Wiegand Ariane, Nieratschker Vanessa, Plewnia Christian
Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Tübingen Tübingen, Germany.
Neurophysiology and Interventional Neuropsychiatry, Department of Psychiatry and Psychotherapy, University of Tübingen Tübingen, Germany.
Front Hum Neurosci. 2016 Dec 22;10:651. doi: 10.3389/fnhum.2016.00651. eCollection 2016.
High inter-individual variability substantially challenges the explanatory power of studies on the modulation of cognitive functions with transcranial direct current stimulation (tDCS). These differences in responsivity have been linked with a critical state-dependency of stimulation effects. In general, genetic diversity is a decisive biological basis of variations in neuronal network functioning. Therefore, it is most likely that inter-individual variability of tDCS-induced changes in cognitive functions is due to specific interactions between genetically determined network properties and the specific type of stimulation. In this context, predominantly the brain-derived neurotrophic factor (BDNF) Val66Met and the catechol-O-methyltransferase (COMT) Val108/158Met polymorphisms have been investigated. The studies on the interaction between the BDNF Val66Met polymorphism and the effect of brain stimulation indicate a critical but yet heterogeneous interaction. But up to now, data on the interplay between this polymorphism and tDCS on cognitive functioning are not available. However, recently, the functional Val(108/158)Met polymorphism in the COMT gene, that is particularly involved in the regulation of executive functions by means of the dopaminergic tone in frontal brain areas, has been demonstrated to specifically predict the effect of tDCS on cognitive control. Following an inverted U-shaped function, the high dopaminergic activity in Met allele homozygous individuals has been shown to be associated with a reduction of executive functioning by anodal tDCS to the prefrontal cortex. Consistently, Val homozygous individuals with lower dopaminergic tone show a clear reduction of response inhibition with cathodal tDCS. These findings exemplify the notion of a complex but neurophysiologically consistent interaction between genetically determined variations of neuronal activity and tDCS, particularly in the cognitive domain. Consequently, a systematic analysis and consideration of genetic modulators of tDCS effects will be helpful to improve the efficacy of brain stimulation and particularly tDCS in the investigation and treatment of cognitive functions.
个体间的高度变异性对经颅直流电刺激（tDCS）调节认知功能的研究的解释力构成了重大挑战。这些反应性差异与刺激效应的关键状态依赖性有关。一般来说，遗传多样性是神经网络功能变化的决定性生物学基础。因此，tDCS诱导的认知功能变化的个体间变异性很可能是由于基因决定的网络特性与特定刺激类型之间的特定相互作用。在这种背景下，主要对脑源性神经营养因子（BDNF）Val66Met和儿茶酚-O-甲基转移酶（COMT）Val108/158Met多态性进行了研究。关于BDNF Val66Met多态性与脑刺激效应之间相互作用的研究表明存在关键但异质性的相互作用。但到目前为止，关于这种多态性与tDCS对认知功能相互作用的数据尚不可用。然而，最近，COMT基因中的功能性Val(108/158)Met多态性已被证明能特异性预测tDCS对认知控制的影响，该多态性尤其通过额叶脑区的多巴胺能张力参与执行功能的调节。遵循倒U形函数，已表明Met等位基因纯合个体中的高多巴胺能活性与经阳极tDCS刺激前额叶皮质后执行功能的降低有关。一致地，多巴胺能张力较低的Val纯合个体在经阴极tDCS刺激后反应抑制明显降低。这些发现例证了基因决定的神经元活动变化与tDCS之间复杂但神经生理学上一致的相互作用的概念，特别是在认知领域。因此，系统分析和考虑tDCS效应的基因调节因子将有助于提高脑刺激尤其是tDCS在认知功能研究和治疗中的疗效。
