fMRI and TMS Analysis of Cerebellar Cognitive Function

描述(申请人提供)：本研究的总体目标是通过将功能磁共振成像(FMRI)和经颅磁刺激(TMS)技术与言语工作记忆任务相结合，更好地了解小脑和脑小脑网络对认知功能的贡献。Sternberg言语工作记忆任务包括编码、维持和提取三个不同的时间阶段，是研究大脑-小脑对认知贡献的理想模型系统。到目前为止，我们的研究支持了一个小脑语言工作记忆模型，该模型强调了新皮质关节控制区(如Broca区)与小脑上部之间的功能联系，以及第二个网络，将位于顶下区的新皮质语音存储底物与小脑下部联系起来。我们建议在三个具体目标上进一步测试和扩展该模型。第一个阶段将强调编码阶段，并将检验这样的假设，即小脑上部和额后区参与关节轨迹的初始准备，而不依赖于刺激通道。第二个目标将强调维护阶段。我们将检验这样一种假设，即右侧小脑下部在功能上与左侧顶下部有关，当系统地操纵语音存储需求时，这些区域的激活将受到同步调节。此外，我们将测试这样一个假设，即在TMS实验室中，通过刺激左侧顶下和右侧小脑下部区域，可以复制出与在左侧颞顶-顶叶损害患者中观察到的类似的短暂性语音存储缺陷综合征。第三个目标将强调检索阶段。Sternberg任务的提取阶段需要利用存储的信息，在我们的事件相关研究中，引起的小脑激活量最少。我们假设，通过增加任务的执行要求--通过施加额外的处理要求--我们将观察到与提取相相关的小脑激活的增加。我们进一步假设，TMS在提取阶段产生的行为扰乱的量将与与提取相相关的小脑激活量相关。

DESCRIPTION (provided by applicant): The overall goal of this research is to better understand the contribution of the cerebellum and cerebrocerebellar networks to cognitive function by combining functional MRI (fMRI) and transcranial magnetic stimulation (TMS) techniques with tasks of verbal working memory. The Sternberg verbal working memory task, with three temporally distinct phases of encoding, maintenance, and retrieval, is an ideal model system for studying cerebro-cerebellar contributions to cognition. Our studies to date have supported a cerebrocerebellar verbal working memory model that emphasizes a functional link between neocortical articulatory control regions, such as 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. We propose to further test and extend this model in three specific aims. The first will emphasize the encoding phase and will test the hypothesis that the superior cerebellum and posterior frontal regions participate in the initial preparation of the articulatory trajectory independent of stimulus modality. The second aim will emphasize the maintenance phase. We will test the hypothesis that the right inferior cerebellum is functionally linked to the left inferior parietal region and that activation in these regions will be modulated in tandem when phonological storage demands are systematically manipulated. In addition, we will test the hypothesis that a transient phonological storage deficit syndrome, similar to that observed in left temporal-parietal lesioned patients, can be reproduced in the TMS lab using stimulation to left inferior parietal and right inferior cerebellar regions. The third aim will emphasize the retrieval phase. The retrieval phase of the Sternberg task, which requires utilization of the stored information, has elicited the least amount of cerebellar activation in our event-related investigations. We hypothesize that by increasing the executive demands of the task - by imposing additional processing requirements - we will observe increases in retrieval-phase-related cerebellar activation. We further hypothesize that the amount of behavioral disruption produced by TMS in the retrieval phase will be correlated with the amount of retrieval-phase related cerebellar activation.