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

运动学习与经颅直流电的相互作用 - 功效和机制

• 批准号: 10577313
• 负责人: John H Martin
• 金额: $ 57.46万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10577313
• 关键词: Address; Affect; Algorithms; Animal Experimentation; Animal Experiments; Animals; Association Learning; Behavioral; Brain-Derived Neurotrophic Factor; Calibration; Cephalic; Clinical; Consensus; Dose; Double-Blind Method; Electrical Stimulation of the Brain; Electrodes; Electrophysiology (science); Engineering; Esthesia; Fingers; Future; Genetic; Human; Human Experimentation; In Vitro; Inherited; Latino; Learning; Light; Link; Literature; Maps; Measures; Mediating; Membrane; Minority-Serving Institution; Modeling; Molecular; Motor; Motor Cortex; Motor Evoked Potentials; Movement; Neurons; Neurophysiology - biologic function; Outcome; Outcome Measure; Pathway interactions; Physiological; Process; Protocols documentation; Rattus; Reporting; Research; Rest; Rodent; Sample Size; Scalp structure; Signal Transduction; Specificity; Stroke; Synapses; Synaptic plasticity; Testing; Training; Transcranial magnetic stimulation; Translations; Underrepresented Populations; Work; clinical efficacy; cohort; designer receptors exclusively activated by designer drugs; electric field; experience; experimental study; human subject; in vivo; motor learning; motor rehabilitation; neural; neurophysiology; novel; programs; recruit; repaired; response; sequence learning; skills; tool; transcranial direct current stimulation; treatment strategy

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.

项目概要 尽管对经颅直流电刺激的机制和应用进行了数十年的研究 (tDCS)，将 tDCS 转化为广泛使用且有意义的疗法的过程已停止。我们建议这是一个 本提案将解决三个因素的结果。一、刺激强度保持不变 有限的;其次，对于刺激是否应该与特定的行为相结合尚不明确。 任务;第三，对根本行动机制缺乏共识。我们已经在体外展示了 电场刺激可以使神经元与所施加的场成比例地极化，该场与 同时诱导突触可塑性，因此具有功能特异性。有鉴于此，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。这个假设将是 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 并与极性相反。在人体中，我们将使用新开发的电极蒙太奇来测试这一点，该电极可以实现 迄今为止运动皮层上的最高场强，对运动序列产生强烈的影响大小 学习。对于大鼠，我们将使用一种新的刺激方案，该方案对颗粒到达的学习有很强的影响 任务。目标 2 是在人类和大鼠中测试预测，即效果特定于受刺激的运动皮层 而且，对于人类来说，这种效果是特定于训练任务的。结果测量将是运动学习和 运动皮层兴奋性（运动诱发电位）。目标 3 是在大鼠中测试行为假设 经颅直流电刺激 (tDCS) 的好处与运动皮层的空间特定功能和结构变化有关 （使用 2D 运动图和突触标记进行测量），因果关系取决于运动皮层的调节 活性（通过化学遗传学失活控制）。这些实验的结果，无论是否 他们证实或反驳基本假设，将直接解决限制进展的因素。经过 强调严谨性，该项目将产生强大的首选实验，可以作为未来的标准工具 勘探。通过关注运动学习，这项工作可以立即应用于运动康复。