Using High Definition transcranial Direct Current Stimulation Guided by Electrophysiology and Diffusion Tensor Imaging to Treat Verbal Retrieval Deficits Secondary to Chronic Traumatic Brain Injury

项目摘要 语言功能障碍是创伤性脑损伤（TBI）常见的认知后遗症，占TBI的31%~ 44 幸存者最普遍的后遗症之一，找词困难（言语检索缺陷），可以持续更长时间， 受伤后12个月。然而，有效的治疗和基于机制的治疗研究， 仍然缺乏。高清晰度经颅直流电刺激（HD-tDCS）是一种新型的无创性 电调制方法已被证明可以改善TBI的言语检索缺陷， 前辅助运动区（pre-SMA）。涉及前SMA的同步活动中断， 与前SMA相关的白色物质连接可导致言语提取缺陷。尤其是左额叶 倾斜束（FAT）和额纹状体束（FST）通过将SMA前体连接到 左额下回和基底神经节。该提案的三个目标是：1）确定 使用脑电图对涉及SMA前体的同步活动的HD-tDCS调节作用 (EEG)2）使用扩散张量成像（DTI）检查左侧FAT和FST的基线完整性如何影响 SMA前HD-tDCS治疗效果，以及3）建立HD-tDCS诱导变化的预测模型， 整合基线EEG和DTI测量。无论是退伍军人还是轻度到中度TBI的平民， 接受10次20分钟的主动或假HD-tDCS治疗，并将立即进行评价， 治疗结束后的几周。中心假设是SMA前HD-tDCS将调节SMA前 相关的同步活动，以提高口头检索，这些影响将取决于 基线白色物质完整性和同步活动的破坏程度。预期结果将提供 一种新的神经康复方法，用于治疗平民和退伍军人TBI人群的语言检索缺陷， 沿着基本机制的澄清，并提供一个框架，以指导未来的研究和 电调制治疗TBI相关认知后遗症的临床应用。这一建议符合《 NIDCD在“声音、言语和语言研究”下的战略计划，包括优先领域2（“确定 常见和罕见声音、言语和语言的病理生理和认知机制 优先领域3（“检测、诊断和基于假设的干预”）。我建议的 研究将有助于理解TBI中的言语检索缺陷，并治疗由TBI引起的个体。 由于这些缺陷而导致的沟通障碍。K99/R 00职业发展奖将使我能够 获取数据并在认知神经心理学、DTI分析和预测建模方面进行高级培训， K99阶段。有了这个基础，我将在R 00阶段建立我的独立研究， 随后通过NIH R 01机制或其等效机制在年底前获得独立资金。 奖励期。

PROJECT SUMMARY Language dysfunction is a common cognitive sequela of traumatic brain injury (TBI) in 31% to 44% of TBI survivors. One of the most prevalent sequelae, word finding difficulty (verbal retrieval deficit), can persist more than 12 months after injury. Effective treatment and mechanism-based studies for such treatment, however, are still lacking. High-definition transcranial direct current stimulation (HD-tDCS) is a novel non-invasive electromodulation approach that has been shown to improve verbal retrieval deficits in TBI by targeting the pre-Supplementary Motor Area (pre-SMA). Disrupted synchronized activity involving the pre-SMA and impaired white matter connectivity linked to the pre-SMA can result in verbal retrieval deficits. Particularly, the left frontal aslant tract (FAT) and fronto-striatal tract (FST) support verbal retrieval function by connecting the pre-SMA to the left inferior frontal gyrus and basal ganglia, respectively. The 3 aims of this proposal are 1) to determine HD-tDCS modulatory effects on synchronized activity involving the pre-SMA using electroencephalography (EEG), 2) to use diffusion tensor imaging (DTI) to examine how baseline integrity of the left FAT and FST affect pre-SMA HD-tDCS therapeutic effects, and 3) to establish predictive models of HD-tDCS induced changes by integrating baseline EEG and DTI measures. Both veterans and civilians with mild to moderate TBI will undergo ten 20-minunte sessions of active or sham HD-tDCS and will be evaluated immediately and at 8 weeks after treatment completion. The central hypothesis is that pre-SMA HD-tDCS will modulate pre-SMA associated synchronized activity to improve verbal retrieval, and that those effects will be predicated on the degree of disruption in baseline white matter integrity and synchronized activity. The expected results will offer a novel neurorehabilitation approach for verbal retrieval deficits across civilian and veteran TBI populations, along with clarification of underlying mechanisms, and provide a framework to guide future research and clinical application of electromodulation to treat TBI-related cognitive sequelae. This proposal is in line with the NIDCD’s strategic plan under “Voice, Speech, and Language Research” including priority area 2 (“Identify the pathophysiologic and cognitive mechanisms underlying both common and rare voice, speech, and language impairments”) and priority area 3 (“Detection, Diagnosis and Hypothesis-Driven Interventions”). My proposed research will contribute to understanding verbal retrieval deficits in TBI and treating individuals inflicted by impaired communication due to such deficits. The K99/R00 Career Development Award will allow me to acquire data and advance training in cognitive neuropsychology, DTI analysis and predictive modeling in the K99 phase. With this foundation, I will then establish my independent research in the R00 phase that will subsequently lead to independent funding through the NIH R01 mechanism or its equivalent by the end of the award period.