Treating Intention in Aphasia: Neuroplastic Substrates

描述（由申请人提供）：开发了一种新的治疗方法，在“非流利”失语症患者中操纵意图底物进行语言产生。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，这种治疗的命名准确率的变化速度比没有意图成分的类似治疗更快。然而，治疗引起语言产生功能从左到右额叶的转移的假设仅在少数患者（N = 5）中进行了测试，这些患者在治疗前侧化是可变的，并且没有使用适当的严格控制程序来验证侧化的转移是由于意图成分。这项研究将在更大样本的“非流利性”失语症患者和适当的对照组中讨论偏侧化的假设变化。在平行组设计中，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，除了意向成分不存在。所有受试者将在治疗前后参加功能性磁共振成像（fMRI）单词查找扫描，以测量侧额叶和前SMA活动的偏侧化变化。只有治疗前扫描显示左额叶活动程度较高的患者才可参与研究。长期目标是确定意向治疗是否产生了假设的侧额叶和SMA前活动的移位。有三个具体目标：（1）确定用复杂的左手运动重复启动单词产生是否导致SMA前体和侧额叶活动的右半球偏侧化增加，以及这些变化是否可归因于治疗的意图成分，（2）为了确定后外侧裂周皮质的活动是否被夹带到右额叶活动中，右额叶活动的增加是否更大，从治疗前到治疗后fMRI，与对照组相比，大脑半球对意图的偏侧化，以及（3）确定右运动/前运动皮层中的血流动力学反应（HDR）的开始是否与参与者在意图治疗与对照治疗之间的口头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：首先，如果成功的话，治疗可以提供一种新的治疗手段，增加语言功能，减少“非流利”失语症患者的痛苦。第二，通过强调在语言产生的大脑机制中产生所需变化的机制，并通过功能磁共振成像验证目标变化，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.