Repetitive Transcranial Magnetic Stimulation Induced Hypoconnectivity Within the Default Mode Network Yields Cognitive Improvements in Amnestic Mild Cognitive Impairment: A Randomized Controlled Study

Article type: Research Article

Authors: Cui, Hailun^{a; 1} | Ren, Rujing^{a; 1} | Lin, Guozhen^b | Zou, Yang^a | Jiang, Lijuan^c | Wei, Zhengde^{c; d} | Li, Chunbo^{c; e; f; 2; *} | Wang, Gang^{a; 2; *}

Affiliations: [a] Department of Neurology & Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China | [b] Department of Psychiatry, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China | [c] Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China | [d] Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, China | [e] Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China | [f] CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT), Chinese Academy of Science, Shanghai, China

Correspondence: [*] Correspondence to: Gang Wang, MD, PhD, Department of Neurology& Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Tel.: +86 021 64454473; Fax: +86 021 64454473; E-mail: wgneuron@hotmail.com and Chunbo Li, MD, Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center (SMHC), Shanghai Jiao Tong University School of Medicine, Shanghai, China. Tel.: +86 021 34773243; Fax: +86 021 64387986; E-mail: licb@smhc.org.cn.

Note: [1] These authors contributed equally to this work.

Note: [2] These authors contributed equally to this work as corresponding authors.

Abstract: Background:Repetitive transcranial magnetic stimulation (rTMS) is thought to be effective in alleviating cognitive symptoms in patients with amnestic mild cognitive impairment (aMCI), but the mechanisms related to network modification are poorly understood. Objective:Here we tested rTMS efficacy and explored the effect of rTMS-induced changes in the default mode network (DMN) and their predictive value for treatment response. Methods:Twenty-one subjects clinically diagnosed with aMCI were recruited to complete a 10-session randomized and sham-controlled rTMS treatment targeting the right dorsolateral prefrontal cortex. Resting-state functional magnetic resonance imaging in tandem with neuropsychological assessments were administered before and after the intervention. Changes in functional connectivity of the DMN and relevant brain regions, as well as the correlations between baseline functional connectivity and clinical rating scales were calculated in order to elucidate the mechanism of treatment response to rTMS therapy. Results:Compared to the sham group, the rTMS group achieved improvement of neuropsychological performance and significant functional connectivity changes within the DMN. Group×Time interactions were found between posterior cingulate gyrus and right fusiform gyrus (F (1,19)  = 17.154, p = 0.001), and also left anterior cingulate gyrus (F (1,19)  = 3.908, p = 0.063), showing an rTMS-induced deactivation of functional connectivity within the DMN. Baseline functional connectivity analysis of seeds within the DMN in the rTMS group revealed negative correlation with AVLT-Recognition score changes. Conclusion:rTMS-induced hypoconnectivity within DMN is associated with clinical cognitive improvements in patients with aMCI. Further, pre-rTMS baseline activity of the DMN at rest may be a predictor for favorable rTMS treatment response.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, default mode network, repetitive transcranial magnetic stimulation, resting-state functional MRI

DOI: 10.3233/JAD-181296

Journal: Journal of Alzheimer's Disease, vol. 69, no. 4, pp. 1137-1151, 2019