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.

中文翻译：

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MR 成像中央丘脑深部脑刺激恢复了大鼠的自闭症样社会缺陷

背景社交缺陷是自闭症谱系障碍（ASD）的核心症状。尽管已提出深部脑刺激 (DBS) 作为 ASD 的潜在治疗方法，但尚未确定理想的靶核。众所周知，丘脑中央核 (CTN) 的 DBS 会改变皮质纹状体和边缘回路，并随后增加神经精神和神经退行性疾病的探索性运动行为、认知表现和技能学习。目标我们首先研究了 CTN-DBS 选择性地参与不同大脑回路的能力，并比较了诱发网络活动和调制的空间分布。其次，我们调查了 CTN-DBS 干预是否改善了暴露于丙戊酸的 ASD 大鼠后代模型中的社会互动。方法通过使用磁共振 (MR) 兼容的神经探针通过 CTN-DBS 激活大脑区域，该探针能够在功能性 MRI (fMRI) 期间诱导位点选择性微刺激。然后，我们进行了功能连接 MRI、三腔社会互动测试和蛋白质印迹分析，以评估 CTN-DBS 在 ASD 大鼠后代模型中的治疗效果。结果 DBS诱发的fMRI结果表明，激活的脑区主要位于皮质区、边缘相关区和背侧纹状体。我们观察到 CTN-DBS 后皮质纹状体和皮质边缘回路中大脑功能连接 (FC) 的恢复，伴随着三室社交互动测试中社交互动的增加和社交回避的减少。CTN-DBS 治疗后多巴胺 D2 受体显着下降，表明突触可塑性发生了变化，大脑回路发生了改变。结论将 CTN-DBS 应用于 ASD 大鼠后代会增加 FC 并改变皮质边缘和皮质纹状体回路中的突触可塑性。这表明 CTN-DBS 可能是改善 ASD 个体社交行为的有效治疗方法。