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

Lin, Ting-Chun; Lo, Yu‐Chun; H, Lin; Li, Ssu‐Ju; Lin, Sheng-Di; Wu, Han-Fang; Chu, Ming-Chia; Lee, Chi‐Wei; Lin, I-Cheng; Chang, Chen‐Wang; Liu, Yin-Chieh; Chen, Ting-Chieh; Lin, Yu‐Ju; Shih, Yen‐Yu Ian; Chen, You‐Yin

doi:10.1016/j.brs.2019.07.004

Cited by 20 publications

(9 citation statements)

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“…The dysfunction of the cortico-striato-thalamo-cortical (CSTC) loop is common model for neuropsychiatric disorders ( 84 ). Recently, the effects of DBS to the ALIC, the nucleus accumbens (NAcc), basolateral amygdala, and hypothalamus for self-injury behavior in subjects with ASD were reported ( 85 , 86 ), and these areas are in anatomical proximity with the targets of DBS for obsessive compulsive disorder(OCD) ( 87 ). In this study, TAND behavioral level difficulty was associated with FNX and ST, and the ALIC was associated with autistic features.…”

Section: Discussionmentioning

confidence: 99%

Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders

et al. 2022

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ObjectiveTuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. The neurological symptoms of TSC include epilepsy and tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Although TAND affects TSC patients' quality of life, the specific region in the brain associated with TAND remains unknown. We examined the association between white matter microstructural abnormalities and TAND, using diffusion tensor imaging (DTI).MethodsA total of 19 subjects with TSC and 24 age-matched control subjects were enrolled. Tract-based spatial statistics (TBSS) were performed to assess group differences in fractional anisotropy (FA) between the TSC and control groups. Atlas-based association analysis was performed to reveal TAND-related white matter in subjects with TSC. Multiple linear regression was performed to evaluate the association between TAND and the DTI parameters; FA and mean diffusivity in seven target regions and projection fibers.ResultsThe TBSS showed significantly reduced FA in the right hemisphere and particularly in the inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and genu of corpus callosum (CC) in the TSC group relative to the control group. In the association analysis, intellectual disability was widely associated with all target regions. In contrast, behavioral problems and autistic features were associated with the limbic system white matter and anterior limb of the internal capsule (ALIC) and CC.ConclusionThe disruption of white matter integrity may induce underconnectivity between cortical and subcortical regions. These findings suggest that TANDs are not the result of an abnormality in a specific brain region, but rather caused by connectivity dysfunction as a network disorder. This study indicates that abnormal white matter connectivity including the limbic system is relevant to TAND. The analysis of brain and behavior relationship is a feasible approach to reveal TAND related white matter and neural networks. TAND should be carefully assessed and treated at an early stage.

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Section: Discussionmentioning

confidence: 99%

Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders

et al. 2022

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“…Previous studies have revealed that HF-DBS applied to the infralimbic prefrontal cortex diminished hyperlocomotion and improved social interaction in olfactory bulbectomized (OBX) rats and the VPA-induced rat model [ 12 , 47 ]. HF-DBS at the central thalamus can restore social interaction via the enhancement of the corticolimbic and corticostriatal circuits [ 13 ]. Furthermore, in both ASD mouse models Shank3B −/− and Viaat-Mecp2 −/y , HF-DBS inhibited self-grooming at the subthalamic nucleus, and HF-DBS in both the internal capsule and striatum reduced excessive grooming in Sapap3 mutant mice [ 14 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model

et al. 2022

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Background Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. Methods VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0–7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. Results Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. Conclusions Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

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“…The parents were also often concerned about socialization (Gray, 2002;Havighurst et al, 2010). Since the individual socialization methods had to change in this process (Wright et al, 2020), it could be argued that it was more difficult for individuals with ASD who already experience difficulties in social interaction and communication (Hattier & Matson, 2012;Lin et al, 2019). It was suggested that isolation during the pandemic could regress or falter certain previously acquired skills.…”

Section: Discussionmentioning

confidence: 99%

Reflections of COVID-19 Pandemic on Autism Spectrum Disorder: A Descriptive Case Study

Sani-Bozkurt¹,

Bozkuş-Genç²,

Yıldız³

2020

ENAD

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The aim of this study was to explore type of studies implemented for the autism spectrum disorders (ASD) community by institutions that directly deal with ASD during the COVID-19 pandemic in Turkey and in the world. The descriptive case study design was used in the study. The contents on the websites of the institutions were analyzed through document analysis. According to the results, it was observed that the data consisted of supporting contents related to education, health, and public policies regarding the COVID-19 process and that the contents were frequently presented through webinars, visual representations, electronic text sources, online communication platforms, and social media environments. During this process, informative studies were frequently carried out and practical studies were rarely conducted. While it is considered that institutional studies both in Turkey and in the world may serve as an example to other institutional studies, it is considered that the diversity of these examples should be increased through cooperation between institutions.

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

Cited by 20 publications

References 84 publications

Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders

Abnormal White Matter Microstructure in the Limbic System Is Associated With Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders

Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model

Reflections of COVID-19 Pandemic on Autism Spectrum Disorder: A Descriptive Case Study

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