MR imaging central thalamic deep brain stimulation restored autistic-like social deficits in the rat

Brain Stimulation

Ching-Wen Chang¹  Hui-Ching Lin²  Ming-Chia Chu³  Ssu-Ju Li³  Chi-Wei Lee³  Ting-Chun Lin⁴  Ting-Chieh Chen⁴  Yen-Yu Ian Shih⁴  Sheng-Huang Lin⁴  Yu-Ju Lin⁴  Han-Fang Wu⁵  You-Yin Chen⁶  Yin-Chieh Liu⁷  I-Cheng Lin⁸  Yu-Chun Lo⁸ 

[1] Department and Institute of Physiology, National Yang Ming University, No.155, Sec.2, Linong St, Taipei, 11221, Taiwan, ROC;Research Center for Brain and Consciousness, Taipei Medical University, Shuang Ho Hospital, No. 291, Zhongzheng Rd, New Taipei City, 23561, Taiwan, ROC;Department and Institute of Physiology, National Yang Ming University, No.155, Sec.2, Linong St, Taipei, 11221, Taiwan, ROC;Department of Biomedical Engineering, National Yang Ming University, No.155, Sec.2, Linong St, Taipei, 11221, Taiwan, ROC;Department of Neurology, Tzu Chi General Hospital, Tzu Chi University, No. 707, Sec. 3, Chung Yang Rd, Hualien, 97002, Taiwan, ROC;Department of Psychiatry, Far Eastern Memorial Hospital, No.21, Sec. 2, Nanya S. Rd, New Taipei City, 22060, Taiwan, ROC;Department of Psychiatry, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Rd, New Taipei City, 23561, Taiwan, ROC;The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, No. 250 Wu-Xing St, Taipei, 11031, Taiwan, ROC;

关键词: Autism;    Central thalamic nucleus;    Deep brain stimulation;    Magnetic resonance imaging;    Functional connectivity;    Social behavior;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Social deficit is a core symptom in autism spectrum disorder (ASD). Although deep brain stimulation (DBS) has been proposed as a potential treatment for ASD, an ideal target nucleus is yet to be identified. DBS at the central thalamic nucleus (CTN) is known to alter corticostriatal and limbic circuits, and subsequently increase the exploratory motor behaviors, cognitive performance, and skill learning in neuropsychiatric and neurodegenerative disorders. Objective: We first investigated the ability of CTN-DBS to selectively engage distinct brain circuits and compared the spatial distribution of evoked network activity and modulation. Second, we investigated whether CTN-DBS intervention improves social interaction in a valproic acid–exposed ASD rat offspring model. Methods: Brain regions activated through CTN-DBS by using a magnetic resonance (MR)-compatible neural probe, which is capable of inducing site-selective microstimulations during functional MRI (fMRI), were investigated. We then performed functional connectivity MRI, the three-chamber social interaction test, and Western blotting analyses to evaluate the therapeutic efficacy of CTN-DBS in an ASD rat offspring model. Results: The DBS-evoked fMRI results indicated that the activated brain regions were mainly located in cortical areas, limbic-related areas, and the dorsal striatum. We observed restoration of brain functional connectivity (FC) in corticostriatal and corticolimbic circuits after CTN-DBS, accompanied with increased social interaction and decreased social avoidance in the three-chamber social interaction test. The dopamine D2 receptor decreased significantly after CTN-DBS treatment, suggesting changes in synaptic plasticity and alterations in the brain circuits. Conclusions: Applying CTN-DBS to ASD rat offspring increased FC and altered the synaptic plasticity in the corticolimbic and the corticostriatal circuits. This suggests that CTN-DBS could be an effective treatment for improving the social behaviors of individuals with ASD.

【 授权许可】

Unknown