TMS to explore interhemispheric interactions and to treat aphasia and neglect

描述（由申请人提供）：本提案的主要目的是进一步表征在对偏侧脑损伤做出反应时出现的半球间相互作用，并将此理解应用于卒中诱导的失语症和忽视的治疗。失语症将作为研究右半球在左半球功能中的作用的模型;忽视将作为阐明左半球在右半球功能中的作用的模型。第一个具体的目标是确定左额叶不同领域的语言处理的解剖学差异。经颅磁刺激（TMS）将被施加到正常受试者的左额下回，以破坏表现，揭示语言域之间的分离。第二个具体目标是识别右半球空间认知不同方面的解剖学差异。TMS将被施加到正常受试者的右额叶和顶叶皮层，以改变表现，阐明注意力背后的结构-功能关系。这项研究的解剖学假设将在一项涉及患有失语症或忽视症的慢性中风患者的治疗试验中得到进一步验证。每组将在10次每日对侧病灶TMS治疗前后进行评估。该项目通过发展他对研究设计，心理测量和TMS的熟练程度，并通过促进他对皮层可塑性行为影响的长期兴趣，满足候选人的近期目标。它推进了他的长期目标，即在学术机构中作为认知神经科学和神经学的独立研究者建立职业生涯。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。候选人还将通过大学提供的课程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。失语症影响超过20%的缺血性卒中患者，而半侧空间忽视发生在25-30%的卒中患者中。TMS诱导的失语症和忽视恢复的特征特异性作用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.