Uncovering the Modulatory Interactions of Brain Networks in Cognition with Central Thalamic Deep Brain Stimulation Using Functional Magnetic Resonance Imaging

Ssu-Ju Li; Yu-Chun Lo; Hsin-Yi Lai; Sheng-Huang Lin; Hui-Ching Lin; Ting-Chun Lin; Ching-Wen Chang; Ting-Chieh Chen; Christine Chin-Jung Hsieh; Shih-Hung Yang; Feng-Mao Chiu; Chao-Hung Kuo; You-Yin Chen

doi:10.1016/j.neuroscience.2020.05.022

Uncovering the Modulatory Interactions of Brain Networks in Cognition with Central Thalamic Deep Brain Stimulation Using Functional Magnetic Resonance Imaging

Neuroscience. 2020 Aug 1:440:65-84. doi: 10.1016/j.neuroscience.2020.05.022. Epub 2020 May 22.

Authors

Affiliations

¹ Department of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan, ROC.
² The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Xing Street, Taipei 11031, Taiwan, ROC. Electronic address: aricalo@tmu.edu.tw.
³ Department of Neurology of the Second Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Zhejiang University, No. 866, Yuhangtang Road, Hangzhou City, Zhejiang Province 310029, China; College of Biomedical Engineering and Instrument Science, Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, No. 866, Yuhangtang Road, Hangzhou City, Zhejiang Province 310029, China; Department of Neurology of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, No. 866, Yuhangtang Road, Hangzhou City, Zhejiang Province 310029, China.
⁴ Department of Neurology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Chung Yang Road, Hualien 97002, Taiwan, ROC; Department of Neurology, School of Medicine, Tzu Chi University, No. 701, Sec. 3, Zhongyang Road, Hualien 97004, Taiwan, ROC.
⁵ Department and Institute of Physiology, National Yang Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan, ROC.
⁶ Department of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan, ROC; Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Yang Ming University and Academia Sinica, No. 128, Sec. 2, Academia Road, Taipei 11529, Taiwan, ROC.
⁷ Department of Mechanical Engineering, National Cheng Kung University, No. 1 University Road, Tainan 70101, Taiwan, ROC.
⁸ Department of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan, ROC; Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan, ROC; Department of Neurological Surgery, University of Washington, No. 1959 NE Pacific Street, Seattle, WA 98195-6470, USA.
⁹ Department of Biomedical Engineering, National Yang Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan, ROC; The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Xing Street, Taipei 11031, Taiwan, ROC; Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Yang Ming University and Academia Sinica, No. 128, Sec. 2, Academia Road, Taipei 11529, Taiwan, ROC. Electronic address: irradiance@so-net.net.tw.

PMID: 32446855
DOI: 10.1016/j.neuroscience.2020.05.022

Abstract

Deep brain stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. It acts by altering brain networks and facilitating synaptic plasticity. For enhancing cognitive functions, the central thalamus (CT) has been shown to be a potential DBS target. The network-level mechanisms contributing to the effect exerted by DBS on the CT (CT-DBS) remain unknown. Combining CT-DBS with functional magnetic resonance imaging (fMRI), this study explored brain areas activated while applying CT-DBS in rats, using a newly developed neural probe that was compatible with MRI and could minimize the image distortion and resolve safety issues. Results showed activation of the anterior cingulate cortex, motor cortex, primary and secondary somatosensory cortices, caudate putamen, hypothalamus, thalamus, and hippocampus, suggesting that the corticostriatal, corticolimbic, and thalamocortical brain networks were affected. Behaviorally, the CT-DBS group required a shorter time than sham controls to learn a water-reward lever-pressing task and made more correct choices in a T-maze task. Concurrent with enhanced learning performance, bilateral CT-DBS resulted in alteration in the functional connectivity of brain networks determined by resting-state fMRI. Western blot analyses showed that the protein level of both dopamine D1 and α4-nicotinic acetylcholine receptors was increased, and dopamine D2 receptor was decreased. These data suggest that CT-DBS can enhance cognitive performance as well as brain connectivity through the modulation of synaptic plasticity, such that CT is a target providing high potential for the remediation of acquired cognitive learning and memory disabilities.

Keywords: central thalamus; deep brain stimulation; functional connectivity; magnetic resonance compatibility; neural probe; resting-state fMRI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / diagnostic imaging
Cognition
Deep Brain Stimulation*
Magnetic Resonance Imaging
Rats
Thalamus / diagnostic imaging