Cortical and subcortical underpinnings of typical and dysarthric speech - Resubmission - 1

项目总结/摘要 患有运动性语言障碍如构音障碍的个体已知表现出异常的发声和关节音， 言语精确度，这可能导致参与社会和职业活动时的清晰度降低。 其中最常见的构音障碍是与帕金森病，其中涉及非典型的在线 音调（发音）和共振峰频率（发音）的调制。尽管构音障碍的发病率很高，但 这一人群的急剧下降可能导致积极参与言语康复的能力降低。 这项研究的长期目标是开发一种治疗方法， 提高构音障碍患者的可懂度的方法，包括操纵听觉的方法， 反馈，同时将神经调节应用于皮层区域。为此，我们利用稀有的 神经外科数据（癫痫的皮质电描记术、帕金森病的脑深部电刺激）来绘制 发声和发音控制的皮层基质，同时解释皮层下结构的作用。 根据语音产生的著名模型，言语运动控制的缺陷是客观的反映。 在跨越皮层和皮层下结构的运动回路中的神经元。实时实验扰动 听觉反馈与神经成像同时进行，这推进了目前对大脑皮层的理解， 用于将听觉反馈典型地结合到语音输出（“感觉运动控制”）中的定位。同时， 对帕金森病患者感觉运动控制的研究有助于阐明 在非典型感觉运动控制中的皮质-皮质下运动回路中的丘脑底核。以前的种马- 研究表明，音高和共振峰在运动前区的不同亚区中受到不同的调制， 皮质和丘脑底核内。然而，研究之间的差异阻止了强大的 皮层和皮层下结构的分隔，用于专门控制不同的声学特征。 为了精确定位典型的基于反馈的感觉运动控制的神经机制，Aim 1绘制了 与对音高和共振峰扰动的补偿反应有关的皮层活动， 癫痫患者的脑皮层电图为了分离丘脑底核在感觉运动控制中的作用， trol，目标2比较了健康对照组对音高和共振峰扰动的代偿反应 与帕金森病患者在脑深部电刺激开启与关闭条件下的对比。 建议的实验范式是重要的，因为它将澄清有关专业化的冲突报告， 皮层和皮层下结构在音高与共振峰的感觉运动控制中的作用。影响的证据 神经外科手术对常见运动障碍患者语音结果的影响可以直接为围手术期决策提供信息， 临床护理这项研究将直接应用于未来的神经调制发展，以提高 帕金森病患者的语言治疗。结果还可以为一系列运动障碍的治疗提供信息。 语言障碍，最终最大限度地提高发音和发音控制，以改善患者的沟通。

Project Summary/Abstract Individuals with motor speech disorders such as dysarthria are known to show aberrant phonatory and artic- ulatory precision, which can lead to reduced intelligibility when participating in social and vocational activities. Among the most common dysarthrias is that associated with Parkinson’s disease, which involves atypical online modulation of pitch (phonation) and formant frequencies (articulation). Despite high incidence of dysarthria, cog- nitive decline in this population may lead to a reduced capacity to engage actively with speech rehabilitation. The long-term goal of this research is to develop treatment approaches that tap into automatic pro- cesses to improve intelligibility in patients with dysarthria, including approaches that manipulate auditory feedback while applying neuromodulation to cortical regions. Toward this end, we leverage the availability of rare neurosurgical data (Electrocorticography in Epilepsy, Deep Brain Stimulation in Parkinson’s disease) to map out the cortical substrates of phonatory and articulatory control while accounting for the role of subcortical structures. According to prominent models of speech production, deficits in speech motor control are a reflection of ab- normalities in motor circuits spanning cortical and subcortical structures. Experimental perturbation of real-time auditory feedback concurrent with neuroimaging has advanced the current understanding of the cortical under- pinnings for typical incorporation of auditory feedback into speech output (“sensorimotor control”). Meanwhile, investigations of sensorimotor control in patients with Parkinson’s disease have helped elucidate the role of the subthalamic nucleus within the cortical-subcortical motor circuit in atypical sensorimotor control. Some past stud- ies have suggested that pitch and formants are differentially modulated in distinct subregions within premotor cortex, and within the subthalamic nucleus. However, discrepancies across studies have prevented the robust parcellation of cortical and subcortical structures for the specialized control of distinct acoustic features. To pinpoint the neural mechanisms underlying typical feedback-based sensorimotor control, Aim 1 maps out cortical activity associated with compensatory responses to perturbations of pitch and formants using electrocorticography in patients with Epilepsy. To isolate the subthalamic nucleus’s role in sensorimotor con- trol, Aim 2 compares compensatory responses to perturbations of pitch and formants in healthy controls versus patients with Parkinson’s disease in conditions with Deep Brain Stimulation ON versus OFF. The proposed experimental paradigm is significant in that it will clarify conflicting reports about the specializa- tion of cortical and subcortical structures in sensorimotor control of pitch versus formants. Evidence for the effects of neurosurgery on speech outcomes in common motor disorders could directly inform perioperative decisions in clinical care. This research will have direct applications for the future development of neuromodulation to enhance speech treatment for patients with Parkinson’s disease. Results could also inform treatments for a range of motor speech disorders, ultimately maximizing phonatory and articulatory control to improve patient communication.