TMS to explore interhemispheric interactions and to treat aphasia and neglect

描述（由申请人提供）：本提案的中心目的是进一步表征脑侧化损伤后出现的半球间相互作用，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半球在左半球功能中的作用的模型；忽视将成为阐明左半球在右半球功能中的作用的模型。第一个具体目标是确定左额叶中不同语言处理领域的解剖差异。将经颅磁刺激（TMS）用于正常受试者的左额下回，以破坏其表现，揭示语言域之间的分离。第二个具体目标是确定右半球空间认知不同方面的解剖差异。将对正常受试者的右额叶和顶叶皮层进行经颅磁刺激，以改变其表现，阐明注意力背后的结构-功能关系。该研究的解剖学假设将在一项涉及失语或忽视的慢性中风患者的治疗试验中得到进一步验证。每组将在每天10次的对抗性经颅磁刺激前后对其缺陷进行评估。该项目通过提高候选人在研究设计、心理测量和经颅磁刺激方面的熟练程度，并进一步加深他对皮质可塑性行为影响的长期兴趣，满足了候选人的直接目标。它推进了他的长期目标，即在学术机构中建立作为认知神经科学和神经学独立研究者的职业生涯。宾夕法尼亚大学为实现这些目标提供了丰富的环境，以认知神经科学中心（CCN）等资源为特色。候选人还将通过大学提供的课程和方法培训机会来促进他的职业发展。最后，这项工作对健康的影响是深远的。失语症影响超过20%的缺血性中风患者，而25-30%的中风患者出现半脑忽视。经颅磁刺激诱发的对失语症和忽视恢复的特征特异性影响可能为未来的治疗方法指明道路，这种治疗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.