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.

项目摘要 尽管有数十年的工作在经颅直流刺激的机制和应用方面进行的工作 （TDC），将TDC转换为广泛使用且有意义的疗法被停止。我们建议这是 该提案将解决三个因素的结果。首先，刺激的强度仍然存在 有限的;其次，缺乏对是否应与特定行为配对的刺激 任务;第三，就基本的作用机理缺乏共识。我们已经在体外显示 电场刺激可以与所施加的场成比例地使神经元偏振，后者与 同时诱导突触可塑性，因此在功能上是特异性的。鉴于此，TDC应该继承 并发行为训练和效果的特异性应以强度扩展。这个假设将是 在运动学习的背景下，在这里进行的人类和大鼠实验进行了测试。目标1是测试 预测刺激必须与行为运动学习以及强度效果量表并发 并与极性相反。在人类中，我们将用新开发的电极蒙太奇进行测试 运动皮层上最高的现场强度，导致运动序列的强大效应大小 学习。对于大鼠，我们将使用一种新的刺激协议，对颗粒的学习有很大影响 任务。 AIM 2是在人类和大鼠中测试预测，该预测特定于刺激的运动皮层 而且，在人类中，这种影响是针对训练有素的任务的。结果措施将是运动学习和 运动皮层兴奋性（电动诱发电位）。目标3是测试大鼠的假设 TDC的好处与运动皮层的空间特异性功能和结构变化有关 （用2D电机图和突触标记测量），并因果关系取决于运动皮层的调节 活性（用化学发生灭活控制）。这些实验的结果，无论是否 他们确认或反驳基本假设，将直接解决限制进展的因素。经过 强调严格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 勘探。通过专注于运动学习，这项工作立即适用于运动康复。