Cortical mechanisms and modulation of somatosensation in older adults with foot sole somatosensory impairments

提案摘要 我的职业目标是：1）了解脊髓上的感觉运动通路，通过它，年龄-和年龄- 相关的条件削弱了运动控制系统的功能，以及2）使用该信息来 开发新的疗法来改善老年人的步态和平衡。我希望通过过渡来实现这一目标 成为一名独立的科学家，并领导着一个衰老和平衡控制领域的研究项目。 在老年人中，下肢躯体感觉减弱是非常普遍的，也是主要原因之一。 平衡差，活动能力下降，跌倒的风险增加。绝大多数的研究和临床工作 迄今为止，已经尝试通过恢复脑的外周元件的功能来改善躯体感觉。 躯体感觉系统然而，躯体感觉也依赖于激活神经元的能力。 适当的皮质网络对给定的刺激做出反应，这在老年人中也会改变。治疗 因此，旨在增强躯体感觉皮层网络兴奋性的策略， 改善该人群足底体感的潜力。我们的初步研究表明， 传统的经颅直流电刺激（tDCS），它产生一个扩散电场， 初级躯体感觉皮层，改善老年人的足底躯体感觉。在K 01大奖中，我们 我将首先确定对行走相关的足底刺激有反应的特定皮层网络 在有和没有足底躯体感觉的老年人中（目的1）。我们将使用模块设计的功能性磁共振成像 范例与定制设计的，MRI兼容的足底刺激系统，以应用个性化 模拟参与者行走时的足底压力，但当他们躺下时， 在扫描仪里一动不动。基于从目标1获得的这些知识，我们将开发一种新的多- 目标tDCS干预针对所识别的皮层网络，并测试这种单一会话的效果。 对老年人轻中度足跖躯体感觉、平衡和活动能力干预 躯体感觉障碍（目标2）。然后，我们将使用参与者的大脑MRI和电场建模， 建立tDCS诱导的靶电流强度与其急性毒性之间的“剂量-反应”关系， 对足底刺激皮质反应的影响（目的3）。通过这项工作，我们将了解如何 慢性下肢躯体感觉障碍影响感觉反馈的皮层处理 参与平衡和移动性的控制，证明这种处理可以通过tDCS调节， 从而获得设计更大更明确的试验以测试tDCS潜力所需的关键信息 以改善该人群的足底感觉、平衡和活动性。该职业发展奖将 为我提供了独特的培训经验，在神经生理学的躯体感觉在老龄化，临床护理 这些老年人，并增加我在先进的神经成像和脑刺激技术的专业知识， 这两点加在一起，将极大地促进我向独立学术科学家过渡的努力。

PROPOSAL SUMMARY My career goals are to 1) understand the supraspinal sensorimotor pathways through which age- and age- related conditions diminish the functionality of the locomotor control system, and 2) use this information to develop new therapies to improve gait and balance in older adults. I hope to achieve this goal by transitioning into an independent scientist and leading an research program in the fields of aging and balance control. In older adults, diminished lower-extremity somatosensation is highly prevalent and a primary contributor to poor balance, reduced mobility, and increased risk of falling. The vast majority of research and clinical efforts to date have attempted to improve somatosensation by restoring the function of peripheral elements of the somatosensory system. However, somatosensation is also dependent upon the capacity to activate the appropriate cortical networks in response to a given stimulus, which is also altered in older adults. Therapeutic strategies aimed at enhancing the excitability of the somatosensory cortical network thus offer untapped potential to improve foot-sole somatosensation in this population. Our preliminary studies suggest that a single session of traditional transcranial direct current stimulation (tDCS), which produces a diffuse electric field over the primary somatosensory cortex, improves foot-sole somatosensation in older adults. In this K01 Award, we will first work to identify the specific cortical network that is responsive to walking-related foot-sole stimulation in older adults with and without foot-sole somatosensation (Aim 1). We will use a block-design functional MRI paradigm with a custom-designed, MRI-compatible foot sole stimulation system to apply individualized pressures to the participant’s foot soles that mimic those experienced when they walk, yet while they lay motionless in the scanner. Based upon this knowledge obtained from Aim 1, we will develop a novel multi- target tDCS intervention targeting the identified cortical network and test the effects of a single session of this intervention on foot-sole somatosensation, balance and mobility in older adults with mild-to-moderate foot-sole somatosensory impairments (Aim 2). We will then use participant brain MRIs and electric field modeling to establish the “dose-response” relationship between on-target current intensity induced by tDCS and its acute effect on the cortical response to foot sole stimulation (Aim 3). Through this work we will learn about how chronic lower-extremity somatosensory impairments influence the cortical processing of sensory feedback involved in the control of balance and mobility, demonstrate that such processing can be modulated by tDCS, and thus, obtain critical information needed to design a larger more definitive trial to test the potential for tDCS to improve foot sole sensation, balance, and mobility in this population. This career development award will provide me with unique training experiences in neurophysiology of somatosensation in aging, the clinical care of these older adults, and increase my expertise in advanced neuroimaging and brain stimulation techniques, which, taken together, will greatly facilitate my efforts to transition into an independent academic scientist.