Thalamic activity and structure and surface neural oscillations in autism

自闭症的丘脑活动和结构以及表面神经振荡

• 批准号: 9117646
• 负责人: James Christopher EDGAR
• 金额: $ 18.25万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9117646
• 关键词: 16 year old; Accounting; Alpha Rhythm; Anisotropy; Area; Autistic Disorder; Biological; Brain; Chemicals; Child; Clinical; Cognitive; Communication; Coupling; Data; Data Set; Diffusion; Diffusion Magnetic Resonance Imaging; Equilibrium; Etiology; Evaluable Disease; Failure; Foundations; Health; Impairment; Individual; Laboratories; Lateral Geniculate Body; Left; Link; Magnetoencephalography; Measures; Multimodal Imaging; Myelin; National Institute of Mental Health; Neurons; Noise; Pathway interactions; Pattern; Phase; Plant Roots; Process; Property; Publishing; Recruitment Activity; Regression Analysis; Reporting; Research Personnel; Rest; Role; Route; Sensory; Signal Transduction; Source; Structural defect; Structure; Surface; Thalamic Nuclei; Thalamic structure; Ventral Posterior Nucleus; aged; autism spectrum disorder; base; brain dysfunction; interest; non-compliance; relating to nervous system; repetitive behavior; restoration; sensory input; sensory integration; signal processing; social; theories; white matter

 DESCRIPTION (provided by applicant): Atypical neural activity at the brain surface is frequently reported in individuals with autism spectrum disorder (ASD). Many researchers hypothesize that this atypical surface neural activity is due to an incorrect balance in the brain chemicals that control the firing rate of neurons. Although there is evidence to support this hypothesis, a more important influence on surface brain rhythms may be the contribution of deeper and more central brain structures to surface brain activity. One of these deep brain structures - the thalamus - is a central rely station that controls the flow of information from th outside world into the brain and thus controls the pattern of surface brain activity. Given the central role of the thalamus in modulating and coordinating neural activity, understanding the contribution of the thalamus to surface neural abnormalities in ASD is of high priority. The proposed R21 examines the most fundamental brain oscillation: resting-state (RS) alpha (8 to 12 Hz). RS alpha oscillations are strongest when at rest but modulated when performing tasks, with alpha rhythms providing a foundation for local and long-range communication. Focusing on RS alpha activity is optimal as: (1) RS alpha is the dominant brain oscillation, with a high signal to-noise ratio making RS alpha a sensitive probe, and (2) the thalamic nuclei and thalamocortical pathways modulating cortical RS alpha are known, allowing for a hypothesis- driven assessment of association between cortical alpha activity and thalamic structure. Our laboratory's published data show that (a) thalamic structure (specifically volume) is related to this RS brain rhythm, and (b) this fundamental brain rhythm is abnormal in idiopathic ASD. Taken together, these findings suggest that thalamic abnormalities might account for cortical brain neural abnormalities in ASD. To formally examine this hypothesis, children with idiopathic ASD and typically developing controls (TDC) aged 12-to-16-years-old will be recruited (N = 26 per group), and non-invasive multimodal imaging (magnetoencephalography, MEG, and structural and diffusion MRI) will examine associations between thalamic structure and function and properties of the resting-state brain alpha rhythm (strength of local activity as well as local and long-range functional connectivity). Establishing the role of thalamic and thalamocortical abnormalities in idiopathic ASD will inform the biological basis of ASD, will potentially account for the broad array of phenotypic domains in ASD given the central role of thalamus, and will indicate the need for new treatments that target restoration of thalamic function.

 描述（由申请人提供）：患有自闭症谱系障碍（ASD）的个体经常报告大脑表面的非典型神经活动。许多研究人员推测，这种非典型的表面神经活动是由于控制神经元放电率的大脑化学物质的不正确平衡造成的。尽管有证据支持这一假设，但对表面大脑节律更重要的影响可能是更深、更中央的大脑结构对表面大脑活动的贡献。这些深层大脑结构之一 - 丘脑 - 是一个中央依赖站，它控制从外部世界到大脑的信息流，从而控制表面大脑活动的模式。鉴于丘脑在调节和协调神经活动中的核心作用，了解丘脑对 ASD 表面神经异常的贡献是当务之急。拟议的 R21 检查最基本的大脑振荡：静息态 (RS) α（8 至 12 Hz）。 RS 阿尔法振荡在休息时最强，但在执行任务时会受到调节，阿尔法节律为本地和远程通信提供了基础。关注 RS α 活动是最佳选择，因为：(1) RS α 是占主导地位的大脑振荡，具有高信号 信噪比使 RS α 成为敏感探针，并且 (2) 调节皮质 RS α 的丘脑核和丘脑皮质通路是已知的，允许对皮质 α 活动和丘脑结构之间的关联进行假设驱动的评估。我们实验室发表的数据表明，(a) 丘脑结构（特别是体积）与这种 RS 脑节律相关，(b) 这种基本脑节律在特发性自闭症谱系障碍中是异常的。总而言之，这些发现表明丘脑异常可能是自闭症谱系障碍患者皮质脑神经异常的原因。为了正式检验这一假设，将招募 12 至 16 岁的特发性自闭症谱系障碍儿童和典型发育对照 (TDC) 儿童（每组 26 名），并通过非侵入性多模态成像（脑磁图、脑磁图以及结构和扩散 MRI）检查丘脑结构和功能以及静息态大脑 α 节律特性（α 节律的强度）之间的关联。 当地的活动以及当地的 和远程功能连接）。确定丘脑和丘脑皮质异常在特发性自闭症谱系障碍中的作用将有助于了解自闭症谱系障碍的生物学基础，考虑到丘脑的核心作用，可能会解释自闭症谱系障碍的广泛表型域，并表明需要针对丘脑功能恢复的新治疗方法。