Research Paper Volume 13, Issue 1 pp 1314—1331

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

Jiu Chen1,2, *, , Nan Ma3, *, , Guanjie Hu1,2, , Amdanee Nousayhah8, , Chen Xue2,4, , Wenzhang Qi2,4, , Wenwen Xu5, , Shanshan Chen5, , Jiang Rao2,6, , Wan Liu6, , Fuquan Zhang7, , Xiangrong Zhang2,8, ,

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

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

https://doi.org/10.18632/aging.202313
How to Cite

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.

Abbreviations

HIPsub: Hippocampal subregions; SCD: subjective cognitive decline; rTMS: repetitive transcranial magnetic stimulation; HIPe: hippocampal emotional region; HIPc: hippocampal cognitive region; HIPp: hippocampal perceptual region; AD: Alzheimer's disease; MCI: amnestic mild cognitive impairment; NBH-ADsnp: Nanjing Brain Hospital-Alzheimer’s Disease Spectrum Neuroimaging Project; CN: healthy controls; ITV: intracranial volumes; GLM: general linear model; RMS: root mean square; FD: framewise displacement; TFCE: Threshold-Free Cluster Enhancement; FDR: false discovery rate; ROI: regions of interest; MT: motor threshold; FWE: family-wise error; CEREpos.R: right cerebellum posterior lobe; FusG.L: left fusiform gyrus; PHG.L: left parahippocampal gyrus; IFGorb.R: right inferior frontal gyrus, orbital part; MTG.R: right middle temporal gyrus; MTG.L: left middle temporal gyrus; MFG.L: left medial frontal gyrus; PreCUN.L: left Precuneus.