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

Ting Chun Lin, Yu Chun Lo, Hui Ching Lin, Ssu Ju Li, Sheng Huang Lin, Han Fang Wu, Ming Chia Chu, Chi Wei Lee, I. Cheng Lin, Ching Wen Chang, Yin Chieh Liu, Ting Chieh Chen, Yu Ju Lin, Yen Yu Ian Shih, You Yin Chen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalBrain Stimulation
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Deep Brain Stimulation
Thalamic Nuclei
Magnetic Resonance Imaging
Interpersonal Relations
Brain
Neuronal Plasticity
Exploratory Behavior
Aptitude
Dopamine D2 Receptors
Social Behavior
Therapeutics
Neurodegenerative Diseases
Autism Spectrum Disorder
Magnetic Resonance Spectroscopy
Western Blotting
Learning

Keywords

  • Autism
  • Central thalamic nucleus
  • Deep brain stimulation
  • Functional connectivity
  • Magnetic resonance imaging
  • Social behavior

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biophysics
  • Clinical Neurology

Cite this

MR imaging central thalamic deep brain stimulation restored autistic-like social deficits in the rat. / Lin, Ting Chun; Lo, Yu Chun; Lin, Hui Ching; Li, Ssu Ju; Lin, Sheng Huang; Wu, Han Fang; Chu, Ming Chia; Lee, Chi Wei; Lin, I. Cheng; Chang, Ching Wen; Liu, Yin Chieh; Chen, Ting Chieh; Lin, Yu Ju; Ian Shih, Yen Yu; Chen, You Yin.

In: Brain Stimulation, 01.01.2019.

Research output: Contribution to journalArticle

Lin, TC, Lo, YC, Lin, HC, Li, SJ, Lin, SH, Wu, HF, Chu, MC, Lee, CW, Lin, IC, Chang, CW, Liu, YC, Chen, TC, Lin, YJ, Ian Shih, YY & Chen, YY 2019, 'MR imaging central thalamic deep brain stimulation restored autistic-like social deficits in the rat', Brain Stimulation. https://doi.org/10.1016/j.brs.2019.07.004
Lin, Ting Chun ; Lo, Yu Chun ; Lin, Hui Ching ; Li, Ssu Ju ; Lin, Sheng Huang ; Wu, Han Fang ; Chu, Ming Chia ; Lee, Chi Wei ; Lin, I. Cheng ; Chang, Ching Wen ; Liu, Yin Chieh ; Chen, Ting Chieh ; Lin, Yu Ju ; Ian Shih, Yen Yu ; Chen, You Yin. / MR imaging central thalamic deep brain stimulation restored autistic-like social deficits in the rat. In: Brain Stimulation. 2019.
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abstract = "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.",
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AU - Lo, Yu Chun

AU - Lin, Hui Ching

AU - Li, Ssu Ju

AU - Lin, Sheng Huang

AU - Wu, Han Fang

AU - Chu, Ming Chia

AU - Lee, Chi Wei

AU - Lin, I. Cheng

AU - Chang, Ching Wen

AU - Liu, Yin Chieh

AU - Chen, Ting Chieh

AU - Lin, Yu Ju

AU - Ian Shih, Yen Yu

AU - Chen, You Yin

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N2 - 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.

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