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.

每年，德国约有27万人维持咨询（TBI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（每年最高5％）。复发性TBI通常会导致持续的认知和运动定义。流行病学研究将复发性TBI确定为发展阿尔茨海默氏症的独立危险因素。重复的TBI导致大脑中γ氨基丁酸（GABA）的终生增加。 GABA抑制突触可塑性的形成，例如长期电位（LTP）。在具有复发性TBI史的运动员中，可以证明增加的GABA活性和减少的LTP可以证明，并且可能导致这些个体中的认知缺陷。一种有望降低GABA并提高学习能力和皮质可塑性的希望方法是trancranial直接电流刺激（TDCS）。正如磁共振光谱（MRS）所检测到的那样，已经证明了原发性运动皮层（M1）上的阳极TDC（ATDC）（M1）可降低GABA浓度。 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 subjects with a history of recurrent TBI, and compare these results to a healthy control group.我们将评估GABA浓度和GABA活性的变化（通过MRS和特定的TMS范式衡量），运动学习，类似LTP的可塑性以及功能连接性（使用功能性MRI），ATDC和ATDCS之后和假手术刺激后的功能连接性（对照状态）。与对健康和受伤大脑中的机制ATDC的重要见解相比，可塑性，运动学习和功能连通性，该研究将对认知定义的机制产生更透彻的理解。在原理证明方法中，我们还希望探索TBI之后患者ATDC的治疗潜力。将来，ATDC可能是改善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