Effects of transcranial direct current stimulation (tDCS) on executive functions: Influence of COMT Val/Met polymorphism

Christian Plewnia; Bastian Zwissler; Isabella Längst; Brigitte Maurer; Katrin Giel; Rejko Krüger

doi:10.1016/j.cortex.2012.11.002

Effects of transcranial direct current stimulation (tDCS) on executive functions: Influence of COMT Val/Met polymorphism

Christian Plewnia^*, Bastian Zwissler, Isabella Längst, Brigitte Maurer, Katrin Giel, Rejko Krüger

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

114 Citations (Scopus)

Abstract

Introduction: Transcranial direct current stimulation (tDCS) is a frequently used technique to investigate healthy and impaired neuronal functions. Its modulatory effect on executive functions is 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 (COMT) gene would interact with tDCS interventions in this domain. In this study, we hypothesized that the COMT Metallele homozygosity, associated with higher levels of prefrontal dopamine, would influence the effect of tDCS on higher-level executive functions. Method: Forty-six healthy subjects participated in a double-blind sham-controlled crossover study and underwent COMT genotyping. Anodal tDCS (20min, 1mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation was applied during the performance of a parametric Go/No-Go (PGNG) test measuring sustained attention, response inhibition and cognitive flexibility as measured by set-shifting. Results: In COMT Met/Metallele 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. Conclusions: 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. Therefore, we 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.

Original language	English
Pages (from-to)	1801-1807
Number of pages	7
Journal	Cortex
Volume	49
Issue number	7
DOIs	https://doi.org/10.1016/j.cortex.2012.11.002
Publication status	Published - Jul 2013
Externally published	Yes

Keywords

Brain stimulation
Dopamine
Executive functions
Genetics
Neurophysiology

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10.1016/j.cortex.2012.11.002

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title = "Effects of transcranial direct current stimulation (tDCS) on executive functions: Influence of COMT Val/Met polymorphism",

abstract = "Introduction: Transcranial direct current stimulation (tDCS) is a frequently used technique to investigate healthy and impaired neuronal functions. Its modulatory effect on executive functions is 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 (COMT) gene would interact with tDCS interventions in this domain. In this study, we hypothesized that the COMT Metallele homozygosity, associated with higher levels of prefrontal dopamine, would influence the effect of tDCS on higher-level executive functions. Method: Forty-six healthy subjects participated in a double-blind sham-controlled crossover study and underwent COMT genotyping. Anodal tDCS (20min, 1mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation was applied during the performance of a parametric Go/No-Go (PGNG) test measuring sustained attention, response inhibition and cognitive flexibility as measured by set-shifting. Results: In COMT Met/Metallele 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. Conclusions: 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. Therefore, we 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.",

keywords = "Brain stimulation, Dopamine, Executive functions, Genetics, Neurophysiology",

author = "Christian Plewnia and Bastian Zwissler and Isabella L{\"a}ngst and Brigitte Maurer and Katrin Giel and Rejko Kr{\"u}ger",

note = "Funding Information: Dr. Plewnia received research grants of the German Research Council (DFG; PL 525/1–1) and the Werner Reichardt Centre for Integrative Neuroscience (CIN, PP2011_11). Funding Information: Dr. Kr{\"u}ger serves as Editor of Parkinsonism and Related Disorders, the European Journal of Clinical Investigation, the Journal of Neural Transmission, and Associate Editor of BMC Neurology; has received research grants of the German Research Council (DFG; KR2119/3-2; KR2119/8-1), the Michael J Fox Foundation, the Fritz Thyssen foundation (10.11.2.153) and the Federal Ministry for Education and Research [BMBF, NGFNplus; 01GS08134], as well as speakers honoraria and/or travel grants from UCB Pharma, Cephalon, Abbott Pharmaceuticals, Takeda Pharmaceuticals and Medtronic.",

year = "2013",

month = jul,

doi = "10.1016/j.cortex.2012.11.002",

language = "English",

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pages = "1801--1807",

journal = "Cortex",

issn = "0010-9452",

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number = "7",

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T1 - Effects of transcranial direct current stimulation (tDCS) on executive functions

T2 - Influence of COMT Val/Met polymorphism

AU - Plewnia, Christian

AU - Zwissler, Bastian

AU - Längst, Isabella

AU - Maurer, Brigitte

AU - Giel, Katrin

AU - Krüger, Rejko

N1 - Funding Information: Dr. Plewnia received research grants of the German Research Council (DFG; PL 525/1–1) and the Werner Reichardt Centre for Integrative Neuroscience (CIN, PP2011_11). Funding Information: Dr. Krüger serves as Editor of Parkinsonism and Related Disorders, the European Journal of Clinical Investigation, the Journal of Neural Transmission, and Associate Editor of BMC Neurology; has received research grants of the German Research Council (DFG; KR2119/3-2; KR2119/8-1), the Michael J Fox Foundation, the Fritz Thyssen foundation (10.11.2.153) and the Federal Ministry for Education and Research [BMBF, NGFNplus; 01GS08134], as well as speakers honoraria and/or travel grants from UCB Pharma, Cephalon, Abbott Pharmaceuticals, Takeda Pharmaceuticals and Medtronic.

PY - 2013/7

Y1 - 2013/7

N2 - Introduction: Transcranial direct current stimulation (tDCS) is a frequently used technique to investigate healthy and impaired neuronal functions. Its modulatory effect on executive functions is 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 (COMT) gene would interact with tDCS interventions in this domain. In this study, we hypothesized that the COMT Metallele homozygosity, associated with higher levels of prefrontal dopamine, would influence the effect of tDCS on higher-level executive functions. Method: Forty-six healthy subjects participated in a double-blind sham-controlled crossover study and underwent COMT genotyping. Anodal tDCS (20min, 1mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation was applied during the performance of a parametric Go/No-Go (PGNG) test measuring sustained attention, response inhibition and cognitive flexibility as measured by set-shifting. Results: In COMT Met/Metallele 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. Conclusions: 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. Therefore, we 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.

AB - Introduction: Transcranial direct current stimulation (tDCS) is a frequently used technique to investigate healthy and impaired neuronal functions. Its modulatory effect on executive functions is 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 (COMT) gene would interact with tDCS interventions in this domain. In this study, we hypothesized that the COMT Metallele homozygosity, associated with higher levels of prefrontal dopamine, would influence the effect of tDCS on higher-level executive functions. Method: Forty-six healthy subjects participated in a double-blind sham-controlled crossover study and underwent COMT genotyping. Anodal tDCS (20min, 1mA) to the left dorsolateral prefrontal cortex (dlPFC) or sham stimulation was applied during the performance of a parametric Go/No-Go (PGNG) test measuring sustained attention, response inhibition and cognitive flexibility as measured by set-shifting. Results: In COMT Met/Metallele 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. Conclusions: 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. Therefore, we 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.

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KW - Dopamine

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ER -

Effects of transcranial direct current stimulation (tDCS) on executive functions: Influence of COMT Val/Met polymorphism

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