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是不确定的。小脑测序 假设小脑获取序列信息，进行序列预测，并 通过正向模型检测序列违规。排序要求在两个口头上都很突出 工作记忆与语言习得。尽管在许多患者中观察到小脑激活 VWM和语言研究，认知中排序的脑干/小脑神经相关性，以及 关于小脑序列预测对新皮质靶点的影响，人们知之甚少。在目标1中，我们将 探讨VWM的小脑排序假说。我们的初步数据显示橄榄(IO)质量较差 参与序列获取，而序列违规的特征是大量增加 大脑-小脑功能连接(FC)。我们假设小脑性共济失调患者 灰质和白质变性，在测序中应该表现出神经和行为异常- 依赖于VWM性能。使用功能磁共振成像，我们假设在序列过程中IO激活的组差异 VWM(左下方)小脑和已知关键前脑区(CFR)的习得和FC 额叶回[LIFG]、辅助运动区和左侧颞叶/顶叶皮质)。 利用结构神经成像，我们预测了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。我们将把这些结构性的和 功能测量与任务表现，以推断大脑与行为的关系。在目标2中，我们将测试 统计学习/语言习得范式中小脑排序的泛化。共济失调和 对照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在其中检测音素的测试阶段 顺序违规。我们假设共济失调患者在检测错误序列或 音节的新奇变化。与目标1一样，我们假设在序列过程中IO激活的组差异 在序列破坏过程中，小脑和已知CFRs之间的获得和FC的变化，但对于 统计学习这些CFRs是左额叶上回、纹状体和LIFG。最后，小脑是 假设为新皮质目标提供ITS序列预测计算，并在目标3中使用 小脑经颅磁刺激(TMS)与同步功能磁共振成像，我们将验证这一假设 TMS在测序任务期间的中断将在新皮质激活中产生相对于 一种没有预测组件的模拟控制任务。这些调查将改善我们的 小脑受累对认知功能及认知功能异常的认识 小脑损伤，或与小脑有关的疾病。

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.