Recovering from chronic brain damage by Transcranial Direct Current Stimulation

描述(申请人提供)：在过去的三年里，生物医学界见证了侵入性和非侵入性脑神经调节方法的使用激增，以促进局部脑损伤后的功能恢复。这类技术的运作原理是，神经可塑性--受损大脑补偿行为缺陷的能力--可以通过能够在备用或受影响的神经网络中“塑造”兴奋性功能模式的技术来增强和指导。在最著名的脑深部刺激(DBS)、硬膜外脑刺激(EDBS)和最近的经颅磁刺激(TMS)中，在慢性中风患者中提供了非常令人鼓舞的初步结果。这些刺激方法的机制、真正的治疗潜力、副作用和神经“成本”谱仍有待在动物模型和临床应用中充分探索。然而，它们为行为神经学和精神病学在医学领域和条件下的治疗带来了新的希望，在许多情况下，诊断是最终的也是最后的步骤。在这种新出现的情况下，经颅直流电刺激(TDC)的效果最早在20世纪60年代初被研究，最近被重新发现，并正在重新评估临床和治疗用途。经颅直流电刺激提供了一种非侵入性、易于应用和低成本的方法来刺激或极化脑组织，并具有相当大的潜力来产生神经活动的引导改变，并导致脑损伤后显著的恢复模式。尽管如此，关于它对完整和备用的神经网络产生长期持续影响的能力，特别是这种调制如何在系统水平上解释行为恢复的成就，人们还知之甚少。为了充分评估其治疗潜力和研究其空间网络的特异性，我们建议在一个经过充分研究的猫单侧顶叶损伤导致视觉空间忽视的模型中测试其效果。我们计划通过两种策略实现退化的视觉空间检测定位能力的长期改善，这两种策略都旨在促进由备用皮质或皮质下区域塑料接管丧失的功能。更重要的是，通过全脑代谢性葡萄糖标记技术，我们将努力详细了解这种恢复的机制的性质和程度，以便能够最佳地应用。公共卫生相关性：我们将测试经颅直流电刺激(Tdcs)在改善慢性脑损伤后功能方面的应用。我们将研究其潜在的作用机制，并得出结论，为未来人类治疗应用于临床环境。

DESCRIPTION (provided by applicant): In the last three years, the biomedical community has seen an explosion in the use of invasive and non- invasive brain neuromodulation methods to increase recovery of function after localized brain damage. Such techniques operate on the principle that neural plasticity -the ability of a damaged brain to compensate for behavioral deficits- can be boosted and guided by techniques able to "sculpt" the functional patterns of excitability in spared or affected neural networks. Among the best known, Deep Brain Stimulation (DBS), Epidural Brain Stimulation (EDBS), and more recently Transcranial Magnetic Stimulation (TMS) have stood out in providing very encouraging preliminary results in chronic stroke patients. The mechanisms, real therapeutic potential, side effects and spectrum of neural "costs" of these stimulation methods remain to be fully explored in animal models and clinical applications. Nevertheless, they have provided behavioral neurology and psychiatry with new hopes of treatment in medical fields and conditions for which diagnosis was in many cases the ultimate and final step. In this emerging scenario, transcranial Direct Current Stimulation (tDCS), the effects of which were first studied during the early 1960s, has been recently "re-discovered" and is being re-evaluated for clinical and therapeutic use. Transcranial DC Stimulation provides a non-invasive, easy to apply and low cost method to stimulate or polarize brain tissue and has considerable potential to produce guided changes in neural activity and result in significant patterns of recovery after brain damage. Notwithstanding, not much is yet known on its ability to induce long lasting effects on intact and spared neural networks and particularly how such modulation can explain at the system's level the achievement of behavioral recovery. In order to fully assess its therapeutic potential and study its spatial network specificity we propose to test its effects in a well- studied feline model of unilateral parietal damage resulting into visual-spatial neglect. We plan on achieving long-lasting improvements in degraded visuo-spatial detection-localization abilities by means of two strategies both aimed at facilitating plastic take over of lost functions by spared cortical or subcortical regions. More importantly, by means of whole-brain metabolic glucose labeling techniques, we will try to develop a detailed understanding of the nature and extent of the mechanisms underlying such recovery, so that it can be optimally applied. PUBLIC HEALTH RELEVANCE: We will test the use of transcranial Direct Current Stimulation (tDCS) for improving function after chronic cerebral damage. We will study its underlying mechanisms of action and derive conclusions for future human therapeutic applications in clinical settings.