When genetics prevail: brain stimulation fails to overcome learning deficits from brain-derived neurotrophic factor Val66Met.

Abstract

Background: The dorsolateral prefrontal cortex (DLPFC) is a key contributor to memory categorization. Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism affects the efficacy of neuronal plasticity induction. We investigated whether DLPFC-transcranial direct current stimulation (tDCS) influences categorization performance, and whether BNDF genotype modulates this effect. Methods: Sixty-two healthy individuals were randomized to receive 10 min of either anodal right DLPFC-tDCS at 1 mA, or sham tDCS during the training phase of a prototype distortion task. Categorization performance was assessed during, shortly after, and the morning following the stimulation. Val66Met polymorphism status was determined through BNDF genotyping. Results: Val66Met carriers showed poorer categorization ability than Val/Val homozygotes (p < 0.0001). tDCS did not enhance categorization performance overall, or reduce genotype-associated differences with these specific stimulation parameters. However, tDCS extinguished the prototype effect of the categorization task observed in our sample. Conclusions: Our findings underscore the importance of BDNF polymorphism in category learning. 1 mA anodal right DLPFC over the right DLPFC does not improve performance or offset genotype differences under tested conditions. Significance: BDNF Val66Met polymorphism influences category learning, and low-intensity tDCS does not counteract this effect, emphasizing the need to refine stimulation protocols for genotype-specific cognitive enhancement.