Brain Biomarkers of Response to Treatment for Apraxia of Speech

描述(由申请人提供)： 已经开发了许多治疗获得性言语失用(AOS)的发音障碍的方法。一种这样的干预是声音产生治疗(SPT)，它采用了由言语建模/重复、图形提示、整体刺激和发音位置指导组成的反应-应变型层次结构。一般认为，SPT等干预措施可以提高患者的语音准确性，但程度各不相同。在目前的研究中，我们将检验病变部位在SPT反应的变异性中起作用的假设。我们将使用最先进的MRI成像和后处理技术来更好地了解哪些患者最能从AOS治疗中受益，以及治疗效果背后的神经变化。具体地说，我们将使用基于体素的病变症状映射来确定最能预测治疗反应程度的病变部位，并使用先进的扩散成像技术来绘制从治疗前到治疗后白质束完整性的变化。为此，我们将使用严格的纳入和排除标准，在四年的时间里从退伍军人事务部北加州患者群体中招募30名患有AOS的患者。参与者将在弗吉尼亚州马丁内斯园区的3T核磁共振扫描仪上进行扫描。结构磁共振成像和扩散成像序列将在三个时间点收集：治疗基线阶段之前和之后(以测量治疗前扫描-重新扫描的可靠性)和治疗后再次(以测量与治疗相关的神经变化)。治疗将由熟悉这一患者群体的有执照的语言病理学家提供，并接受声音产生治疗方案的培训。患者将接受三种不同发音(例如，辅音、元音)的训练，这三种发音在预测试中产生70%的错误率。测试刺激将包括训练的和未训练的声音，以测试泛化能力。为了识别预测SPT治疗反应的Brin区域，我们将在标准化病变重建上运行基于体素的病变症状映射分析，自变量为病变状态(受损与否)，因变量为声音产生精度的变化，并对训练和未训练项目进行单独分析。根据我们以前的工作和相关文献，我们预测治疗和未治疗项目的SPT反应的大小(效应大小)都将受到累及左侧中央前上回的病变的影响。接下来，将使用扩散成像衍生的纤维束造影术重建8个 将为每个通路中的特定感兴趣区域计算主要白质通路和分数各向异性值。据预测，治疗对训练和未训练刺激的反应程度与脑岛中央前上回、左侧弓状回、纵上上回和内侧扣带下束周围白质的各向异性分数相关，因为这些束被认为与流利性和运动性言语障碍的研究有关。为了测量与SPT方案相关的神经可塑性，我们将计算从扫描2到扫描3的八个纤维束中每一个的分数各向异性值的差值。我们的预测再次集中在文献中与言语产生直接相关的那些束，弧形的、上纵的和内侧的穹隆下神经束，以及极囊的纤维。简而言之，当前的建议具有重要意义，因为它解决了文献中关于前瞻性地识别特定灰色和 白质与预测AOS治疗反应的相关性，以及这种治疗的神经机制。拟议的项目将提高我们对言语语言治疗潜在机制的科学理解，并为临床医生提供关键信息，他们可以利用这些信息来改善患者护理。

DESCRIPTION (provided by applicant): A number of treatments have been developed to treat articulatory deficits in acquired apraxia of speech (AOS). One such intervention is sound production treatment (SPT), which employs a response-contingent hierarchy made up of verbal modeling/repetition, graphic cueing, integral stimulation, and articulatory placement instruction. Interventions such as SPT are generally found to improve patients' speech accuracy but to varying degrees. In the current study, we will test the hypothesis that lesion site plays a role in the variability of SPT response. We will use state-of-the-art MRI imaging and post-processing techniques to better understand which patients are best able to benefit from AOS treatment, as well as the neural changes underlying treatment effects. Specifically, we will use voxel-based lesion symptom mapping to identify lesion sites most predictive of the degree of treatment response and advanced diffusion imaging techniques to map changes in the integrity of white matter tracts from pre- to post-treatment. To do this, we will recruit 30 individuals with AOS from the VA Northern California patient populations over the course of four years, using strict inclusion and exclusion criteria. Participants will be scanned on a 3T MRI scanner on the VA Martinez campus. Structural MRI and diffusion imaging sequences will be collected at three time points: before and after the baseline phase of treatment (to measure scan-rescan reliability prior to treatment) and again following treatment (to measure the neural changes associated with treatment). Treatment will be delivered by licensed speech-language pathologists familiar with this patient population and trained on the sound production treatment protocol. Patients will be trained on three different sounds (e.g., consonant, vowel sounds) that produce error rates >70% on pre-testing. Test stimuli will include both trained and untrained sounds to test for generalizability. To identify brin regions predictive of response to the SPT treatment, we will run voxel-based lesion symptom mapping analyses on normalized lesion reconstructions, with the independent variable being lesion status (lesioned or not) and the dependent variable, the change in sound production accuracy, with separate analyses for trained and untrained items. Based on our previous work and the relevant literature, we predict that the size of the SPT response (effect size) for both treated and untreated items will be affected by lesions involving the left superior pre-central gyrus of the insula. Next, diffusion imaging-derived tractography will be used to reconstruct eight major white matter pathways, and fractional anisotropy values will be calculated for specific regions of interest in each pathway. The degree of treatment response to both trained and untrained stimuli is predicted to correlate with fractional anisotropy values in the white matter surrounding the superior pre-central gyrus of the insula, the left arcuate, superior longitudinal, and medial subcallosal fasciculi, as these tracts have been implicated in studies of fluency and motor speech disorders. To measure neuroplasticity associated with the SPT protocol, we will calculate the difference in fractional anisotropy values from Scan 2 to 3 for each of the eight fiber tracts. Our predictions again focus on those tracts that have been directly associated with speech production in the literature, the arcuate, superior longitudinal, and medial subcallosal fasciculi, and fibers of the extreme capsule. In short, the current proposal is significant in thatit addresses a large gap in the literature with respect to prospectively identifying specific grey and white matter correlates that predict AOS treatment response, as well as the neural mechanisms underlying such treatment. The proposed project will improve our scientific understanding of the mechanisms underlying speech-language treatment and provide clinicians with critical information that they can use to improve patient care.