Research Paper|Volume 13, Issue 1|pp 1314—1331

rTMS modulates precuneus-hippocampal subregion circuit in patients with subjective cognitive decline

Jiu Chen^1,², Nan Ma³, Guanjie Hu^1,², Amdanee Nousayhah⁸, Chen Xue^2,⁴, Wenzhang Qi^2,⁴, Wenwen Xu⁵, Shanshan Chen⁵, Jiang Rao^2,⁶, Wan Liu⁶, Fuquan Zhang⁷, Xiangrong Zhang^2,⁸

¹Institute of Neuropsychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
²Institute of Brain Functional Imaging, Nanjing Medical University, Nanjing 210029, China
³Department of Neurology, Xi'an Children's Hospital, Xi'an 710003, Shaanxi, China
⁴Department of Radiology, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China
⁵Department of Neurology, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210009, China
⁶Department of Rehabilitation, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China
⁷Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China
⁸Department of Geriatric Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing 210029, China

* Equal contribution

Received: August 25, 2020Accepted: October 22, 2020Published: November 30, 2020

https://doi.org/10.18632/aging.202313

Copyright: © 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hippocampal subregions (HIPsub) and their network connectivities are generally aberrant in patients with subjective cognitive decline (SCD). This study aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS) could ameliorate HIPsub network connectivity by modulating one node of HIPsub network in SCD. In the first cohort, the functional connectivity (FC) of three HIPsub (i.e., hippocampal emotional, cognitive, and perceptual regions: HIPe, HIPc, and HIPp) were analyzed so as to identify alterations in HIPsub connectivity associated with SCD. Afterwards, a support vector machine (SVM) approach was applied using the alterations in order to evaluate to what extent we could distinguish SCD from healthy controls (CN). In the second cohort, a 2-week rTMS course of 5-day, once-daily, was used to activate the altered HIPsub network connectivity in a sham-controlled design. SCD subjects exhibited distinct patterns alterations of HIPsub network connectivity compared to CN in the first cohort. SVM classifier indicated that the abnormalities had a high power to discriminate SCD from CN, with 92.9% area under the receiver operating characteristic curve (AUC), 86.0% accuracy, 83.8% sensitivity and 89.1% specificity. In the second cohort, changes of HIPc connectivity with the left parahippocampal gyrus and HIPp connectivity with the left middle temporal gyrus demonstrated an amelioration of episodic memory in SCD after rTMS. In addition, SCD exhibited improved episodic memory after the rTMS course. rTMS therapy could improve the posterior hippocampus connectivity by modulating the precuneus in SCD. Simultaneous correction of the breakdown in HIPc and HIPp could ameliorate episodic memory in SCD. Thus, these findings suggested that rTMS manipulation of precuneus-hippocampal circuit might prevent disease progression by improving memory as the earliest at-risk state of Alzheimer’s disease in clinical trials and in practice.