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Frequency-specific and state-dependent neural responses to brain stimulation

Molecular Psychiatry volume 30, pages 2880–2890 (2025)Cite this article

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Abstract

Non-invasive brain stimulation is promising for treating many neuropsychiatric and neurological conditions. It could be optimized by understanding its intracranial responses in different brain regions. We implanted multi-site intracranial electrodes and systematically assessed the acute responses in these regions to transcranial alternating current stimulation (tACS) at different frequencies. We observed robust neural oscillation changes in the hippocampus and amygdala in response to non-invasive tACS procedures, and these effects were frequency-specific and state-dependent. Notably, the hippocampus responded most strongly and stably to 10 Hz stimulation, with pronounced changes across a wide frequency range, suggesting the potential of 10 Hz oscillatory stimulation to modulate a broad range of neural activity related to cognitive functions. Future work with increased sample sizes is required to determine the clinical implications of these findings for therapeutic efficiency.

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Fig. 1: Experimental setup and electric fields in hippocampus and amygdala.
Fig. 2: Characterization of tACS response properties in hippocampus and amygdala.
Fig. 3: Relative power change of the neural oscillations in the hippocampus during- and post-stimulation with tACS at different stimulation frequencies.
Fig. 4: Relative power change of the neural oscillations in the amygdala during- and post-stimulation with tACS at different stimulation frequencies.
Fig. 5: State-dependence of the neural responses to tACS in the hippocampus and amygdala.

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Data availability

The data that support the findings of this study are openly available at the Open Science Foundation repository (https://doi.org/10.17605/OSF.IO/G9BCT).

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Acknowledgements

The authors would like to acknowledge Professor Jian Jiang of Lingang Laboratory for supporting technical to help test the robust of tACS equipment, Hui Zheng for his great help in visualization and all volunteers for participating in this study.

Funding

This work was supported by the National Natural Science Foundation of China (T2394535, T2394533, 82325019, 32241015, 82401432), the Shanghai Yangfan Program (21YF1439700), the Science and Technology Commission of Shanghai Municipality (23XD1423000, 23ZR1480800, 24ZR1461000), Shanghai Municipal Commission of Health (2022JC016), Shanghai Municipal Education Commission - Gaofeng Clinical Medicine Grant Support (20181715), and Excellent Young Scientists Fund in Shenzhen (RCYX20231211090405003).

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Author notes

  1. These authors contributed equally: Huichun Luo, Xiaolai Ye, Hui-Ting Cai, Mo Wang.

Authors and Affiliations

  1. Department of Neurosurgery, Clinical Neuroscience Center Comprehensive Epilepsy Unit, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Huichun Luo, Xiaolai Ye, Qiangqiang Liu & Jiwen Xu

  2. Shanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine and School of Psychology, Shanghai, China

    Huichun Luo, Hui-Ting Cai, Ying Xu & Ti-Fei Yuan

  3. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China

    Huichun Luo & Ti-Fei Yuan

  4. Department of Neurosurgery, Clinical Neuroscience Center Comprehensive Epilepsy Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Xiaolai Ye, Qiangqiang Liu, Ziyu Mao, Yanqing Cai, Jing Hong & Jiwen Xu

  5. Department of Neurology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Xiaolai Ye

  6. Shanghai Xuhui Mental Health Center, Shanghai, China

    Hui-Ting Cai

  7. Shenzhen Key Laboratory of Smart Healthcare Engineering, Southern University of Science and Technology, Shenzhen, China

    Mo Wang, Yue Wang & Quanying Liu

  8. Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Chencheng Zhang

  9. Shenzhen Key Laboratory of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Fundamental Research Institutions, Shenzhen, China

    Pengfei Wei

  10. Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Yong Lu

Authors
  1. Huichun Luo
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  2. Xiaolai Ye
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  16. Ti-Fei Yuan
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Contributions

Conceptualization: Ti-Fei Yuan, Jiwen Xu, Quanying Liu. Funding acquisition: Ti-Fei Yuan, Quanying Liu, Pengfei Wei, Huichun Luo. Data collection: Huichun Luo, Xiaolai Ye, Hui-Ting Cai, Qiangqiang Liu, Ying Xu, Ziyu Mao, Yanqing Cai, Jing Hong. Methodology: Huichun Luo, Xiaolai Ye, Hui-Ting Cai, Mo Wang. Writing - original draft: Huichun Luo, Xiaolai Ye, Hui-Ting Cai, Mo Wang, Yue Wang, Chencheng Zhang. Writing - review & editing: Huichun Luo, Hui-Ting Cai, Pengfei Wei, Yong Lu, Quanying Liu, Jiwen Xu, Ti-Fei Yuan.

Corresponding authors

Correspondence to Quanying Liu, Jiwen Xu or Ti-Fei Yuan.

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Luo, H., Ye, X., Cai, HT. et al. Frequency-specific and state-dependent neural responses to brain stimulation. Mol Psychiatry 30, 2880–2890 (2025). https://doi.org/10.1038/s41380-025-02892-7

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