Mechanisms underlying atDCS-effects in patients with recurrent traumatic brain injury - a multi-modal analysis using electrophysiology, MR-spectroscopy and functional MRI

复发性创伤性脑损伤患者 atDCS 效应的潜在机制 - 使用电生理学、MR 能谱和功能 MRI 的多模态分析

• 批准号: 240331393
• 负责人: Professorin Dr. Agnes Flöel
• 金额: --
• 依托单位: Klinik und Poliklinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/240331393?language=en
• 关键词: Mechanisms; underlying; atDCS; effects; patients

Around 270,000 people in Germany sustain a concussion (traumatic brain injury, TBI) each year. In sports like ice hockey and American football the probability of suffering a TBI is particularly high (up to 5% / year). Recurrent TBI often lead to persistent cognitive and motor deficits. Epidemiological studies identified recurrent TBI as an independent risk factor for the development of Alzheimer´s dementia.Repeated TBI lead to a lifelong increase of Gamma aminobutyric acid (GABA) in the brain. GABA inhibits the formation of synaptic plasticity like long term potentiation (LTP). Increased GABA-activity and reduced LTP could already be demonstrated in athletes with a history of recurrent TBI, and may be responsible for the cognitive deficits in these individuals.A promising method to reduce both GABA and to increase learning ability and cortical plasticity is transcranial direct current stimulation (tDCS). Anodal tDCS (atDCS) over the primary motor cortex (M1) has been shown to reduce GABA concentration, as detected by magnetic resonance spectroscopy (MRS). Moreover, a positive effect of atDCS over M1 is known to improve LTP-like plasticity (as measured by transcranial magnetic stimulation, TMS) and motor learningIn a multimodal approach, we want to explore the effects of atDCS over M1 on behavioral, neurophysiological, neurochemical and functional and connectivity parameters in athletes with a history of recurrent TBI, and compare these results to a healthy control group. We will evaluate changes of GABA-concentration and GABA-activity (as measured by MRS and specific TMS paradigms), motor learning, LTP-like plasticity, as well as functional connectivity (using functional MRI), after atDCS and after sham stimulation (control condition).We expect that atDCS will significantly decrease GABA-concentration and GABA-activity , and will enhance LTP-like plasticity, motor learning and functional connectivity, as compared to sham stimulationIn addition to important insights into the mechanisms atDCS in the healthy and the injured brain, the study will yield a more thorough understanding of the mechanisms underlying cognitive deficits after recurrent TBI. In a proof-of-principle approach, we also want to explore the therapeutic potential of atDCS in patients after TBI. In the future, atDCS could be an important tool to improve TBI-associated memory impairment and may help to prevent neurodegenerative dementias.

德国每年约有 270,000 人遭受脑震荡（创伤性脑损伤，TBI），在冰球和美式足球等运动中，遭受 TBI 的可能性特别高（每年高达 5%）。流行病学研究发现，复发性 TBI 是发生阿尔茨海默氏痴呆的一个独立危险因素。反复 TBI 会导致体内伽马氨基丁酸 (GABA) 的终生增加。 GABA 抑制突触可塑性的形成，如长期增强 (LTP)，GABA 活性增加和 LTP 减少已经在有复发性 TBI 病史的运动员中得到证实，并且可能是这些个体认知缺陷的原因。一种减少 GABA 并提高学习能力和皮质可塑性的有前景的方法是对初级运动皮层 (M1) 进行经颅直流电刺激 (tDCS)。通过磁共振波谱 (MRS) 检测发现，atDCS 可以降低 GABA 浓度。此外，atDCS 相对于 M1 具有积极作用，可以改善 LTP 样可塑性（通过经颅磁刺激 (TMS) 测量）和运动学习。我们希望探索 atDCS 相对于 M1 对有复发性 TBI 病史的运动员的行为、神经生理学、神经化学以及功能和连接参数的影响，并将这些结果与健康对照组进行比较，我们将评估变化。 atDCS 和假刺激（对照条件）后，GABA 浓度和 GABA 活性（通过 MRS 和特定 TMS 范式测量）、运动学习、LTP 样可塑性以及功能连接（使用功能 MRI）。预计与假刺激相比，atDCS 将显着降低 GABA 浓度和 GABA 活性，并将增强 LTP 样可塑性、运动学习和功能连接性除了对机制的重要见解之外atDCS 在健康和受伤大脑中的应用，该研究将更全面地了解复发性 TBI 后认知缺陷的机制。通过原理验证方法，我们还希望探索 atDCS 对 TBI 后患者的治疗潜力。未来，atDCS 可能成为改善 TBI 相关记忆障碍的重要工具，并可能有助于预防神经退行性痴呆。

项目成果

No Effect of Anodal Transcranial Direct Current Stimulation on Gamma-Aminobutyric Acid Levels in Patients with Recurrent Mild Traumatic Brain Injury.

• DOI: 10.1089/neu.2016.4399
• 发表时间: 2017-01
• 期刊: Journal of neurotrauma
• 影响因子: 4.2
• 作者: S. Wilke;J. List;R. Mekle;R. Lindenberg;M. Bukowski;S. Ott;F. Schubert;B. Ittermann;A. Flöel