Improving Learning in MS: A Randomized Clinical Trial

描述（由申请人提供）：新学习和记忆障碍是多发性硬化症（MS）患者最常见的缺陷之一。我们NIH资助的临床试验（RO1 HD045798）是一项随机、双盲、安慰剂对照的临床试验，旨在通过特定的行为技术来修复MS患者的学习和记忆，这些技术针对的是主要缺陷：获取（或学习）新信息的障碍。患有多发性硬化症的个体被随机分配到记忆再训练组或安慰剂对照组。结果通过：(1)传统的神经心理学（NP）测试和(2)检查治疗对日常活动影响的整体功能评估（AGF）来衡量。虽然这项资助的研究将能够从行为上证明有针对性的干预对受损的学习和记忆有任何潜在的好处，但它并没有提供治疗后大脑发生什么变化的信息。目前提议的拨款补充将使用功能性磁共振成像（fMRI）检查针对性行为干预对功能性脑活动的影响。我们的目标是证明大脑底物水平的变化也伴随着治疗后学习和记忆方面的行为变化。我们将在fMRI上确定学习和记忆的改善是否与特定的功能性大脑活动模式有关。为了达到这些目标，我们寻求补充我们目前资助的临床试验。受试者将接受治疗前和治疗后的功能磁共振成像评估，并同时评估行为表现。此外，参与者将完成治疗后6个月的功能磁共振成像（fMRI），以检查治疗效果随时间的维持，以及从神经功能的角度来看，“强化课程”的影响，以促进治疗效果的维持。美国国立卫生研究院建议研究分析现有的康复技术，经验性地评估其有效性，并为消费者和从业者提供理由，以促进医学康复研究领域的发展，并认为这是一个高度优先的研究领域。我们的研究就是专门针对这些问题设计的。

DESCRIPTION (provided by applicant): Impairments in new learning and memory are among the most common deficits in persons with Multiple Sclerosis (MS). Our NIH funded clinical trial (RO1 HD045798) is a randomized, double blind, placebo- controlled clinical trial designed to remediate learning and memory in persons with MS using specific behavioral techniques which target the primary deficit: impairments in the acquisition (or learning) of new information. Individuals with MS, are randomly assigned to a memory retraining group or a placebo control group. Outcome is measured through: (1) a traditional neuropsychological (NP) battery and (2) an assessment of global functioning (AGF) examining the impact of the treatment on daily activities. While this funded study will be able to demonstrate behaviorally any potential benefits of the targeted intervention for impaired learning and memory, it does not provide information on what changes are occurring in the brain following treatment. The currently proposed grant supplement will examine the impact of the targeted behavioral intervention on functional cerebral activity using functional Magnetic Resonance Imaging (fMRI). We aim to demonstrate that changes at the level of the cerebral substrate also accompany the behavioral changes in learning and memory noted following treatment. We will determine if improvement in learning and memory is associated with particular patterns of functional, cerebral activity on fMRI. To meet these objectives, we seek to supplement our currently funded clinical trial. Subjects will receive pre and post- treatment fMRI evaluations, which will be correlated with behavioral performance assessed concurrently. Additionally, participants will complete a 6-month post-treatment fMRI to examine the maintenance of treatment effects over time, as well as the impact of "booster sessions" to facilitate the maintenance of treatment effects from a neurofunctional perspective. The NIH recommends research analyzing existing rehabilitation techniques, empirically assessing their validity, and providing justification to the consumer and practitioner for the advancement of the field of medical rehabilitation research and recognizes this as a high priority research area. Our study is designed to specifically address these issues.