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

德国每年约有27万人遭受脑震荡（创伤性脑损伤，TBI）。在冰球和美式足球等运动中，患TBI的可能性特别高（高达5% /年）。复发性TBI经常导致持续的认知和运动缺陷。流行病学研究发现，反复TBI是阿尔茨海默氏痴呆症发展的独立危险因素。反复TBI导致大脑中γ氨基丁酸（GABA）终身增加。GABA抑制突触可塑性的形成，如长时程增强（LTP）。GABA活性增加和LTP降低已经在有反复TBI病史的运动员中得到证实，并且可能是这些个体的认知缺陷的原因。经颅直流电刺激（tDCS）是一种有前途的降低GABA活性并提高学习能力和皮层可塑性的方法。通过磁共振波谱（MRS）检测，初级运动皮层（M1）上的阳极tDCS（atDCS）已被证明可降低GABA浓度。此外，已知atDCS相对于M1的积极作用可以改善LTP样可塑性（通过经颅磁刺激，TMS测量）和运动学习。在多模式方法中，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，神经化学和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GABA浓度和GABA活性的变化（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），在atDCS和假刺激后我们预期atDCS将显著降低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，除了对健康和受伤大脑中DCS机制的重要见解外，该研究还将对复发性TBI后认知缺陷的潜在机制产生更透彻的理解。在原理验证方法中，我们还希望探索atDCS在TBI后患者中的治疗潜力。在未来，atDCS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。

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.