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

建议书摘要 我的职业目标是：1)了解脊柱上的感觉运动通路，年龄--和年龄-- 相关条件降低了运动控制系统的功能，并且2)使用该信息 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，并领导衰老和平衡控制领域的研究计划。 在老年人中，下肢躯体感觉减弱是非常普遍的，也是一个主要因素。 导致平衡不良，行动不便，摔倒的风险增加。绝大多数的研究和临床工作 到目前为止，已经尝试通过恢复脑血管周围元素的功能来改善躯体感觉 体感系统。然而，躯体感觉也依赖于激活 适当的皮质网络对给定的刺激做出反应，这在老年人中也会发生变化。治疗性的 旨在增强躯体感觉皮层网络兴奋性的策略因此提供了未开发的 在这一人群中改善脚底躯体感觉的潜力。我们的初步研究表明，单一的 传统的经颅直流电刺激(Tdcs)，它会产生弥散电场。 初级躯体感觉皮质，改善老年人的脚底躯体感觉。在这个K01奖项中，我们 我将首先致力于确定对行走相关的脚底刺激做出反应的特定皮质网络 在有和没有脚底体感的老年人中(目标1)。我们将使用模块化设计的功能磁共振成像 具有定制设计的、与MRI兼容的脚底刺激系统的范例，可应用个性化 对参与者脚底的压力，模拟他们行走时的感受，但当他们躺下时 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 以已识别的皮质网络为靶点进行tdcs干预，并测试单次会话的效果 干预对轻、中度足底老年人足底感觉、平衡和活动能力的影响 躯体感觉障碍(目标2)。然后我们将使用参与者的大脑核磁共振和电场建模来 建立tdcs诱发的靶上电流强度与其急性损伤之间的“剂量-反应”关系 足底刺激对皮质反应的影响(目标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 参与平衡和机动性的控制，证明这种处理可以由tdcs调制， 因此，获得设计一项更大、更明确的试验以测试tdcs潜力所需的关键信息。 以改善这一人群的脚底感觉、平衡和活动能力。这个职业发展奖将 为我提供独特的神经生理学方面的训练经验，体感在衰老中的临床护理 并增加我在高级神经成像和脑刺激技术方面的专业知识， 综上所述，这将极大地促进我向独立学术科学家的转变。

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.