Recovering from chronic brain damage by Transcranial Direct Current Stimulation

描述（由申请人提供）：在过去三年中，生物医学界在使用侵入性和非侵入性脑神经调节方法以增加局部脑损伤后功能恢复方面取得了爆炸式增长。这些技术的原理是，神经可塑性——受损大脑补偿行为缺陷的能力——可以通过能够“塑造”未受损或受影响的神经网络中兴奋性的功能模式的技术来增强和指导。其中最著名的是脑深部刺激（DBS），硬膜外脑刺激（EDBS），以及最近的经颅磁刺激（TMS）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。尽管如此，它们为行为神经病学和精神病学在医学领域的治疗带来了新的希望，在许多情况下，诊断是最终和最后的步骤。在这种新情况下，经颅直流电刺激（tDCS）的效果在20世纪60年代初首次被研究，最近被“重新发现”，并正在重新评估其临床和治疗用途。经颅直流电刺激提供了一种无创、易于应用和低成本的刺激或极化脑组织的方法，具有相当大的潜力，可以产生神经活动的指导性变化，并导致脑损伤后显著的恢复模式。尽管如此，对于其对完整的和未受损的神经网络产生持久影响的能力，特别是这种调节如何在系统层面上解释行为恢复的实现，目前还知之甚少。为了充分评估其治疗潜力和研究其空间网络特异性，我们建议在一个研究充分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来实现对退化的视觉空间检测定位能力的长期改善，这两种策略都旨在通过保留的皮层或皮层下区域促进对丢失功能的可塑性接管。更重要的是，通过全脑代谢葡萄糖标记技术，我们将尝试详细了解这种恢复机制的性质和程度，以便它可以得到最佳应用。公共卫生相关性：我们将测试使用经颅直流电刺激（tDCS）改善慢性脑损伤后的功能。我们将研究其潜在的作用机制，并得出结论，为未来在临床环境中的人类治疗应用。

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.