Thalamic activity and structure and surface neural oscillations in autism

 描述（由申请人提供）：在患有自闭症谱系障碍（ASD）的个体中经常报告脑表面的非典型神经活动。许多研究人员假设，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。虽然有证据支持这一假设，但对表层脑节律更重要的影响可能是更深、更中央的脑结构对表层脑活动的贡献。这些大脑深层结构之一-丘脑-是一个中央依赖站，控制着从外部世界进入大脑的信息流，从而控制着表层大脑活动的模式。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具有重要意义。拟议的R21检查最基本的大脑振荡：静息态（RS）α（8至12 Hz）。RS α振荡在休息时最强，但在执行任务时被调制，α节律为本地和远程通信提供了基础。关注RS α活动是最佳的，因为：（1）RS α是主导的脑振荡，具有高信号 噪声比使得RS α成为灵敏的探针，以及（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活性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RS脑节律有关，（B）这种基本脑节律在特发性ASD中是异常的。总之，这些发现表明，丘脑异常可能占皮质脑神经异常ASD。为了正式检验这一假设，将招募12至16岁的特发性ASD和典型发育对照（TDC）儿童（每组N = 26）和非侵入性多模式成像（脑磁图，MEG，以及结构和弥散MRI）将检查丘脑结构和功能之间的关联以及静息态脑α节律的特性（当地活动的强度以及当地 和远程功能连接）。确定丘脑和丘脑皮质异常在特发性ASD中的作用将为ASD的生物学基础提供信息，将潜在地解释ASD中广泛的表型结构域，因为丘脑起着核心作用，并将表明需要靶向恢复丘脑功能的新治疗方法。

 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.