Role of the Olivocerebellar System in Sensory Processing and Cognition

橄榄小脑系统在感觉处理和认知中的作用

• 批准号: 8331806
• 负责人: Khalaf O Bushara
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331806
• 关键词: Address; Affect; Age; Age-Years; Animals; Attention; Behavioral; Biphasic Pattern; Brain; Brain Stem; Cerebellar Diseases; Cerebellar cortex structure; Cerebellum; Cognition; Cognition Disorders; Data; Disease; Elderly; Essential Tremor; Event; Fiber; Fire - disasters; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Funding; General Population; Goals; Health; Human; Impulsivity; Inferior; Learning; Mental disorders; Methods; Monitor; Motor; Movement; Neurons; Olives - dietary; Outcome; Output; Parkinson Disease; Pattern; Perceptual learning; Phase; Population; Post-Traumatic Stress Disorders; Process; Progressive Disease; Property; Relative (related person); Research; Resolution; Rest; Role; Schizophrenia; Sensory; Sensory Process; Specificity; Staging; Stimulus; Stroke; Structure; System; Tactile; Testing; Time; Touch sensation; Veterans; Visual; Work; base; classical conditioning; cognitive control; disability; human subject; imaging modality; innovation; mossy fiber; neuromechanism; novel; relating to nervous system; response; sensory stimulus; stimulus interval; theories

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. PUBLIC HEALTH RELEVANCE: Relevance of the Proposed Research to Veterans' Health. This proposal addresses the cerebellar and specifically the inferior olive and climbing fiber system mechanisms of timing and learning. Cerebellar dysfunction (predominantly stroke) is relatively common in veterans. Another disease specifically attributed to inferior olive/ climbing fiber system dysfunction is essential tremor (ET); a common disease that is 20 times more prevalent than Parkinson's disease affecting approximately 3 % of the general population. ET is a progressive disease leading to more disability at older age. Currently, about 40 percent veterans are > 65 years of age (compared to about 12 % in the general population). Therefore, similar to other diseases of the elderly, disabling ET is likely to be more common in veterans than in the general population. The inferior olive and cerebellar timing mechanisms have also been implicated in multiple psychiatric and cognitive disorders including schizophrenia and impulsivity in post-traumatic stress disorder which are common in veterans.

描述(由申请人提供)： 在过去的二十年里，功能成像促进了我们对小脑功能的理解的范式转变，特别是在感觉处理和认知方面。然而，功能成像方法在小脑研究中的应用受到了极大的限制，因为无法将爬行纤维对小脑皮质激活的作用与苔藓纤维的作用分开。攀爬纤维系统是将感觉信息传递到小脑的两个系统之一。攀援纤维完全来自下橄榄，这是脑干中的一个小结构。在退伍军人事务部的资助下，我们在3特斯拉下使用高分辨率功能磁共振成像(FMRI)显示，当受试者感知视觉和触觉的时机时，下橄榄得到可靠的激活(D.Xu等人，2006年；T.Liu等人，2008年)。这项拟议的工作具有创新性，因为它利用了最近的这一新发现。我们通过功能磁共振方法检测下橄榄活动的能力使我们能够非侵入性地监测受试者下橄榄小脑皮质和全脑网络的神经活动，以具体解决关于下橄榄/攀援纤维系统功能的基本问题。正在考虑的建议涉及计时和学习的机制，这是关于下等橄榄功能的两个主要的长期假设。我们的中心假设是，橄榄球-小脑系统对运动和非运动过程都有贡献，包括通过编码感觉输入的时间来进行学习，而不是自愿的认知控制或注意。我们计划通过实现以下具体目标来检验这一假说并实现该建议的目标：1.确定下橄榄反应的时间尺度，2.确定注意对下橄榄事件定时反应的影响，3.在学习到事件定时的过程中确定下橄榄活动的特异性，4.在学习过程中识别下橄榄活动模式，5.确定下橄榄活动模式 对由自我启动的运动产生的感觉输入的反应。因为下橄榄是小脑功能理论的核心，定义下橄榄被激活的行为条件将会促进我们对小脑的功能以及计时、注意力和学习的神经机制的理解。这项拟议的工作还有望确定激活下层橄榄的实验范式。这样的范例可以用来探索人类疾病知之甚少的潜在机制，在这些疾病中，下橄榄和小脑计时机制已被牵连。这些包括精神分裂症的计时机制改变，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障碍。 公共卫生相关性： 拟议的研究与退伍军人健康的相关性。这项建议涉及小脑，特别是下橄榄和攀缘纤维系统的计时和学习机制。小脑功能障碍(主要是中风)在退伍军人中相对常见。另一种具体归因于下橄榄/攀援纤维系统功能障碍的疾病是特发性震颤(ET)；这是一种常见疾病，患病率是帕金森氏症的20倍，影响大约3%的普通人群。ET是一种进行性疾病，导致老年人更多的残疾。目前，约40%的退伍军人年龄为65岁(相比之下，一般人口的这一比例约为12%)。因此，与老年人的其他疾病类似，致残ET在退伍军人中可能比普通人群更常见。下橄榄和小脑的计时机制也与多种精神和认知障碍有关，包括精神分裂症和创伤后应激障碍中的冲动，这在退伍军人中很常见。