence affects repeated-measures TMS studies in stress contexts. Findings highlight expectancy effects and suggest a potential reduction in TBS impact due to strong hemodynamic responses during stress. HIGHLIGHTS: • High ruminators showed increased stress and negative affect after iTBS during the TSST. • Neural data showed increased cortical oxygenation in the left Ventrolateral Prefrontal Cortex (VLPFC) following cTBS to the left Dorsolateral Prefrontal Cortex (DLPFC) in high ruminators. • In low ruminators, cTBS led to decreased activation, but only when active stimulation was administered first, highlighting the role of stimulation order in TBS outcomes. • Expectancy effects and habituation are important aspects to be considered in repeated measures designs involving TBS and stress-reactive rumination.

Keywords: Dorsolateral Prefrontal Cortex; Rumination; Stress; Theta Burst Stimulation; Trier Social Stress Test.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflicts of interest/Competing interests: The authors have no competing interests to declare that are relevant to the content of this article. Ethics approval: This study was approved by the ethics committee at the University Hospital and University of Tübingen (673/2019BO1). Consent to participate: All participants gave written informed consent prior to study participation. Consent for publication: All authors consent to publication of the manuscript.

Similar articles

See all similar articles

Cited by

References

    1. Allen, A. P., Kennedy, P. J., Cryan, J. F., Dinan, T. G., & Clarke, G. (2014). Biological and psychological markers of stress in humans: Focus on the Trier Social Stress Test. Neuroscience & Biobehavioral Reviews, 38, 94–124. https://doi.org/10.1016/j.neubiorev.2013.11.005 - DOI
    1. Allen, A. P., Kennedy, P. J., Dockray, S., Cryan, J. F., Dinan, T. G., & Clarke, G. (2017). The Trier Social Stress Test: Principles and practice. Neurobiology of Stress, 6, 113–126. https://doi.org/10.1016/j.ynstr.2016.11.001 - DOI - PubMed
    1. Baeken, C., Vanderhasselt, M.-A., Remue, J., Rossi, V., Schiettecatte, J., Anckaert, E., & De Raedt, R. (2014). One left dorsolateral prefrontal cortical HF-rTMS session attenuates HPA-system sensitivity to critical feedback in healthy females. Neuropsychologia, 57, 112–121. - DOI - PubMed
    1. Beck, A. T., Steer, R. A., Brown, G. K., et al. (1996). Beck depression inventory. APA PsycTests.
    1. Berman, M. G., Peltier, S., Nee, D. E., Kross, E., Deldin, P. J., & Jonides, J. (2011). Depression, rumination and the default network. Social Cognitive and Affective Neuroscience, 6(5), 548–555. https://doi.org/10.1093/scan/nsq080 - DOI - PubMed

LinkOut - more resources