Investigation of Cerebellar Involvement in Cognitive Function

 描述(由申请人提供)：本研究的总体目标是利用功能磁共振成像(FMRI)、经颅磁刺激(TMS)和同时TMS/fMRI来研究小脑参与认知功能的性质。小脑激活存在于多种认知任务中，包括语言流利性、概念推理、计划和心理理论。虽然已经提出了许多关于小脑参与认知的理论，但到目前为止，对于小脑提供的有助于认知功能的具体操作还没有达成共识。此外，一些小脑研究人员质疑，与认知相关的小脑激活是否受到附带运动的影响，例如眼睛的运动或发音的运动。在这个项目中，我们使用语言工作记忆来解决这些问题，作为一种模型认知系统，语言工作记忆可靠而有力地引起小脑激活。言语工作记忆是一种基本的认知功能，具有很强的理论框架。我们认为小脑可以整合到这个框架中：到目前为止，我们的研究支持大脑-小脑言语工作记忆模型，该模型强调新皮质关节控制区之间的功能联系，如运动前皮质/Broca区，到小脑上部，以及第二个网络，将位于顶下区的新皮质语音存储底物连接到小脑下部。我们的第一个具体目标是使用新的同时进行的TMS/fMRI研究来测试这些电路假设，这些研究采用了我们最新开发和发布的方法，在扫描仪中精确识别大脑中的刺激部位和TMS轨迹。我们的第二个具体目标是通过系统地改变言语工作记忆中的眼睛运动、关节运动和手指运动的要求来评估附带运动功能在言语工作记忆中对小脑激活的贡献，以确定这些运动功能是否能够解释小脑中工作记忆负荷依赖的激活。我们的第三个目标是评估不同的理论解释 小脑认知激活的基本计算，使用言语工作记忆作为我们的模型系统。我们的言语工作记忆协议，Sternberg任务，包含了许多被不同研究人员理论认为是小脑功能基础的组成部分。这些组件包括感觉获取、定时、序列偏差检测和正演建模/纠错。这个项目中的实验将检验这些不同的成分对语言工作记忆引发的小脑激活的贡献。这个项目的影响是，结果将帮助我们理解小脑在认知中提供的基本功能(S)。这一理解对于解释大量的功能神经成像研究以及在小脑患者中观察到的认知缺陷模式都是至关重要的。

 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.