Abstract
Introduction The effects of transcranial direct current stimulation (tDCS) on executive functions are of particular interest for understanding the mechanisms underlying integration of cognition and behavior. The key role of prefrontal dopamine function for executive functions suggest that differences of the Val158Met polymorphism of the catechol-O-methyltransferase gene (COMT) would interact with tDCS interventions in this domain. Objective In this study, we investigated if COMT Met allele homozygosity, associated with higher levels of prefrontal dopamine, modulates the effect of tDCS on higher-level executive functions. Materials and methods Forty-six healthy subjects participated in a double-blind sham-controlled crossover study and underwent COMT genotyping. Anodal tDCS (20 min, 1 mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation was applied during the performance of a parametric Go/No-Go Test (PGNG) measuring sustained attention, response inhibition and cognitive flexibility as measured by set-shifting. Results In COMT Met/Met allele carrier anodal tDCS of the dlPFC was associated with a deterioration of set-shifting ability, which is assessed by the most challenging level of the PGNG. Without regard to the carrier status of the COMT Val158Met polymorphism no effects of anodal tDCS on executive functions could be determined. Conclusion In line with the model of non-linear effects of L-dopa on cortical plasticity high dopaminergic prefrontal activity mediated by COMT Val158Met polymorphism predicts a detrimental effect of anodal tDCS on cognitive flexibility. These data suggest that the individual genetic profile may modulate behavioral effect of tDCS. More precise application of brain stimulation techniques according to the individual genetic patterns may support the development of personalized treatment approaches. To further extend this knowledge, we currently investigate the interaction of cathodal stimulation and the COMT Val158Met polymorphism on executive function.
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