Combining tDCS and neurorehabilitation to treat age-related deficits of mobility and cognition

结合tDCS和神经康复治疗年龄相关的流动和认知缺陷

DAVID CLARK (2017-06-01 to 2019-05-31) $407,204

Project ID: R21AG053736 (NIA)

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Abstract

Loss of mobility and cognitive ability are serious conditions that threaten the independence of older adults. Importantly, both of these conditions are mechanistically linked by impairment of frontal lobe brain function. Frontal lobe dysfunction has been implicated as a factor contributing to gait deficits in some individuals with Alzheimer's disease, frontotemporal dementia and vascular dementia. There is a critical gap in knowledge about what therapeutic strategies are effective for maintaining or reinstating function in this critical brain region in order to preserve physical and cognitive health in older adults. The goal of our research is to develop a novel therapeutic intervention to enhance both mobility and cognition via neuroplasticity of frontal/executive control circuits. We will engage neuroplasticity of frontal circuits in two ways. The first is through neurorehabilitation with ?complex walking tasks? (CWTs), such as obstacle crossing, obstacle avoidance and walking on non- uniform surfaces. CWTs are a potent behavioral approach for engaging prefrontal circuits. Furthermore, CWTs are crucial to successful ambulation in the home and community settings and therefore provide an ecologically valid therapeutic approach. The second approach that we will use to engage neuroplasticity of frontal circuits is anodal transcranial direct current stimulation (tDCS). Anodal tDCS is a safe, non-invasive neuromodulation technique. It has previously been shown to induce excitatory effects on brain tissue and, in single-session assessments, to improve performance during complex walking tasks. tDCS has also been shown to be an effective adjuvant for enhancing the effects of cognitive training. The objective of this study is to calculate effect size, establish variance of response and demonstrate feasibility of the experimental interventions in order to plan for a full scale clinical trial. Participants will include thirty older adults who demonstrate evidence of frontal/executive impairment. Participants will be randomized to one of three groups: 1) standard walking neurorehabilitation with sham tDCS (`standard/sham' group), 2) complex walking neurorehabilitation with sham tDCS (`complex/sham' group), or 3) complex walking neurorehabilitation with active anodal tDCS (`complex/active' group). Functional near infrared spectroscopy (fNIRS) will be used to explore intervention- induced changes in prefrontal cortical activity. Assessments will be conducted at baseline, post-treatment and 3-month follow up. We propose the following specific aims: Specific Aim 1: Determine preliminary efficacy for recovery of mobility and cognitive function. Specific Aim 2: Demonstrate feasibility/safety of tDCS as an adjuvant to rehabilitation. Specific Aim 3: Explore the relationship between prefrontal activity and behavioral outcomes The data collected here will provide the information needed to justify and plan a future full scale clinical trial to assess the relative efficacy and underlying mechanisms of each intervention approach.

流动性和认知能力的丧失是威胁老年人独立性的严重条件。重要的是，这两种病症都与额叶脑功能的损害在机理上有关。额叶功能障碍已被认为是导致阿尔茨海默病，额颞叶痴呆和血管性痴呆的一些人步态缺陷的一个因素。关于哪些治疗策略在这个关键的大脑区域维持或恢复功能有效的治疗策略以保持老年人的身体和认知健康方面存在着重要的差距。我们研究的目标是开发一种新的治疗干预措施，通过额叶/执行控制电路的神经可塑性来增强机动性和认知能力。我们将以两种方式参与正面电路的神经可塑性。首先是通过神经康复治疗进行复杂的步行任务？（CWTs），例如障碍物穿越，避障和在非均匀表面上行走。 CWT是一种有效的行为方式，可用于吸引前额回路。此外，CWT对于在家庭和社区环境中成功行走至关重要，因此提供了一种生态有效的治疗方法。我们将用于参与额叶电路的神经可塑性的第二种方法是阳极经颅直流电刺激（tDCS）。 Anodal tDCS是一种安全的非侵入性神经调节技术。先前已经证明它可以诱导对脑组织的兴奋作用，并且在单次评估中，可以改善复杂步行任务中的表现。 tDCS也被证明是增强认知训练效果的有效佐剂。本研究的目的是计算影响大小，建立反应方差并证明实验干预措施的可行性，以便规划全面的临床试验。参与者将包括30名证明有正面/行政障碍证据的老年人。参与者将被随机分为三组：1）标准步行神经康复与假tDCS（“标准/假”组），2）复杂的行走神经康复与假tDCS（“复杂/假”组），或3）复杂的步行神经康复具有活性阳极tDCS（“复杂/活跃”组）。功能性近红外光谱（fNIRS）将用于探索干预引起的前额皮质活动变化。评估将在基线，治疗后和3个月的随访中进行。我们提出以下具体目标：具体目标1：确定恢复活动性和认知功能的初步疗效。具体目标2：证明tDCS作为康复辅助的可行性/安全性。具体目标3：探索前额叶活动与行为结果之间的关系此处收集的数据将提供证明和规划未来全面临床试验所需的信息，以评估每种干预方法的相对功效和潜在机制。