Low frequency rTMS and fluoxetine for motor recovery after ischemic stroke

描述（由申请人提供）：本提案的目的是研究重复经颅磁刺激（rTMS）联合药物治疗（氟西汀）对脑卒中后受试者康复的影响。本研究将有助于揭示缺血性脑卒中患者通过药物干预与无创神经调节相结合的功能恢复之间的关系。中风是美国致残的主要原因（Nowak et al., 2009）。根据美国心脏协会的数据，美国每年有超过79.5万人经历中风（Lloyd-Jones et al., 2009）。不幸的是，中风后运动功能的恢复往往是不完全的，大多数中风患者在中风后6个月就不能执行专业职责或日常生活活动（Hummel和Cohen， 2006）。目前，只有少数治疗方法可以改善中风患者的运动功能；大多数都是基于运动学习策略。虽然这些治疗可以显著改善运动功能，但其效果往往有限。本研究项目的总体目标是评估rTMS和氟西汀促进脑卒中后受试者运动功能恢复的临床和神经生理特性，并以临床运动功能量表为指标。这将通过在受试者接受氟西汀治疗时对未受影响半球的大脑初级运动皮层（M1）进行低频rTMS来完成，受试者将在干预后1个月和3个月进行评估。最后，我们将通过研究诱导的神经生理和功能变化来探讨这种治疗的机制。这将通过运动诱发电位、皮质兴奋性/抑制测量、经胼胝体抑制评估和配对联想刺激来索引。关于成功的保证，该建议有两个主要的具体目的：目的1：确定低频rTMS联合氟西汀是否比单独药物治疗在运动康复和运动技能保留方面提供额外的好处。目的2：确定rTMS联合药物治疗对皮质兴奋性的影响，氟西汀是否能够诱导M1神经调节的积极或消极作用。

DESCRIPTION (provided by applicant): The goal of this proposal is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with pharmacotherapy (fluoxetine) in the rehabilitation of post-stroke subjects. This research will help to reveal the relationship between function restorations via pharmacological intervention when combined with noninvasive neuromodulation in patients after ischemic stroke. Stroke is the leading cause of disability in the United States (Nowak et al., 2009) According to the American Heart Association, over 795,000 people experience stroke annually in the USA (Lloyd-Jones et al., 2009). Unfortunately, restitution of post-stroke motor function is frequently incomplete, with the majorit of stroke patients unable to perform professional duties or activities of daily living by six month after their stroke (Hummel and Cohen, 2006). Currently, there are only a few treatments available to improve motor function in stroke; most of them are based on motor learning strategies. Although these treatments may improve motor function significantly, their effects are often limited. The general objective of this research project is to assess the clinical and neurophysiological properties of rTMS and fluoxetine to promote motor recovery in post-stroke subjects as indexed by clinical motor function scales. This will be done by delivering low-frequency rTMS over the brain primary motor cortex (M1) in the unaffected hemisphere while the subjects are receiving fluoxetine treatment, subjects will be assessed at one and three months post intervention. Finally, we will investigate the mechanisms of this treatment by studying the induced neurophysiological and functional changes. This will be indexed by motor evoked potentials, cortical excitability/inhibition measurements, transcallosal inhibition evaluation, and paired associative stimulation. Regarding assurance of success, this proposal has two main specific aims: Aim 1: To determine whether low-frequency rTMS associated with fluoxetine offers additional benefits on motor rehabilitation and retention of motor skills, than pharmacotherapy alone. Aim 2: To determine the effects on cortical excitability when rTMS is combined with pharmacotherapy, whether fluoxetine is capable to induce positive or negative effects in M1 neuromodulation.