Treating Intention in Aphasia: Neuroplastic Substrates

描述(申请人提供)：开发了一种新的治疗方法，通过操纵意图底物来产生“不流利的”失语症患者的语言。意图部分包括用复杂的左手运动启动单词查找试验。在一项初步研究中，这种处理的命名准确率的变化速度比没有意图成分的类似处理更快。然而，治疗引起语言输出功能从左侧向右侧额叶转移的假设只在少数患者(N=5)中得到了验证，这些患者在治疗前的偏侧化是不同的，并且没有使用适当的严格控制程序来验证偏侧化的变化是由于意图成分。这项拟议的研究将解决“不流利的”失语症患者和适当的对照组的更大样本中偏侧的假设转移。在平行分组设计中，13名患者将接受意向治疗，13名患者将接受与意向相同的对照治疗，只是意向成分缺失。所有受试者将在治疗前和治疗后接受功能磁共振成像(FMRI)的单词查找扫描，以测量侧额叶和SMA前活动的偏侧化变化。只有在治疗前扫描中有相当程度的左额叶活动的患者才会参与。长期目标是确定意向治疗是否产生假设的外侧额叶和SMA前活动的右移。有三个具体目标：(1)确定重复启动具有复杂左手运动的单词产生是否导致SMA前和侧额叶活动的右半球偏侧化增加，以及这些变化是否可以归因于治疗的意图成分，(2)确定从治疗前到治疗后的fMRI，被牵连到右额叶活动的后视盘周围皮质的活动是否显示出意图的右半球偏侧化比对照组更大的增加，以及(3)确定右侧运动/运动前皮质的血流动力学反应(HDR)的开始是否与参与者跨意图治疗与对照治疗的言语反应的时间开始更密切相关。这项拟议的研究有以下潜在的好处：第一，如果治疗成功，该治疗可以提供一种新的治疗工具，提高语言功能，减少“不流利”失语患者的痛苦。其次，通过强调在语言产生的大脑机制中产生所需变化的机制，以及通过功能磁共振成像验证目标变化，这种治疗可以在失语症治疗的发展中产生范式转变。

DESCRIPTION (provided by applicant): A new treatment manipulating intention substrates for language production in "nonfluent" aphasia patients was developed. The intention component involves initiating word-finding trials with a complex left-hand movement. In a preliminary study, the rate of change in naming accuracy was faster for this treatment than for a similar treatment without the intention component. However, the assumption that the treatment evokes a shift of language production functions from the left to the right frontal lobe has been tested only in a small number of patients (N = 5) whose lateralization was variable before treatment, and appropriate stringent control procedures to verify that the shift in lateralization was due to the intention component were not used. The proposed study will address the hypothesized shift in lateralization in a larger sample of "nonfluent" aphasia patients and with an appropriate control group. In a parallel group design, 13 patients will receive the intention treatment and 13 patients will receive a control treatment that is identical to the intention except that the intention component is absent. All subjects will participate in functional magnetic resonance imaging (fMRI) scans of word-finding before and after treatment to measure changes in lateralization of lateral frontal and pre-SMA activity. Only patients with a substantial degree of left frontal activity on the pre-treatment scan will participate. The long-term objective is to determine if the intention treatment produces the hypothesized rightward shift in lateral frontal and pre-SMA activity. There are three specific aims: (1) to determine if repetitive initiation of word production with a complex left-hand movement leads to increased right- hemisphere lateralization of pre-SMA and lateral frontal activity and if these changes can be attributed to the intention component of treatment, (2) to determine whether activity in posterior perisylvian cortices that is entrained to right frontal activity shows a greater increase in right-hemisphere lateralization for the intention than for the control group from pre- to post-treatment fMRI, and (3) to determine whether onset of hemodynamic responses (HDRs) in right motor/premotor cortex becomes more closely associated with the temporal onset of participants' spoken responses across treatment for the intention vs the control treatment. The proposed study has the following potential benefits: First, if successful, the treatment can provide a new treatment vehicle for increasing language function and reducing suffering in patients with "nonfluent" aphasia. Second, the treatment can produce a paradigm shift in the development of aphasia treatment by emphasizing mechanisms for producing desirable changes in the brain mechanisms for language production and by verifying the target changes with fMRI.