Investigation of Cerebellar Involvement in Cognitive Function

 描述（由申请人提供）：本研究的总体目标是使用功能性MRI（fMRI）、经颅磁刺激（TMS）和同时TMS/fMRI研究小脑参与认知功能的性质。小脑激活已被发现在各种各样的认知任务，包括语言流畅性，概念推理，规划和心理理论。虽然已经提出了许多小脑参与认知的理论，但迄今为止，对于小脑提供的有助于认知功能的特定操作还没有达成共识。此外，一些小脑研究人员质疑认知相关的小脑激活是否受到偶然运动的污染，例如，眼睛的运动，或者关节的运动。在这个项目中，我们解决这些问题，使用言语工作记忆，可靠和强大的electrically小脑激活，作为一个模型的认知系统。言语工作记忆是一种基本的认知功能，具有很强的理论基础。我们建议，小脑可以整合到这个框架中：我们的研究迄今为止已经支持了小脑-小脑言语工作记忆模型，强调新皮质的发音控制区域之间的功能联系，如运动前皮质/布罗卡区，到上级小脑，和第二个网络，连接新皮质的语音存储基板，位于下顶叶区域，到下小脑。我们的第一个具体目标是测试这些电路假设使用新的并发TMS/fMRI调查，采用我们新开发和公布的方法，在扫描仪中精确识别刺激部位和TMS在大脑中的轨迹。我们的第二个具体目标是通过系统地改变眼球运动，发音运动和手指运动的要求，在言语工作记忆，以确定这些运动功能是否可以解释工作记忆负荷依赖性激活小脑在言语工作记忆过程中的小脑激活的偶然运动功能的贡献。我们的第三个目标是评估替代的理论解释， 小脑认知激活的基础计算，使用语言工作记忆作为我们的模型系统。我们的语言工作记忆协议，斯滕贝格任务，包含了许多组成部分，已经被不同的研究人员理论化为小脑功能的基础。这些组件包括传感器采集、定时、序列偏差检测和前向建模/纠错。本项目的实验将研究这些不同的成分对小脑激活的言语工作记忆的贡献。这个项目的影响是，结果将帮助我们了解小脑在认知中提供的基本功能。这种理解对于解释许多功能性神经影像学研究至关重要，这些研究表明在控制良好的认知任务中小脑激活，以及在小脑患者中观察到的认知缺陷模式。

 DESCRIPTION (provided by applicant): The overall goal of this research is to investigate the nature of cerebellar involvement in cognitive function, using functional MRI (fMRI), transcranial magnetic stimulation (TMS), and concurrent TMS/fMRI. Cerebellar activation has been found in a wide variety of cognitive tasks, including verbal fluency, conceptual reasoning, planning, and theory of mind. Although a number of theories of cerebellar involvement in cognition have been proposed, there is no consensus to date on a specific operation that is provided by the cerebellum that contributes to cognitive function. In addition some cerebellar researchers question whether cognitive-related cerebellar activations are contaminated by incidental motor movements, e.g., movements of the eyes, or movements of articulation. In this project we address these issues using verbal working memory, which reliably and robustly elicits cerebellar activation, as a model cognitive system. Verbal working memory is a fundamental cognitive function with a strong theoretical framework. We propose that the cerebellum can be integrated into this framework: Our studies to date have supported a cerebro-cerebellar verbal working memory model that emphasizes a functional link between neocortical articulatory control regions, such as premotor cortex/Broca's Area, to the superior cerebellum, and a second network that links neocortical substrates of phonological storage, located in inferior parietal regions, to the inferior cerebellum. Our first specific aim is to test these circuitry assumptions using novel concurrent TMS/fMRI investigations that employ our newly developed and published methods for precisely identifying in the scanner the stimulation site and TMS trajectory in the brain. Our second specific aim is to assess the contribution of incidental motor function to cerebellar activation during verbal working memory by systematically varying the eye movement, articulatory movement, and finger movement requirements during verbal working memory to determine if these motor functions can explain working memory-load-dependent activations in the cerebellum. Our third aim is to evaluate alternative theoretical explanations of the fundamental computation underlying cerebellar cognitive activations, using verbal working memory as our model system. Our verbal working memory protocol, the Sternberg Task, contains a number of components that have been theorized by different researchers to be fundamental to cerebellar function. These components include sensory acquisition, timing, sequence deviation detection, and forward modeling/error correction. The experiments in this project will examine the contribution of these different components to verbal working memory elicited cerebellar activations. The impact of this project is that the results will help us understand the fundamental functions(s) that the cerebellum provides in cognition. This understanding is essential for interpreting both the numerous functional neuroimaging studies that show cerebellar activation in well controlled cognitive tasks, as well as the patterns of cognitive deficits observed in cerebellar patients.