High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats

Qi Wu; Xingjun Xu; Chenyuan Zhai; Zhiyong Zhao; Wenjun Dai; Tong Wang; Ying Shen

doi:10.3389/fnins.2022.974940

High-frequency repetitive transcranial magnetic stimulation improves spatial episodic learning and memory performance by regulating brain plasticity in healthy rats

Front Neurosci. 2022 Aug 5:16:974940. doi: 10.3389/fnins.2022.974940. eCollection 2022.

Authors

Qi Wu^{1

2}, Xingjun Xu¹, Chenyuan Zhai¹, Zhiyong Zhao³, Wenjun Dai¹, Tong Wang¹, Ying Shen¹

Affiliations

¹ Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Rehabilitation, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China.
³ College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.

Abstract

Background: Repetitive transcranial magnetic stimulation (rTMS) is an effective way to stimulate changes in structural and functional plasticity, which is a part of learning and memory. However, to our knowledge, rTMS-induced specific activity and neural plasticity in different brain regions that affect cognition are not fully understood; nor are its mechanisms. Therefore, we aimed to investigate rTMS-induced cognition-related neural plasticity changes and their mechanisms in different brain regions.

Methods: A total of 30 healthy adult rats were randomly divided into the control group and the rTMS group (n = 15 rats per group). The rats in the control and the rTMS group received either 4 weeks of sham or high-frequency rTMS (HF-rTMS) over the prefrontal cortex (PFC). Cognitive function was detected by Morris water maze. Functional imaging was acquired by resting-state functional magnetic resonance imaging (rs-fMRI) before and after rTMS. The protein expressions of BDNF, TrkB, p-Akt, Akt, NR1, NR2A, and NR2B in the PFC, hippocampus, and primary motor cortex (M1) were detected by Western blot following rTMS.

Results: After 4 weeks of rTMS, the cognitive ability of healthy rats who underwent rTMS showed a small but significant behavioral improvement in spatial episodic learning and memory performance. Compared with the pre-rTMS or the control group, rats in the rTMS group showed increased regional homogeneity (ReHo) in multiple brain regions in the interoceptive/default mode network (DMN) and cortico-striatal-thalamic network, specifically the bilateral PFC, bilateral hippocampus, and the left M1. Western blot analyses showed that rTMS led to a significant increase in the expressions of N-methyl-D-aspartic acid (NMDA) receptors, including NR1, NR2A, and NR2B in the PFC, hippocampus, and M1, as well as an upregulation of BDNF, TrkB, and p-Akt in these three brain regions. In addition, the expression of NR1 in these three brain regions correlated with rTMS-induced cognitive improvement.

Conclusion: Overall, these data suggested that HF-rTMS can enhance cognitive performance through modulation of NMDA receptor-dependent brain plasticity.

Keywords: N-methyl-D-aspartic acid receptors; cognitive improvement; healthy rat; neural plasticity; repetitive transcranial magnetic stimulation; resting-state functional magnetic resonance imaging.