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Lack of effects of eight-week left dorsolateral prefrontal theta burst stimulation on white matter macro/microstructure and connection in autism

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Abstract

Whether brain stimulation could modulate brain structure in autism remains unknown. This study explored the impact of continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) on white matter macro/microstructure in intellectually able children and emerging adults with autism. Sixty autistic participants were randomized (30 active) and received active or sham cTBS for eight weeks twice per week, 16 total sessions using a double-blind (participant-, rater-, analyst-blinded) design. All participants received high-angular resolution diffusion MR imaging at baseline and week 8. Twenty-eight participants in the active group and twenty-seven in the sham group with good imaging quality entered the final analysis. With longitudinal fixel-based analysis and network-based statistics, we found no significant difference between the active and sham groups in changes of white matter macro/microstructure and connections following cTBS. In addition, we found no association between baseline white matter macro/microstructure and autistic symptom changes from baseline to week 8 in the active group. In conclusion, we did not find a significant impact of left DLPFC cTBS on white matter macro/microstructure and connections in children and emerging adults with autism. These findings need to be interpreted in the context that the current intellectually able cohort in a single university hospital site limits the generalizability. Future studies are required to investigate if higher stimulation intensities and/or doses, other personal factors, or rTMS parameters might confer significant brain structural changes visible on MRI in ASD.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to thank all of our participants and their family members for partaking in this study and the anonymous reviewers for comments that significantly improved the manuscript. We want to pay tribute to the late Professor Ying-Zu Huang, who guided and inspired this study with wisdom, insight, and tenacity.

Funding

This work is supported by grants from the Ministry of Science and Technology of Taiwan (108–2628-B-182A-006-; 109–2628-B-182A-010-; 110–2628-B-182A-016-; 112–2221-E-182–029). Hsiang-Yuan Lin is supported by the Azrieli Adult Neurodevelopmental Centre at Centre for Addiction and Mental Health, and an Academic Scholar Award from the Department of Psychiatry, University of Toronto. The funders had no role in the study's design, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

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Authors and Affiliations

  1. Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan

    Chun-Hung Yeh & Rung-Yu Tseng

  2. Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, No.5 Fusing St. Gueishan, Taoyuan, 333, Taiwan

    Chun-Hung Yeh, Po-Chun Lin & Hsing-Chang Ni

  3. Deparment of Computer Science and Information Engineering, Chang Gung University, Taoyuan, Taiwan

    Yi-Ping Chao

  4. Department of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

    Yi-Ping Chao

  5. Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

    Chen-Te Wu

  6. Department of Psychology, National Taiwan University, Taipei, Taiwan

    Tai-Li Chou

  7. Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan

    Tai-Li Chou & Susan Shur-Fen Gau

  8. Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan

    Tai-Li Chou

  9. Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

    Rou-Shayn Chen

  10. Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan

    Susan Shur-Fen Gau

  11. College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Hsing-Chang Ni

  12. Azrieli Adult Neurodevelopmental Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada

    Hsiang-Yuan Lin

  13. Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Hsiang-Yuan Lin

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  1. Chun-Hung Yeh
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Contributions

All authors read and approved the final manuscript. Conceptualization and design: Hsing-Chang Ni, Hsiang-Yuan Lin; Methodology: Yi-Ping Chao, Chen-Te Wu, Rou-Shayn Chen, Chun-Hung Yeh; Clinical data collection: Hsing-Chang Ni; Neuroimaging data collection: Hsing-Chang Ni, Yi-Ping Chao, Chen-Te Wu; Formal analysis: Hsiang-Chang Ni, Rung-Yu Tseng, Chun-Hung Yeh, Hsiang-Yuan Lin; Interpretation: Hsiang-Chang Ni, Po-Chun Lin, Chun-Hung Yeh, and Hsiang-Yuan Lin; Writing—original draft preparation: Hsiang-Chang Ni, Po-Chun Lin, Chun-Hung Yeh, and Hsiang-Yuan Lin; Figures: Hsiang-Chang Ni, Rung-Yu Tseng, Chun-Hung Yeh; Writing—review and editing: All authors; Funding acquisition: Hsing-Chang Ni; Resources: Tai-Li Chou and Susan Shur-Fen Gau; Supervision: Hsiang-Yuan Lin.

Corresponding author

Correspondence to Hsing-Chang Ni.

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The authors declare no competing interests.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Research Ethics Committee approved the study at Chang Gung Memorial Hospital, Linkou, Taiwan (201802246A0), and registered with ClinicalTrials.gov (NCT04993144).

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All participants provided informed consent to publish the data.

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Yeh, CH., Lin, PC., Tseng, RY. et al. Lack of effects of eight-week left dorsolateral prefrontal theta burst stimulation on white matter macro/microstructure and connection in autism. Brain Imaging and Behavior (2024). https://doi.org/10.1007/s11682-024-00874-x

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