TMS to explore interhemispheric interactions and to treat aphasia and neglect

描述(由申请人提供)：本提案的中心目标是进一步描述由于偏侧化的脑损伤而出现的大脑半球间的相互作用，并将这一理解应用于中风引起的失语和忽视的治疗。失语症将作为研究右脑在左脑功能中的作用的模型；忽略将成为阐明左脑在右脑功能中的作用的模型。第一个具体目标是确定左额叶在不同语言处理领域的解剖学差异。经颅磁刺激(TMS)将在正常受试者的左侧额下回进行，以扰乱操作，揭示语言领域之间的分离。第二个具体目标是确定右脑在空间认知的不同方面的解剖学差异。TMS将在正常受试者的右侧额叶和顶叶皮质进行，以改变表现，阐明潜在的注意结构-功能关系。这项研究的解剖学假设将在一项针对患有失语症或忽视的慢性中风患者的治疗试验中得到进一步验证。每组在每天10次对照TMS治疗前和治疗后对他们的缺陷进行评估。该项目通过发展考生对研究设计、心理测量和TMS的熟练程度，并通过促进他对皮质可塑性的行为影响的长期兴趣，来满足考生的直接目标。它推进了他的长期目标，即在一家学术机构建立认知神经科学和神经学独立研究员的职业生涯。宾夕法尼亚大学是追求这些目标的丰富环境，拥有认知神经科学中心(CCN)等资源。应聘者还将通过大学提供的课程作业和方法培训机会来加强他的职业发展。最后，这项工作对健康的影响是深远的。失语症影响了超过20%的缺血性中风患者，而中风患者中有25%-30%的人出现了半空间忽视。TMS对失语症和忽视康复的特征特异性效应可能为未来的治疗方法指明方向，这些方法可能比目前的治疗方法更有效，更有针对性。

DESCRIPTION (provided by applicant): The central aims of this proposal are to further characterize interhemispheric interactions that emerge in response to lateralized brain injury, and to apply this understanding to the treatment of stroke-induced aphasia and neglect. Aphasia will serve as a model for investigating the right hemisphere's role in left hemisphere function; neglect will be the model for elucidating the left hemisphere's role in right hemisphere function. The first specific aim is to identify anatomical distinctions in the left frontal lobe for different domains of language processing. Transcranial magnetic stimulation (TMS) will be administered to the left inferior frontal gyrus in normal subjects to disrupt performance, revealing dissociations between language domains. The second specific aim is to identify anatomical distinctions in right hemisphere for different aspects of spatial cognition. TMS will be administered to the right frontal and parietal cortex in normal subjects to alter performance, elucidating structure-function relationships underlying attention. The anatomic hypotheses of the study will be tested further in a treatment trial involving chronic stroke patients who have aphasia or neglect. Each group will undergo assessment of their deficit before and after 10 daily sessions of contralesional TMS. This project meets the candidate's immediate goals by developing his proficiency with study design, psychological measures, and TMS, and by furthering his longstanding interest in the behavioral effects of cortical plasticity. It advances his long-term goal of establishing a career as an independent investigator in cognitive neuroscience and neurology in an academic institution. The University of Pennsylvania is a rich environment for pursuing these goals, featuring resources such as the Center for Cognitive Neuroscience (CCN). The candidate will also augment his career development through coursework and methodological training opportunities offered through the university. Finally, the health implications of this work are far-reaching. Aphasia affects more than 20% of patients with ischemic stroke while hemispatial neglect occurs in 25-30% of stroke-affected individuals. TMS-induced feature-specific effects on aphasia and neglect recovery could point the way toward future therapeutic approaches that may be both more efficacious and better targeted than current therapies.