Back to front: importance of cerebro-cerebellar interactions in goal-directed behaviour.

从后到前：脑-小脑相互作用在目标导向行为中的重要性。

• 批准号: BB/P000959/1
• 负责人: Richard Apps
• 金额: $ 52.44万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP000959%2F1
• 关键词: Back; front; importance; cerebro; cerebellar

A substantial part of animal, including human behaviour is goal-directed. Learning how to achieve a defined goal requires the interplay between higher brain centres involved in planning and decision making, and subcortical structures that co-ordinate the desired movement. The prefrontal areas of the cerebral cortex are thought to be especially concerned with the planning and decision making aspects of such tasks, while the cerebellum is heavily involved in co-ordinating the desired action. However, recent studies in humans and patients are challenging this division of labour and it is increasingly being recognised that the contribution of the cerebellum goes beyond movement control to include many other aspects of brain function, including a contribution to cognitive processes. The cerebellum is linked to structures throughout the central nervous system, from the spinal cord to prefrontal cortex. An important organizational principle of the cerebellum for understanding these widespread connections is a division into a series of anatomical/functional units called modules. How individual modules contribute to goal-directed behaviour remains far from clear. Individual cerebellar modules are thought to contain representations (internal models) of predictable behaviour that allow us, through practice, to execute tasks more rapidly and with increased accuracy. The current project uses the modular organization of the cerebellum combined with the computational capability of internal models as a structural and theoretical framework to study prefrontal-cerebellar network interactions during goal-directed behaviour.An important gap in our understanding of prefrontal-cerebellar interactions is investigation in animal models of large scale brain networks in terms of information processing at the level of recording neural population activity and spike trains of individual neurones; and also interventionist work to dissect out the functional importance of the interactions. Linking the study of higher centres to movement control also has the advantage that 'cognition' is constrained in the sense that it is being studied in relation to well defined behavioural outputs. In collaboration with our industrial partner (Takeda Cambridge Ltd) we will therefore use the combined power of multichannel electrophysiological recording, stimulation, functional anatomical and behavioural techniques at the systems level of analysis to advance our understanding of the function of brain circuits involved in goal-directed behaviour. Choice of experimental model: cerebellar network architecture and patterns of connectivity are highly conserved across mammalian species, including human. However, adult rats are the experimental animal of choice because our understanding of the basic neuroanatomy and physiology is most complete in this species. Importantly, our experiments will include study of neural network interactions during behavioural situations that have been well characterized in rats and that correlate to human cognitive performance. We will study neural network dynamics in prefrontal-cerebellar circuits during cognitive task performance before and after transcranial stimulation of the cerebellum. The latter has been shown in human studies to improve cognitive task performance but the underlying neurobiology is unknown. In complementary functional anatomical studies our industry partner will chart the pattern of neural network activation produced by transcranial cerebellar stimulation.The results of our project aim to provide fundamental new insights into how neural circuits within the brain give rise to our ability to modify our actions to achieve a particular goal.

包括人类在内的动物行为的很大一部分是目标导向的。学习如何实现一个明确的目标需要参与计划和决策的高级大脑中心与协调所需运动的皮层下结构之间的相互作用。大脑皮层的前额叶区域被认为特别关注这些任务的计划和决策方面，而小脑则主要参与协调期望的行动。然而，最近对人类和患者的研究正在挑战这种分工，越来越多的人认识到小脑的贡献超越了运动控制，包括大脑功能的许多其他方面，包括对认知过程的贡献。小脑与整个中枢神经系统的结构相连，从脊髓到前额皮质。小脑的一个重要的组织原则是理解这些广泛的连接是分为一系列的解剖/功能单位称为模块。各个模块如何促进目标导向的行为仍然很不清楚。小脑的各个模块被认为包含了可预测行为的表征（内部模型），通过练习，这些行为使我们能够更快、更准确地执行任务。目前的项目使用小脑的模块化组织结合内部模型的计算能力作为结构和理论框架来研究目标导向行为中前额叶-小脑网络的相互作用。小脑相互作用是在记录神经群体活动水平上的信息处理方面在大规模脑网络的动物模型中进行的研究和单个神经元的尖峰序列;以及干涉主义者的工作，解剖出相互作用的功能重要性。将高级中枢的研究与运动控制联系起来也有一个好处，即“认知”在某种意义上是受限制的，因为它是在与明确定义的行为输出有关的情况下被研究的。因此，我们将与我们的工业合作伙伴（武田剑桥有限公司）合作，在系统层面的分析中利用多通道电生理记录、刺激、功能解剖和行为技术的综合力量，以促进我们对大脑功能的理解参与目标导向行为的回路。实验模型的选择：小脑网络结构和连接模式在包括人类在内的哺乳动物物种中高度保守。然而，成年大鼠是首选的实验动物，因为我们对该物种的基本神经解剖学和生理学的了解最完整。重要的是，我们的实验将包括在行为情况下的神经网络相互作用的研究，这些行为情况在大鼠中得到了很好的表征，并与人类的认知表现相关。我们将研究经颅刺激小脑前后认知任务执行过程中前额叶-小脑回路的神经网络动力学。在人类研究中，后者已被证明可以改善认知任务的表现，但其潜在的神经生物学尚不清楚。在功能解剖学的补充研究中，我们的行业合作伙伴将绘制经颅小脑刺激产生的神经网络激活模式。我们项目的结果旨在为大脑内的神经回路如何提高我们修改行动以实现特定目标的能力提供新的基本见解。

项目成果

Cerebro-cerebellar networks facilitate learning through feedback decoupling

脑小脑网络通过反馈解耦促进学习

• DOI: 10.1101/2022.01.28.477827
• 发表时间: 2022
• 作者: Boven E

Neuromethods: Measuring Cerebellar Function

神经方法：测量小脑功能

• 发表时间: 2021
• 作者: Apps R,

Measuring Cerebellar Function

测量小脑功能

• DOI: 10.1007/978-1-0716-2026-7_4
• 发表时间: 2022
• 作者: Apps R

Cortico-cerebellar networks as decoupling neural interfaces

• 发表时间: 2021-10
• 期刊: ArXiv
• 作者: J. Pemberton;E. Boven;Richard Apps;R. P. Costa

Cerebro-cerebellar networks facilitate learning through feedback decoupling.

• DOI: 10.1038/s41467-022-35658-8
• 发表时间: 2023-01-04
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Boven, Ellen;Pemberton, Joseph;Chadderton, Paul;Apps, Richard;Costa, Rui Ponte
• 通讯作者: Costa, Rui Ponte