Role of the Olivocerebellar System in Sensory Processing and Cognition

描述（由申请人提供）： 在过去的二十年里，功能成像有助于我们理解小脑功能，特别是在感觉处理和认知方面的范式转变。然而，功能成像方法在小脑研究中的应用受到了很大的限制，因为无法将爬行纤维对小脑皮质激活的贡献与苔藓纤维的贡献分开。攀爬纤维系统是将感觉信息传递到小脑的两个系统之一。攀爬纤维完全来自下橄榄;脑干中的一个小结构。在退伍军人事务部的资助下，我们使用高分辨率功能性磁共振成像（fMRI）在3特斯拉下显示了下橄榄的可靠激活，当受试者感知视觉和触觉的时间时（D。Xu等人，2006; T. Liu等人，2008年）。拟议的工作是创新的，因为它利用了最近的新发现。我们的能力，通过功能磁共振成像方法检测下橄榄的活动，使我们能够非侵入性地监测下橄榄小脑皮质和整个大脑网络的神经活动在人类受试者，以具体解决有关的功能下橄榄/攀爬纤维系统的基本问题。 正在考虑的建议解决的时机和学习的机制，两个主要的长期假设有关的功能，劣质橄榄。我们的中心假设是，橄榄小脑系统有助于运动和非运动过程，包括通过编码独立于自愿认知控制或注意的感觉输入的时间来学习。我们计划通过实现以下具体目标来验证这一假设并实现本提案的目标：1.为了确定下橄榄反应的时间尺度，2。为了确定注意力对下橄榄反应事件时间的影响，3。为了确定学习过程中下橄榄活动的特异性事件定时，4。o识别学习过程中的下橄榄活动模式; 5.为了确定劣质橄榄 对自我发起的运动引起的感觉输入的反应。 由于下橄榄是小脑功能理论的核心，因此定义下橄榄被激活的行为条件将通过促进我们对小脑功能和计时，注意力和学习的神经机制的理解产生积极的影响。这项拟议中的工作也有望确定激活下橄榄的实验范例。这样的范例可以用来探测基本机制知之甚少的人类疾病，其中下橄榄和小脑定时机制已牵连。这些包括精神分裂症的时间机制改变，创伤后应激障碍的冲动以及特发性震颤;退伍军人中相对常见的疾病。

DESCRIPTION (provided by applicant): Over the last two decades, functional imaging has contributed to what might be considered a paradigm shift in our understanding of cerebellar function especially in sensory processing and cognition. However, the utility of functional imaging methods in cerebellar research has been greatly limited by the inability of to dissociate the climbing fibers' contribution to cerebellar crtex activation from that of mossy fibers. The climbing fiber system is one of the two systems that carry sensory information to the cerebellum. The climbing fibers originate exclusively from the inferior olive; a small structure in the brain-stem. With funding from the Department of Veterans Affairs, we have shown reliable activation of the inferior olive using high resolution functional magnetic resonance imaging (fMRI) at 3 Tesla, when subjects perceived the timing of visual and touch sensation (D. Xu et al., 2006; T. Liu et al., 2008). The proposed work is innovative because it capitalizes on this recent novel finding. Our ability to detect the activity of the infeior olive by fMRI methods allows us to non-invasively monitor the neural activity of the inferior olive cerebellar cortex and whole brain networks in human subjects to specifically address fundamental questions regarding the function of the inferior olive/climbing fiber system. The proposal under consideration addresses the mechanisms of timing and learning; the two major longstanding hypotheses regarding the function of the inferior olive. Our central hypothesis is that the olivo-cerebellar system contributes to both motor and non-motor processes including learning by encoding the timing of sensory input independent of voluntary cognitive control or attention. We plan to test this hypothesis and accomplish the objectives of this proposal by carrying out the following specific aims: 1. To determine the timing scale of the inferior olive response, 2. To determine the effect of attention on the inferior olive response to event timing, 3. To determine the specificity of the inferior olive activity during learning to event timing, 4. o identify the inferior olive activity pattern during learning and 5. To determine the inferior olive response to sensory input resulting from self-initiated movement. Because the inferior olive is central to theories of cerebellar function, defining the behavioral conditions in which the inferio olive is activated will have a positive impact by advancing our understanding of the functions of the cerebellum and neural mechanisms of timing, attention and learning. The proposed work is also expected to identify experimental paradigms that activate the inferior olive. Such paradigms can be used to probe the underlying mechanisms of poorly understood human disorders in which the inferior olive and the cerebellar timing mechanisms have been implicated. These include altered timing mechanisms in schizophrenia, impulsiveness in post-traumatic stress disorder as well as essential tremor; relatively common disorders in the veterans population.