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

Huichun Luo; Xiaolai Ye; Hui-Ting Cai; Mo Wang; Yue Wang; Qiangqiang Liu; Ying Xu; Ziyu Mao; Yanqing Cai; Jing Hong; Chencheng Zhang; Pengfei Wei; Yong Lu; Quanying Liu; Jiwen Xu; Ti-Fei Yuan

doi:10.1038/s41380-025-02892-7

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

Mol Psychiatry. 2025 Jan 20. doi: 10.1038/s41380-025-02892-7. Online ahead of print.

Authors

Huichun Luo^#^{1

2

3}, Xiaolai Ye^#^{1

4

5}, Hui-Ting Cai^#^{2

6}, Mo Wang^#⁷, Yue Wang⁷, Qiangqiang Liu^{1

4}, Ying Xu², Ziyu Mao⁴, Yanqing Cai⁴, Jing Hong⁴, Chencheng Zhang⁸, Pengfei Wei⁹, Yong Lu¹⁰, Quanying Liu¹¹, Jiwen Xu^{12

13}, Ti-Fei Yuan^{14

15}

Affiliations

¹ Department of Neurosurgery, Clinical Neuroscience Center Comprehensive Epilepsy Unit, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
³ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
⁴ Department of Neurosurgery, Clinical Neuroscience Center Comprehensive Epilepsy Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Neurology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁶ Shanghai Xuhui Mental Health Center, Shanghai, China.
⁷ Shenzhen Key Laboratory of Smart Healthcare Engineering, Southern University of Science and Technology, Shenzhen, China.
⁸ Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
¹⁰ Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹¹ Shenzhen Key Laboratory of Smart Healthcare Engineering, Southern University of Science and Technology, Shenzhen, China. [email protected].
¹² Department of Neurosurgery, Clinical Neuroscience Center Comprehensive Epilepsy Unit, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
¹³ Department of Neurosurgery, Clinical Neuroscience Center Comprehensive Epilepsy Unit, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
¹⁴ 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. [email protected].
¹⁵ Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. [email protected].

^# Contributed equally.

PMID: 39833357
DOI: 10.1038/s41380-025-02892-7

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.