Enhancing cerebellar-dependent motor learning by focalized tDCS

小脑经颅直流电刺激（cerebellar tDCS）作为一种了解小脑功能和治疗小脑疾病的工具，具有重要的意义。然而，即使在同一个实验室中，小脑tDCS的效果也往往难以复制，这表明个体参与者之间存在相当大的差异，阻碍了更广泛的应用。本项目的目的是测试基于个体小脑解剖的局部tDCS是否可靠地增强小脑依赖的运动学习，了解局部小脑tDCS效应的神经元机制，并以高度系统和全面的方式确定个体小脑tDCS效应的预测因子。我们将使用眨眼条件反射来研究小脑tDCS对运动学习的影响，因为它强烈依赖小脑，并且相关的小脑区域是众所周知的。此外，获得条件性眨眼反应的能力随着年龄的增长而下降，并受到小脑疾病的阻碍。重要的是，最初描述的阳极小脑tDCS对条件性眨眼反应获得的增强作用在后来的研究中很难复制。因此，眨眼条件反射是在个体水平上优化小脑刺激方案的一个很好的模型，以提高干预效果，并更好地了解小脑tDCS对个体参与者运动学习影响的可能预测因素。在更广泛的RU背景下，本研究（项目6）是八个研究tDCS对跨功能域（项目1-8）和健康人类寿命的学习和记忆形成影响的项目之一。这些经验项目所采用的高度系统和协调的方法将允许首次分析潜在的神经机制和行为刺激反应的预测因素，不仅在每个项目内，而且在不同的任务和功能领域（在项目9中）。目前的项目将补充项目5中对tDCS诱导的运动序列学习增强的研究，该项目还研究了个体化的、局灶性tDCS在运动域的行为和神经调节，但在该范式中，初级运动皮层是相关的中枢。总的来说，RU的实证项目的结果将增加我们目前对tdcs诱导的神经网络效应、它们的区域特异性、刺激效应的个体间变异机制以及由于实足年龄的潜在变化的理解。从方法学的角度来看，在这些项目中获得的数据将有助于优化和验证电流的生物物理模型（在项目9+10中），从而推进tDCS在健康和疾病方面的未来实验和转化应用。

There is significant interest to use cerebellar transcranial direct current stimulation (cerebellar tDCS) as a tool to understand cerebellar function and to treat cerebellar disease. Cerebellar tDCS effects, however, are often difficult to replicate even within the same laboratory, indicating considerable variability between individual participants and hampering more widespread use. The aim of the present project is to test whether focalized tDCS based on the individual cerebellar anatomy reliably enhances cerebellar-dependent motor learning, to understand the neuronal mechanisms underlying focalized cerebellar tDCS effects and to identify the predictors of individual cerebellar tDCS effects in a highly systematic and comprehensive manner. We will use eyeblink conditioning to study cerebellar tDCS effects on motor learning because it is strongly cerebellar-dependent and the associated cerebellar areas are well known. Furthermore, the ability to acquire conditioned eyeblink responses declines with increasing age and is impeded by cerebellar disease. Importantly, the initially described enhancing effects of anodal cerebellar tDCS on the acquisition of conditioned eyeblink responses were difficult to replicate in later studies. Therefore, eyeblink conditioning is an excellent model to optimize cerebellar stimulation protocols on an individual level in order to increase efficacy of the intervention, and to better understand possible predictors of cerebellar tDCS effects on motor learning in individual participants.Within the broader context of the RU, the present study (Project 6) is one of eight projects investigating tDCS effects on learning and memory formation across functional domains (Projects 1-8) and the healthy human lifespan. The highly systematic and coordinated approach pursued by these empirical projects will allow for the first time analyzing the underlying neural mechanisms and predictors of behavioral stimulation response not only within each project, but also across the different tasks and functional domains (in Project 9). The current project will complement the investigation of tDCS-induced enhancement of motor sequence learning in Project 5 that also investigates behavioral and neural modulation of individualized, focal tDCS in the motor domain, but with the primary motor cortex as the relevant hub in this paradigm. Collectively, the results of the empirical projects of the RU will increase our current understanding of tDCS-induced neural network effects, their regional specificity, the mechanisms underlying inter-individual variability of stimulation effects, and potential changes due to chronological age. From a methodological point of view, data acquired in these projects will contribute to optimizing and validating biophysical models of current flow (in Projects 9+10), thereby advancing future experimental and translational applications of tDCS in health and disease.