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Comparative effects of 10-Hz rTMS and iTBS on cortico-striatal connectivity in major depressive disorder: a sham-controlled study

Molecular Psychiatry (2025)Cite this article

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Abstract

Abnormalities in the prefrontal cortex (PFC)-related network play an important role in the pathophysiology of major depressive disorder (MDD). Accumulating evidence indicated that fronto-striatal dysconnectivity is critical to MDD pathogenesis. Whether non-invasive brain stimulation, including 10-Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS), may change cortico-striatal functional connectivity (FC) in MDD patients is unclear. Whether the change of cortico-striatal FC is associated with the antidepressant effects is also unknown. In total, 68 adult MDD subjects were randomly assigned to one of three groups: iTBS, 10-Hz rTMS, or sham group. Functional connectivity was analyzed using MRI and seed-based methods. Seeds included left and right dorsal caudate (DC), dorsal rostral putamen (DRP), and ventral rostral putamen (VRP). The results revealed that significant group-by-time interactions in FC were found in all the striatal seeds. Post-hoc analyses revealed significant increases in FC of the left DRP and VRP for both iTBS and rTMS treatments, particularly with the right frontal pole. Greater FC changes of the fronto-striatal networks correlated with the antidepressant effects. The effects of rTMS and iTBS on FCs of the intra-striatal network, default mode network, and other cortico-striatal networks were distinct. In conclusion, the first study demonstrated that iTBS and rTMS had common but unique effects on the cortico-striatal and intra-striatal networks. These results suggest that both treatments regulate brain reward systems and might be used to treat various striatum-related neuropsychiatric illnesses.

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Data availability

The data that support the findings of this study are available from the first author, CTL, upon reasonable request.

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Acknowledgements

We would like to thank all the patients who kindly participated in this study and all the research assistants, physicians, and staff who assisted with the study and imaging procedures. This study was sponsored by grants from Taipei Veterans General Hospital (V108D44-003-MY3-1; V111-B-019) [CTL], University System of Taiwan Joint Research Program (VGHUST111-G1-2-1), and the National Science and Technology (MOST108-2321-B-075-004-MY2; NSC 111-2314-B-075-085-MY3) [CTL]. This work was also supported by the Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Neither of the aforementioned organizations had any role in the study design, data collection, analysis, interpretation of results, writing of the report, or ultimate decision to submit the paper for publication.

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Authors and Affiliations

  1. Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

    Cheng-Ta Li, Wan-Chen Chang, Chih-Ming Cheng, Tung-Ping Su, Ya-Mei Bai & Pei-Chi Tu

  2. Department of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Cheng-Ta Li, Ya-Mei Bai & Pei-Chi Tu

  3. Institute of Brain Science and Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Cheng-Ta Li & Ya-Mei Bai

  4. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

    Wan-Chen Chang & Pei-Chi Tu

  5. Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Wan-Chen Chang

  6. Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan

    Tung-Ping Su

  7. Institute of Philosophy of Mind and Cognition, National Yang Ming Chiao Tung University, Taipei, Taiwan

    Pei-Chi Tu

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Contributions

Drs CTL and PCT designed the study; Drs CTL, CMC, TPS, and YMB enrolled the candidate patients and helped with the clinical trial; Miss WCC and Dr PCT analyzed the neuroimaging data; Dr CTL performed the literature reviews; Drs CTL and PCT drafted the manuscript; all authors reviewed the final manuscript and agreed for the publication.

Corresponding author

Correspondence to Pei-Chi Tu.

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The authors declare no competing interests.

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This study was performed in accordance with the Declaration of Helsinki and was approved by the Taipei Veterans General Hospital Institutional Review Board. The study was preregistered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR). Registration number: UMIN000044951. Informed consent was provided by all the participants.

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Li, CT., Chang, WC., Cheng, CM. et al. Comparative effects of 10-Hz rTMS and iTBS on cortico-striatal connectivity in major depressive disorder: a sham-controlled study. Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-03091-0

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