Interaction of Motor Learning with Transcranial Direct Current - Efficacy and Mechanisms

项目总结 尽管几十年来对经颅直流电刺激的机制和应用进行了研究 (Tdcs)，tdcs向广泛使用和有意义的治疗方法的转换被停止。我们建议这是一种 这是本提案将涉及的三个因素的结果。首先，刺激力度保持不变 有限；第二，对于刺激是否应该与特定的行为相匹配，缺乏明确性 第三，对基本的行动机制缺乏共识。我们已经在体外展示了 电场刺激可以与外加电场成比例地极化神经元，而外加电场与神经元相互作用 同时诱导突触可塑性，因此在功能上是特异的。鉴于此，tdcs应该继承。 同时进行的行为训练的特异性和效果应随强度而变化。这一假设将是 在运动学习的背景下，在人类和大鼠的平行实验中进行了测试。目标1是测试 预测刺激必须与行为运动学习同时进行，并且效果随强度而变化 并用极性反转。在人类身上，我们将用一种新开发的电极蒙太奇来测试这一点，这种蒙太奇可以实现 迄今为止运动皮质上的最高场强，导致对运动序列的强烈影响大小 学习。对于大鼠，我们将使用一种新的刺激方案，对学习有很强的影响-到达颗粒 任务。目标二是在人类和大鼠身上验证这种预测，即这种影响是受刺激的运动皮质所特有的 而且，在人类身上，这种影响是特定于受过训练的任务的。结果衡量标准将是运动学习和 运动皮质兴奋性(运动诱发电位)。目标3是在大鼠身上测试这一假设 TDCs的益处与运动皮质中特定的空间功能和结构变化相关 (使用2D运动地图和突触标记进行测量)，并且因果上取决于运动皮质的调制 活性(通过化学生成失活来控制)。这些实验的结果，无论是否 他们证实或驳斥了基本假设，将直接解决限制进展的因素。通过 强调严谨这个项目将产生强大的首选实验，可以作为未来的标准工具 探险。通过专注于运动学习，这项工作立即适用于运动康复。

PROJECT SUMMARY Notwithstanding decades of work on the mechanisms and applications of transcranial direct current stimulation (tDCS), the translation of tDCS to a broadly-used and meaningful therapy is halted. We propose that this is a result of three factors that will be addressed in this proposal. First, the intensity of stimulation has remained limited; Second, there is a lack of clarity as to whether stimulation should be paired with a specific behavioral task; and third, there is a lack of consensus on the underlying mechanisms of action. We have shown in vitro that electric field stimulation can polarize neurons in proportion to the applied field, which interacts with concurrent induction of synaptic plasticity, and is thus functionally specific. In light of this, tDCS should inherit the specificity of concurrent behavioral training and effects should scale with intensity. This hypothesis will be tested here in parallel human and rat experiments in the context of motor learning. Aim 1 is to test the prediction that stimulation has to be concurrent to behavioral motor learning, and effects scale with intensity and reverse with polarity. In humans we will test this with a newly-developed electrode montage that achieves the highest field-intensities on the motor cortex to-date, resulting in strong effect sizes for motor sequence learning. For rats, we will use a new stimulation protocol with strong effects on learning in a pellet-reaching task. Aim 2 is to test the prediction, in humans and rats, that effects are specific to the stimulated motor cortex and, in humans, that effects are specific to the trained task. Outcome measures will be motor learning and motor cortex excitability (motor-evoked potentials). Aim 3 is to test the hypothesis in rats that behavioral benefits of tDCS are associated with spatially specific functional and structural changes in the motor cortex (measured with 2D motor map and synaptic markers), and causally depends on modulation of motor cortex activity (controlled with chemogenetic inactivation). The outcomes of these experiments, regardless of whether they confirm or refute the basic hypothesis, will directly address the factors that are limiting progress. By emphasizing rigor this project will yield robust go-to experiments that can serve as standard tools for future exploration. By focusing on motor learning, the work is immediately applicable to motor rehabilitation.