Investigation of cerebellar involvement in cognitive sequencing

尽管越来越多的人认识到小脑与认知和运动功能有关， 小脑对认知的贡献方式尚不确定。小脑序列 假设小脑获得序列信息，进行序列预测， 通过前向模型检测序列违规。排序要求在两个语言中都很突出 工作记忆（VWM）与语言习得虽然小脑激活已被观察到在许多 VWM和语言研究，脑干/小脑神经相关的认知排序， 小脑序列预测对新皮层靶点的影响，知之甚少。在目标1中，我们 研究VWM中的小脑序列假说。我们的初步数据表明下橄榄（IO） 参与序列获取，而序列违规的特征是大量增加， 小脑功能连接（FC）。我们假设，小脑共济失调患者，谁表现出 灰质和白色质变性，在测序中应该表现出神经和行为异常- 依赖VWM性能。使用fMRI，我们假设在序列期间IO激活的组差异 小脑和已知的VWM关键前脑区域（CFR）之间的采集和FC（左下 额回[LIFG]、辅助运动区和左颞/顶叶皮层）。 使用结构神经成像，我们预测小脑灰质和脚完整性的组间差异， 以及小脑和CFRs之间的结构连接。我们将把这些结构和 功能测量与任务表现，以推断大脑行为关系。在目标2中，我们将测试 在统计学习/语言习得范例中的小脑排序的概括。共济失调和 对照组受试者将在学习阶段接受功能磁共振成像，在学习阶段，他们听一种伪语言来学习， 音素序列的转移概率，以及它们将检测音素的测试阶段 序列违规我们假设共济失调患者在检测不正确的序列时会受损， 新的音节转换。与目标1一样，我们假设在序列中IO激活的组间差异， 在序列破坏过程中，小脑和已知CFR之间的FC获得和变化，但对于 统计学学习这些CFR是左上级颞回、纹状体和LIFG。最后，小脑是 假设将其序列预测计算提供给新皮层目标，并且在目标3中，使用 小脑经颅磁刺激（TMS）与同步功能MRI，我们将测试的假设 在排序任务期间TMS中断将产生更大的新皮层激活变化， 一个类似的控制任务，没有预测的组成部分。这些调查将改善我们的 了解小脑参与认知功能以及认知障碍患者的认知异常 小脑损伤或与小脑相关的疾病。

Although there is increasing recognition that the cerebellum is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. The cerebellar sequencing hypothesis posits that the cerebellum acquires sequence information, makes sequence predictions, and detects sequence violations via a forward model. Sequencing requirements are prominent in both verbal working memory (VWM) and language acquisition. Although cerebellar activation has been observed in many VWM and language investigations, the brainstem/cerebellar neural correlates of sequencing in cognition, and the influence of cerebellar sequence predictions on neocortical targets, are poorly understood. In Aim 1, we will investigate the cerebellar sequencing hypothesis in VWM. Our preliminary data indicate inferior olive (IO) involvement in sequence acquisition, whereas sequence violations are characterized by large increases in cerebro-cerebellar functional connectivity (FC). We hypothesize that cerebellar ataxia patients, who exhibit gray and white matter degeneration, should exhibit neural and behavioral abnormalities in sequencing- dependent VWM performance. Using fMRI, we hypothesize group differences in IO activation during sequence acquisition and FC between cerebellum and known critical forebrain regions (CFRs) for VWM (left inferior frontal gyrus [LIFG], supplementary motor area, and left temporal/parietal cortex) during sequence violation. Using structural neuroimaging, we predict group differences in cerebellar gray matter and peduncle integrity, as well as in structural connectivity between cerebellum and CFRs. We will correlate these structural and functional measures with task performance to infer brain-behavior relationships. In Aim 2, we will test the generalization of cerebellar sequencing in a statistical learning/language acquisition paradigm. Ataxia and control subjects will receive fMRI during a learning phase in which they listen to a pseudo language to learn transition probabilities of sequences of phonemes, and a test phase in which they will detect phoneme sequence violations. We hypothesize that ataxia patients will be impaired in detecting incorrect sequences or novel transitions of syllables. As in Aim 1, we hypothesize group differences in IO activation during sequence acquisition and changes in FC between cerebellum and known CFRs during sequence violation, but for statistical learning those CFRs are left superior temporal gyrus, striatum, and LIFG. Finally, the cerebellum is hypothesized to provide its sequence prediction computation to neocortical targets, and in Aim 3, using cerebellar transcranial magnetic stimulation (TMS) with concurrent functional MRI, we will test the hypothesis that TMS disruption during a sequencing task will produce greater changes in neocortical activation relative to an analogous control task that does not have the predictive component. These investigations will improve our understanding of cerebellar involvement in cognitive function as well as cognitive abnormalities in patients with cerebellar damage, or with diseases linked to the cerebellum.